biological indicator of sterilization and method of use thereof

专利摘要:
The present invention relates to a biological sterilization indicator (B1) and the method of use thereof. B1 can include a compartment and a container positioned in the compartment. The container may contain a liquid and at least a portion of the container may be frangible. B1 may further include a first chamber and a second chamber. The second chamber can include at least one source of biological activity. The B1 may further include a first fluid path positioned to fluidly couple the first chamber and the second chamber, and a second fluid path positioned to allow displaced gas to move out of the second chamber. The method may include moving gas displaced out of the second chamber through the second fluid path as the sterilant is moved into the second chamber through the first fluid path and/or as the liquid is moved into the second chamber through the first trajectory for fluids.
公开号:BR112013010254B1
申请号:R112013010254-3
申请日:2011-10-28
公开日:2021-05-18
发明作者:Jeffrey C. Pederson；Sailaja Chandrapati；Jeffrey D. Smith
申请人:3M Innovative Properties Company；
IPC主号:

专利说明:

Field of Invention
[001] This description refers, in general, to sterilization indicators and, particularly, to biological indicators of sterilization. Background
[002] In a variety of industries, such as the healthcare industry as well as other industrial applications, it may be necessary to monitor the effectiveness of processes used to sterilize equipment such as medical devices and other disposables and non-disposable items. In these settings, sterilization is generally defined as the process of complete destruction of all viable sources of biological activity, such as microorganisms, including structures such as viruses and spores. As standard practice, hospitals include a sterility indicator with a batch of articles to test the lethality of the sterilization process. Both biological and chemical sterilization indicators have been used.
A standard type of biological indicator of sterilization includes a known amount of test microorganisms, for example spores of Geobacillus stearothermophilus (formerly Bacillus stearothermophilus) or Bacillus atrophaeus (formerly Bacillus subtilis), which may be many times more resistant to a sterilization process that other contaminating organisms. After the indicator is exposed to the sterilization process, the sources of biological activity (eg, spores) can be incubated in a nutrient medium to determine whether any of the sources survived the sterilization process, with metabolism and/or source growth indicating that the sterilization process was insufficient to destroy all sources of biological activity.
[004] The chemical sterilization indicators can be evaluated immediately at the end of the sterilization process. However, the results only indicate that a particular condition was present during the sterilization process, such as the presence of a particular chemical or a temperature, and potentially, that the condition was reached during a certain period of time. Rather, the response of biologically active sources to all conditions actually present can be a more direct and reliable test of how effective a sterilization process is in achieving sterilization. summary
[005] Some aspects of this description provide a biological indicator of sterilization. The biological sterilization indicator can include a compartment and a container. The container can contain a liquid and can be sized to be positioned in the compartment. At least a portion of the container may be frangible, and the container may have a first state in which the container is intact and the liquid is not in fluid communication with an interior of the compartment, and a second state in which the container is fractured and the liquid is in fluid communication with the interior of the compartment. The biological sterilization indicator may further include a first chamber in the compartment in which the container is positioned when the container is in the first state, and a second chamber in the compartment in which the container and liquid are not positioned when the container is in the first state, and to which a sterilant moves when the container is in the first state and to which the liquid moves when the container is in the second state. The second chamber may include at least one source of biological activity which is not in fluid communication with the liquid when the container is in the first state, and which is in fluid communication with the liquid when the container is in the second state. The biological sterilization indicator may further include a first fluid path positioned to fluidly couple the first chamber and the second chamber. The first fluid path can be positioned to allow a sterilant to move from the first chamber to the second chamber when the container is in the first state, and to allow liquid to move from the first chamber to the second chamber when the container is in the second state. The biological sterilization indicator may further include a second fluid path positioned to fluidly couple the second chamber and another chamber of the biological sterilization indicator. The second fluid path can be positioned to allow displaced gas to move out of the second chamber as the sterilant or liquid moves from the first chamber to the second chamber.
[006] Some aspects of the present description may provide a method for using a biological indicator of sterilization. The method may include providing a biological indicator of sterilization. The biological sterilization indicator can include a compartment and a container. The container can include a liquid and can be positioned in the compartment. At least a portion of the container may be frangible. The container may have a first state in which the container is intact and the liquid is not in fluid communication with an interior of the compartment, and a second state in which the container is fractured and the liquid is in fluid communication with the interior of the compartment. The biological sterilization indicator may further include a first chamber in the compartment in which the container is positioned when the container is in the first state, and a second chamber in the compartment in which the container and liquid are not positioned when the container is in the first state, and to which the sterilant moves when the container is in the first state and to which the liquid moves when the container is in the second state. The second chamber may include at least one source of biological activity which is not in fluid communication with the liquid when the container is in the first state, and which is in fluid communication with the liquid when the container is in the second state. The method may further include at least one of: (a) moving a sterilant from the first chamber to the second chamber via a first fluid path when the container is in the first state, and moving the displaced gas out of the second chamber via a second fluid path as a sterilant is moved from the first chamber to the second chamber via the first fluid path; and (b) moving liquid from the first chamber to the second chamber by means of a first fluid path when the container is in the second state, and moving the displaced gas out of the second chamber by means of a second fluid path as per the liquid is moved from the first chamber to the second chamber via the first fluid path.
[007] Other features and aspects of the present description will become apparent from consideration of the detailed description and attached drawings. Brief Description of Drawings
[008] Figure 1 is an anterior perspective view of a biological sterilization indicator according to an embodiment of the present description, wherein the biological sterilization indicator includes a compartment that includes a first portion and a second portion.
[009] Figure 2 is a rear perspective view of the biological sterilization indicator of Figure 1.
[0010] Figure 3 is a front exploded view of the biological sterilization indicator of Figures 1 to 2.
[0011] Figure 4 is a side cross-sectional view of the biological sterilization indicator of Figures 1 to 3, taken along line 4-4 of Figure 1, the biological sterilization indicator shown in a first state, and the second portion of the biological sterilization indicator compartment shown in a first position.
[0012] Figure 5 is a top cross-sectional view of the biological sterilization indicator of Figures 1 to 4, taken along line 55 of Figure 1.
[0013] Figure 6 is a side cross-sectional view of the biological sterilization indicator of Figures 1 to 5, with the biological sterilization indicator shown in a second state, and the second portion of the biological sterilization indicator compartment shown in a second position.
[0014] Figure 7 is a top cross-sectional view of the biological sterilization indicator of Figures 1 to 6, with portions removed for clarity. Detailed Description
[0015] Before any embodiments of the present description are explained in detail, it should be understood that the invention is not limited in its application to the details of construction and the arrangement of components demonstrated in the description below or illustrated in the drawings below . The invention may comprise other embodiments and be practiced or carried out in various ways. It is also to be understood that the phraseology and terminology used in the present invention are for descriptive purposes, and should not be considered limiting. The use of "including", "comprising", or "having" and variations thereof of the present invention are intended to encompass the items mentioned thereafter and the equivalents thereof as well as additional items. Unless otherwise specified, or otherwise limited, the terms “sustained” and “coupled” and variations thereof are widely used and cover both direct and indirect supports and couplings. Additionally, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings. It should be understood that other modalities can be used, and that structural or logical changes can be made without departing from the scope of this description. Furthermore, terms such as "front", "rear", "top", "bottom" and the like are only used to describe the mutual relationship between the elements, however, they are in no way intended to refer to the specific orientations of the apparatus, indicate or confer necessary or required directions on the apparatus, or specify how the invention described herein will be used, assembled, displayed or positioned in use.
[0016] The present description refers, in general, to a sterilization indicator, and particularly, to a biological indicator of sterilization. A biological indicator of sterility is sometimes referred to as a “biological indicator of sterility”, or simply a “biological indicator”. Some sterilization biological indicator modalities in this description are one-piece, and can be used to determine the lethality of the sterilization process. The present description generally refers to the construction of the biological sterilization indicator that allows one or more of the following: to house a liquid (for example, an aqueous mixture) separated from one or more sources of biological activity during the sterilization and allow the combination of liquid and sources of biological activity after sterilization; facilitate movement of the sterilant to a location (eg, a closed end) of the biological sterilization indicator where one or more sources of biological activity are housed; keep a frangible container (eg, an ampoule, such as a glass ampoule) that contains the liquid in a separate location from the source(s) of biological activity in the sterilization biological indicator during sterilization; releasing the liquid from the frangible container during activation of the biological sterilization indicator (for example, when fracturing the container); controlling and/or facilitating the movement of liquid during activation to a location on the biological sterilization indicator where the source(s) of biological activity are housed; provide a substantially constant sterilant trajectory; collect and/or maintain portions of the fractured container (eg, to inhibit movement of fractured portions into proximity to sources of biological activity); minimize the diffusion of source(s) of biological activity and/or detectable signals or products away from the source location or a detection region of the sterilization biological indicator (eg, to enhance detection); and generally controlling and/or facilitating the flow of fluids in the biological sterilization indicator (for example, by employing one or more internal air vents).
[0017] Pressurized water vapor or other common sterilants can be used to sterilize equipment and supplies used in healthcare environments. Small one-piece indicators, such as biological sterilization indicators, can be used to verify the effectiveness of sterilization processes. These indicators can be biological and can contain sources of biological activity.
[0018] The nutrient medium used to nourish sources of biological activity (eg, spores) following a sterilization procedure may be introduced through the sterilization procedure, but may not be accessible by sources of biological activity until desired. For example, a containment bag or frangible container (eg an ampoule such as a glass ampoule) can house the medium 'on the plate' separately from the sources of biological activity, and the container can be fractured to place the sources of activity biological and the medium in fluid communication with each other, when desired (for example, after a sterilization process). Nutrients and nutrient media to facilitate the growth of microorganisms are known in the art and can be found, for example, in "Handbook of Microbiological Media" by Ronald Atlas, published by CRC Press, Boca Raton, FL, USA. Matner et al. (US Patent No. 5,073,488), which is incorporated herein in its entirety by reference, describe a nutrient medium for the growth and detection of bacterial spores in a sterilization biological indicator that can be employed in the sterilization biological indicators of the present disclosure.
[0019] In general, sources of biological activity (eg, microorganisms) are chosen to be used in a biological indicator of sterilization that are resistant to a particular sterilization process. Biological indicators of sterilization of the present description include a viable amount, or culture, of one or more known sources of biological activity (e.g., microorganism species). Such sources of biological activity can be in the form of microbial spores. The test source in the sterilization biological indicator is killed by a successful sterilization cycle, or survives if the sterilization cycle is not suitable for some reason. Bacterial spores, in addition to the vegetative form of the organisms, are sometimes used at least partially because vegetative bacteria are known to be killed relatively easily by sterilization processes. Spores can also have superior storage characteristics and can remain in their latent state for years. As a result, in some modalities, sterilization of an inoculum from a standardized spore strain can provide a high degree of confidence that inactivation of all microorganisms in a sterilization chamber has occurred successfully.
[0020] By way of example, this description describes one or more sources of biological activity used in the biological indicator of sterilization as being "spores"; however, it should be understood that the type of source (eg, spore) used in a particular modality of the biological sterilization indicator is selected to be highly resistant to the particular sterilization process contemplated. Consequently, different modalities of the present description may use different sources of biological activity, depending on the sterilization process for which the modality is envisioned. The term "spores" is used throughout this description for the sake of simplicity, but it should be understood that other sources of biological activity, such as microorganisms (eg bacteria, fungi, viruses, etc.), spores (by example, bacterial, fungal, etc.), enzymes, substrates for enzymatic activity, ATP, microbial metabolites, or a combination thereof, may be used in the sterilization biological indicator of the present description instead.
[0021] The phrase "biological activity" refers generally to any specific catalytic process or groups of processes associated with a biological cell. Some non-limiting examples of biological activities include catabolic enzyme activities (eg, carbohydrate fermentation pathways), anabolic enzyme activities (eg, nucleic acid, amino acid, or protein synthesis), coupled reactions (eg, a pathway metabolic), biomolecule-mediated redox reactions (eg, electron transport systems), and bioluminescent reactions. “Predetermined” biological activity means that the method is directed towards detecting a specific biological process (eg an enzyme reaction) or group of biological processes (eg a biochemical trajectory). It will be understood by a person having ordinary skill in the art that certain predetermined biological activities may be associated with a particular type of cell (eg, cancer cell or micro-organism) or a pathological process.
[0022] Similarly, it should be understood that phrases used in the present description which include the term "spore", such as "spore support", "spore reservoir", "spore region", "spore growth chamber" ” and the like are used merely for the sake of simplicity, but that such components, elements or phrases apply equally to other sources of biological activity and are not intended to refer only to spores. For example, the above phrases can also be called a “font holder”, a “source region”, a “font reservoir”, a “font growth chamber” and the like.
[0023] The process of bringing the spores and the medium can be called "activation" of the biological indicator of sterilization. That is, the term "activation" and variations thereof, when used in relation to a biological indicator of sterilization, can generally refer to placing one or more sources of biological activity (for example, spores) in fluid communication with a liquid or medium (eg a nutrient medium for the spores of interest). For example, when a frangible container in the biological sterilization indicator that contains the medium is at least partially fractured, punctured, perforated, crushed, cracked or the like, so that the medium has been placed in fluid communication with the source(s) ) of biological activity, the biological sterilization indicator can be described as having been “activated”. In other words, a biological indicator of sterilization was activated when the source(s) of biological activity were exposed to medium that was previously housed separately from the source(s) of biological activity.
[0024] Some existing sterilization indicators, and particularly biological sterilization indicators, include a compartment that defines a single chamber therein, and in which various components are positioned, such as a source holder (eg, a spore strip) that is adapted to locate the source(s) of biological activity at a desired location (eg a closed end) on the biological sterilization indicator, and a container comprising a liquid (eg a nutrient medium). However, the present description is generally directed to biological indicators of sterilization having more than one chamber formed in a compartment, so that the container and the source(s) of biological activity can be housed separately from each other and in separate regions of the biological sterilization indicator, particularly during sterilization. Although the biological sterilization indicators of this description may include more than one chamber and provide separation of the container and the source(s) of biological activity, the biological sterilization indicators of this description have been designed so that such separation between components may not adversely affect other functions of the biological sterilization indicator. For example, the biological sterilization indicators in this description may also facilitate (1) moving a sterilant to the source(s) of biological activity during sterilization, and/or (2) moving the liquid in contact with the( s) source(s) of biological activity when desired (eg after sterilization and during activation of the biological sterilization indicator).
[0025] In some embodiments, fluid flow facilitated through and/or in the biological sterilization indicator can be provided by employing one or more internal air outlets or air outlet channels. Such internal air outlets can be provided by path for fluids that are formed in the biological sterilization indicator. The phrases "air outlet", "internal air outlet", "air outlet channel", or variations thereof may generally refer to a fluid path that is positioned to allow gas present in a region (eg chamber, reservoir, volume, portion, etc.) of the biological sterilization indicator is shifted when another fluid (eg a liquid, gas or combinations thereof) is moved into that region. In particular, such phrases generally refer to internal fluid pathways that allow one region on the biological sterilization indicator to be vented to another region on the biological sterilization indicator (for example, when the biological sterilization indicator is sealed from the environment) to facilitate movement of fluid in a desired region of the biological sterilization indicator. Additionally, such ventilation in the biological sterilization indicator can facilitate fluid moving from a larger region to a smaller region (e.g., a closed end) of the biological sterilization indicator, particularly when the volume of fluid to be moved is greater than the volume of the smaller region. In some embodiments, such internal ventilation can facilitate the flow of fluids in or through the biological sterilization indicator even without employing substantial external force, or of any kind, such as centrifuging, shaking, tapping, or the like.
[0026] In some embodiments, the biological sterilization indicators of the present description may include a first fluid path positioned to fluidly couple a first chamber and a second chamber, and a second fluid path positioned to fluidly couple the second chamber with another chamber (eg the first chamber) on the biological sterilization indicator. The first fluid path can generally be used to move a sterilizer (i.e., during sterilization) and/or liquid (i.e., during activation) from the first chamber to the second chamber, and the second fluid path can be generally used as an air outlet for the second chamber to allow gas to escape from the second chamber and to facilitate movement of the sterilizer and/or liquid within the second chamber. In such embodiments, the first chamber can be used to house the container containing the liquid, and the second chamber can be used to house one or more sources of biological activity.
[0027] After a biological sterilization indicator has been exposed to a sterilization cycle, the sterilization load (for example, including the items desired to be sterilized and the biological sterilization indicator) can be removed from the sterilizer. One of the first steps in processing the biological sterilization indicator may include activating the biological sterilization indicator. In some embodiments, activation may include closing the sterilization biological indicator, which may include moving a portion (eg, a cap) of the sterilization biological indicator relative to another portion of the sterilization biological indicator (eg, a tube , a base, a tubular body, etc.). In some modalities, the interior of the biological sterilization indicator may remain in fluid communication with the environment during sterilization, but closed off from the environment after sterilization. For example, in some embodiments, the sterilization biological indicator cap can be attached to the sterilization biological indicator tube during sterilization in a first position that maintains fluid communication between the interior of the sterilization biological indicator and the environment. After sterilization, the cap can be further pressed onto the tube (eg to a second position in which the interior of the biological sterilization indicator is no longer in fluid communication with the environment) to maintain sterility and reduce the evaporation rate of a medium (eg, a liquid) used to support metabolic activity and/or spore growth (ie, if still viable). The medium can be contained during sterilization and released into the biological sterilization indicator after sterilization. For example, the medium can be housed separately from the spores during sterilization in a frangible container that can be at least partially fractured after sterilization during an activation step (for example, in response to movement of the cap relative to the tube or base of the biological sterilization indicator) to place the medium in fluid communication with the spores to ensure proper nutrition to the spores.
[0028] In some embodiments of the present description, closing the biological sterilization indicator (e.g., moving one portion relative to the other portion to seal the interior) may include or cause fracturing of a frangible container containing the medium, from so that closing the biological sterilization indicator causes the activation of the biological sterilization indicator.
[0029] The biological sterilization indicator of the present description can be used with a variety of sterilization processes including, but not limited to, exposure to water vapor (e.g., pressurized water vapor), dry heat, gaseous or liquid agents (eg, ethylene oxide, hydrogen peroxide, peracetic acid, ozone, or combinations thereof), radiation, or combinations thereof. In at least some of the sterilization processes, an elevated temperature, for example, 50°C, 100°C, 121°C, 132°C, 134°C, or the like, is included or can be found in the process. In addition, high pressures and/or vacuum can be found, for example, 1 X 105 Pa (15 psi)
[0030] As mentioned above, the sources of biological activity used in a particular system are selected according to the sterilization process used. For example, for a steam sterilization process, Geobacillus stearothermophilus or Bacillus stearothermophilus, or spores thereof can be used. In another example, for an ethylene oxide sterilization process, Bacillus atrophaeus (formerly Bacillus subtilis), or spores thereof, can be used. In some embodiments, spores resistant to the sterilization process may include, but are not limited to, at least one of Geobacillus stearothermophilus, Bacillus stearothermophilus, Bacillus subtilis, Bacillus atrophaeus, Bacillus megaterium, Bacillus coagulans, Clostridium sporogenes, Bacillus pumilus, or combinations of the same.
[0031] Enzymes and substrates that may be suitable for use in the biological indicator of sterilization of the present description are identified in US Patent Nos. 5,073,488 (Matner et al), 5,418,167 (Matner et al.), and 5,223. 401 (Foltz et al.), which are incorporated herein by reference and in their entirety.
Suitable enzymes may include hydrolytic enzymes and/or enzymes derived from spore-forming microorganisms such as Bacillus stearothermophilus and Bacillus subtilis. Enzymes from spore-forming microorganisms that may be useful in the biological sterilization indicators of the present disclosure may include beta-D-glycosidase, alpha-D-glycosidase, alkaline phosphatase, acid phosphatase, butyrate esterase, caprylate esterase lipase, myristate lipase , leucine aminopeptidase, valine aminopeptidase, chymotrypsin, phosphohydrolase, alpha-D-galactosidase, beta-D-galactosidase, tyrosine aminopeptidase, phenylalanine aminopeptidase, beta-D-glucuronidase, alpha-L-arabinofuranosidase, N-glycosacetyl-beta- -D-cellobiosidase, alanine aminopeptidase, proline aminopeptidase and fatty acid esterases.
[0033] Some modalities of the sterilization biological indicator may include chromogenic and/or fluorogenic substrates that react with enzymes to form detectable products (M. Roth, Methods of Biochemical Analysis, Vol. 17, D. Block, Ed., Interscience Publishers, New York, 1969, p. 89, incorporated herein by reference; S. Udenfriend, Fluorescence Assay in Biology and Medicine, Academic Press, New York, USA, 1962, p. 312; and DJR Lawrence, Fluorescence Techniques for the Enzymologist , Methods in Enzymology, Vol. 4, SP Colowick and NO Kaplan, Eds., Academic Press, New York, USA, 1957, p. 174). These substrates can be classified into two groups based on the way in which they create a visually detectable signal or product. Substrates in the first group react with enzymes to form enzyme-modified products that are chromogenic or fluorescent. The substrates in the second group form enzyme-modified products that must further react with an additional compound, or compounds, to create a detectable product that can generate a fluorescent color or signal.
[0034] As a result, the phrase "detectable product" can refer to any molecule, compound, substance, substrate, or the like, or combinations thereof, which can be detected by any of the detection methods or processes described below. For example, such detectable products can be a sign of the viability of a source of biological activity, and detection of such products can generally indicate the failure or inadequacy of a sterilization process.
[0035] In some embodiments, the source of active enzyme may be (1) purified, isolated enzyme derived from a suitable microorganism; (2) a microorganism to which the enzyme is native or added by genetic engineering; and/or (3) a micro-organism to which the enzyme has been added during sporulation or growth, such that the enzyme is incorporated into or associated with the micro-organism, for example, an enzyme added to a spore during sporulation that becomes makes it incorporated into the spore. In some embodiments, microorganisms that can be used as a source of an enzyme include bacteria or fungi in the spore or vegetative state. In some embodiments, the enzyme source includes Bacillus, Clostridium, Neurospora, Candida, or a combination of these microorganism species.
The enzyme alpha-D-glycosidase has been identified in Bacillus stearothermophilus spores, such as those commercially available as "ATCC 8005" and "ATCC 7953" from the American Type Culture Collection, Rockville, Md, USA. The enzyme beta-D-glucosidase has been found in B. subtilis (eg, commercially available as "ATCC 9372" from the American Type Culture Collection).
[0037] In the event that an isolated enzyme is used, or the microorganism used as the source of the enzyme is no more resistant to sterilization conditions than natural contaminants, another microorganism commonly used to monitor sterilization conditions may be exposed to the sterilization cycle together with the enzyme source. In that case, the method of the present description may include the step of incubating any viable microorganism remaining after the sterilization cycle with an aqueous nutrient medium to confirm sterilization effectiveness.
[0038] In general, monitoring the effectiveness of the sterilization process may include placing a biological indicator of sterilization in a sterilizer. In some embodiments, the sterilizer includes a sterilization chamber that can be sized to accommodate a plurality of items to be sterilized, and can be equipped with a means of exhaust air and/or other chamber gases and a means for adding a sterilant to the chamber. The biological sterilization indicator of the present description can be positioned in areas of the sterilizer that are more difficult to sterilize (eg above the drain). Alternatively, the biological sterilization indicator of the present description may be positioned adjacent to (or generally in close proximity to) an article to be sterilized when the biological sterilization indicator is positioned in the sterilization chamber. In addition, the biological sterilization indicator can be positioned on process challenge devices that can be used as sterilizers.
[0039] The sterilization process can also include the exposure of the articles to be sterilized and the biological indicator of sterilization to a sterilant. In some embodiments, the sterilant can be added to the sterilization chamber after evacuating at least a portion of the chamber of any air or other gas present therein. Alternatively, sterilant can be added to the chamber without evacuating the chamber. A series of evacuation steps can be used to ensure that the sterilant reaches all desired areas in the chamber and contacts all items to be sterilized, including the biological sterilization indicator.
[0040] In general, after the biological sterilization indicator has been exposed to a sterilization cycle, a liquid (eg, a growth medium, water that can be mixed with a solid growth medium, etc., or combinations thereof same) can be introduced to the spores. As mentioned above, the step in which liquid is introduced to the spores can be called the “activation step”. If the spores have the sterilization cycle, the liquid will facilitate the metabolic activity and/or growth of the spores, and such activity and/or growth can be investigated. If growth is observed, the sterilization cycle is generally considered ineffective.
[0041] Figures 1 to 7 illustrate a biological sterilization indicator 100 according to an embodiment of the present description. Other suitable embodiments of biological sterilization indicators are described in co-pending PCT application No. WO2011/011189 entitled "Biological Sterilization Indicator and Method of Using Same"; US Patent Application No. 61/409,042, entitled "Biological Sterilization Indicator System and Method"; US Patent Application No. 61/408,997 entitled "Biological Sterilization Indicator System and Method"; and US Patent Application No. 61/408,977 entitled "Biological Sterilization Indicator"; each of which is incorporated herein by reference in its entirety.
[0042] The sterilization biological indicator 100 may include a compartment 102, which may include a first portion 104 and a second portion 106 (e.g., a lid) adapted to be coupled thereto to provide the one-piece sterilization biological indicator . In some embodiments, first portion 104 and second portion 106 can be formed of the same materials, and in some embodiments, first portion 104 and second portion 106 can be formed of different materials. Compartment 102 may define a reservoir 103 of biological sterilization indicator 100 into which other components may be positioned and into which a sterilizer may be directed during a sterilization process.
[0043] Compartment 102 may be defined by at least one liquid impermeable wall, such as wall 108 of first portion 104 and/or a wall 110 of second portion 106. It should be understood that a unitary compartment of a part 102 is also may be employed or that the first and second portions 104 and 106 may assume other shapes, dimensions or relative structures without departing from the character and scope of the present description. Suitable materials for compartment 102 (e.g., walls 108 and 110) may include, but are not limited to, a glass, a metal (e.g., foil), a polymer (e.g., polycarbonate (PC), polypropylene (PP), polyphenylene (PPE), polythiene, polystyrene (PS), polyester (eg polyethylene terephthalate (PET)), polymethyl methacrylate (PMMA or acrylic), acrylonitrile-butadiene-styrene (ABS), cycle polymer olefin (COP), cycloolefin copolymer (COC), polysulfone (PSU), polyether sulfone (PES), polyether imide (PEI), polybutyleneterephthalate (PBT)), a ceramic, a porcelain, or combinations thereof.
[0044] In some embodiments, the biological sterilization indicator 100 may further include a frangible container 120 that contains a liquid (e.g., an aqueous mixture) 122, and which is sized to be received in the biological sterilization indicator 100, for example , in at least a portion of housing 102 (e.g., at least the first portion 104 of housing 102). The frangible container 120 can be formed from a variety of materials, including, but not limited to, one or more of metal (e.g., foil), a polymer (e.g., any of the polymers mentioned above with respect to the compartment. 102), glass (eg a glass ampoule), and combinations thereof. In some embodiments, only a portion of container 120 is frangible, for example, container 120 may include a frangible portion or overcap (e.g., a frangible barrier, film, membrane, or the like). The frangible container 120 may have a first state in which it is intact and the liquid 122 is contained therein, and a second state in which at least a portion of the container 120 is fractured. In the second state of container 120, liquid 122 may be in fluid communication with reservoir 103 of biological sterilization indicator 100, for example, when container 120 is positioned on biological sterilization indicator 100.
[0045] As shown in the illustrated embodiment, the container 120 can be held in place on the biological sterilization indicator 100 and/or fractured by an insert 130, which is described in greater detail below.
[0046] The first portion 104 of compartment 102 may be adapted to house a majority of the components of the biological sterilization indicator 100, and may be called a "tube", "tubular body", "base", or the like. Compartment 102 may include a reservoir 103 which may be defined by one or both of first portion 104 and second portion 106 of compartment 102. Biological sterilization indicator 100 may further include spores or other source(s) of biological activity 115 (or a spore site) positioned in fluid communication with reservoir 103. As shown in Figures 1 to 3, second portion 106 of housing 102 may include one or more apertures 107 to provide fluid communication between the interior. of compartment 102 (e.g. reservoir 103) and the environment. For example, one or more openings 107 can provide fluid communication between spores 115 and the ambience during the sterilization process, and can serve as an input to biological sterilization indicator 100 and as an input to a sterilant pathway 164 (described in more details below). In some embodiments, second portion 106 of housing 102 may be coupled to a first (e.g., open) end 101 of first portion 104 of housing 102, and spores 115 may be positioned at a second (e.g., closed) end. 105, opposite the first end 101, of the first portion 104 of the housing 102.
[0047] In some embodiments, a barrier or filter (e.g., a sterile barrier; not shown) may be positioned in the sterilant path 164 (e.g., at the inlet formed by opening 107) to inhibit contamination or entry of organisms, foreign objects or materials in the biological sterilization indicator 100. This barrier may include a gas-transmissive material impervious to microorganisms, and may be coupled to compartment 102 by a variety of coupling means, including, but not limited to, an adhesive, a heat seal, a sonic weld, or the like. Alternatively, the barrier may be coupled to the sterilant path 164 via a support structure (such as a second portion 106) that is coupled to the first portion 104 of the compartment 102 (e.g., in a snap-on engagement, a by-engagement. screw, a snap fit, or a combination thereof). During exposure to a sterilant, it may cross the barrier in the sterilant pathway 164 and come into contact with spores 115.
[0048] In some embodiments, as shown in the illustrated embodiment, housing 102 may include a lower portion 114 and an upper portion 116, which may be at least partially separated by an inner wall (or partial wall) 118, protrusion, partition, flange or the like, in which an opening 117 may be formed which provides fluid communication between the lower portion 114 and the upper portion 116. In some embodiments, the lower portion 114 of the first portion 104 of the housing 102 (sometimes simply referred to as " the lower portion 114" or "the lower portion 114 of housing 102") may be adapted to house the spores 115 or a spore site. In some embodiments, lower portion 114 may be called the "detection portion" or "detection region" of compartment 102, because at least a portion of lower portion 114 can be interrogated for signs of spore growth. Furthermore, in some embodiments, the upper portion 116 of the first portion 104 of the housing 102 (sometimes called "the upper portion 116" or "the upper portion 116 of the housing 102" for simplicity) may be adapted to accommodate by the minus a portion of the frangible container 120, particularly, prior to activation.
[0049] In some embodiments, the portion of the reservoir 103 that is defined at least partially by the upper portion 116 of the compartment 102 may be called a first chamber (or reservoir, zone, region, or volume) 109 and the portion of the reservoir 103 that is defined at least partially by the lower portion 114 of compartment 102 may be called a second chamber (or reservoir, zone, region, or volume) 111. In some embodiments, the second chamber 111 may be called a "growth chamber" of spore” or a “detection chamber” and may include a volume to be interrogated for spore viability to determine the effectiveness of a sterilization process.
[0050] The first chamber 109 and the second chamber 111 can be positioned in fluid communication with each other to allow a sterilizer and the liquid 122 to move (i.e., through) the first chamber 109 to the second chamber 111. In some In embodiments, the degree of fluid connection between the first chamber 109 and the second chamber 111 (for example, the size of an opening system, such as the opening system 117, which connects the first chamber 109 and the second chamber 111) can increase after, simultaneously with, and/or in response to the activation step (i.e., liquid 122 being released from container 120). In some embodiments, fluid communication control (or fluid connection extension) between the first chamber 109 (eg, upper portion 116) and second chamber 111 (eg, lower portion 114) may be provided by at least a portion of the insert 130.
[0051] The container 120 can be positioned and retained in the first chamber 109 during sterilization and when the container 120 is in a first, unfractured state. Spores 115 can be housed in second chamber 111 and in fluid communication with the environment when container 120 is in the first state. The first chamber 109 and the second chamber 111 can be configured so that the container 120 is not present in the second chamber 111, and particularly not when the container 120 is in its first, unfractured state. A sterilizer may move to the second chamber 111 (for example, through the first chamber 109) during sterilization, and the liquid 122 may move to the second chamber 111 (for example, from the first chamber 109) during activation, when container 120 is fractured and liquid 122 is released into compartment 102.
[0052] As a result, when the container 120 is in the first state, the first chamber 109 and the second chamber 111 can be in fluid communication with each other, and with the environment (e.g., during sterilization). For example, first chamber 109 and second chamber 111 may be in fluid communication with the environment through one or more openings 107. In some embodiments, first chamber 109 and second chamber 111 may be in fluid communication with the environment. such that the first chamber 109 is positioned upstream of the second chamber 111 when a sterilizer is entering the biological sterilization indicator 100. That is, the first chamber 109 can be positioned between the inlet of the sterilizer (e.g., at one or more openings 107) and the second chamber 111, and the inlet of the sterilizer can be positioned on an opposite side of the first chamber 109 with respect to the second chamber 111.
[0053] As shown in Figures 4 and 6, in some embodiments the first chamber 109 may be defined by one or both of the first portion 104 and the second portion 106, particularly when the container 120 is in the first state. Furthermore, in some embodiments, first chamber 109 may include a first end 112 positioned adjacent to the open end 101 of the first portion 104 of the housing 102, adjacent the second portion 106 of the housing 102, and/or at least partially defined by the second portion 106. First chamber 109 may further include a second end 13 positioned adjacent and in fluid communication with second chamber 111 and positioned toward closed end 105 of housing 102. First end 112 of first chamber 109 may be defined by first portion 104 and/or second portion 106 of housing 102.
[0054] As further shown in Figures 4 and 6, in some embodiments, the second chamber 111 may include a first end 124 positioned adjacent and in fluid communication with the first chamber 109 and positioned toward the open end 101 of the housing 102, and a second end 125 at least partially defined by, including, or positioned adjacent to closed end 105 of housing 102.
In other words, as shown in Figures 4 and 6, the biological sterilization indicator 100 may include a longitudinal direction DL, and in some embodiments, the first chamber 109 may be positioned longitudinally above the second chamber 111.
[0056] In some embodiments, second chamber 111 may be at least partially defined by, may include, or may be positioned adjacent to closed end 105 of biological sterilization indicator 100. Furthermore, in some embodiments, second chamber 111 may be smaller (e.g., in volume and/or cross-sectional area) than at least one of the first chamber 109 and the volume of liquid 122 in container 120 that will be released when biological sterilization indicator 100 is activated. As a result, in such embodiments, the second chamber 111 can exhibit a tight chamber effect in which gas (e.g., air) that is present in the second chamber 111 can inhibit the movement of fluids in the second chamber 111. In some embodiments, as described in greater detail below, a fluid path that allows the second chamber 111 to flow to another portion of the biological sterilization indicator 100 can facilitate fluid movement to the second chamber 111.
[0057] In some embodiments, wall 118 (sometimes called "separation wall") may be angled or slanted, for example, oriented at an angle other than zero and not straight with respect to the longitudinal direction DL of compartment 102 ( for example, where the longitudinal direction DL extends along the length of compartment 102). This angulation or inclination of wall 118 can facilitate movement of liquid 122 from upper portion 116 to lower portion 114 after sterilization and after container 120 has been ruptured to release liquid 122.
[0058] As shown in Figures 1 to 3, in some embodiments, wall 118 may be at least partially formed by a change in the internal dimension of compartment 102. For example, as shown, wall 118 may be formed by a decrease in a cross-sectional area from a first longitudinal position in the first chamber 109 to a second longitudinal position in the second chamber 111. Also, by way of example only, the internal cross-sectional shape of the compartment 102 may change in the transition of the first chamber 109 to the second chamber 111, from a substantially round shape (e.g. with a flat side forming less than 50% of the perimeter) in the first chamber 109 until it is substantially parallelepiped (e.g. substantially square) in the second chamber 111 .
[0059] Additionally, in some embodiments, wall 118 may be at least partially formed by a change in the external dimension of housing 102. As shown in Figures 1 to 3, in some embodiments, housing 102 includes a step (or overhang, shoulder, transition, or the like) 123 which is angled consistently with wall 118 (if wall 118 is angled), and which includes a change in the external shape and dimension of housing 102. However, it should be understood that in some embodiments , even if the internal dimension of compartment 102 changes to create a second chamber 111 that has a different cross-sectional shape or dimension than the first chamber 109, the external shape and dimension of compartment 102 need not change, or change from consistent with the change in internal format and/or dimension. For example, in some embodiments, step 123 may be oriented substantially perpendicular to the longitudinal direction DL.
[0060] In some embodiments, reservoir 103 has a volume of at least about 0.5 millimeters (ml), in some embodiments at least about 1 ml, and in some embodiments at least about 1.5 ml . In some embodiments, reservoir 103 has a volume no greater than about 5 ml, in some embodiments no more than about 3 ml, and in some embodiments no more than about 2 ml.
In some embodiments, the frangible container 120 has a volume of at least about 0.25 ml, in some embodiments at least about 0.5 ml, and in some embodiments at least about 1 ml. In some embodiments, frangible container 120 has a volume no greater than about 5 ml, in some embodiments no more than about 3 ml, and in some embodiments no more than about 2 ml.
In some embodiments, the volume of liquid 122 contained in frangible container 120 is at least about 50 microliters, in some embodiments at least about 75 microliters, and in some embodiments at least about 100 microliters. In some embodiments, the volume of liquid 122 contained in frangible container 120 is no more than about 5 ml, in some embodiments no more than about 3 ml, and in some embodiments no more than about 2 ml.
[0063] In some embodiments, the first chamber 109 (i.e., formed by the upper portion 116 of the first portion 104 of the compartment 102) has a volume of at least about 500 microliters (or cubic millimeters), in some embodiments at least about 1000 microliters, in some embodiments at least about 2000 microliters, and in some embodiments at least about 2,500 microliters. In some embodiments, first chamber 109 has a volume no greater than about 5,000 microliters, in some embodiments no more than about 4,000 microliters, and in some embodiments no more than about 3,000 microliters. In some embodiments, the first chamber 109 has a volume of about 2,790 microliters, or 2800 microliters.
[0064] In some embodiments, second chamber 111 (i.e., formed by lower portion 114 of first portion 104 of compartment 102) has a volume of at least about 5 microliters, in some embodiments at least about 20 microliters, and, in some embodiments, at least about 35 microliters. In some embodiments, second chamber 111 has a volume no greater than about 250 microliters, in some embodiments no more than about 200 microliters, in some embodiments no more than about 175 microliters, and in some embodiments no more than about 100 microliters. In some embodiments, second chamber 111 has a volume of about 208 microliters, or 210 microliters.
[0065] In some embodiments, the volume of the second chamber 111 is at least about 5% of the volume of the first chamber 109, and in some embodiments at least about 7%. In some modalities, the volume of the second chamber 111 is not greater than about 20% of the volume of the first chamber 109, in some modalities not greater than about 15%, in some modalities not greater than about 12%, and in some modalities modalities no greater than about 10%. In some embodiments, the volume of the second chamber 111 is about 7.5% of the volume of the first chamber 109.
[0066] In some embodiments, the volume of the second chamber 111 is no greater than about 60% of the volume of liquid 122 housed in container 120, in some embodiments no greater than about 50%, and in some embodiments no greater than about 25%. In some embodiments, designing the second chamber 111 to have a volume that is substantially less than that of the liquid 122 housed in the container 120 can ensure that the additional liquid volume can compensate for unintended evaporation.
[0067] In some embodiments, the first chamber 109 (i.e., formed by the upper portion 116 of the first portion 104 of the compartment 102) has a cross-sectional area (or average cross-sectional area) at the transition between the first chamber 109 and the second chamber 111, or in the position adjacent to the second chamber 111, of at least about 25 mm2; in some embodiments, at least about 30 mm2; and in some embodiments, at least about 40 mm2. In some embodiments, first chamber 109 has a cross-sectional area at the transition between first chamber 109 and second chamber 111, or adjacent to second chamber 111, not greater than about 100 mm2, in some embodiments no greater than about 75 mm2, and in some modes no more than about 50 mm2.
[0068] In some embodiments, the second chamber 111 (i.e., formed by the lower portion 114 of the first portion 104 of the housing 102) has a cross-sectional area at the transition between the first chamber 109 and the second chamber 111, or at the position adjacent to first chamber 109, at least about 5 mm2; in some embodiments at least about 10 mm2; and in some embodiments at least about 15 mm2. In some embodiments, the second chamber 111 has a cross-sectional area (or average cross-sectional area) of no greater than about 30 mm2, in some embodiments no greater than about 25 mm2, and in some embodiments no greater than about mm2.
[0069] In some embodiments, the cross-sectional area of the second chamber 111 at the transition between the first chamber 109 and the second chamber 111 may not be greater than about 60% of the cross-sectional area of the first chamber 109 at the transition, in some modalities no more than about 50%, in some modalities no more than about 40%, and in some modalities no more than about 30%.
[0070] In some embodiments, biological sterilization indicator 100 may further include a substrate 119. In some embodiments, as shown in Figures 1 to 4 and 6, substrate 119 may be sized to be positioned adjacent to wall 118, and particularly to rest on wall 118. Substrate 119 may be positioned between upper portion 116 (i.e., first chamber 109) and lower portion 114 (i.e., second chamber 111) of biological sterilization indicator 100 and , in some embodiments may at least partially define first chamber 109 and second chamber 111. As such, in some embodiments, substrate 119 may be positioned between container 120 and spores 115. In some embodiments, substrate 119 may be positioned in the first chamber 109, or on a side of the first chamber of the wall 118, so that the substrate 119 is not positioned in the second chamber 111.
[0071] In addition, the substrate 119 can be positioned to minimize the scattering of an assay signal (eg, fluorescence) out of the second chamber 111. In some embodiments, depending on the material constitution of the substrate 119, the substrate 119 it may also absorb dyes, indicator reagents, or other materials from the solution that may inhibit the accurate reading of a sterilization biological indicator signal 100 (ie, “inhibitors”). In some embodiments, as shown in Figures 1 to 4, 6 and 7, substrate 119 may include one or more apertures 121, which may be configured to control (i.e., facilitate and/or limit, depending on number, size, shape, , and/or location) the movement of fluids between the first chamber 109 and the second chamber 111 of the biological sterilization indicator 100, and particularly, which can facilitate the movement of the liquid 122 to the spores 115 when the container 120 is fractured. By way of example only, particular benefits or advantages were observed when opening 121 was positioned in front of (or "ahead of") the center of substrate 119, as shown. In the embodiment illustrated in Figures 1 to 7, the "front" of the biological sterilization indicator 100 or components thereof can generally be described as being toward a flat face 126. In general, the "front" of the biological sterilization indicator 100 may refer to the portion of the biological sterilization indicator 100 that will be interrogated by a reading apparatus.
[0072] Furthermore, by way of example only, opening 121 is illustrated as being circular or round; however, other cross-sectional opening shapes are possible and within the scope of the present description. Additionally, by way of example only, and as shown in Figure 3, substrate 119 is shaped to substantially fill the cross-sectional area of the first chamber at the transition between first chamber 109 and second chamber 111. However, other substrate shapes 119 are possible and can be adapted to accommodate compartment 102, first chamber 109, second chamber 111, wall 118, or other component of biological sterilization indicator 100.
[0073] As mentioned above, the second chamber 111 may include a volume to be interrogated. Such volume can be assayed for spore viability to determine lethality or effectiveness of a sterilization procedure. In some embodiments, the volume to be interrogated can be the whole or a portion of second chamber 111. In some embodiments, substrate 119 can be positioned outside the volume to be interrogated, which can minimize the number of structures in the volume that can interfere with testing processes. For example, in some embodiments, substrate 119 can be positioned so that substrate 119 is not in direct contact with at least one of spores 115, spore holder 135, and spore reservoir 136. In some embodiments, substrate 119 may be positioned such that substrate 119 is not located between a detection system (e.g., an optical detection system, such as a fluorescence excitation source and an emission detector) and at least one of the spores 115, spore holder 135, and spore reservoir 136. Substrate 119 may have the above positions when container 120 is in the first state and/or second state, but particularly when container 120 is in the second state.
[0074] In addition, substrate 119 can be positioned on biological sterilization indicator 100 so that substrate 119 is not in direct contact with container 120 when container 120 is in the first state. For example, in some embodiments, substrate 119 may be positioned in first chamber 109 (e.g., adjacent to the bottom end (e.g., second end 113) of first chamber 109), but even in such embodiments, substrate 119 can be positioned such that substrate 119 does not contact container 120. For example, as shown in Figures 1 to 2 and 4 to 6, in some embodiments, insert 130 can be positioned between container 120. and substrate 119 when container 120 is in the first state, such that insert 130 retains container 120 in the first state. Inserter 130, or a portion thereof, may be positioned adjacent to substrate 119. For example, as shown in the illustrated embodiment, substrate 119 may be positioned between (e.g., sandwiched between) inserter 130 and the wall 118. As such, in some embodiments, substrate 119 may be positioned between insert 130 and second chamber 111. In some embodiments, when container 120 is in the second state, fractured portions, or fragments, of container 120 may contact substrate 119, but in some embodiments, fractured portions of container 120 do not contact substrate 119.
[0075] As mentioned above, in some embodiments, substrate 119 may be positioned and configured to control or affect the flow of fluid in the biological sterilization indicator 100, and particularly to control the flow of fluid between the first chamber 109 and the second chamber 111. For example, in some embodiments, substrate 119 can be configured (e.g., sized, shaped, oriented, and/or constructed from certain materials) to control the rate at which a sterilizer is released to second chamber 111 (and spores 115), and may thereby control the "kill rate" of spores 115. For example, the sterilizer release rate may be lower than otherwise if substrate 119 were not present. between first chamber 109 and second chamber 111. That is, in some embodiments, substrate 119 can control the kill rate by selectively protecting spores 115. In some embodiments, substrate 119 p It can serve as a "valve" to control fluid flow, and particularly, to control the release of sterilizer in the biological sterilization indicator 100. Additionally, in some embodiments, substrate 119 may have properties that enhance or modulate a response generated by the spores 115, for example, if spores 115 survive a sterilization process.
[0076] Additionally, in some embodiments, substrate 119 can be configured (e.g., sized, formatted, positioned, oriented and/or constructed from certain materials) to control the rate at which detectable products diffuse from the volume to be interrogated. In some embodiments, the detectable product can include a signal (e.g., a fluorescent signal) that indicates spore viability, and in some embodiments, the detectable product can be the spore(s) 115 itself. Controlling the diffusion of detectable products from the volume to be interrogated can be particularly useful in embodiments where the volume of liquid 122 is greater than the volume of the second chamber 111 (or the volume to be interrogated), since the liquid 112 in such embodiments may extend in biological sterilization indicator 100 to a higher level than second chamber 111 (or the volume to be interrogated) when container 120 is in its second, fractured state. In such embodiments, detectable products may be free to move through the total volume of liquid 122 (i.e., to a volume outside the volume to be interrogated), unless there is some barrier or means to control such diffusion, such as the substrate 119. For example, in some embodiments, substrate 119 can be positioned at a level just above the volume to be interrogated (ie, below the liquid level 122), to inhibit movement of detectable products into the liquid portion 122. which is positioned above the substrate 119.
[0077] In some embodiments, the substrate 119 can control the sterilizer release rate (for example, in the second chamber 111) and/or the diffusion rate of detectable products (for example, out of the second chamber 111) by providing a physical barrier or blockage to the sterilizer and/or detectable products. Such a physical barrier can also function to collect broken portions of container 120 when container 120 is in the second state, fractured, to inhibit movement of the broken portions in the volume to be interrogated, where the broken portions could block, refract, reflect, or interfere otherwise in detection processes (eg optical detection processes).
[0078] Furthermore, in some embodiments, liquid 122, before or after being in fluid communication with spores 115, may include one or more inhibitors, or other components, which may interfere with an accurate detection assay or process. In some embodiments, examples of inhibitors may include at least one of dyes, indicator reagents, other materials or substances that can inhibit a reaction (eg, an enzymatic reaction) needed for detection of spore viability (eg, salts, etc. .), other materials or substances that may interfere with the detection process, or combinations thereof. In such embodiments, substrate 119 can be configured to selectively absorb and/or concentrate one or more inhibitors from the liquid 122, or at least the volume of liquid 122 to be interrogated.
[0079] For example, in some embodiments, more than one indicator reagent may be present in liquid 122, either prior to bringing spores 115 into contact or as a result of contacting spores 115. In such embodiments, although a first reagent of an indicator reagent (eg used for fluorescence detection) may be required for detection of spore viability, a second indicator reagent (eg a pH indicator) may actually interfere with detection of the first indicator reagent. By way of example only, in modalities where the second indicator reagent is a pH indicator (for example, one or more of the pH indicators described below), the pH indicator may conflict or interfere with the reading of fluorescence of the first indicator reagent, for example, in modalities in which the pH indicator emits electromagnetic radiation at a wavelength that is similar to the spectral range of the first indicator reagent's fluorescence (for example, when the pH indicator has a color change). In such embodiments, substrate 119 can be configured (e.g., formed from a suitable material) to selectively absorb and/or concentrate the second indicator reagent when positioned in contact with liquid 122 in order to reduce the concentration of the second. indicator reagent in the liquid 122, or at least in the volume of the liquid 122 to be interrogated.
[0080] Furthermore, in some embodiments (for example, in embodiments in which wall 118 is oblique and substrate 119 is positioned adjacent to wall 118), substrate 119 may be angled or oblique, for example oriented at an angle different from zero and not straight with respect to the longitudinal direction DL of compartment 102. Such angulation or inclination of substrate 119 can facilitate the movement of liquid 122 from first chamber 109 to second chamber 111 after sterilization and after container 120 has been ruptured for the release of liquid 122.
[0081] In some embodiments, substrate 119 can be formed from a variety of materials to perform one or more of the above functions. Examples of substrate materials may include, but are not limited to, cotton, glass wool, cloth, non-woven polypropylene, non-woven rayon, polypropylene/non-woven rayon blend, non-woven nylon, non-woven fiberglass, or others. non-woven fibers, filter papers, hydrophobic and hydrophilic microporous films, glass fibers, open cell polymeric foams, and semipermeable plastic films (e.g., particle filled films, thermally induced phase separation membranes (TIPS), etc. ), and combinations thereof. For example, in embodiments in which substrate 119 can be used to selectively concentrate one or more indicator reagents (eg, bromocresol purple (BCP)), substrate 119 can be formed from a charged nylon (such as a charged transfer membrane for resonating available from GE Water Process Technologies, Trevose, PA, USA under the trade name “MAGNAPROBE” (eg, 0.45 micron pore size, 30 cm X 3 m cylinder, catalog no. NP0HY00010, material no. 1226566)).
[0082] Substrate 119 is described in greater detail in co-pending US patent application No. 61/408,977, which is incorporated herein in its entirety by way of reference. Examples of methods and systems that can employ substrate 119 are also described in co-pending US Patent Application No. 61/408,887, entitled "Method of Detecting a Biological Activity" and US Patent Application No. 61/408,966, entitled "Method of Detecting a Biological Activity”, each of which is incorporated herein by reference in its entirety.
[0083] In some embodiments, at least a portion of one or more of the insert 130, the wall 118, and/or the substrate 119, or an opening therein, can provide fluid communication between the first chamber 109 (e.g. , in the upper portion 116) and the second chamber 111 (e.g., in the lower portion 114), and/or can control fluid communication between the first chamber 109 and the second chamber 111 (e.g., by controlling the extent of the fluid connection between the first chamber 109 and the second chamber 111).
[0084] The biological sterilization indicator 100 can include a first fluid path 160 that can be positioned to fluidly couple the first chamber 109 and the second chamber 111, and that can enable the sterilizer (e.g., during sterilization, when container 120 is in a first, unfractured state) and/or liquid 122 (e.g., after sterilization and during activation, when container 120 is in a second, fractured state) to reach spores 115. In the illustrated embodiment, the first fluid path 160 may generally be defined by one or more of the following: (1) the insert 130, for example, by means of an opening 177 described below, a passage formed in the insert 130 , and/or any open spaces around insert 130, such as between insert 130 (e.g., a front portion thereof) and housing 102; (2) wall 118, e.g. opening 117 defined by wall 118; (3) substrate 119, e.g., opening 121 formed therein, or any open spaces around substrate 119, such as between substrate 119 (e.g., a front portion thereof) and housing 102; (4) compartment 102, for example any passages or spaces formed therein; and combinations thereof. As a result, the first fluid path 160 is generally represented in the embodiment illustrated by an arrow in Figures 4 and 7.
The biological sterilization indicator 100 may further include a second fluid path 162 positioned to fluidly couple the second chamber 111 with another chamber or portion of the biological sterilization indicator 100, such as the first chamber 109. fluid path 162 may be further positioned to allow gas that was previously present in second chamber 111 to be displaced and exit second chamber 111, for example, when sterilizer and/or liquid 122 is moved to second chamber 111. As such, the second fluid path 162, which is described in greater detail below, can serve as an internal air outlet in biological sterilization indicator 100.
[0086] In some embodiments, the substrate 119 can provide a physical barrier or blockage between the first chamber 109 and the second chamber 111, which can allow at least one of the following: to control the release rate/extermination rate of the sterilant in the which sterilant is released into the second chamber 111; controlling the diffusion of spores 115 and/or detectable products out of the second chamber 111; controlling the rate of release of liquid 122 to the second chamber 111 (and to the spores 115) when the container 120 is in the second, fractured state; or a combination of them.
[0087] Since, in some embodiments, the substrate 119 can provide a physical barrier to release liquid 122 into the second chamber 111 during activation (i.e., when the container 120 is in the second state), the opening 121 in the substrate 119 and/or the angle of substrate 119 can be controlled to affect a desired liquid release rate. Additionally, or alternatively, the second fluid path 162 may provide an air outlet for any gas or air that is entrapped in the second chamber 111 to facilitate movement of the liquid 122 through or beyond the substrate 119 and into the second chamber. 111 when desired.
[0088] Additionally, or alternatively, the compartment 102 can be configured (e.g., formed from a suitable material and/or configured with microstructured grooves or other physical surface modifications) to facilitate the movement of liquid 122 to the second camera 111 when desired.
[0089] In some embodiments, liquid 122 may include a nutrient medium for the spores, such as a germination medium that will promote the germination of surviving spores. In some embodiments, liquid 122 can include water (or other solvent) that can be combined with nutrients to form a nutrient medium. Suitable nutrients may include nutrients needed to promote germination and/or growth of surviving spores in a dry form (eg, powdered form, tablet form, caplet form, capsule form, a film or coating, trapped in a microsphere or another support, another suitable shape or configuration, or a combination thereof) in the reservoir 103, for example, in a region of the sterilization biological indicator 100 near the spores 115.
[0090] The nutrient medium can be, in general, selected to induce germination and initial flowering of the spores, if this is feasible. The nutrient medium can include one or more sugars, including, but not limited to, glucose, fructose, celibiose, or the like, or a combination thereof. The nutrient medium can also include a salt, including, but not limited to, potassium chloride, calcium chloride, or the like, or a combination thereof. In some embodiments, the nutrient can further include at least one amino acid, including, but not limited to, at least one of methionine, phenylalanine, and tryptophan.
[0091] In some embodiments, the nutrient medium may include reagents or indicator molecules, for example, indicator molecules that have optical properties that are altered in response to spore germination or growth. Suitable indicator molecules or reagents may include, but are not limited to, pH indicator molecules (eg, bromocresol purple (BCP), bromocresol green (BCG), chlorophenol red (CPR), bromothymol blue (BTB), bromophenol blue (BPB), other sulphonphthalein dyes, methyl red, or combinations thereof), enzyme substrates (eg 4-methylumberliferyl-aD-glycoside), DNA binding dyes, RNA binding dyes, other suitable indicator molecules, or a combination thereof. In some embodiments, the combination of bromocresol purple and 4-methylumberliferyl-α-D-glycoside represents an example of a pair of indicator reagents that can be used together. This combination can be used to detect a first biological activity, such as the fermentation of a carbohydrate to acidic products, and a second biological activity, such as α-D-glucosidase enzymatic activity, for example. These activities can indicate the presence or absence of a viable spore following exposure of a biological indicator of sterilization to a sterilization process, for example. Bromocresol purple can be used at a concentration of about 0.03 g/l, for example, in an aqueous mixture. 4-Methylumberliferyl-α-D-glycoside can be used, for example, at a concentration of about 0.05 to about 0.5 g/l (e.g., about 0.05 g/l, about 0.06 g/l, about 0.07 g/l, about 0.08 g/l, about 0.09 g/l, about 0.1 g/l, about 0.15 g/l l, about 0.2 g/l, about 0.25 g/l, about 0.3 g/l, about 0.35 g/l, about 0.4 g/l, about 0 .45 g/l, about 0.5 g/l), for example, in an aqueous mixture.
[0092] As shown in Figures 1 to 7, the biological sterilization indicator 100 may further include an insert 130. In some embodiments, the insert 130 may be adapted to hold or transport the container 120, so that the container 120 is kept intact in a location separate from the spores 115 during sterilization. That is, in some embodiments, insert 130 may include (or function as) a holder 132 (see Figure 3) for container 120, particularly before container 120 is ruptured during the activation step (i.e., the step in which liquid 122 is released from container 120 and introduced to spores 115, which may typically occur after the sterilization process). In some embodiments, insert 130 may be further adapted to allow container 120 to move at least somewhat in housing 102, for example, longitudinally relative to housing 102. Insert member 130 of the illustrated embodiment is described in more detail below. Examples of other suitable inserts and carriers are described in copending US patent application no. 61/226,937 (Dossier no. 65578US002).
[0093] In some embodiments, biological sterilization indicator 100 may further include a spore holder 135, as shown in Figures 1 to 4 and 6. However, in some embodiments, insert 130 may be modified to include a portion adapted to house the spores 115. For example, in some embodiments, the insert 130 and the spore holder 135 may be integrally formed as an insert that comprises a first portion adapted to retain and eventually fracture the container 120 , where desired, and a second portion adapted to house the spores 115 in a region of the sterilization biological indicator 100 that is separated from the container 120 during sterilization (i.e., prior to fracture).
[0094] As shown in Figures 1 to 4 and 6, the spore holder 135 may include a spore reservoir 136 (which may also be called a depression, recess, cavity, recess, or the like), in which the spores 115 may be positioned either directly or on a substrate. In embodiments employing a nutrient medium that is positioned to be mixed with liquid 122 when it is released from container 120, the nutrient medium may be positioned near or within the spore reservoir 136, and the nutrient medium may be mixed with (eg dissolved in) water when water is released from container 120. By way of example only, in embodiments in which the nutrient medium is provided in a dry form, the dry form may be present in reservoir 103, the spore reservoir 136, on a substrate for the spores, or a combination thereof. In some embodiments, a combination of liquid and dry nutrient media may be employed.
In some embodiments, the spore reservoir 136 has a volume of at least about 1 microliter, in some embodiments at least about 5 microliters, and in some embodiments at least about 10 microliters. In some embodiments, spore reservoir 136 has a volume no greater than about 250 microliters, in some embodiments no more than about 175 microliters, and in some embodiments no more than about 100 microliters.
[0096] As shown in Figures 4 and 6, in some embodiments, the biological sterilization indicator 100 may further include a rib or protrusion 165 that can be coupled to or integrally formed with a wall 108 of compartment 102, which can be positioned to hold the spore holder 135 in a desired location in compartment 102 and/or at a desired angle or orientation, for example, relative to detection systems (eg, optical detection systems) of the reader 12.
[0097] As shown in Figures 1 to 4 and 6, the second portion 106 of the housing 102 can be adapted to be coupled to the first portion 104. For example, as shown, the second portion 106 can be adapted to be coupled to the upper portion 116 (e.g., first end 101) of first portion 104 of housing 102. In some embodiments, as shown in Figures 1 to 4, second portion 106 may be in the form of a cap that can be sized to receive at least one portion of the first portion 104 of the housing 102.
[0098] As shown in Figures 1 to 2 and 4 to 5, during sterilization and before activation, the second portion 106 may be in a first "disabled" position 148 relative to the first portion 104, and the container 120 may be in a first state, intact. As shown in Figure 6, second portion 106 of housing 102 may be moved to a second "activated" position 150 (e.g., when second portion 106 is fully recessed) relative to first portion 104, and container 120 may be in a second state, fractured. For example, after sterilization, the biological sterilization indicator 100 can be activated by moving the second portion 106 from the first position 148 to the second position 150 (i.e., a sufficient amount) to cause the fracturing of the container 120 and the release of the liquid 122 from container 120, to allow liquid 122 to be in fluid communication with spores 115. Biological sterilization indicator 100 may be activated prior to positioning biological sterilization indicator 100 in a cavity of a reading apparatus after the positioning the biological sterilization indicator 100 in the cavity, or as the biological sterilization indicator 100 is positioned in the cavity (i.e., the biological sterilization indicator 100 can be slid into place in the reading apparatus, and the second portion 106 can continue to be pressed until it is in its second position 150, for example, in which the bottom of the cavity provides enough resistance to move. r the second portion 106 to its second position 150). The second position 150 may be located closer to the closed end 105 of the first portion 104 of the biological sterilization indicator 100 than the first position 148.
[0099] As shown in the illustrated embodiment, in some embodiments, the first portion 104 of the housing 102 may include a step, shoulder, or plan-to-round transition 152. The step 152 is shown as being exposed when the second portion 106 is in its first position 148 and as being obscured or covered when the second portion 106 is in its second position 150. As such, the step 152 can be detected to determine if the second portion 106 is in the first position 148 (i.e., the indicator sterilization biological indicator 100 is off), or is in second position 150 (ie, sterilization biological indicator 100 is on). The use of such features of the sterilization biological indicator 100 to determine a status of the sterilization biological indicator 100, for example, to confirm that the sterilization biological indicator 100 has been activated, is described in more detail in co-pending US patent application no. 61/409,042. The longitudinal position of rung 152 is shown as an example only; however, it should be understood that step 152 may instead be located in a different longitudinal position (eg closer to the closed end 105 of biological sterilization indicator 100), or, in some embodiments, the transition of a rounded portion for a flat face can be gradual, tapered, or ramped.
[00100] A variety of coupling means may be employed between the first portion 104 and the second portion 106 of the housing 102 to allow the first portion 104 and the second portion 106 to be removably coupled together, including but not limited to, gravity (for example, one component may be fixed on top of another component, or a joined portion thereof), threads, press fit couplings (sometimes called "friction fit coupling" or “forced fit coupling”), snap fit coupling, magnets, adhesives, thermobonding, other suitable removable coupling means, and combinations thereof. In some embodiments, biological sterilization indicator 100 need not be reopened and first portion 104 and second portion 106 need not be coupled together, but instead may be permanently or semi-permanently coupled together. These permanent or semi-permanent coupling means may include, but are not limited to adhesives, sutures, staples, threads, nails, rivets, headless nails, crimping, welding (e.g., sonic welding (e.g., ultrasonic)), any technique heat welding (e.g., heat and/or pressure applied to one or both of the components to be coupled), snap-fit engagement, press-fit engagement, heat seal, other permanent or semi-permanent coupling means, and combinations of same. The person skilled in the art will recognize that some of the semi-permanent or permanent coupling means may also be adapted to be removable and vice versa, and are categorized in this way by way of example only.
[00101] As shown in Figures 4 and 6, the second portion 106 can be movable between a first longitudinal position 148 relative to the first portion 104 and a second longitudinal position 150 relative to the first portion 104; however, it should be understood that the biological sterilization indicator 100 may instead be configured differently so that the first and second positions 148 and 150 are not necessarily longitudinal positions with respect to one or both of the first portion 104 and the second portion 106 of housing 102.
[00102] The second portion 106 may further include a seal 156 (e.g., a protrusion, a protrusion, a tab, flange, o-ring, or the like, or combinations thereof) that may be positioned to contact the first end 101 of first position 104 and particularly an open upper end 157 of first position 104 for closing or sealing (e.g., hermetically sealing) the biological sterilization indicator 100 after the second portion 106 has been moved to the second position 150 , and liquid 122 has been released from container 120 (i.e., when container 120 is in a second, fractured state). That is, spores 115 can be sealed from the environment when container 120 is in the second state. Seal 156 may take a variety of shapes and is shown in Figures 4 and 6, by way of example, forming an inner ring or cavity which, together with wall 110 of second portion 106, is sized to receive upper end 157 of the first portion 104 of compartment 102 for sealing biological sterilization indicator 100.
[00103] In some embodiments, one or both of the seal 156 and the upper end 157 may further include a structure (e.g., a protrusion) configured to engage the other of the upper end 157 and the seal 156, respectively, to couple second portion 106 of housing 102 to first portion 104 of housing 102.
[00104] Furthermore, in some embodiments, the second portion 106 of the compartment 102 may be coupled to the first portion 104 of the compartment 102 to seal the sterilization biological indicator 100 from the environment after activation. This seal can inhibit contamination, evaporation, or spillage of liquid 122 after it has been released from container 120, and/or can inhibit contamination of the interior of biological sterilization indicator 100.
[00105] The seal 156 can be configured to have a length in the longitudinal direction DL of the biological sterilization indicator 100 to accommodate different degrees or levels of closure. That is, in some embodiments, the "second position" 150 of the second portion 106 of the housing 102 can be any position in which at least a portion of the seal 156 has engaged a portion (e.g., upper end 157) of the first portion 104 of the compartment 102, so that the interior of the biological sterilization indicator 100 is sealed from the environment. The sterilization biological indicator 100 and the sterilization biological indicator system 10 can be correspondingly configured such that, if the reading apparatus 12 detects that the second portion 106 has been moved to the second position 150, the user knows that seal 156 is engaged.
[00106] Insertion element 130 will now be described in more detail.
[00107] As shown in Figures 1 to 2 and 4, during sterilization and before activation, the second portion 106 can be in a first position 148 relative to the first portion 104. In the first position 148, the container 120 can be held intact in a position separate from the lower portion 114, the second chamber 111 or the spores 115, and the liquid 122 can be contained in the container 120.
[00108] As shown in Figure 6, after sterilization, the biological sterilization indicator 100 can be activated to release the liquid 122 from the container 120 to move the liquid 122 to the second chamber 111. That is, the second portion 106 of the compartment 102 can be moved to a second position 150 relative to the first portion 104. When the second portion 106 is moved from the first position 148 to the second position 150, the seal 156 of the second portion 106 of the housing 102 can engage the upper end 157 of the first portion 104 for sealing the reservoir 103 of the biological sterilization indicator 100 from the environment. In these embodiments, second portion 106 may reversibly engage first portion 104 at second position 150, and in some embodiments, second portion 106 may irreversibly engage first portion 104. However, it should be understood that the structures and coupling means for the first portion 104 and the second portion 106 are shown in the illustrated embodiment by way of example only, and any of the coupling means described above may instead be employed between the first portion 104 and second portion 106 of housing 102.
[00109] The insert 130 can be adapted to retain or transport the container 120 so that the container 120 is kept intact in a location separate from the spores 115 during sterilization. That is, as mentioned above in some embodiments, insert 130 may include (or function as) a support 132 for container 120, particularly before container 120 is ruptured during the activation step (i.e., the step in which liquid 122 is released from container 120 and introduced to spores 115, which typically occurs after the sterilization process).
[00110] In addition, the insert 130 can be adapted to keep the container 120 intact in a position in the compartment 102 that maintains at least a minimum spacing (e.g., a minimum cross-sectional area of space) between the container. 120 and compartment 102 and/or between container 120 and any other components or structures in compartment 102 (e.g., at least a portion of insert 130, such as holder 132, etc.), e.g. substantially constant sterilant path 164 in biological sterilization indicator 100. In some embodiments, insert 130 may be adapted to hold container 120 in a substantially consistent location in compartment 102.
[00111] In some embodiments, as shown in Figure 3, at least a portion of housing 102 may include a tapered portion 146 in which housing 102 (e.g., wall 108, and/or an inner surface thereof) generally it tapers in the longitudinal direction DL of compartment 102. As a result, the cross-sectional area in compartment 102 can generally decrease along the longitudinal direction DL.
[00112] In some cases, without providing the means to maintain at least a minimum spacing around the container 120 (for example, between the container 120 and the surrounding structure), there may be a possibility that the container 120 will be positioned in the compartment 102 (e.g., at the tapered portion 146) so that it obstructs or blocks the sterilant path 164. However, the biological sterilization indicator 100 of the present description is designed to prevent this from occurring. For example, in the illustrated embodiment, the insert 130 (and particularly the holder 132) may be configured to hold the container 120 out of the tapered portion 146 of the housing 102 so that at least a minimum cross-sectional area is maintained at the around container 120 in any orientation of biological sterilization indicator 100 prior to activation. For example, in the embodiment illustrated in Figures 1 to 5, even if biological sterilization indicator 100 is turned upside down, container 120 may leave contact with insert 130, but in no orientation, container 120 is moved closer to tapered portion 146, or spores 115 until activation of biological sterilization indicator 100. In addition, until activation, at least a minimum spacing (and particularly, a cross-sectional area of that spacing) between the container 120 and housing 102 and/or insert 130 may be maintained to provide a substantially constant sterilant path 164, for example, around container 120, through first fluid path 160 and into second chamber 111.
[00113] In some embodiments, the sizing and relative positioning of the components of the biological sterilization indicator 100 can be configured so that, prior to activation, the container 120 is kept intact in a substantially consistent location on the biological sterilization indicator 100. The configuration can provide a substantially constant sterilant path 164 and can hold container 120 in a position such that container 120 is not able to move substantially, or at all, in biological sterilization indicator 100 prior to activation.
[00114] In some embodiments, at least a portion of insert 130 may be adapted to allow container 120 to move in compartment 102, for example, longitudinally relative to compartment 102, between a first (longitudinal) position in which container 120 is intact and a second (longitudinal) position in which at least a portion of container 120 is fractured. By way of example only, insert 130 may include one or more projections or arms 158 (two separate projections 158 around container 120 are shown by way of example only) adapted to hold and support container 120 prior to activation and allowing container 120 to move in housing 102 during activation, e.g. when second portion 106 is moved relative to first portion 104 of housing 102. Projections 158 may also be adapted (e.g., shaped and/or positioned ) to fracture container 120 in a desired manner when the biological sterilization indicator is activated. As a result, insert 130 may sometimes function to keep container 120 intact prior to activation, and may function to rupture container 120 during activation. As a result, the insert 130, or a portion thereof, may sometimes be referred to as a "support" (e.g., support 132) and/or an "opener".
[00115] By way of example only, the projections 158 are shown in Figures 1 and 3 to 7 as coupled to a base or support 127 adapted to abutment wall 118. For example, the base 127 can be dimensioned to be received in reservoir 103 and sized to rest upon, or abut, or otherwise cooperate with, or be coupled to a partition wall 118. Such coupling with an internal structure of sterilization biological indicator 100 can provide the strength and strength necessary to rupture container 120 when desired. In some embodiments, however, insert 130 does not include base 127, and projections 158 may be coupled to or form a portion of housing 102. In some embodiments, insert 130 is formed integrally with or provided by housing. 102.
[00116] As shown, the insert 130 may further include a side wall 131 that connects the projections 158 and is shaped to accommodate an inner surface of compartment 102 and/or an outer surface of container 120. Such side wall 131 can provide support and rigidity to the projections 158 to assist in the reliable rupture of the container 120 in a consistent manner. Sidewall 131 may also be shaped and sized to guide container 120 in a desired manner as it is moved in housing 102 during activation, for example, to bring projections 158 into contact in a desired manner to reliably fracture container 120. Side wall 131 and/or wall 108 of compartment 102 (or an inner surface thereof) may also be shaped to define at least a portion of the second fluid path 162 of biological sterilization indicator 100, for example, between a surface. an outer surface of insert 130 and an inner surface of housing 102. For example, in some embodiments, as shown in Figures 1 to 2, 5 and 7, sidewall 131 of insert 130 may include a groove (or groove, recess, or the like) 169 configured to form at least a portion of the second fluid path 162.
[00117] The second fluid path 162 may function as an "internal air outlet" or an "air outlet channel" within the biological sterilization indicator 100 to allow gas (e.g., displaced gas such as air that was captured in the second chamber 111 (e.g., near the closed end 105 of the biological sterilization indicator 100) escape from the second chamber 111 of the biological sterilization indicator 100. In some embodiments, the second fluid path 162 may provide an escape, or internal air outlet, for a gas present in second chamber 111 during activation to facilitate movement of liquid 122 into second chamber 111 from first chamber 109 as it is released from container 120. Additionally or alternatively, in some embodiments , the second fluid path 162 may provide an exhaust, or internal air outlet, for a gas present in the second chamber 111 during sterilization to facilitate movement. of a sterilizer in the second chamber 111 of the biological sterilization indicator 100 and for the spores 115, with more effective sterilizer penetration into the second chamber 111.
[00118] By way of example only, as shown in Figures 2 and 7, the second fluid path 162 may be at least partially defined by both a portion of the insert 130 (e.g., channel 169) and by a channel (or groove, recess, or the like) 163 formed in wall 108 of housing 102 (e.g., in an inner surface of wall 108). However, it should be understood that, in some embodiments, the second fluid path 162 may be formed entirely from compartment 102 or various combinations of other components of the biological sterilization indicator 100, so that the second fluid path 162 provides fluid connection between second chamber 111 and another portion or inner region of biological sterilization indicator 100. For example, second fluid path 162 need not be formed by both compartment 102 and insert 130, but may be formed by one of these components, or other components. Furthermore, as shown in Figures 2 and 7, the channel 163 defining at least a portion of the second fluid path 162 is molded into an outer surface and an inner surface of the housing 102 so that the channel 163 is visible from the side. inside and outside of housing 102. However, the outer surface of housing 102 need not include such a shape, and instead, in some embodiments, the outer surface of housing 102 may remain substantially uniform or unaltered, and the inner surface of housing. compartment 102 (e.g., a wall 108 of compartment 102) may include channel 163.
[00119] Additionally, in some embodiments, neither insert 130 nor housing 102 include channel 169 or channel 163, respectively, but rather insert member 130 and housing 102 are shaped and sized accordingly. such that a space or span is provided between the insert 130 and the housing 102 which is in fluid communication with the second chamber 111, and such space or span functions as the second fluid path 162.
[00120] As further shown in Figures 4 and 6, in some embodiments, the first fluid path 160 and/or the second fluid path 162 may be at least partially defined by one or more of the wall 118, of the substrate 119, of the inserter 130, and housing 102. Furthermore, at least one of the first fluid path 160 and the second fluid path 162 may be defined at least partially by the spore holder 135, or a portion thereof.
[00121] In some embodiments, the biological sterilization indicator 100 may include the following components arranged in the following order when the container 120 is in a first, unfractured state: the closed end 105 of the compartment 102 of the biological sterilization indicator 100, the second chamber 111, substrate 119, insert 130, first chamber 109, container 120, open end 101 of housing 102 (or second portion 106 of housing 102).
[00122] As shown in the illustrated embodiment, the second fluid path 162 may allow the second chamber 111 to flow to another portion of the sterilization biological indicator 100, such as the first chamber 109. In some embodiments, the second fluid path 162 may exit the second chamber 111 at a position located above (e.g., vertically above) the position at which the first fluid path 160 enters the second chamber 111, particularly in embodiments in which the second fluid path 162 drains the second fluid path 111 from returns to the first chamber 109. In other words, in some embodiments, the second fluid path 162 may extend from the second chamber 111 to a position (eg, a fourth level L4, described below) on the biological sterilization indicator 100 which is above the position (for example, a first level L1 or a second level L2, described below) in which the first fluid path 160 enters the second chamber 111. Additionally, in some embodiments, the position at which the second fluid path 162 enters the first chamber 109 may be above (e.g., vertically above) the position at which the first fluid path 160 enters the second chamber 111.
[00123] In some embodiments, the first fluid path 160 may be positioned to fluidly couple the second chamber 111 with a proximal portion of the biological sterilization indicator 100 (e.g., a portion of the first chamber 109 that is located so that proximal to or adjacent to the second chamber 111, for example at the first level L1 and/or the second level L2), and the second fluid path 162 may be positioned to fluidly couple the second chamber 111 with a distal portion of the biological indicator of sterilization 100 (i.e. a portion of the first chamber 109 that is located farthest from the second chamber 111, for example, at a third level L3, described below, and/or at the fourth level L4). As a result, the position at which the second fluid path 162 enters the first chamber 109 can be positioned further away from the second chamber 111 than the position at which the first fluid path 160 enters the second chamber 111.
[00124] More specifically and by way of example only, with reference to Figures 4 and 6, in some embodiments, fluids may enter the second chamber 111 at a variety of locations, such as at the first level, height, or position (for example , longitudinal position) L1 located generally at the front of insert 130, substrate 119, housing 102, and/or second chamber 111, as well as at the second level, height, or position (e.g., longitudinal position) L2 located approximately at the level of opening 121 in substrate 119. As described above, it should be understood that the variety of openings and spaces between first chamber 109 and second chamber 111 that allow fluid to move in second chamber 111 may collectively be called of first fluid path 160. As further illustrated in Figure 4, in some embodiments, gas (e.g., displaced gas) may exit the second chamber 111 through the second path for fluids 162 (i.e., as the fluid moves to the second chamber 111 through the first fluid path 160) at the third level, height, or position (e.g., longitudinal position) L3 located generally at the rear of the insert 130, substrate 119, housing 102, and/or second chamber 111.
[00125] In the vertically upright orientation of the biological sterilization indicator 100 shown in Figures 4 and 6, the third level L3 is situated at or above both the first level L1 and the second level L2. Furthermore, in some embodiments, the third level L3 may still be located at or above both the first level L1 and the second level L2 in operation of the biological sterilization indicator 100 (for example, when seated in a cavity of a sterilization apparatus reading, during sterilization, and/or during activation). That is, in some modalities, the biological sterilization indicator 100 can be tilted in operation (for example, towards the left side of Figure 4 or 6, towards the right side of Figure 4 or 6, within the page of Figure 4 or 6, and/or off the page of Figure 4 or 6).
[00126] The first, second, and third levels L1, L2, and L3 are shown for example purposes only; however, it should be understood that the exact location at which the first fluid path 160 enters the second chamber 111 and/or the exact location at which the second fluid path 162 exits the second chamber 111 may be different from what is illustrated in the Figures. 4 and 6.
[00127] As shown in Figures 4 and 6, the second fluid path 162 is at least partially defined by channel 169 of insert 130 and/or channel 163 of housing 102, which will be generically referred to simply as "the channel" in the following discussion, which may be interpreted to refer to at least a portion of channel 163 and/or channel 169 of the illustrated embodiment. In the illustrated embodiment, the channel has an inlet that can be described as being located at any point in the second chamber 111, or in the third level L3, and an outlet that is generally positioned in the fourth level, height, or position (e.g., position longitudinal) L4. As shown in Figures 4 and 6, the exit position of the trough (i.e., the fourth level L4) is generally located above the position at which the first fluid path 160 connects with the second chamber 111 (i.e., the first level L1 and/or the second level L2), for example, in the operation of the biological sterilization indicator 100.
In other words, the first fluid path 160 can be positioned to fluidly couple the second (bottom) end 113 of the first chamber 109 to the first (top) end 124 of the second chamber 111. The second fluid path 162, on the other hand, may be positioned to fluidly couple second chamber 111 (e.g., first (top) end 124 of second chamber 111) to an upper portion (e.g., first (upper) end 112) of the first chamber 109.
[00129] Additionally, in some embodiments, the position or level at which the second fluid path 162 (or the channel) connects with the second chamber 111 can be described as being located in the portion of the second chamber 111 that is the last to be filled with liquid 122 when container 120 is in its second, fractured state.
[00130] In some embodiments, when container 120 is in the second, fractured state, and second chamber 111 is at least partially filled with liquid 122, liquid 122 may have a level, height or position (e.g., longitudinal position ) L, and the second fluid path 162 may extend between a position below level L and a position above level L. As a result, as the second chamber 111 fills with liquid 122 when the container is in the second state, the second chamber 111 can be continuously vented by second fluid path 162.
[00131] In some embodiments, the first fluid path 160 may function as the primary or primary fluid communication path between the first chamber 109 and the second chamber 111, and the second fluid path 162 may serve as an accessory or secondary fluid communication between the second chamber 111 and the first chamber 109 (e.g. when the second fluid path 162 exits the first chamber 109 and not another portion of the biological sterilization indicator 100). In such embodiments, the collective space, volume and/or area of the second fluid path 162 may be substantially less than that of the first fluid path 160. In some embodiments, at least a portion of the first fluid path 160 and the second path for fluids 162 can be described as being substantially isolated from each other, or as being substantially parallel and non-intersecting. In some embodiments, the first fluid path 160 and the second fluid path 162 may each extend substantially longitudinally (e.g., substantially parallel to the longitudinal direction DL) between the first chamber 109 and the second chamber 111.
[00132] That is, generally the biological sterilization indicator 100 that includes (1) a first fluid path, such as the first fluid path 160, configured to accommodate at least the majority of fluid movement from the first chamber 109 to the second chamber 111, and (2) a second fluid path, such as second fluid path 162, configured to vent gas from second chamber 111 would have advantages over a biological sterilization indicator 100 that includes only one inner chamber, or only one a fluid path connecting the first chamber 109 and the second chamber 111, so that the gas would have to exit the second chamber 111 via the same fluid path in which the fluid enters the second chamber 111.
[00133] By configuring the first fluid path 160 and the second fluid path 162 as shown in the illustrated embodiment, in some embodiments, the biological sterilization indicator 100 can at least partially eliminate any sealed chamber effect that may occur as a result of attempt to move a sterilizer and/or liquid 122 into the second chamber 111. Also, in some embodiments, the second fluid path 162 may allow the biological sterilization indicator 100 to be activated, and the liquid 122 to be moved to the second chamber 111 due to gravity, while the biological sterilization indicator 100 remains in the same orientation (e.g., a substantially vertical upright orientation as shown in Figures 1 to 2, 4 and 6), without requiring the biological indicator to sterilization 100 is tilted upside down, or otherwise reoriented in order to move the liquid 122 to the second chamber 111.
[00134] With continuous reference to the insert 130, the projections 158 of the insert 130 are illustrated as being relatively rigid and stationary. That is, in some embodiments, the projections 158 may not be adapted to substantially flex, distort, deform, or otherwise follow the orientation of container 120 as it is moved in housing 102. Rather, in some embodiments, as shown in Figures 1 to 4 and 6, the projections 158 can each be configured to have an upper end 159 on which the container 120 can be positioned and kept intact prior to activation. As shown in Figures 1 to 2 and 4, in some embodiments, the projections 158 may be positioned to fracture the container 120 at its radiated end, for example, when an oblong or capsule-shaped container 120 is employed.
[00135] A potential advantage of having the projections 158 forming at least a portion of the support 132 is that the bottom of the container 120 can be unrestricted when the container 120 is fractured so that the liquid 122 can be released from the container 120 and moved towards the spores 115 with relative ease and reliability.
[00136] In these embodiments, the insert 130 can be used to fracture the container 120 in a direction that is substantially perpendicular to a flat side of the container 120, for example when an oblong or capsule-shaped container 120 is employed. In these embodiments, fracturing of container 120 along its side can be achieved, along with maintaining some open spaces around the lower end of container 120 to facilitate movement of liquid 122 from container 120 to the proximity of spores 115 when container 120 is fractured.
[00137] As mentioned above, the projections 158 can be adapted to fracture the container 120 as the container 120 is moved relative to the compartment 102 (e.g., along the longitudinal direction DL), for example, in response to the second portion 106 of housing 102 being moved relative to first portion 104 of housing 102 (e.g., from first position 148 to second position 150).
[00138] In some embodiments, the projections 158 may include one or more edges (e.g., tapered edges) or points, or otherwise be configured to concentrate the crushing force to increase pressure on the container 120 in regions adjacent to the projections 158, and to facilitate fracturing of container 120 more easily in one or more desired regions. In some embodiments, this concentration of force can reduce the total effort or force required to move second portion 106 relative to first portion 104 and to fracture container 120 (or a portion thereof).
[00139] As shown in Figures 1 to 4 and 6, the projections 158 are integrally formed with the base 127 of the insert 130; however, it should be understood that the projections 158 may instead be integrally formed with the wall 108 of the housing 102. Also, in some embodiments, the projections 158 may be coupled to the housing 102, or the projections 158 and the base. 127 can be provided by separate insert elements. In these embodiments, the projections 158 may each consist of a separate insert, or multiple projections 158 may be provided by one or more inserts. In addition, insert 130 may be configured to be in abutment position with wall 118 to inhibit movement of first portion of insert 130 into proximity of spores 115 (e.g., lower portion 114 of housing 102) .
[00140] Furthermore, in some embodiments, as shown in Figures 1 to 4 and 6, the projections 158 may extend a certain distance along the longitudinal direction DL, and the length and/or thickness (for example, they may vary along the length) of the projections 158 can be adjusted to control the fracturing of the container 120 into a desired position in the housing 102 and in the desired manner. The configuration of the projections 158 is shown in Figures 1 to 7 by way of example only.
[00141] In general, each of the projections 158 is shown by way of example only as responsible for the increase in thickness (e.g., inwards towards container 120 or center of compartment 102) along the longitudinal direction DL towards the spores 115. This configuration can decrease the cross-sectional area that is available to the container 120, as the container 120 is moved towards the spores 115, for example, in response to the second portion 106 being moved to the second position 150.
[00142] Additionally, the biological sterilization indicator 100 is shown in Figures 1 to 7 as including two projections 158 and a side wall 131 for example only, but it should be understood that a projection 158 or as many are structurally possible, and others settings can be employed. In addition, the projections 158 can be shaped and sized as desired, depending on the shape and dimensions of the compartment 102, the shape and dimensions of the container 120, or the shape and dimensions of the insert 130, and/or the desired manner and position. to fracture the container 120.
[00143] As mentioned above, in some embodiments, at least a portion of housing 102 may be tapered (see, for example, tapered portion 146 in Figure 3). As a result, the cross-sectional area in housing 102 can generally decrease along the longitudinal direction DL. However, it should be understood that the internal dimensions of housing 102 can generally decrease in the tapered portion along the longitudinal direction D1 without the external dimensions of housing 102 being changed. In some embodiments, the outer dimensions of housing 102 may be uniform along its length, even though the inner portion of housing 102 tapers along its length. In some embodiments, the one or more projections 158 alone may vary in thickness (i.e., toward container 120, e.g., in a radial direction) along the longitudinal direction DL, so that the cross-sectional area available for the container 120 generally decreases as the container 120 is moved in the compartment 102 during activation, even if the dimensions of the compartment 102 do not change (e.g., even if the compartment 102 does not include any tapered, inner portion 146 or externally).
[00144] As shown in Figures 1 to 7, the upper end 159 of each of the projections 158 includes a rounded, curved or arcuate surface, which can facilitate movement of the container 120 from the first position 148 in which the container 120 rests at least partially above the upper end 159 of the projection 158 to a position where the container 120 is forced, at least partially, into a region of smaller cross-sectional area between the projections 158 (or between the wall 108 of the housing 102 and one or more projections 158). In addition, the rounded top end 159 can inhibit premature rupture of container 120, which can inhibit premature activation of biological sterilization indicator 100 (i.e., premature release of liquid 122).
[00145] In some embodiments, as shown in Figure 3, the insert 130 may be sized and shaped to allow the container 120 to be held above the projections 158 and outside the adjacent region of any portion of an inwardly facing surface. one or more of the projections 158 to inhibit accidental or premature activation of the biological sterilization indicator 100. This setting can also inhibit inadvertent rupture due to shock or material expansion (eg due to exposure to heat during a sterilization process ).
[00146] Support 132, which may be formed at least partially by the upper ends 159 of the projections 158, can be configured to hold the lower portion of the container 120, and the projections 158 can be positioned to fracture the container 120 at a nearby location. to the bottom of the container 120 as it is positioned in the compartment 102. This configuration can allow the rupture of the container 120 near its bottom and can facilitate the removal of the liquid 122 from the container 120, which can improve the availability of the liquid 122 for spores 115, and can improve the reliability of release of liquid 122 in fluid communication with spores 115 (e.g., with spore reservoir 136). This configuration is shown by way of example only, however, it is to be understood that the projections 158 can be configured and positioned to fracture container 120 in any desired manner.
[00147] Some embodiments of the present description provide optimal and safe breaking of a frangible container 120 with relatively little force, while enhancing the transfer of liquid 122 to the spore region (eg, the second chamber 111 of compartment 102) of the biological indicator of sterilization 100, and/or accentuates the confinement of liquid 122 in the spore region of biological sterilization indicator 100. In addition, some embodiments of the present description operate to direct a liquid to a particular area of biological sterilization indicator 100, such as a detection chamber (e.g., second chamber 111) of biological sterilization indicator 100.
[00148] In the embodiment illustrated in Figures 1 to 7, the insert 130 is illustrated as including two projections 158 that are approximately equally spaced around the container 120 and/or around the sidewall 131. However, in some embodiments, sidewall 131 may include a solid projection 158 (e.g., substantially annular or semi-annular) that extends radially inward from sidewall 131. Additionally, in some embodiments, sidewall 131 may extend further in around the inner surface of housing 102 than shown. However, employing one or more narrower projections 158 (e.g., in an angular dimension), such as those shown in Figures 1 to 7, can provide a substantially constant or substantially unobstructed sterilant path 164 around container 120.
[00149] If inserter 130 includes one or more projections 158 or sidewalls 131, inserter 130 may be configured to hold container 120 in compartment 102 in a consistent location to provide a substantially constant sterilizer path 164 during sterilization. For example, rather than allowing container 120 to move or reach (e.g., radially and/or longitudinally) into compartment 102 prior to activation (e.g., during sterilization), inserter 130 may hold container 120 in a substantially consistent position, which allows a sterilant to have a substantially consistent and relatively unobstructed path between an outer surface of compartment 120 and an inner surface of compartment 102, with little or no opportunity for inadvertent blockage.
[00150] As shown in the illustrated embodiment, the insert 130 may further include one or more projections 161 positioned substantially horizontal or perpendicular to the longitudinal direction DL of a biological sterilization indicator (e.g. when the insert 130 is positioned on a biological sterilization indicator). Projections 161 may be called "second projections" or "horizontal projections", while projections 158 used to hold and/or break container 120 may be called "first projections" or "vertical projections". The second projections 161 are not angled down like the base 127. As a result, the second projections 161 can be used for a variety of purposes. For example, second projections 161 may stabilize insert 130 (e.g., assist in retaining insert 130 in a desired position in compartment 102 of biological sterilization indicator 100) under the fracturing force of container 120. In addition, the second projections 161 may function to maintain and/or collect fractured portions of the container 120 after it has been fractured to inhibit the movement of such portions in the vicinity of spores in the biological sterilization indicator, which could negatively affect the growth of spore and/or the detection of spore growth. Other shapes and configurations of the second projections 161 can be employed that still allow the movement of fluids downward to the spores 115 while inhibiting the movement of solids downward to the spores 115.
[00151] In some embodiments, the insert 130 (eg base 127) may be adapted to one or more of facilitating or permitting fluid movement (eg liquid movement 122) in the second chamber 111 (i.e. is, the lower portion 114) of the compartment 102; minimize the movement of fractions or portions (eg, solids) from the fractured container 120 to the second chamber 111 of the compartment 102, i.e., collecting and/or maintaining portions of the fractured container 120; and/or minimize the diffusion of spores 115 and/or signals out of the second chamber 111 of housing 102. For example, in some embodiments, base 127 may be configured to function as a screen or filter. In some embodiments, spore growth is determined by fluorescent indicators/molecules (eg, fluorophores) or other markers. In some embodiments, if the liquid level after activation of the biological sterilization indicator 100 is above the spore site 115, these molecules or markers, or the spores 115 themselves, may move or diffuse away from or out of the reservoir of spore 136 and potentially out of second chamber 111 of compartment 102. As a result, portions of biological sterilization indicator 100 (e.g. insert 130) can be configured to inhibit unwanted diffusion of various indicators, molecules, and/or markers out of the second chamber 111 of the biological sterilization indicator 100. In some embodiments, as described above, substrate 119 can also inhibit such undesirable diffusion.
[00152] In the embodiment illustrated in Figures 1 to 4, the base 127 of the insert 130 is generally U-shaped or horseshoe shaped and includes a central opening 177 (see Figure 2) that facilitates movement of the sterilant toward to spores 115 during sterilization and movement of liquid 122 towards spores 115 during activation. The horseshoe shape of the base 127 can increase the passage between the upper portion 116 (i.e., the first chamber 109) and the lower portion 114 (i.e., the second chamber 111) of the housing 102; however, this format is shown as an example only, and other formats may be employed.
[00153] In some embodiments, insert 130 may be described as including one or more downwardly extending projections 127 adapted to be in a boundary position or otherwise engage with wall 118 or other internal structure of the biological sterilization indicator 100 to provide a base or support for the insert 130, to inhibit movement of the insert 130 and container 120 relative to the housing 102 prior to activation, and/or to provide strength or strength to aid rupture of the container 120 during activation. As a result, in some modalities, base 127 can be called “third projections” 127 instead.
[00154] As shown in the illustrated embodiment, in some embodiments, the insert 130 may be configured to reside entirely in the first chamber 109 of the biological sterilization indicator 100 so that the insert 130 does not extend into the second chamber 111 where it could potentially interfere with the interrogation or detection processes. Additionally, insert 130 may be configured to inhibit movement of other portions of biological sterilization indicator 100 (e.g., fractured container 120) to second chamber 111.
[00155] Insert 130 of the illustrated embodiment is generally symmetrical about a central longitudinal line of symmetry, such that there are two identical first projections 158, two identical second projections 161, and two identical third projections 127. insert 130 need not include any lines of symmetry, and first projections 158 need not be equal to each other, second projections 161 need not be equal to each other, and third projections 127 need not be equal to each other. Inserter 130, and various projections 158, 161 and 127 can be sized and positioned to control the trajectory of sterilizer 164, for example, to adjust the kill/survival rate of biological sterilization indicator 100, to inhibit fracture inadvertent movement of container 120, to facilitate movement of container 120 in compartment 120, to engage with or engage compartment 102, and/or to control breakage of container 120.
[00156] By way of example only, the illustrated insert 130 is shown as being a unitary device that includes at least the following: means for holding container 120 prior to activation, for fracturing container 120 during activation; to allow movement of container 120 in compartment 102; to provide a substantially constant sterilant path 164, to collect and/or maintain portions of fractured container 120 after activation (or at least partially inhibit movement of portions of fractured container 120 to second chamber 111 of compartment 102); and/or to minimize diffusion of spores 115 and/or signals from second chamber 111 to first chamber 109 of compartment 102 after activation. However, it should be understood that in some embodiments, the insert 130 may include multiple portions that may not be part of a single unitary device, and each portion may be adapted to perform one or more of the above functions.
[00157] Insertion member 130 is called an "insertion member" due to the fact that, in the illustrated embodiment, the device that performs the above functions is a device that can be inserted into the reservoir 103 (and particularly into the first chamber 109) of compartment 102. However, it should be understood that inserter 130 may instead be provided by compartment 102 or other component of biological sterilization indicator 100 and not necessarily be insertable into compartment. 102. The term "insertion element" will be described throughout this description for the sake of simplicity, but it should be understood that this term is not intended to limit, and should be considered, other equivalent structures that carry out one or more of the The above functions can be used instead of, or in combination with, insert 130. Furthermore, in the illustrated embodiment, insert 130 is insertable. in and removable from the housing 102, and particularly, into and out of the first portion 104 (and the first chamber 109) of the housing 102. However, it should be understood that even if the insert 130 is insertable into the housing 102, insert 130 need not be removable from housing 102, but rather can be fixedly coupled to housing 102, in a manner that inhibits removal of insert 130 from housing 102 after positioning of insert 130 in a desired location.
[00158] In some embodiments, at least a portion of compartment 102, for example, the lower portion 114 of compartment 102, may be transparent to an electromagnetic radiation wavelength or range of wavelengths (e.g., light transparent to visible when optical visible light detection methods are used), which can facilitate the detection of spore growth. That is, in some embodiments, as shown in Figures 3, 4 and 6, at least a portion of housing 102 may include or form a detection window 167.
[00159] Furthermore, in some embodiments, as shown in Figure 3, at least a portion of the compartment 102, for example, the lower portion 114 may include one or more planar walls 168. These planar walls 168 may facilitate detection, ( eg optical detection) of spore growth. In addition, as shown and described above, wall 108 of first portion 104 of housing 102 may include one or more stepped or tapered regions, such as step 152, step 123, and a tapered wall, or step, 170. tapered wall 170 can function to reduce the overall thickness and size of the lower portion, or sensing portion, 114 of housing 102, so that the outer dimensions of housing 102 are reduced in addition to the inner dimensions. Such a reduction in size and/or thickness of the lower portion 114 of the biological sterilization indicator 100 can facilitate detection. In addition, the fact that there are one or more features, such as steps and/or tapered walls 123, 152, 170 may allow the biological sterilization indicator 100 to be coupled to a reader or detection device only in one orientation, so that the biological sterilization indicator 100 is “linked” to the reading device, which can minimize user error and improve the reliability of a detection process. In some embodiments, one or more portions of the biological sterilization indicator 100 may be linked with respect to a reading device.
[00160] The biological sterilization indicator of the present description generally keeps the liquid 122 and the spores 115 separate but in relatively close proximity (for example, in the one-piece biological sterilization indicator 100) during sterilization, so that the liquid 122 and spores 115 can be readily combined after exposure to a sterilization process. Liquid 122 and spores 115 can be incubated during a detection process (for example, reading apparatus 12 can incubate sterilization biological indicator 100), or sterilization biological indicator 100 can be incubated prior to a detection process . In some embodiments, during incubation of the spores with liquid 122, an incubation temperature above room temperature can be used. For example, in some embodiments, the incubation temperature is at least about 37°C, in some embodiments, the incubation temperature is at least about 50°C (eg, 56°C), and in some embodiments, at least about 60°C. In some embodiments, the incubation temperature is no more than about 60°C, in some embodiments, no more than about 50°C, and in some embodiments, no more than about 40°C.
[00161] A detection process can be adapted to detect a detectable change from the spores 115 (eg from the spore reservoir 136) or from the liquid 122 surrounding the spores 115. That is, a detection process can be adapted to detect a variety of characteristics, including, but not limited to, electromagnetic radiation (eg, in the ultraviolet, visible, and/or infrared light bands), fluorescence, luminescence, light scattering, electronic properties (eg, conductance, impedance, or the like, or combinations thereof), turbidity, absorption, Raman spectroscopy, ellipsometry, or the like, or a combination thereof. The detection of these characteristics can be performed by one or more of a fluorimeter, spectrophotometer, colorimeter, or similar, or combinations thereof. In some modalities, such as modalities that measure fluorescence, visible light, etc., the detectable change is measured by detection at a particular wavelength.
The spores and/or liquid 122 can be adapted (e.g., labeled) to produce one or more of the following characteristics as a result of a biochemical reaction that is a sign of spore viability. As a result, no detectable change (eg, when compared to a baseline or background reading) can mean an effective sterilization process, while a detectable change can mean an ineffective sterilization process. In some embodiments, the detectable change may include a rate at which one or more of the above characteristics is changing (eg, increased fluorescence, decreased turbidity, etc.).
[00163] In some modalities, the viability of spores can be determined by exploiting the enzymatic activity. As described in Matner et al., U.S. Patent No. 5,073,488 entitled "Rapid Method for Determining Efficacy of Sterilization Cycle and Rapid Read-out Biological Indicator", which is incorporated herein by reference, enzymes can be identified. for a particular type of spore in which the enzyme has particularly useful characteristics that can be exploited to determine the effectiveness of a sterilization process. Such characteristics may include the following: (1) the enzyme, when subjected to sterilization conditions that would be sufficient to decrease a 1 X 106 population of test microorganisms by about 6 logs (ie, in a population of about of zero, as measured due to the absence of outgrowth of the test microorganisms), has a residual activity that is equal to the “background” as measured by reaction with a substrate system for the enzyme; and (2) the enzyme, when subjected to sterilization conditions only sufficient to reduce the 1 X 106 population of test microorganisms by at least 1 log, but less than 6 logs, has greater enzyme activity than the "background", as measured by reaction with the enzyme substrate system. The enzyme substrate system can include a substance, or mixture of substances, that is influenced by the enzyme to produce a product modified by a detectable enzyme, as evident by a detectable change.
[00164] In some embodiments, the biological sterilization indicator 100 can be tested in a one-way mode, with the biological sterilization indicator 100 including only one detection window (for example, detection window 167 of Figure 3) that is positioned, for example, close to spores 115. In some embodiments, however, the biological sterilization indicator 100 may include more than one detection window (eg, a window formed by all or a portion of both parallel walls 168 of the lower portion 114 of compartment 102), so that the biological sterilization indicator 100 can be tested through more than one detection window. In modalities that employ multiple sensing windows, sensing windows can be placed side by side (similar to one-way mode), or sensing windows can be oriented at an angle (eg, 90 degrees, 180 degrees, etc.) in relation to each other.
[00165] In general, the spores 115 are positioned in the spore reservoir 136 which is in fluid communication with the reservoir 103. In some embodiments, the spore reservoir 136 forms a portion of the reservoir 103 (e.g., a portion of the second chamber 111). As shown in Figure 4, reservoir 103 is in fluid communication with the environment (eg, through opening 107) during sterilization to allow sterilant to enter reservoir 103 during a sterilization process to sterilize spores 115. container 120 may be configured to contain liquid 122 during sterilization to inhibit fluid communication of liquid 122 with spores 115, reservoir 103, and the sterilant during sterilization.
[00166] Various details of spores 115 and/or spore reservoir 136 will now be described in greater detail.
[00167] In some embodiments, the spores 115 can be positioned directly in the lower portion 114 of the compartment 102, or the spores 115 can be positioned in a spore reservoir, such as the spore reservoir 136 (e.g., provided by the spore holder 135). Whether spores 115 are positioned directly in the lower portion 114 of compartment 102 or in a spore reservoir, spores 115 can be provided in a variety of ways. In some embodiments, the spores 115 can be a spore suspension that can be positioned in a desired location on the biological sterilization indicator 100 and dried. In some embodiments, spores 115 may be provided on a substrate (not shown) that can be positioned and/or secured in a desired location on biological sterilization indicator 100. Some embodiments may include a combination of spores 115 provided in a dry form and spores 115 provided on a substrate.
[00168] In some embodiments, the substrate may be positioned to support spores 115 and/or help hold spores 115 in a desired location. Such substrate may include a variety of materials, including, but not limited to, paper, a polymer (for example, any of the polymers mentioned above in relation to compartment 102), an adhesive (for example, acrylate, synthetic or natural rubber , silicone, silicone polyurea, isocyanate, epoxy, or combinations thereof), a woven cloth, a non-woven cloth, a microporous material (eg a microporous polymeric material), a reflective material (eg a metallic foil), a glass, a porcelain, a ceramic, a gel-forming material (eg, guar gum), or combinations thereof. Additionally, or alternatively, such substrate may include or be coupled with a hydrophilic coating to facilitate intimate contact of the liquid 122 with the spores 115 (e.g., when the liquid 122 employed is aqueous). Additionally, or alternatively, such a hydrophilic coating can be applied to any fluid path positioned to fluidly couple the liquid 122 and the spores 115. In some embodiments, in addition to or in place of a hydrophilic coating, a coating hydrophobic may be applied to other portions of housing 102 (e.g., lower portion 114 of housing 102) and/or of spore reservoir 136, so that liquid 122 is preferably moved to contact spores 115.
[00169] Some embodiments of the sterilization biological indicator 100 do not include the spore holder 135. Instead, the spore reservoir 136 is provided by the lower portion 114 of the compartment 102 itself, and the spores 115 can be positioned in the lower portion. 114, adsorbed onto an inner surface or wall of the lower portion 114, or combinations thereof. In some embodiments, spores 115 may be provided on a substrate that is positioned in lower portion 114 of housing 102.
[00170] In some embodiments, the spores 115 can be positioned at a spore site or a plurality of spore sites, all of which can be positioned in the reservoir 103, the lower portion 114 of the housing 102, and/or the reservoir of spores 136. In some embodiments, having multiple spore sites can maximize spore exposure to the sterilant and liquid 122, can optimize preparation (for example, spore placement can be facilitated by placing each spore site in a depression in biological sterilization indicator 100), and can optimize detection characteristics (eg due to the fact that spores may not be so easily detected in the middle of a large spore site). In embodiments employing a plurality of spore sites, each spore site can include a different known number of spores, and/or each spore site can include different spores, so that a plurality of spore types can be tested. By employing multiple spore types, the Biological Sterilization Indicator 100 can be used for a variety of sterilization processes and a specific spore site can be analyzed for a specific sterilization process, or multiple spore types can be used to test additionally the effectiveness, or reliability, of a sterilization process.
[00171] Furthermore, in some embodiments, the biological sterilization indicator 100 may include a plurality of spore reservoirs 136, and each spore reservoir 136 may include one or more spore sites 115. In some embodiments, employing one the plurality of spore reservoirs 136, the plurality of spore reservoirs 136 may be positioned in fluid communication with the reservoir 103.
[00172] In some embodiments, the spores 115 may be covered with a cover (not shown) adapted to fit into or over the spores 115 and/or the spore reservoir 136. This cover may help to keep the spores in a region of the biological sterilization indicator 100 during preparation, sterilization and/or use. The cover, if employed, may be formed of a material which does not substantially impede a detection process, and/or which is at least partially transmissible at electromagnetic radiation wavelengths of interest. In addition, depending on the makeup of the material of the covering, in some embodiments, the covering may facilitate capillary absorption of liquid 122 (e.g., the nutrient medium) with spores 115. In some embodiments, the covering may also contain features to facilitate fluid flow within the spore reservoir 136 (or for the spores 115), such as capillary channels, hydrophilic microporous fibers or membranes, or the like, or a combination thereof. Also, in some modalities, coverage can isolate a signal, or enhance the signal, which can facilitate detection. Such a cover can be employed whether the spores 115 are positioned in the spore reservoir 136 or directly in the lower portion 114 of the compartment 102. Furthermore, this cover can be employed in embodiments that employ a plurality of spore sites. The cover can include a variety of materials, including, but not limited to, paper, a polymer (for example, any of the polymers mentioned above in relation to compartment 102), an adhesive (for example, acrylate, natural or synthetic rubber , silicone, silicone polyurea, isocyanate, epoxy, or combinations thereof), a woven cloth, a non-woven cloth, a microporous material (eg, a microporous polymeric material), a glass, a porcelain, a ceramic, a forming material gel (eg guar gum), or combinations thereof.
[00173] In some embodiments, the biological sterilization indicator 100 may further include a modified inner surface, such as a reflective surface, a white surface, a black surface, or other suitable surface modification to optimize the optical properties of the surface. A reflective surface (e.g., provided by a foil) may be positioned to reflect a signal sent to the spore reservoir 136 from a testing or detection device and/or to reflect any signal generated in the spore reservoir 136 of back to the test device. As a result, the reflective surface can function to optimize (e.g., optimize the intensity of) a signal from the biological sterilization indicator 100. Such a reflective surface can be provided by an inner surface of the compartment 102; a material coupled to the inner surface of housing 102; an inner surface of the spore reservoir 136; a material coupled to the inner surface of the spore reservoir 136; or similar; or the reflective surface can form a portion of or be coupled to a spore substrate; or a combination of them.
[00174] Similarly, in some embodiments, biological sterilization indicator 100 may further include a white and/or black surface positioned to increase and/or decrease a particular signal sent to spore reservoir 136 from a device of testing and/or increasing and/or decreasing a particular signal generated in the spore pool 136. By way of example only, a white surface can be used to enhance the signal, and a black surface can be used to reduce the signal (i.e. is, noise).
[00175] In some embodiments, spores 115 can be positioned on a functionalized surface to promote immobilization of spores 115 on the desired surface. For example, such functionalized surface may be provided by an inner surface of housing 102, an inner surface of spore reservoir 136, may form a portion of or if coupled to a spore substrate, or the like, or a combination thereof.
[00176] In some embodiments, spores 115 are positioned (eg, applied by coating or an application method) onto a microstructured or microreplicated surface (eg, as the microstructured surfaces presented in Halverson et al., PCT publication no. WO 2007/070310, Hanschen et al., US publication no. 2003/0235677, and Graham et al., PCT publication no. WO 2004/000569, all of which are incorporated herein by reference). For example, the microstructured surface may be provided by an inner surface of housing 102, may be provided by an inner surface of spore reservoir 136, may form a portion of or be coupled to a spore substrate, or the like, or a combination of the same.
[00177] In some embodiments, the biological sterilization indicator 100 may further include a gel-forming material positioned to be combined with the spores 115 and the liquid 122 when the liquid 122 is released from the container 120. For example, the material gel former can be positioned close to spores 115 (e.g. in spore reservoir 136), in lower portion 114 of compartment 102, can form a portion to be coupled to a spore substrate, or the like, or a combination thereof . Such gel-forming material can form a gel (eg, a hydrogel) or a matrix comprising spores and nutrients when liquid 122 comes in contact with the spores. A gel-forming material (eg, guar gum) can be particularly useful as it has the ability to form a gel upon hydration, and can aid in localizing a signal (eg, fluorescence), can anchor spores. on site, can help minimize spore diffusion 115 and/or a signal from spore reservoir 136, and can improve detection.
[00178] In some embodiments, the biological sterilization indicator 100 may further include an absorbent or a material for capillary absorption. For example, the capillary absorption material may be positioned close to spores 115 (e.g. in spore reservoir 136), may form at least a portion of, or be coupled to, a spore substrate, or the like, or combination of them. Such capillary absorption material includes a porous capillary absorption block, an immersion block, or the like, or a combination thereof, to facilitate bringing the liquid 122 into intimate contact with the spores.
[00179] In some embodiments, the frangible container 120 may be configured to facilitate the frangible container 120 to be fractured in the desired manner. For example, in some embodiments, a lower portion of frangible container 120 may be formed of a thinner and/or weaker material such that the lower portion preferably fractures into another portion of frangible container 120. , in some embodiments, frangible container 120 can include a variety of features positioned to facilitate fracture of frangible container 120 in a desired manner, including, but not limited to, a thin and/or weakened area, a cut line, a perforation, or the like, or combinations thereof.
[00180] The frangible container 120 may have a first closed state in which the liquid 122 is contained in the frangible container 120, and a second open state in which the frangible container 120 has been fractured and the liquid 122 is released into the reservoir 103 and/or spore reservoir 136, and in fluid communication with spores 115.
[00181] In some embodiments, the biological sterilization indicator 100 can be activated (for example, the second portion 106 can be moved to the second position 150) manually. In some embodiments, the biological sterilization indicator 100 can be activated by a reading device (for example, as the biological sterilization indicator 100 is positioned on the reading device). In some embodiments, the biological sterilization indicator 100 can be activated with a device (e.g., an activation device) independent of such a reading apparatus, for example, by positioning the biological sterilization indicator 100 on the device prior to positioning the indicator. sterilization biologic 100 in a cavity of a reading device. In some embodiments, the biological sterilization indicator 100 can be activated by a combination of two or more of the reading apparatus, a device independent of the reading apparatus, and manual activation.
[00182] One or both of the sterilization biological indicator 100 and another device, such as a reading apparatus, may be additionally configured to inhibit premature or accidental fracture of the frangible container 120. For example, in some embodiments, the sterilization biological indicator sterilization 100, activation device, or reading apparatus may include a latch or locking mechanism that is positioned to inhibit second portion 106 of housing 102 from moving to second position 150 until desired. In these modalities, the biological sterilization indicator 100 cannot be activated until the lock is moved, removed or unlocked. Additionally, or alternatively, in some embodiments, the biological sterilization indicator 100, activation device, and/or reading apparatus may include a latch or locking mechanism that is positioned to prevent the second portion 106 of housing 102 from severing. move from second position 150 back to first position 148 after activation.
[00183] In some embodiments, as shown in the illustrated embodiment, at least a portion of the compartment may be flat (e.g., parallel walls 168), and may be substantially planar with respect to the spore reservoir 136, and one or both of the parallel walls 168 or a portion thereof (e.g., sensing window 167) may be dimensioned such that at least one dimension of wall 168 (or sensing window 167) substantially equals at least one dimension of the reservoir. spores 136 and/or spore site 115. In other words, wall 168 or a portion thereof (e.g., detection window 167) may include a cross-sectional view that is substantially the same size as the area. of cross section of the spore pool 136 and/or the spore site 115. This size equality test between the wall 168/sensing window 167 and the spore pool 136 and/or the spore site 115 can maximize the sin. al detected during a detection or test process. Alternatively, or additionally, wall 168 or detection window 167 can be sized to match reservoir 103 (e.g., at least one dimension or cross-sectional areas can be sized to match). This test of size equality between detection zones can improve the spore detection test.
[00184] The biological sterilization indicator 100 illustrated in Figures 1 to 7, at least the portion of the biological sterilization indicator 100 in which the spores 115 are positioned, is relatively thin (i.e., the "z dimension" is minimized), such that the optical path of the spores to wall 168 (or detection window 167) is minimized and/or any interfering effect of substances in liquid 122 (or nutrient medium) is minimized.
[00185] In use, the biological sterilization indicator 100 can be placed together with a batch for sterilization during a sterilization process. During sterilization, a sterilizer is in fluid communication with reservoir 103 (i.e., first chamber 109 and second chamber 111), spore reservoir 136, and spores 115 primarily through sterilizer path 164, so that the sterilizer can reach the spores to produce sterilized spores. As described above, the cooperation of the first fluid path 160 and the second fluid path 162 can facilitate movement of the sterilizer to the second chamber 111, and particularly to the closed end 105 of the biological sterilization indicator 100. sterilization, frangible container 120 is in a closed state, kept intact at least partially by holder 132 of insert 130. When frangible container 120 is in a closed state, liquid 122 is protected from the sterilizer and is not in fluid communication with the reservoir 103 (particularly the second reservoir 111 formed at least partially by the lower portion 114 of the housing 102), the spore reservoir 136, the spores 115, or the sterilizer path 164.
[00186] Sterilization may further include moving a sterilizer from the first chamber 109 to the second chamber 111 through the first fluid path 160 when the container 120 is in the first state, and moving the displaced gas (e.g., trapped air) out of the second chamber 111 through the second fluid path 162 in response to, or to facilitate, movement of the sterilizer from the first chamber 109 to the second chamber 111.
[00187] After sterilization, the effectiveness of the sterilization process can be determined using the biological sterilization indicator 100. The second portion 106 of compartment 102 can be unlocked, if previously locked in the first position 148, and moved from the first position 148 (see Figure 3) to second position 150 (see Figure 4) to cause activation of biological sterilization indicator 100. This movement of second portion 106 can cause frangible container 120 to move in compartment 102, by example, along the longitudinal direction DL, from a position above the upper ends 159 of the projections 158 to a position within the projections 158, which can lead to fracture of the frangible container 120. Fracture of the frangible container 120 can alter the container frangible 120 from its closed state to its open state and release the liquid 122 in the reservoir 103, and in liquid communication with the spore reservoir 13 6 and the spores 115. The liquid 122 may include a nutrient medium (e.g., germination medium) for the spores, or the liquid 122 may contact the nutrient medium in a dry form (e.g., in a powdered or in tablet) to form the nutrient medium so that a mixture including the sterilized spores and the nutrient medium is formed. The mixture can then be incubated prior to, or during, a test or detection process, and the biological sterilization indicator 100 can be interrogated for signs of spore growth.
[00188] Activation may further include moving the liquid 122 from the first chamber 109 to the second chamber 111 through the first fluid path 160 when the container 120 is in the second state, and moving the displaced gas (e.g., trapped air ) out of the second chamber 111 through the second fluid path 162 in response to or to facilitate movement of liquid 122 from the first chamber 109 to the second chamber 111 through the first fluid path 160.
[00189] To detect a detectable change in spores 115, biological sterilization indicator 100 can be tested immediately after liquid 122 and after spores 115 have been combined to achieve a baseline reading. Thereafter, any detectable change in the baseline reading can be detected. The biological sterilization indicator 100 can be monitored and measured continuously or intermittently. In some embodiments, a portion of the incubation step, or the entire incubation step, can be performed before measuring the detectable change. In some modalities, incubation can be performed at one temperature (eg 37 °C, 50 to 60 °C, etc.), and measurement of detectable change can be performed at a different temperature (eg at room temperature, 25 °C, or at 37 °C).
[00190] The reading time of the biological sterilization indicator 100 (that is, the time to determine the effectiveness of the sterilization process) may be, in some modalities, less than 8 hours, in some modalities less than 1 hour, in some modalities less than 30 minutes, in some modalities less than 15 minutes, in some modalities less than 5 minutes, and in some modalities less than 1 minute. Modalities
[00191] Mode 1 is a biological sterilization indicator comprising: a compartment; a container containing a liquid and which is sized to be positioned in the compartment, wherein at least a portion of the frangible container, wherein the container has a first state in which the container is intact and the liquid is not in fluid communication with an interior of the compartment, and a second state in which the container is fractured and the liquid is in fluid communication with the interior of the compartment; a first chamber in the compartment in which the container is positioned when the container is in the first state; a second chamber in the compartment in which the container and liquid are not positioned when the container is in the first state, and to which the sterilant moves when the container is in the first state and to which the liquid moves when the container is in the second state, wherein the second chamber comprises at least one source of biological activity which is not in fluid communication with the liquid when the container is in the first state and which is in fluid communication with the liquid when the container is in the second state; a first fluid path positioned to fluidly couple the first chamber and the second chamber, the first fluid path being positioned to allow a sterilizer to move from the first chamber to the second chamber when the container is in the first state, and to allowing liquid to move from the first chamber to the second chamber when the container is in the second state; and a second fluid path positioned to fluidly couple the second chamber and another chamber of the sterilization biological indicator, the second fluid path being positioned to allow displaced gas to move out of the second chamber in accordance with the sterilizer or the liquid moves from the first chamber to the second chamber.
[00192] Mode 2 is a method for using a sterilization biological indicator, wherein the method comprises: providing a sterilization biological indicator including: a compartment, a container that comprises a liquid and is positioned in the compartment, at least one being portion of the frangible container, in which the container has a first state in which the container is intact and the liquid is not in fluid communication with an interior of the compartment, and a second state in which the container is fractured and the liquid is in fluid communication with the interior of the compartment, a first chamber in the compartment in which the container is positioned when the container is in the first state, and a second chamber in the compartment in which the container and liquid are not positioned when the container is in the first state, and to which the sterilant moves when the container is in the first state and to which the liquid moves when the container is in the second state. in the second state, wherein the second chamber comprises at least one source of biological activity which is not in fluid communication with the liquid when the container is in the first state and which is in fluid communication with the liquid when the container is in the second state; and at least one of: (a) moving a sterilant from the first chamber to the second chamber via a first fluid path when the container is in the first state, and moving the displaced gas out of the second chamber via a second path for fluids as a sterilant is moved from the first chamber to the second chamber via the first fluid path, and (b) moving the liquid from the first chamber to the second chamber via a first fluid path when the container is in the second state, and moving the displaced gas out of the second chamber through a second fluid path as liquid is moved from the first chamber to the second chamber through the first fluid path.
[00193] Mode 3 is the biological sterilization indicator of mode 1 or the method of mode 2, in which the second fluid path is positioned to fluidly couple the second chamber and the first chamber, the second path being for fluids positioned to allow the displaced gas to move from the second chamber to the first chamber.
[00194] Mode 4 is the biological sterilization indicator or method of mode 3, wherein the first fluid path enters the second chamber in a first position, wherein the second fluid path enters the first chamber in a second position, and wherein the second position is positioned above the first position, in the operation of the biological sterilization indicator.
[00195] Mode 5 is the biological sterilization indicator of mode 3 or 4, or the method of mode 3 or 4, in which the first fluid path is positioned to fluidly couple the second chamber with a proximal portion of the first chamber, and wherein the second fluid path is positioned to fluidly couple the second chamber with a distal portion of the first chamber.
[00196] Mode 6 is the biological sterilization indicator of any one of modes 1 and 3 to 5 or the method of any one of modes 2 to 5, wherein the second chamber is at least partially filled with liquid when the container it is in the second state, the liquid having a level, and the second fluid path extending between a position below the liquid level and a position above the liquid level.
[00197] Mode 7 is the biological sterilization indicator of any one of modes 1 and 3 to 6 or the method of any one of modes 2 to 6, wherein the second fluid path is at least partially defined by a channel that extends from the second chamber to a position on the biological sterilization indicator that is above the position at which the first fluid path enters the second chamber.
[00198] Mode 8 is the biological sterilization indicator of any one of modes 1 and 3 to 7 or the method of any one of modes 2 to 7, wherein the second fluid path extends from the second chamber to a position in the biological sterilization indicator that is above the position at which the first fluid path enters the second chamber.
[00199] Mode 9 is the biological sterilization indicator of any one of modes 1 and 3 to 8 or the method of any one of modes 2 to 8, in which the first fluid path connects to the second chamber in a first position, wherein the second fluid path connects to the second chamber in a second position, and the second position being situated vertically at or above the first position, in operation of the biological sterilization indicator.
[00200] Mode 10 is the biological sterilization indicator of any one of modes 1 and 3 to 9 or the method of any one of modes 2 to 9, wherein the second fluid path connects to the second chamber at a level of the second chamber which is the last to be filled with liquid when the container is in the second state.
[00201] Mode 11 is the biological sterilization indicator of any one of modalities 1 and 3 to 10 or the method of any of modalities 2 to 10, in which the source of biological activity is not in fluid communication with the environment when the second portion of the compartment is in the second position.
[00202] Mode 12 is the biological sterilization indicator of any one of modes 1 and 3 to 11 or the method of any one of modes 2 to 11, wherein the first chamber and the second chamber each have a volume , and the volume of the second chamber is not greater than 20% of the volume of the first chamber.
[00203] Mode 13 is the biological sterilization indicator of any one of modes 1 and 3 to 12 or the method of any one of modes 2 to 12, wherein the first chamber and the second chamber each have a volume , and the volume of the second chamber is not greater than 10% of the volume of the first chamber.
[00204] Mode 14 is the biological sterilization indicator of any one of modes 1 and 3 to 13 or the method of any one of modes 2 to 13, wherein the first chamber and the second chamber each have an area of average cross-sectional area, and wherein the average cross-sectional area of the second chamber is not greater than 50% of the average cross-sectional area of the first chamber.
[00205] Mode 15 is the biological sterilization indicator of any one of modes 1 and 3 to 14 or the method of any one of modes 2 to 14, wherein the first chamber and the second chamber each have an area of average cross-section, and wherein the average cross-sectional area of the second chamber is not greater than 40% of the average cross-sectional area of the first chamber.
[00206] Mode 16 is the biological sterilization indicator of any one of modes 1 and 3 to 15 or the method of any one of modes 2 to 15, which further comprises an insert positioned in the compartment, being the element set for at least one of the actions of keeping the container intact and fracturing the container.
[00207] Mode 17 is the biological sterilization indicator or method of mode 16, wherein the inserter defines at least a portion of the second fluid path.
[00208] Mode 18 is the biological sterilization indicator of mode 16 or 17 or the method of mode 16 or 17, wherein the insert defines at least a portion of the first fluid path.
[00209] Mode 19 is the biological sterilization indicator of any one of modes 16 to 18 or the method of any one of modes 16 to 18, with the inserter positioned in the first chamber.
[00210] Mode 20 is the biological sterilization indicator of any one of modes 16 to 19 or the method of any one of modes 16 to 19, the second fluid path being defined by the insert element and an inner surface of the compartment.
[00211] Mode 21 is the biological sterilization indicator of any one of modes 16 to 20 or the method of any one of modes 16 to 20, wherein the second fluid path is at least partially defined by at least one of the housing, the insert, a source carrier positioned to house at least one source of biological activity in the second chamber, and a substrate positioned between the first chamber and the second chamber.
[00212] Mode 22 is the biological sterilization indicator of any one of modes 16 to 21 or the method of any one of modes 16 to 21, wherein the first fluid path is at least partially defined by at least one of the housing, the insert, a source carrier positioned to house at least one source of biological activity in the second chamber, and a substrate positioned between the first chamber and the second chamber.
[00213] Mode 23 is the biological sterilization indicator of any one of modes 16 to 22 or the method of any one of modes 16 to 22, wherein the insert is positioned to at least partially define the first chamber and the second chamber.
[00214] Mode 24 is the biological sterilization indicator of any one of modes 1 and 3 to 23 or the method of any one of modes 2 to 23, wherein the second chamber is defined at least partially by a closed end of the compartment .
[00215] Mode 25 is the biological sterilization indicator of any one of modes 1 and 3 to 24 or the method of any one of modes 2 to 24, wherein the first chamber and the second chamber are in fluid communication with the environment when the container is in the first state through at least one opening in the compartment, the at least one opening being positioned adjacent an end of the first chamber which is situated opposite the first chamber of the second chamber.
[00216] Mode 26 is the biological sterilization indicator of any one of modes 1 and 3 to 25 or the method of any one of modes 2 to 25, wherein the first chamber includes a first end positioned toward a first end of the housing and a second end positioned toward a second end of the housing, and the second chamber including a first end in fluid communication with the second end of the first chamber and a second end defined at least partially by the second end of the housing.
[00217] Mode 27 is the biological sterilization indicator of any one of modes 1 and 3 to 26 or the method of any one of modes 2 to 26, wherein the compartment includes a longitudinal direction, the first chamber being positioned above the second chamber, and the first fluid path and the second fluid path extending substantially longitudinally between the first chamber and the second chamber.
[00218] Mode 28 is the biological sterilization indicator of any one of modes 1 and 3 to 27 or the method of any one of modes 2 to 27, wherein the compartment includes a first end and a second end, and wherein the first chamber is positioned adjacent the first end and the second chamber is positioned adjacent the second end.
[00219] Mode 29 is the biological sterilization indicator of any one of modes 1 and 3 to 28 or the method of any one of modes 2 to 28, wherein at least a portion of the second fluid path is defined by a surface inside the compartment.
[00220] Mode 30 is the biological sterilization indicator of any one of modes 1 and 3 to 29 or the method of any one of modes 2 to 29, the compartment including a first portion, and a second portion adapted to be coupled to the first portion, the second portion being movable relative to the first portion, when coupled to the first portion, between a first position and a second position.
[00221] Mode 31 is the biological sterilization indicator or method of mode 30, in which the container is changed from the first state to the second state in response to the second portion of the compartment being moved from the first position to the second position.
[00222] Mode 32 is the biological sterilization indicator of mode 30 or 31 or the method of mode 30 or 31, wherein the interior of the compartment is sealed from the environment when the second portion of the compartment is in the second position.
[00223] Mode 33 is the biological sterilization indicator of any one of modes 30 to 32 or the method of any one of modes 30 to 32, wherein the liquid is moved to the second chamber in response to the second portion of the compartment being moved from the first position to the second position.
[00224] Mode 34 is the biological sterilization indicator of any one of modes 30 to 33 or the method of any one of modes 30 to 33, wherein the at least one source of biological activity is in fluid communication with the environment when the second portion of the compartment is in the first position.
[00225] Mode 35 is the biological sterilization indicator of any one of modes 30 to 34 or the method of any one of modes 30 to 34, in which the at least one source of biological activity is not in fluid communication with the environment when the second portion of the compartment is in the second position.
[00226] Mode 36 is the biological sterilization indicator of any one of modes 1 and 3 to 35 or the method of any one of modes 2 to 35, wherein the container includes a glass ampoule.
[00227] Mode 37 is the biological sterilization indicator of any one of modes 1 and 3 to 36 or the method of any one of modes 2 to 36, which further comprises a source carrier positioned in the second chamber and configured to house at least one source of biological activity.
[00228] Mode 38 is the biological sterilization indicator of any one of modes 1 and 3 to 37 or the method of any one of modes 2 to 37, wherein at least one of the first chamber and the second chamber is at least partially defined by a partial wall.
[00229] Mode 39 is the biological sterilization indicator or the method of mode 38, in which the partial wall is oriented at an unright angle to a longitudinal direction of the biological sterilization indicator.
[00230] Mode 40 is the biological sterilization indicator of any one of modes 1 and 3 to 39 or the method of any one of modes 2 to 39, wherein the first chamber and the second chamber are at least partially defined by a substrate.
[00231] Mode 41 is the biological sterilization indicator or the method of mode 40, in which the substrate is oriented at a non-right angle to a longitudinal direction of the biological sterilization indicator.
Mode 42 is the method of any one of embodiments 2 to 41, wherein moving the displaced gas out of the second chamber includes moving the displaced gas from the second chamber to the first chamber.
[00233] Mode 43 is the method of any one of embodiments 2 to 42, wherein the housing includes a first portion, and a second portion adapted to be coupled to the first portion, the second portion being movable relative to the first portion, when coupled to the first portion between a first position and a second position, and further comprising moving the second housing portion relative to the first housing portion from the first position to the second position.
[00234] Mode 44 is the method of mode 43, which further comprises fracturing the container to change the container from the first state to the second state, with the fracturing of the container occurring in response to the movement of the second portion of the compartment. first position to second position.
[00235] Mode 45 is the method of mode 44, wherein fracturing the container includes crushing a glass ampoule.
[00236] Mode 46 is the method of any one of modes 2 to 45, which further comprises facilitating the flow of sterilant from the first chamber to the second chamber during sterilization, by internally venting the gas from the second chamber to the first chamber through the second fluid path.
[00237] Mode 47 is the method of any one of embodiments 2 to 46, further comprising: fracturing the container to change the container from the first state to the second state; and sealing the interior of the compartment from the environment during or after fracturing the container, moving the displaced gas out of the second chamber includes internally venting the second chamber. Mode 48 is the method of any one of embodiments 2 to 47, wherein the movement of liquid from the first chamber to the second chamber occurs via gravity.
[00238] The modalities described above and illustrated in the figures are presented for example only, and are not intended to limit the concepts and principles of this description. Accordingly, it will be appreciated by a person skilled in the art that various changes in the elements and their configurations and arrangements are possible without departing from the spirit and scope of the present description. Various features and aspects of the present description are set forth in the following claims.

权利要求:
Claims (13)
[0001]
1. Biological sterilization indicator CHARACTERIZED by the fact that it comprises: a compartment; a container containing a liquid and being sized to be positioned in the compartment, at least a portion of the container being frangible, the container having a first state in which the container is intact and the liquid is not in fluid communication with an interior of the compartment, and a second state in which the container is fractured and the liquid is in fluid communication with the interior of the compartment; a first chamber in the compartment in which the container is positioned when the container is in the first state; a second chamber in the compartment in which the container and liquid are not positioned when the container is in the first state, and to which a sterilant moves when the container is in the first state and to which the liquid moves when the container is in the second state, the second chamber comprising at least one source of biological activity which is not in fluid communication with the liquid when the container is in the first state and which is in fluid communication with the liquid when the container is in the second state; a first fluid path positioned to fluidly couple the first chamber and the second chamber, the first fluid path positioned to allow a sterilant to move from the first chamber to the second chamber when the container is in the first state, and to allow that liquid moves from the first chamber to the second chamber when the container is in the second state; a second fluid path positioned to fluidly couple the second chamber and another chamber of the sterilization biological indicator, the second fluid path positioned to allow displaced gas to move out of the second chamber as the sterilant or liquid moves from the first chamber to the second chamber; and an insert positioned in the housing, the insert configured to at least one of keeping the container intact and fracturing the container, wherein the insert is adapted to allow the container to move in the housing between a first position at that the container is in the first state and a second position where the container is in the second state, wherein the second fluid path is positioned to fluidly couple the second chamber and the first chamber, the second fluid path positioned to allow that the displaced gas moves from the second chamber to the first chamber.
[0002]
2. Method for using a biological sterilization indicator, CHARACTERIZED by the fact that it comprises: providing a biological sterilization indicator including: a compartment, a container comprising a liquid and positioned in the compartment, at least a portion of the container being frangible, the container having a first state in which the container is intact and the liquid is not in fluid communication with an interior of the compartment, and a second state in which the container is fractured and the liquid is in fluid communication with the interior of the compartment, a first chamber in the compartment in which the container is positioned when the container is in the first state, and a second chamber in the compartment in which the container and liquid are not positioned when the container is in the first state, and into which a sterilant moves when the container is in the first state and to which the liquid moves when the container is in the second state, the second chamber comprising at least one source of biological activity which is not in fluid communication with the liquid when the container is in the first state and which is in fluid communication with the liquid when the container is in the second state; and at least one of: (a) moving a sterilant from the first chamber to the second chamber through a first fluid path when the container is in the first state, and moving the displaced gas out of the second chamber through a second path to fluids as a sterilant is moved from the first chamber to the second chamber via the first fluid path by internally venting gas from the second chamber to the first chamber via the second fluid path, and (b) moving the liquid from the first chamber to the second chamber through a first fluid path when the container is in the second state, and moving the displaced gas out of the second chamber through a second fluid path as liquid is moved from the first chamber to the second chamber through the first fluid path by internally venting gas from the second chamber to the first chamber via the second path went to fluids.
[0003]
3. Biological sterilization indicator according to claim 1, or the method according to claim 2, CHARACTERIZED by the fact that the first fluid path enters the second chamber at a first position, wherein the second fluid path enters in the first chamber in a second position, and wherein the second position is positioned above the first position, in the operation of the biological sterilization indicator.
[0004]
4. Biological sterilization indicator according to claim 1 or 3, or the method according to claim 2 or 3, CHARACTERIZED by the fact that the first fluid path is positioned to fluidly couple the second chamber with a proximal portion of the first chamber, and wherein the second fluid path is positioned to fluidly couple the second chamber with a distal portion of the first chamber.
[0005]
5. Biological sterilization indicator, according to any one of claims 1 and 3 to 4, or the method according to any one of claims 2 to 4, CHARACTERIZED by the fact that the second chamber is at least partially filled with liquid when the container is in the second state, where the liquid has a level, and where the second fluid path extends between a position below the liquid level and a position above the liquid level.
[0006]
6. Biological sterilization indicator, according to any one of claims 1 and 3 to 5, or the method according to any one of claims 2 to 5, CHARACTERIZED by the fact that the second path for fluids is at least partially defined by a channel extending from the second chamber to a position on the biological sterilization indicator which is above the position at which the first fluid path enters the second chamber.
[0007]
7. Biological sterilization indicator according to any one of claims 1 and 3 to 6 or the method according to any one of claims 2 to 6, CHARACTERIZED by the fact that the second fluid path extends from the second chamber to a position on the biological sterilization indicator that is above the position at which the first fluid path enters the second chamber.
[0008]
8. Biological sterilization indicator, according to any one of claims 1 and 3 to 7, or the method according to any one of claims 2 to 7, CHARACTERIZED by the fact that the first fluid path connects to the second chamber at a first position, wherein the second fluid path connects to the second chamber in a second position, and wherein the second position is situated vertically at or above the first position in operation of the biological sterilization indicator.
[0009]
9. Biological sterilization indicator, according to any one of claims 1 and 3 to 8, or the method according to any one of claims 2 to 8, CHARACTERIZED by the fact that the interior of the compartment is not in fluid communication with the environment when the container is in the second state.
[0010]
10. Biological sterilization indicator, according to any one of claims 1 and 3 to 9, or the method according to any one of claims 2 to 9, CHARACTERIZED by the fact that the first chamber and the second chamber each have , a volume, and in which the volume of the second chamber is not greater than 20% of the volume of the first chamber.
[0011]
11. Biological sterilization indicator, according to any one of claims 1 and 3 to 10, or the method according to any one of claims 2 to 10, CHARACTERIZED by the fact that the first chamber and the second chamber each have , an average cross-sectional area, and wherein the average cross-sectional area of the second chamber is not greater than 50% of the average cross-sectional area of the first chamber.
[0012]
12. Biological sterilization indicator, according to any one of claims 1 and 3 to 11, or the method according to any one of claims 2 to 11, CHARACTERIZED by the fact that the compartment includes a longitudinal direction, in which the first The chamber is positioned above the second chamber, and wherein the first fluid path and the second fluid path extend substantially longitudinally between the first chamber and the second chamber.
[0013]
13. Biological sterilization indicator, according to any one of claims 1 and 3 to 12, or the method according to any one of claims 2 to 12, CHARACTERIZED by the fact that at least one of the first chamber and the second chamber is at least partially defined by a partial wall oriented at a non-right angle to a longitudinal direction of the biological sterilization indicator.

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US9540677B2|2017-01-10|

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CN103189524B|2015-01-28|

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EP2635699B1|2018-03-21|

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EP2635699A1|2013-09-11|

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JP2013542786A|2013-11-28|

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US20130302849A1|2013-11-14|

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WO2012061226A1|2012-05-10|

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CA2816078A1|2012-05-10|

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ES2671346T3|2018-06-06|

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法律状态:
2020-09-15| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2020-10-27| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2021-03-02| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2021-05-18| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 28/10/2011, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US40898810P| true| 2010-11-01|2010-11-01|

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US61/408,988|2010-11-01|

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PCT/US2011/058256|WO2012061226A1|2010-11-01|2011-10-28|Biological sterilization indicator and method of using same|

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