TEST CARTRIDGE SYSTEM, TRANSFER MODULE, AND METHOD FOR PERFORMING FLUID TRANSFER

专利摘要:
test cartridge system, for module to carry out the transfer, and, fluid transfer method. a system including a cartridge housing and a hollow transfer module according to an embodiment is described herein. the cartridge housing further includes at least one sample inlet, a plurality of storage chambers, a plurality of reaction chambers, and a fluid network. the fluid network is designed to connect the at least one sample inlet, a portion of the plurality of storage chambers and the portion of the plurality of reaction chambers with a first plurality of holes located on an inner surface of the cartridge housing. the hollow transfer module includes a second plurality of holes along an outer surface of the transfer module that lead to a central chamber within the transfer module. the transfer module is designed to move sideways within the cartridge housing. lateral movement of the transfer module aligns with at least a portion of the first plurality of holes with at least a portion of the second plurality of holes.
公开号:BR112014022962B1
申请号:R112014022962-7
申请日:2013-03-15
公开日:2021-07-20
发明作者:Jordi Carrera Fabra；Anna Comenges Casas；Rafael Bru Gibert
申请人:Stat-Diagnostica & Innovation, S.L.；
IPC主号:

专利说明:

FUNDAMENTALS Field
[0001] Modalities of the present invention refer to the field of clinical diagnostic tools. Fundamentals
[0002] Given the complexity of automating immunological analysis techniques and molecular testing, there is a lack of products that provide adequate performances to be clinically useful in patient test settings. Appropriate molecular tests include several processes that involve correct dosage of reagents, sample introduction, lysis of the cell to extract DNA or RNA, purification steps, and amplification for its subsequent detection. Even though there are robotic central laboratory platforms that automate these processes, for many tests that require a short turnaround time, the central laboratory cannot provide the results in the necessary time requirements.
[0003] However, it is difficult to implement systems in a clinical setting that provide accurate, reliable results at a reasonable cost. Given the complicated nature of many molecular testing techniques, results are prone to error if test parameters are not carefully controlled or if environmental conditions are not ideal. For example, existing instrumentation for PCR techniques has faced high entry barriers for clinical diagnostic applications due to knowledge generated through exogenous sources of DNA. In the case of pathogen-specific tests, the predominant source of contamination is a result of previous reactions performed in pipettes, tubes, or general laboratory equipment. Additionally, the use of molecular techniques to detect microbial pathogens can produce false negatives. False negatives can result from, for example: improper disposition of agents that inhibit Polymerase Chain Reaction (PCR) such as hemoglobin, urine or phlegm; inefficient release of DNA from cells; or low efficiency in DNA or RNA extraction and purification.
[0004] The fact that molecular techniques have exceptional levels of sensitivity at lower concentrations than previous reference methods makes it difficult to draw clinically relevant conclusions, while avoiding erroneous calls with false positives. To minimize this problem, especially for the detection of pathogenic microorganisms, the tests must be capable of quantification. Therefore it becomes increasingly necessary to perform multiplex arrays and test arrays to consolidate enough data to make confident conclusions. As an example, one of the main limitations of existing PCR-based tests is the inability to perform amplifications of different target genes simultaneously. While techniques such as microarrays provide very high multiplexing capability, their main limitation is the slow speed of obtaining results, which generally have no positive impact on patient management. BRIEF SUMMARY
[0005] A clinical diagnostic platform can integrate a variety of analytical testing processes to reduce testing errors, costs and time.
[0006] In one embodiment, a system includes a cartridge housing and a hollow transfer module. The cartridge housing further includes at least one sample inlet, a plurality of storage chambers, a plurality of reaction chambers, and a fluid network. The fluid network is designed to connect the at least one sample inlet, a portion of the plurality of storage chambers and the portion of the plurality of reaction chambers with a first plurality of holes located on an inner surface of the cartridge housing. The hollow transfer module includes a second plurality of holes along an outer surface of the transfer module that lead to a central chamber within the transfer module. The transfer module is designed to move sideways within the cartridge housing. The lateral movement of the transfer module aligns with at least a portion of the first plurality of holes with at least a portion of the second plurality of holes.
[0007] In one embodiment, a transfer module includes an inner housing that comprises a central chamber and a jacket formed around the inner housing. The jacket includes patterned ridges along the outer surface of the jacket. The patterned ridges are patterned to create a plurality of valve regions along the outer surface of the jacket when the transfer module is positioned within a compartment that contacts the patterned ridges. The jacket additionally includes a plurality of holes extending through the jacket and the inner housing to the central chamber. The plurality of holes are located within one or more of the plurality of valve regions created by the patterned ridges. One of the plurality of valve regions with a corresponding orifice extending into the central chamber is designed to be pressurized separately from other regions in the plurality of valve regions, such that the pressurization generates fluid flow both in and out of the central chamber through one or more of the plurality of holes.
[0008] An example method is described. The method includes laterally translating a transfer module to align a first transfer module hole having a center chamber to a first chamber hole. The method further includes drawing a sample into the central chamber of the first chamber via a first pressure differential. Once the sample is in the central chamber, the method includes laterally translating the transfer module to align a first port of the transfer module to a port of a second chamber and withdrawing the sample to the second chamber from the chamber. through a second pressure differential.
[0009] Another example method is described. The method includes laterally translating a transfer module within a housing to align a frame on an outer surface of the transfer module with a first hole associated with a first chamber and with a first hole associated with a second chamber. The method further includes taking a sample from the first chamber to the second chamber through at least the frame aligned over the first hole and the first hole. The method continues with withdrawing the sample from the second chamber into a third chamber located within the transfer module through a hole through a wall of the transfer module. BRIEF DESCRIPTION OF THE DRAWINGS / FIGURES
[00010] The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate embodiments of the present invention and, together with the description, additionally serve to explain the principles of the invention and to enable one skilled in the pertinent art to make and use the invention.
[00011] FIG. 1 displays a graphical representation of the test cartridge system according to an modality.
[00012] FIGs. 2A through 2D show multiple views of a test cartridge system, according to an embodiment.
[00013] FIGs. 3A to 3D show multiple views of the internal housing of a transfer module, according to an embodiment.
[00014] FIGs. 4A to 4C show three views of a transfer module jacket, according to an embodiment.
[00015] FIGs. 5A and 5B show graphical representations of a test cartridge system, according to an embodiment.
[00016] FIGs. 6A and 6B show various views of a test cartridge system, in accordance with an embodiment.
[00017] FIGs. 7A to 7F show multiple views of a transfer module, according to an embodiment.
[00018] FIGs. 8A and 8B show streaks within a test cartridge system, in accordance with some embodiments.
[00019] FIG. 9 is a diagram illustrating a method performed by a test cartridge system, according to an embodiment.
[00020] FIG. 10 is a diagram illustrating a method performed by a test cartridge system, in accordance with an embodiment.
[00021] The embodiments of the present invention will be described with reference to the attached drawings. DETAILED DESCRIPTION
[00022] Although specific arrangements and configurations are discussed, it should be understood that this is done for illustrative purposes only. One skilled in the pertinent art will recognize that other configurations and arrangements can be used without departing from the spirit and scope of the present invention. It will be apparent to one of skill in the pertinent art that this invention can also be employed in a variety of other applications.
[00023] It is noted that references in the specification to "a modality," "a modality," "an example modality," etc., indicate that the described modality may include a particular functionality, structure, or feature, but every modality necessarily may include a particular functionality, structure or feature. Furthermore, such phrases do not necessarily refer to the same modality. Additionally, when a particular functionality, structure or feature is described in conjunction with an embodiment, it should be within the knowledge of the person skilled in the art to effect such functionality, structure or feature in conjunction with other embodiments whether explicitly described or not.
[00024] Modalities described herein refer to a test cartridge system for performing a variety of biochemical, molecular or immunological analysis, etc. tests. In one embodiment, the test cartridge integrates all the components needed to perform such tests in a single disposable package. The test cartridge can be configured to be analyzed through an external measurement system that provides data related to the reactions taking place within the test cartridge.
[00025] In one example, a single test cartridge can be used to perform a multiplexed immunological analysis with a given sample. The test cartridge contains all necessary buffers, reagents, and labels kept in sealed chambers built into the cartridge to perform immunological analyses.
[00026] In another example, a single test cartridge can be used to perform PCR. DNA and/or RNA can be purified from the rest of a sample (lysate) through a membrane incorporated into the test cartridge. The sample can be extruded through the membrane while a separately stored elution liquid can remove the DNA and/or RNA and bring it to another chamber to begin the temperature cycling process.
[00027] Any test such as that described above requires some form of liquid transport to occur. In one embodiment, the test cartridge includes a movable hollow transfer module which includes a plurality of holes to align with holes along the sides of a cartridge housing. Liquid can be transferred between the various other chambers of the cartridge housing either into or out of the hollow transfer module by applying a pressure differential to the system. In one example, external actuators are used to apply the pressure differential.
[00028] One of the main limitations of molecular diagnostic instrumentation is the problem associated with contamination such as cross contamination, transport contamination, etc. Modalities described here substantially eliminate by design sample contamination to the instrument.
[00029] In one embodiment, the test cartridge provides a self-contained liquid sealed during the manufacturing process. Reagents or sample do not come into contact with the environment or any part of the instrument. This test cartridge functionality is also important to many laboratories and hospitals for the safe disposal of products after use.
[00030] Additional details regarding the components of the test cartridge system are described here with references made to the figures. It is to be understood that the illustrations of each physical component are not to be limiting and that one skilled in the relevant art given the description herein may recognize ways to rearrange or otherwise alter any of the components without departing from the scope or spirit of the invention. First Test Cartridge Mode
[00031] FIGs. 1-4 illustrate various views and components of a test cartridge system in accordance with an embodiment. FIG. 1 illustrates a test cartridge system 100 that includes a cartridge housing 102 and a transfer module 104. Other components may also be considered for inclusion in test cartridge system 100, such as an analyzer module or various active components such as like pumps or heaters.
[00032] Transfer module 104 includes an inner housing 110, a jacket 108, and a cover 106. The jacket 108 is designed to fit around the inner housing 110, according to an embodiment. In one example, inner housing 110 is made of a rigid material such as metal or plastic, while jacket 108 is made of a compatible material such as rubber or soft plastic. In another example, both jacket 108 and inner housing 110 are made of a soft compatible material, which may be the same material or different materials. In another example, both jacket 108 and inner housing 110 are made through a super-injection process. Cover 106 is designed to seal the end of transfer module 104 to prevent leakage. Additional details regarding transfer module 104 components are discussed later with reference to FIGs. 3 and 4.
[00033] The transfer module 104 is designed to be inserted into the cartridge housing 102 through a chamber bay 120. In one embodiment, the transfer module 104 is configured to connect with an external actuator (not shown). The external actuator can laterally move the transfer module 104 within the cartridge housing 102 to align the holes in the transfer module 104 with the holes in the cartridge housing 102. In another embodiment, the transfer module 104 is configured to match. move within the cartridge housing 102 through the operation of an external slider by a user.
[00034] Cartridge housing 102 includes a variety of channels, chambers, and fluid reservoirs. For example, cartridge housing 102 can include a plurality of storage chambers 116 that can contain various buffers or other reagents to be used during an assay or PCR protocol. Storage chambers 116 can be pre-filled with various liquids so that the end user will not need to fill storage chambers 116 before placing the test cartridge system 100 in an analyzer. Cartridge housing 102 may additionally include one or more processing chambers 124A-C connected with fluid channels along one side of cartridge housing 102. Processing chambers 124A-C may be used for a variety of processing and/or applications. or waste. In one example, chamber 124A is a residue chamber, chamber 124B is an elution chamber for PCR protocols, and chamber 124C is a wick elution chamber. In one embodiment, cartridge housing 102 includes a gripping structure 117 to provide easier manipulation of test cartridge system 100.
[00035] Samples are introduced into the cartridge housing 102 through the sampling port 114, according to an embodiment. In one example, sampling hole 114 is sized to fully receive the length of an ordinary medical wick. Thus, the user can position the roving either to a breaking point or completely within the sample hole 114, and subsequently seal the hole with a hole cap 112. In another example, the sample hole 114 receives solid, semi-solid or liquids. In one embodiment, cartridge housing 102 includes more than one inlet for introducing samples.
[00036] The cartridge housing 102 may incorporate one or more structures useful for performing the tests, such as filters, gels, membranes, etc. For example, cartridge housing 102 may include a membrane housed in cavity 122. In one embodiment, the membrane is coupled with fluid channels along the exterior of cartridge housing 102. In another embodiment, the membrane may be disposed within any of the processing chambers 124A-C.
[00037] The various chambers and channels around the cartridge housing 102 can be sealed through the use of covers 118, 126, and 128. The covers may be films capable of sealing the fluid within the cartridge housing 102. In another example , the covers can be plastic sheets or any other means of sealing. In one example, one or more of the covers are transparent.
[00038] The integrated test cartridge system 100 allows the user to place a sample, for example, in sampling hole 114, then place the test cartridge system 100 into an analyzer. In the embodiments, the reaction steps to be carried out including, for example, resuspension lysis, purification, mixing, heating, binding, labeling and/or detection can all be carried out within the test cartridge system 100 through interaction with the analyzer without any need for the end user to intervene. Additionally, since all liquids remain sealed within the test cartridge system 100, after the test is completed, the test cartridge system 100 can be removed from the analyzer and safely disposed of without contaminating the analyzer.
[00039] FIGs. 2A-D illustrate various views of cartridge housing 102, in accordance with embodiments. The description of each view is defined to describe features that may be present in the cartridge housing 102, but should not be limiting to the positioning or dimensional properties of the features.
[00040] FIG. 2A provides an example of a side view of cartridge housing 102. Thus, the view illustrates a plurality of chambers connected by a fluid network and a series of holes extending into cartridge housing 102. Each of these groups will be discussed. in greater detail here.
[00041] The plurality of processing chambers may include a waste chamber 218, an elution chamber 220, and a wick elution chamber 206. Other types of chambers as may be contemplated by one skilled in the relevant arts given the description herein may also be included. Additionally, the purpose of each camera may be different than the names specified here.
[00042] A plurality of reaction chambers 216 is also shown. Such chambers can be similarly shaped, for example, for a centrifuge tube. In one embodiment, liquid can be withdrawn into reaction chambers 216 to mix with the reactants that have been preloaded into each reaction chamber. For example, each reaction chamber can be loaded with a different DNA probe, or real-time PCR master mix, and liquid can be withdrawn in each reaction chamber to create distinct mixtures in each chamber. Reagents can be freeze-dried before loading, or freeze-dry in reaction chambers 216. In another embodiment, reaction chambers 216 are also used for sample detection. Thus, in one embodiment, reaction chambers 216 can also be considered to be detection chambers. Detection can occur using an external optical source and photodetector coupled with an analyzer on which the test cartridge system 100 is positioned. Thus, any walls or covers of reaction chambers 216 can be transparent to allow optical detection. In one example, the photodetector measures the absorbance through the liquid inside the reaction chamber at one or more wavelengths. In another example, the photodetector measures a bloom signal generated from a fluorescent compound inside the reaction chamber. In one embodiment, bloom measurements are taken from below reaction chambers 216. Reaction chambers 216 can be adapted for other means of detection, e.g., electrochemistry, electromechanics, surface plasmon resonance, etc.
[00043] A set of smaller channel widenings 214 are observed upstream from the reaction chambers 216, according to a modality. Channel flares 214 can act as liquid sensing areas. In this way, channel widens 214 can be used in conjunction with an external optical probe to determine whether or not liquid is present within channel widens 214. This determination can be used to activate other system functions of test cartridge 100. In another embodiment, channel widenings 214 may include built-in sensors, such as a standard resistive sensor, to indicate the presence or flow of fluid.
[00044] Several fluid channels connect with each of the chambers or with other elements within the cartridge housing 102. Each channel is also designed to terminate in an orifice that will interface with the orifices or valve regions in the transfer module 104. In one embodiment, cartridge housing 102 includes two main rows of holes such as one row of liquid holes 210, and one row of vent/suction holes 212. chambers depicted in FIG. 2A, or flows through a filter 222. Liquid ports 210 may act either as inlet ports for liquid to be withdrawn to transfer module 104 from cartridge housing 102, or as exit ports for liquid to be withdrawn. expelled from the transfer module 104 into the fluid network of the cartridge housing 102. Vent/suction holes 212 can be used to open a particular fluid channel to the atmosphere so that the liquid can be drawn into its corresponding chamber. . For example, a vacuum pressure can be applied to the hole illustrated to the far left of the row of vent/suction holes 212, which can allow liquid to enter the waste chamber 218 through the first hole to the left hole in the row of liquid holes 210. In another example, a vacuum pressure applied from the first hole to the left hole in the row of vent/suction holes 212 can draw liquid from the third hole to the left liquid hole into the chamber of elution 220. In another embodiment, vent/suction holes 212 may be opened to atmosphere.
[00045] Other processing holes 204 can be observed leading to another section of the cartridge housing 102. Processing holes 204 may lead into or out of an internal processing chamber. For example, the internal processing chamber can be a bead beater chamber to lyse any cells in the sample. In another example, a sample containing solid, semi-solid, or liquid material can be placed directly into the internal processing chamber through a second sample inlet. The material can be homogenized or lysed by the inner processing chamber, and the resulting liquid sample can be withdrawn from the inner processing chamber to the transfer module 104 through an inner orifice (not shown) of the inner processing chamber.
[00046] An orifice may be a small orifice extending through the thickness of the cartridge housing 102. In one embodiment, each of the liquid orifices 210 is designed to align with another orifice located in the transfer module 104, which can be move laterally between the various liquid orifices 210. In one embodiment, each of the vent/suction holes 212 is designed to align with a region around a transfer module 104 that allows the orifice to be vented both to atmosphere how much pressurized. The various orifices may include a hydrophobic material or may have a specific geometry so as to prevent leakage through the orifices in the absence of any applied pressure.
[00047] Filter 222 can be integrated into the fluid network as illustrated. In this way, liquid can pass through filter 222 due to a pressure difference. Filter 222 can include, for example, a silicate matrix to be used to trap nucleic acid sequences. In another example, filter 222 may be a membrane to extract plasma from all blood samples. Other types of filter may also be contemplated, such as a reverse osmosis filter. In another example, filter 222 may include materials suitable for an affinity chromatography column to perform, for example, protein purification protocols.
[00048] FIG. 2B illustrates another example embodiment of cartridge housing 102. This embodiment includes many of the same features as the example cartridge housing illustrated in FIG. 2A including the waste chamber 218, the elution chamber 220, and the wick elution chamber 206. However, the fluid network connected with the liquid ports 210 now includes a reaction chamber 224, the chamber 225, and a plurality of detection chambers 226a-e. In one example, a single fluid path connects each of the reaction chamber 224, chamber 225, and detection chambers 226a-e together. In another example, the fluid path ends at the waste chamber 218. A series of channel widenings 214 are also illustrated and may serve the same purpose as those in the embodiment described above in FIG. 2A. The array of chambers described in this embodiment can be useful for immunological analyzes or other types of binding affinity assays.
[00049] Reaction chamber 224 may contain reagents to be mixed with a sample before passing to detection chambers 226a-e. Reagents can first be freeze-dried and positioned, or freeze-dried for reaction chamber 224, and rehydrated through contact with the liquid sample. Chamber 225 can contain a new set of freeze-dried reagents and can be used during PCR protocols to perform additional amplification of nucleic acid sequences. In another example, chamber 225 may contain additional reagents to be mixed with the sample. Alternatively, chamber 225 may contain a filter or capture probes to separate certain compounds from the sample before it passes to detection chambers 226a-e.
[00050] Detection chambers 226a-e are configured to allow optical interrogation similar to reaction chambers 216 as described above in FIG. 2A. In one example, each detection chamber 226a-e contains an immobilized probe to perform various binding affinity assays. At least one wall of detection chambers 226a-e is made to be transparent to visible light for bloom measurements. In one example, bloom measurements are taken from below detection chambers 226a-e.
[00051] FIG. 2C illustrates a top view of cartridge housing 102, in accordance with one embodiment. A plurality of storage chambers 230A-E is seen and may be similar to storage chambers 116 as described earlier in FIG. 1. A sample inlet window 232 is also disposed on top of the cartridge housing 102, in accordance with an embodiment. Sample Input Window 232 can be used to place samples in the internal processing chamber. For example, solid samples may need to be mixed before testing can begin. These solid samples can be placed in the 232 sample input window and enter directly into the internal processing chamber.
[00052] A row of inlet holes 228 is provided such that each hole is within a single storage chamber, according to an embodiment. Solution stored within the various storage chambers 230A-E can be withdrawn through a corresponding inlet to transfer module 104 at an appropriate time during a test procedure. Thus, transfer module 104 also has another hole located on top of transfer module 104 that can align with each of the inlet holes 228. In one example, lateral movement of transfer module 104 • changes which hole of the input holes inlet 228 is aligned with the top hole of transfer module 104. In another example, inlet holes 228 may lead directly to fluid network within cartridge housing 102 before reaching transfer module 104.
[00053] At least one of the storage chambers 230A-E may be configured to receive a sample that has been positioned in the cartridge housing 102 through the sampling port 114. For example, the storage chamber 230B may be sized to receive a sample cotton swab. In another example, the storage chamber 230B contains a solution to suspend a sample once the sample has been introduced.
[00054] FIG. 2D illustrates an other side view of cartridge housing 102 (opposite the side shown in FIG. 2A). Additionally, cartridge housing 102 includes a pressurized port 236 and a vent port 234, in accordance with one embodiment. The pressurized orifice 236 can be connected with an external pressure source, eg a vacuum pump, a syringe pump, a pressure pump, etc. In one example, the external pressure source is integrated with the analyzer in which the test cartridge system 100 is positioned. The pressure differential applied to the system through pressurized port 236 can be used to transport liquid through the various regions within cartridge housing 102 and transfer module 104. Vent port 234 can be configured to open to the atmosphere by according to a modality. In this way, vent/suction holes 212 may lead to a region around transfer module 104 that is also coupled with vent hole 234. In another example, a pressurized source is connected with pressurized port 236 to draw liquid through vent/suction holes 212. Any number of holes may be included for the purpose of pressurizing various regions in and around cartridge housing 102 and transfer module 104.
[00055] In one embodiment, cartridge housing 102 provides structures configured to center test cartridge system 100 within an automated analyzer. For example, a plurality of holes 235a-b may be present in the cartridge housing 102 to mate with corresponding pins in the analyzer to assist in centering the test cartridge system 100 with respect to an external precision positioning system. Oblong protrusions can also be used to center the test cartridge 100 system within the automated analyzer. At the bottom of the cartridge housing 102 in FIG. 2D, an optical access area 240 is disposed below the reaction chambers 216, according to one embodiment. Optical access area 240 is configured to be substantially transparent to all wavelengths used during the optical detection process. In one example, each individual reaction chamber has its own optical access area. In another example, a single optical access area is ethicized by multiple reaction chambers 216.
[00056] A film or a plurality of films can be positioned over the series of reaction chambers 216. The films can be thin enough to still provide adequate sealing while also allowing for easier heating and/or cooling of the contents within of the reaction chambers 216 through an external source. For example, the films can be in contact with a surface that is thermally controlled by any of, or a combination of, thermoelectric devices, resistive heaters, and forced air.
[00057] FIGs. 3A-D illustrate various views both around and within inner housing 110 of transfer module 104, in accordance with one embodiment. FIG. 3A is a perspective view of the inner housing 110, according to one embodiment. Inner housing 110 is formed from that of housing 302 which may be a rigid material. For example, the box 302 can be a plastic or metallic material. In another example, the box 302 may be a flexible plastic material.
[00058] The inner housing 110 includes one or more holes that extend through the thickness of the housing 302. The holes may include a primary inlet port 306 and a transfer pressure port 308. transfer 306 aligns with several of the inlet ports 228 as depicted in FIG. 2C.
[00059] In one embodiment, the rail 304 is used to retain the valve jacket 108 in place around the inner housing 110. The valve jacket 108 will be described separately in FIGs. 4A-C. Housing 302 may also include a coupling region 310 for connecting transfer module 104 with an actuator. The actuator can be motorized and apply a force to the transfer module 104 to cause movement. In another embodiment, the coupling region 310 may be connected in any manner to the frame which allows a user to apply a force to the frame and consequently move the transfer module 104.
[00060] FIG. 3B illustrates a side view of the inner housing 110. The view shown is the side which is facing away in FIG. 3A. A similar rail 304 is also illustrated on this side of inner housing 110. In another embodiment, inner housing 110 only includes a single rail structure. A primary exit port 312 is also illustrated. In one embodiment, the primary exit port 312 aligns with several of the liquid ports 210 as depicted in FIG. 2A. It should be understood that the inner housing 110 may include any number of holes around the surface of the housing 302, and the illustrations shown here should not be limiting of its placement and number of holes.
[00061] FIG. 3C illustrates a cross-sectional view of the interior of the inner housing 110, in accordance with one embodiment. Housing 302 encompasses transfer chamber 316. A chamber cover 318 is also included to seal fluid or any other type of sample within transfer chamber 316.
[00062] Primary outlet port 312 is illustrated at or near a lower point within transfer chamber 316. Positioning allows any liquids within transfer chamber 316 to properly drain through primary outlet port 312 To further facilitate proper drainage, the inner walls of transfer chamber 316 are angled downwards, according to a modality. In one example, one or more walls of transfer chamber 316 are sloped. In one example, a wedge 320 is disposed within transfer chamber 316 to provide an inclined surface.
[00063] In one embodiment, the transfer chamber 316 contains a stirring element 324. For example, the stirring element 324 may be a magnetic stirring bus. Stirring element 324 can be used to effectively mix the contents of transfer chamber 316. In one example, stirring element 324 is excited by an external magnetic field. In one embodiment, cartridge housing 102 includes one or more magnets disposed along the path of movement of transfer module 104. The presence of the magnets can induce a magnetic force by stirring element 324, causing it to move within the chamber. 316. In another example, agitation element 324 is physically coupled with an actuator configured to move agitation element 324.
[00064] FIG. 3D illustrates a perspective view of the cap 106, according to an embodiment. The cover 106 may include either the chamber cover 318 or the wedge 320 coupled with the chamber cover 318. The integration of the wedge 320 with the chamber cover 318 allows for the easier manufacturing process.
[00065] Returning to FIG. 3A, the various holes arranged around the inner housing 110 can be used to transfer liquid between various chambers of the cartridge housing 102 and the transfer chamber 316. In an example process, the transfer module 104 is moved laterally to align the primary inlet port 306 with one of the plurality of inlet ports 228 of cartridge housing 102. Once aligned, a vacuum pressure can be applied through a transfer pressure port 308 that will withdraw liquid from the storage chamber. from cartridge housing 102 to transfer chamber 316 of transfer module 104. Further lateral movement of transfer module 104 aligns primary inlet port 306 with a different one of the plurality of inlet ports 228 of cartridge housing 102 A second applied vacuum pressure draws liquid from another storage chamber of the cartridge housing 102 pa is the transfer chamber 316. The two liquids within the transfer chamber 316 can be further mixed if desired with the agitation element 324. A third lateral movement of the transfer module 104 aligns the primary outlet port 312 with one of the ports of liquid 210 from the cartridge housing 102. A positive pressure applied to the transfer pressure port 308 expels the liquid from the transfer chamber 316 through the primary outlet port 312 and into the fluid network of the cartridge housing 102 through the outlet port. of liquid lined up. It should be noted that many other liquid withdrawal and expelling procedures can be performed, and that liquid can also be withdrawn into transfer chamber 316 through primary outlet port 312.
[00066] In order to control the flow of fluid along particular fluid channels, as well as to control which regions around the outside of the transfer module 104 are pressurized, a valve system is implemented around the inner housing 110. FIGs. 4A-C illustrate several views of valve jacket 108 disposed around inner housing 110.
[00067] FIG. 4A illustrates a perspective view of valve jacket 108, in accordance with one embodiment. Valve jacket 108 includes a compliant liner 402 that fits around the inner housing 110. The compliant liner 402 may be a flexible material such as rubber. In one embodiment, compliant coating outer surface 402 includes holes which extend through the thickness of compliant coating 402 and align with holes in inner housing 110. For example, a first hole 410 may align with primary exit hole 312 while a first hole 412 may align with the primary inlet hole 306.
[00068] The outer surface of the 402 compliant coating may also include a variety of patterned ridges and shapes, according to a modality. For example, toroidal ridges 404 along one side of valve jacket 108 may be aligned with several of the plurality of vent/suction holes 212. Additional toroidal structures 414 are seen along the top of valve jacket 108. Solid toroidal structures 414 can be aligned over several of the plurality of inlet ports 228 to protect each port from being pressurized in an undesired manner. Solid toroidal structures 414 are preferred for long-term liquid storage in storage chambers 230a-e. Hollow toroidal shapes provide the benefit of reducing friction as transfer module 104 moves within cartridge housing 102.
[00069] Other patterned crests may also be present. For example, indented ridges 406 may extend along a length of valve jacket 108 to seal any of the plurality of liquid ports 210 that are not aligned with first port 410. In another example, straight ridge 408 ensures a homogeneous pressure on the inner surface of the cartridge housing 102.
[00070] The various ridge patterns are patterned to press against the inner walls of the cartridge housing 102. This creates a plurality of regions around the outer surface of the transfer module 104 that are sealed together. Thus, a pressure differential applied in one region will not affect the pressure in other regions. This example design can be seen more clearly in FIG. 4B.
[00071] FIG. 4B illustrates a cross section of transfer module 104 within transfer chamber 102, in accordance with one embodiment. Inner housing 302 and valve jacket 108 of transfer module 104 are shown, as well as protrusions 416 of valve jacket 108. Protrusions 416 may be similar to the ridges and toroidal shapes as previously described with reference to FIG. 4A. Protrusions 416 press against the inner walls of cartridge housing 102 to create a plurality of valve regions, such as regions 418A-C, according to one embodiment. For example, region 418B is separated from regions 418A and 418C due to protrusions 416, and in this way, they can be pressurized separately from regions 418A and 418C.
[00072] In one example, region 418B is associated with pressurized orifice 236 (FIG. 2D) on one side of cartridge housing 102. A pressure differential applied across pressurized orifice 236 (FIG. 2D) will also pressurize the region 418B, without pressurizing the surrounding regions separated by the protrusions 416.
[00073] The cross-sectional view also illustrates how the first hole 410 of the transfer module 104 can align with one of the liquid holes 210 of the cartridge housing 102. The protrusions 416 can surround the hole 410 to prevent fluid leakage or unwanted pressurization of the orifice region.
[00074] FIG. 4C illustrates a side view of valve jacket 108, in accordance with one embodiment. The side view shown is the side facing away in FIG. 4A. valve jacket 108 additionally includes a pressure port 420 that can be aligned with transfer pressure port 308 of inner housing 110, in accordance with an embodiment. Pressure port 420 is disposed within a pressurized region 424 defined by various ridges, such as straight ridge 428 and serpentine ridge 422. Patterns and/or shapes of ridges are not limited to those shown. Another region 426 exists on the other side of the serpentine crest 422, according to one embodiment. The regions described with reference to FIG. 4C may be considered similar to the regions described above with reference to FIG. 4B.
[00075] The pressurized region 424 is associated with an orifice of the cartridge housing 102, according to an embodiment. For example, when transfer module 104 is located within cartridge housing 102, pressurized port 236 may be located within pressurized region 424. In one example, pressurized port is located below the mid-horizontal portion of coil crest 422. As transfer module 104 translates within cartridge housing 102, pressurized region 424 remains associated with pressurized port 236, according to one example. In another example, the translation of transfer module 104 may align vent port 234 within pressurized region 424 and pressurized port 236 within region 426 due to the serpentine shape associated with serpentine crest 422. A pressure differential applied across an aligned orifice within pressurized region 424 will also apply the same pressure differential in transfer chamber 316 through pressure orifice 420. In another example, translation of transfer module 104 aligns pressurized orifice 236 with various regions around of the outer side surface of the valve jacket 108.
[00076] The region 426 is also associated with an orifice of the cartridge housing 102, according to an embodiment. For example, vent hole 234 may be located within region 426, such as just above the mid-horizontal portion of coil crest 422. In this example, region 426 is open to atmospheric pressure. Alternatively, pressurized port 236 may be located within region 426, for example, between a bend of coil crest 422. Vacuum pressure may be applied to pressurized port 236 which similarly pressurizes region 426.
[00077] The region 426 can wrap around the other side of the valve jacket 108 (the side shown in FIG. 4A), according to an embodiment. Thus, the region surrounding toroidal ridges 404 as well as toroidal structures 414 can all be considered the same region as region 426. In an example embodiment, transfer modules 104 move within cartridge housing 102 between discrete steps, toroidal ridges 404 cover all but one of the vent/suction holes 212, according to one embodiment. A vent/suction hole not covered by the toroidal ridges 404 is then subjected to both atmospheric pressure and a pressure differential that has been applied to region 426. Second Test Cartridge Mode
[00078] FIGs. 5 to 8 illustrate various views and components of a test cartridge system in accordance with another embodiment. FIGs. 5A-5B illustrate views of an exploded representation for a test cartridge system 500 that includes a cartridge housing 502 and a transfer module 504. The transfer module 504 has substantially the same function within the system as the transfer module. 104 of the first test cartridge modality. Both transfer modules 504, 104 move laterally within the system to align the holes on the outside of the transfer module with the holes on the sides of the housing 502, 102, in some embodiments. Additionally, transfer module 504 is similar in construction to transfer module 104 with an inner housing 510 surrounded by a jacket 508, and having an inner chamber capped by a cover 506. Additional details of transfer module 504 are described later with reference to to FIGs. 7A-D.
[00079] Host 502 includes many of the same features as host 102, according to some modalities. For example, housing 502 includes a plurality of processing chambers 524a-b, a chamber bay 520 for receiving the transfer module 504, and a sampling port 514 with an orifice cap 512. In one example, the chamber 524a is a residue chamber, and chamber 524b is a wick receptacle chamber. Sampling port 514 leads to chamber 524b, which can be sized to receive the length of a medical wick, according to an embodiment. Housing 502 also includes a plurality of covers 518, 526, 527, and 528 for sealing the various chambers and channels around housing 502, according to an embodiment. In one example, each of covers 526 and 518 is made of substantially the same material as housing 502. In one embodiment, any of covers 526, 528, and 518 is substantially transparent. Cover 527 may be a material with a high thermal conductivity, eg aluminum foil, to allow more efficient heat transfer to the samples within housing 502. An opening 513 may be cut in cover 526 such that heat can be conducted more efficiently from cover 527 to an inner processing chamber of housing 502 through opening 513. The inner processing chamber may also have its own entrance with a cover 532. In one embodiment, housing 502 includes a top opening 522 for receiving various types of filters to be positioned in housing 502. In one example, solid phase extraction materials such as membranes or silica beads may be positioned in a chamber of housing 502 through top opening 522 A plurality of openings is seen in both covers 526 and 527, in accordance with some embodiments. The openings of the cover 526 can align over several small chambers of the housing 502, for example, to allow more space for dry reagents to be positioned in the small chambers. In another example, the openings of the cover 527 may provide optical access to detect areas of the channels of the housing 502.
[00080] The housing 502 also includes an opening 515 for an internal processing chamber, according to an embodiment. Any type of sample, such as solid, semi-solid or liquid samples, can be positioned in the inner processing chamber through the opening 515. The opening 515 can be capped by a cover 532 to prevent any leakage of the samples positioned in the inner processing chamber. The internal processing chamber can be, for example, a bead beater chamber to lyse cells or homogenize a sample. Housing 502 can be sized to incorporate various sizes of bead hitting modules. In one embodiment, bead hitting modules within the 502 housing accept volumes of liquid ranging anywhere from 10 to 5000 microliters. In another modality, the accepted volumes of the bead picker modules vary between 100 and 1000 microliters.
[00081] FIGs. 6A and 6B illustrate side views of housing 502 in greater detail, in accordance with some embodiments. FIG. 6A illustrates the various storage chambers on one side of housing 502. Housing 502 includes seven storage reservoirs 630a-g, according to an embodiment. Other numbers of storage tanks » are also possible. It should be understood that the illustrated shapes and sizes of the various storage tanks 630a-g are not intended to be limiting and should be altered to include virtually any shape and size. Each of the various storage reservoirs 630a-g may include two reservoir openings. A first opening can be coupled with a fluid channel to transfer a fluid both into and out of the reservoir while a second opening can allow to vent the reservoir to atmospheric pressure. The ability to vent a reservoir can allow the reservoir to empty more efficiently when fluid is withdrawn from it. Additionally, air cannot be trapped within the reservoir when fluid is moved into it if the air has the ability to escape from a vent opening.
[00082] Also illustrated are two chambers, a first buffer chamber 642 and a second buffer chamber 643. Each buffer chamber can be used to help prevent liquid from exiting the fluid infrastructure of the test cartridge system, according to with a modality. For example, the first buffer chamber 642 can be designed to trap any “spilling” liquid that accidentally leaks from a channel used to vent the system. The vent channel may also include a liquid sensing area. If liquid crosses the liquid sensing area, a sensor can be designed to turn off any applied force that causes the fluid to flow so as to stop the liquid before it escapes from a vent hole. Similarly, the second buffer chamber 643 can be designed to trap any “spilling” liquid that accidentally leaks from a channel used to apply pressure to the system. In some embodiments, the pressure applied is a vacuum pressure to draw liquid through the various channels and chambers of the test cartridge system 500. The pressure channel may also include a liquid sensing area with an associated sensor designed to work in a similar way with the sensor described above in the vent channel. Additionally, each orifice associated with first buffer chamber 642 and second buffer chamber 643 may include filters 641a and 641b, in accordance with some embodiments. Filters 641a and 641b can be aerosol filters to prevent contamination with the rest of the system when using the orifices to vent and/or pressurize the system.
[00083] In one embodiment, housing 502 includes attachment points 635a and 635b to sweat the housing 502 within a larger analyzer system. The test cartridge can be positioned in an analyzer that includes components to heat and/or cool the system, optically measure certain chambers, provide a pump or vacuum source, and actuate the movement of the 504 transfer module. 502 of test cartridge system 500 can be held in place within the analyzer through attachment points 635a and 635b so that housing 502 moves while the various operations of the analyzer are being performed.
[00084] A waste passage 641 may also be included in housing 502 to guide fluid and any other waste samples to a waste chamber, such as, for example, chamber 524a. The inlet to the waste chamber can be designed to allow only fluid to flow into the chamber and not out of the chamber.
[00085] FIG. 6B illustrates another exemplary embodiment of the opposite side of housing 502. An example fluid arrangement is shown with a plurality of holes 610 aligned for fluid coupling with a transfer module port 504. Pressure port 636 and port are also illustrated. vent 634. Pressure port 636 can be connected with an external pressure source to apply both positive and negative pressure differentials across the system, according to a modality. Vent 634 can either be opened to atmosphere or be connected to another pressure source. For example, a positive pressure difference can be applied to one orifice while a negative pressure difference is applied to another orifice to force faster movement of liquid through the coupled channels of the system.
[00086] Housing 502 also includes reaction chambers 616 that can operate similarly to reaction chambers 216 described earlier with respect to FIG. 2A. In one embodiment, several channels leading to reaction chambers 616 include a premix chamber 631. Premix chamber 631 can include dry chemicals, such as dry or lyophilized reagents. In another example, premix chamber 631 includes biological samples or dry chemical beads. Such chemical or biological compounds can be stored in premix chamber 631 for extended periods of time before use. The dimensions of premix chamber 631 can be specifically designed to fit the size of a dry chemical bead, usually on the order of a few millimeters in diameter, according to a modality. In one example, fluid drawn into reaction chambers 616 mixes with samples stored in premix chamber 631. Several channels also include a sensor region 614, according to an embodiment. Sensor region 614 can be used to determine the presence and/or flow of liquid within the corresponding channel. An external optical probe can be used with sensor region 614 to make the determination. In another example, integrated sensors, such as a resistive sensor, can indicate the presence or flow of liquid. A control system may use the data output from the sensor region 614 to activate the various functions of the test cartridge system 500, or to control the flow of liquid within the respective channel having the sensor region 614.
[00087] Also illustrated on the side of housing 502 is a plurality of frits 633. Each frit 633 can include multiple I materials designed for various entrapment or filter particle sizes. In one example, 633 frit is a plastic material having a fine mesh with selectable pore sizes that can range anywhere from 0.1 micron to 500 micron. In one embodiment, frit 633 has a pore size of about 20 microns.
[00088] At the bottom of the cartridge housing 502 in FIG. 6B, an optical access area 640 is disposed below reaction chambers 616, in accordance with one embodiment. The 640 optical access area is designed to be substantially transparent to all wavelengths used during the optical detection process. In one example, each individual reaction chamber has its own optical access area. In another example, a single optical access area spans multiple reaction chambers 616. In one example, a photodetector measures the absorbance through the liquid within reaction chamber 616 at one or more wavelengths. In another example, the photodetector measures a bloom signal generated from a fluorescent compound within reaction chamber 616. Bloom measurements can be taken from below reaction chambers 616 or from the side of reaction chambers 616. The reaction chambers 216 can be adapted for other means of detection, eg electrochemical, electromechanical, surface plasmon resonance, etc.
[00089] FIGs. 7A-7F provide various views in and around transfer module 504, in accordance with some embodiments. Many of the general features of transfer module 504 are substantially similar to transfer chamber 104 of the first test cartridge embodiment. For example, both transfer modules include a compatible material wrapped around a stiffer internal housing, and have holes on the outside that lead inward to a central chamber. However, the arrangement and design of certain features in the transfer module 504 warrant further discussion, as is provided here in connection with the FIGs. 7A to 7F.
[00090] Two isometric schematic views from different sides of the transfer module 504 are illustrated in FIGs. 7A and 7B, according to some modalities. Transfer Module 504 includes jacket 508 wrapped around an inner housing 510. Transfer Module 504 also includes two holes 712a and 712b. In one embodiment, each of holes 712a and 712b are disposed in a lower portion of transfer module 504. In one example, holes 712a and 712b are substantially crossing each other. Transfer module 504 may also include a third hole 706 along a top portion of transfer module 504. In one embodiment, holes 712a, 712b, and 706 lead to a central chamber within transfer module 504. 712a, 712b, and 706 can be used to mate with various ports of housing 502 for fluid transfer. In another example, both ports 712a, 712b, and 706 can be coupled with a pressurized source to apply a pressure difference to the fluid within test cartridge system 500. In one embodiment, ports 712a and 712b are used to transfer the fluid only while port 706 is used to pressurize or depressurize the central chamber of transfer module 504.
[00091] The 504 transfer module also includes a variety of patterned ridges and shapes, according to a modality. Similar to the patterned structures of the jacket 108 in the transfer module 104, the patterned regions in the transfer module 504 may align multiple holes of the housing 502 and define multiple pressurized or valve regions around the transfer module 504. For example, a toroidal structure 704 may line up over a hole in housing 502 to seal that hole. An array of toroidal structures 714 is also provided, according to an embodiment. The toroidal structure grouping 714 can be arranged to align over multiple holes of the housing 502 simultaneously based on a transfer module position 504. In one embodiment, a toroidal structure from the toroidal structure grouping 714 acts as a fluid bridge between the fur. minus two housing holes 502. In one example, fluid may flow through one channel to another channel by flowing through two holes that are aligned over the same toroidal structure. In this way, it is possible to move the fluid through the different channels of the housing 502 without needing to pass the fluid through the central chamber of the transfer module 504. The fluid may still contain flow into and out of the central chamber of the transfer module 504 through any of holes 712a, 712b, and 706, in accordance with an embodiment.
[00092] Jacket 508 of transfer module 504 may also include multiple ridges 707 and 709. In one embodiment, ridge 707 is used for sealing over multiple holes 610 of housing 502 while only a single hole from holes 610 is aligned with hole 712a. Crest 709 can be used to differentiate between a plurality of regions, such as, for example, regions 711 and 713. In one embodiment, regions 711 and 713 represent areas that can be pressurized separately. For example, region 711 may be pressurized through pressure port 636 due to the position of transfer module 504 within housing 502. Pressurizing region 711 may correspondingly pressurize the central chamber of transfer module 504 through port 706 and withdrawing liquid to, or expelling liquid from, the central chamber of transfer module 504.
[00093] Also illustrated in the transfer module 504 is a coupling region 702 for connecting the transfer module 504 with an actuator, according to an embodiment. The actuator may be laterally designed to translate transfer module 504 within housing 502 as substantially similar to the above-described first embodiment of test cartridge.
[00094] FIG. 7C illustrates a cross-sectional view of transfer module 504 along a length of transfer module 504, in accordance with an embodiment. Transfer module 504 includes a center chamber 716. Cover 506 is used to seal the end of center chamber 716. In one embodiment, cover 506 is designed to be removable. Cover 506 extends to central chamber 716 to provide sloping surfaces to help drain any liquids into central chamber 716, in accordance with an embodiment. A hole 708 is disposed substantially in the middle of the cap 506 within the central chamber 716 to transfer liquid to/from the central chamber 716 from/to other areas of the housing 502. A transfer channel 710 can bring the liquid to either of holes 712a and 712b.
[00095] FIG. 7D provides a view of cover 506 that includes a panel 718 and an inclined frame 720, according to an embodiment. Panel 718 can be used to seal the end of central chamber 716 while inclined structure 720 provides an inclined surface, for example, to facilitate movement of liquid samples within central chamber 716 to either orifices 712a or 712b. orifice 708 is also illustrated at a lower point of inclined structure 720 to adequately drain all liquid when evacuating central chamber 716, according to one embodiment.
[00096] FIG. 7E illustrates another view from below of cap 506 showing port 708 and transfer channel 710, in accordance with one embodiment. One example includes side channels 715 for aligning liquid with holes 712a and 712b on the sides of transfer module 504. The channel configurations illustrated are just an example for directing fluid into and out of central chamber 716 and should not be considered as limiting.
[00097] FIG. 7F illustrates a cross-sectional view of transfer module 504 along a width of transfer module 504, in accordance with an embodiment. Jacket 508 is seen wrapped around inner housing 510. Jacket 508 includes several protrusions 724, according to an embodiment. Protrusions 724 may represent the various patterned structures on jacket 508. In one example, protrusions 724 press against the inner walls of housing 502 to create various regions 722a, 722b, and 722c. each region may be pressurized separately based on a position of transfer module 504 within housing 502. Holes 712a and 712b are illustrated as being aligned with one of holes 610 of housing 502 and a hole associated with the pressure hole. 636 respectively, according to a modality. As transfer module 504 moves laterally within housing 502, holes 712a and/or 712b may align with different holes 610 of housing 502. Further illustrated within central chamber 716 is angled frame 720 and side channel 715 of according to a modality. In the embodiment example, side channel 715 connects each of holes 712a and 712b in a U-shape.
[00098] FIGs. 8A and 8B illustrate wicks that are positioned for the test cartridge system for analysis, according to some embodiments. FIG. 8A illustrates a wick 802 positioned within chamber 524b of the cartridge housing. The chamber is sealed with the 512 hole cap. In one example, the 802 mecha has a round length of 80 mm. It should be understood that chamber 524b can be sized to receive any length of roving without departing from the scope or spirit of the invention.
[00099] FIG. 8B illustrates another embodiment where a larger roving 806 is positioned in chamber 524b and sealed with an extended cover 804. Extended cover 804 can be used to seal over strands that are longer than chamber 524b, and adhere from the opening of chamber. In one example, the longest roving 806 is around 100 mm long. The longer roving 806 can be bent and/or folded inside chamber 524b. Exemplary methods of operation
[000100] Examples of methods for performing fluid transfer between various chambers of both embodiments of the cartridge housing and its corresponding transfer chamber are described below.
[000101] FIG. 9 shows a flowchart of an example method 900 for transporting liquid through a first embodiment of test cartridge system 100. It should be understood that method 900 describes an example sequence of operation that can be performed with the cartridge system. test 100, and should not be considered limiting. Additionally, method 900 can also be performed using the second embodiment of test cartridge system 500.
[000102] In block 902, the transfer module 104 is moved laterally within the cartridge housing 102 to align an inlet port of the transfer module 104 to an outlet port of a first chamber, according to an embodiment. The transfer module inlet port 104 may be, for example, transfer pressure port 306. The first chamber outlet port may be, for example, any one of the row of inlet ports 228.
[000103] In block 904, a sample is taken from the first chamber to the transfer chamber 316 through a first applied pressure differential, according to a modality. In one embodiment, the applied pressure differential is applied to transfer pressure port 308. The applied pressure differential can be a vacuum pressure in order to draw the sample into the transfer chamber 316. The sample can be introduced to the first chamber from a cotton swab or liquid. The first chamber may be, for example, the internal processing chamber or a processing chamber associated with the sample port 114. Additionally, the sample may be any mixture of liquids, semi-solids, solids, etc.
[000104] In block 906, transfer module 104 is moved laterally again within cartridge housing 102 to align a transfer chamber outlet port 316 with an inlet port of a second chamber, according to an embodiment. The transfer chamber outlet port 316 can be, for example, primary outlet port 312. The second chamber inlet port can be, for example, any one of the row of liquid ports 210. inlet of the second chamber may lead to any chamber of cartridge housing 102, such as waste chamber 218, reaction chamber 216, wick elution chamber 206, etc.
[000105] In block 908, the sample is removed from the transfer chamber 316 to the second chamber through a second applied pressure differential, according to a modality. The second pressure differential may be a positive pressure applied at transfer pressure port 308. Alternatively, the second pressure differential may be a vacuum pressure applied at a vent/suction port 212 to draw liquid into the chamber. associated with the corresponding ventilation/suction hole 212.
[000106] It should be understood that many other liquid withdrawal procedures can be performed as can be understood by one skilled in the relevant art given the description herein. For example, after block 904, the transfer chamber may align its inlet port with a first outlet port along the top of cartridge housing 102 to remove other liquid stored in another storage chamber. This procedure can be repeated as often as desired depending on the protocol required for the particular molecular test.
[000107] In another modality, following block 908, additional steps can be performed to withdraw the sample back to the transfer chamber, and expel the liquid to a third chamber. For example, the second chamber may be the wick elution chamber 206 while the third chamber may be one of the detection chambers 216. Any number of chambers may have the liquid withdrawn into or extracted as many times as desired. Thus, the system allows a myriad of patterns to transfer liquid between the various chambers.
[000108] FIG. 10 shows a flowchart of an example method 1000 for transporting liquid through the second embodiment of the test cartridge system 500. It should be understood that method 1000 describes an example operation sequence that can be performed with the test cartridge system 500, and should not be considered limiting.
[000109] In block 1002, the transfer module 504 is moved laterally within the cartridge housing 502 to align a structure on an outer surface of the transfer module 504 with at least a first hole associated with a first chamber and with a first orifice associated with a second chamber, according to an embodiment. The first chamber can be, for example, the inlet reservoir 622 while the second chamber can be any of the storage reservoirs 630a-g. The structure on the outer surface of the transfer module 504 may be toroidal in shape to fit around the first and first holes, according to an embodiment.
[000110] In block 1004, a sample is taken from the first chamber to the second chamber through at least the structure on the external surface of the transfer module 504, according to an embodiment. In this way, the sample can be moved between the first and second chambers without passing through, for example, a central chamber of transfer module 504.
[000111] In block 1006, the sample is taken from the second chamber to a third chamber, according to a modality. The third chamber may be the central chamber 716 of the transfer module 504, and liquid may enter the central chamber 716 through a hole through a wall of the transfer module 504. The orifice can be, for example, any of the holes of fluid 706, 712a, or 712b illustrated in FIGs. 7A and 7B. The third chamber may include components for mixing or filtering the sample. In other embodiments, transfer module 504 may move laterally to align one hole in transfer module 504 to another hole in housing 502 and expel sample into its central chamber through the aligned hole. It should be understood that many other liquid withdrawal procedures can be performed as would be understood by one of skill in the relevant art given the description herein. Examples
[000112] Two example protocols to be performed using the 100 test cartridge system are now discussed. The first example protocol is geared towards real-time PCR detection, while the second example protocol is geared towards immunological analysis. It should be understood that the steps cited here provide possible examples for using the system as well as for performing each test. PCR protocol
[000113] An example PCR protocol uses multiple processing chambers as well as reaction chambers and cartridge housing socket 102. In one example, the PCR protocol uses the cartridge housing modality illustrated in FIG. 2A. It should be understood that the protocol can also be carried out using the cartridge housing modality illustrated in FIGs. 6A to 6B. In this example, five storage chambers are used and each contains a pre-loaded solution. Storage chambers are labeled as follows: RI: Contains wash-2 buffer R2: Contains lysis buffer R3: Contains elution buffer R4: Contains wash-3 buffer R5: Contains 1 wash buffer
[000114] Example PCR procedure can be performed using the workflow described here with reference to example 100 test cartridge system described above. Similar steps can be performed using the various chambers as well as the channels illustrated in the test cartridge system 500. The sample is introduced into the test cartridge system 100 through a wick into the wick receptacle 114. Alternatively, the sample can be introduced through a second inlet directly to an internal processing chamber to be lysed by an integrated bead tapping system.
[000115] Once the sample has been introduced to the 100 test cartridge system, the entire test cartridge is placed in an analyzer. The analyzer provides an actuator to move transfer module 104, one or more heating elements to carry out the PCR reaction, and optical measurement components. The analyzer can additionally couple with the pressure ports around the cartridge housing 102 and apply the necessary pressure differentials.
[000116] The transfer module 104 is aligned to withdraw the lysis buffer from R2 to the transfer chamber. Transfer module 104 is aligned to move the lysis buffer to the swab elution chamber 206, where the sample from the swab is suspended again in the lysis buffer. The sample, along with the lysis buffer, can then be moved into the internal processing chamber through processing holes 204 to falsify the cells in the sample and release the DNA and/or RNA. Following the lysis procedure, the sample hereafter is referred to as "the lysate."
[000117] The lysate is withdrawn into the transfer chamber from the internal processing chamber through a vacuum pressure applied in the transfer chamber. Then, the transfer module 104 is moved laterally to align its exit port with a port associated with the waste chamber. However, a filter is arranged upstream of the residue chamber in order to capture the DNA sequences. Thus, after applying positive pressure to the transfer chamber, the lysate passes through the filter on its way to the waste chamber. The DNA will remain inside the filter, while the bulk of any desired matter will pass through the waste chamber. The filter, for example, can be a silicate matrix or a plurality of silica beads to trap the nucleic acid sequences.
[000118] The transfer module 104 is moved to align with R5 and draw wash buffer-1 into the transfer chamber. Subsequently, wash buffer-1 is passed through the filter to further remove any unwanted material on the filter. The plug passes to the waste chamber. A second wash step is then performed with wash buffer-2. Transfer module 104 aligns with RI to remove wash buffer-2 and moves again to align back with fluid channel containing filter. Wash buffer-2 is passed through the filter and into the waste chamber.
[000119] At this stage, it may be necessary to clear the transfer chamber before the DNA is brought back again. In this way, the transfer module 104 is aligned with R4 and wash buffer-3 is withdrawn into the transfer chamber. Wash buffer can be mixed around the transfer chamber. Additionally, wash buffer-3 can be transferred, for example, to the internal processing chamber.
[000120] The transfer module 104 is moved laterally to align its top inlet hole with the outlet hole of R3. Vacuum pressure is applied to draw the elution buffer into the transfer chamber. Thereafter, the transfer module 104 is moved laterally to align its outer orifice with the orifice associated with the elution chamber 220 in the cartridge housing 102. The elution buffer is moved to the elution chamber 220 through positive pressure applied to the transfer chamber or through a vacuum pressure from a vent/suction port connected with elution chamber 220.
[000121] The DNA is now ready to be removed from the filter and brought back to the transfer chamber. The elution buffer from the elution chamber 220 of the cartridge housing 102 is withdrawn through the filter using vacuum pressure back into the transfer chamber which is aligned with the correct hole to receive the DNA solution. The transfer module 104 can now move sequentially moves between the holes of the various reaction chambers and, through an applied positive pressure, transfer liquid into each chamber.
[000122] Each reaction chamber may contain a reagent needed to perform PCR on the DNA. In one embodiment, the reagent is a pre-loaded freeze-dried globule that contains any reagents needed to perform PCR. Reagents will be rapidly rehydrated when DNA solution is brought to each chamber.
[000123] Once the DNA solution has finally been transferred to one or more of the reaction chambers, the rest of the process can be carried out by the analyzer. That is, the cycle of heating and cooling steps in order to activate, denature, annealing, and extend the DNA can be accomplished. Once the cycle is complete, the analyzer's optical measurement system can collect data from each reaction chamber to provide test results to the end user. 4 Immunobiological analysis
[000124] An example of immunobiological analysis uses at least three of the storage chambers as well as a variety of processing chambers around the cartridge housing 102. In one example, the immunobiological analysis uses the modality cartridge housing illustrated in FIG. 2B. Similar to a PCR protocol, storage chambers contain pre-loaded solutions to perform the assay. Additionally, typical capture antibodies can be immobilized within detection chambers 226 to provide binding sites for the antigens of interest. Fluorescently labeled antibodies can also be preloaded in a lyophilized state into reaction chamber 224. In this example, the storage chambers are labeled as follows: R1: Wash Buffer-1 R2: Assay Buffer R3: Assay Buffer wash-2
[000125] Immunobiological analysis can be performed using the workflow described here with reference to the 100 test cartridge system example for clarity. Sample can be introduced into cartridge housing 102 through an inlet that leads directly to an internal processing chamber. Once inserted, test cartridge system 100 is positioned on the analyzer. The rest of the protocol can be performed automatically by the analyzing system. The transfer module 104 is laterally aligned with the internal processing chamber and the sample is withdrawn into the transfer chamber through an applied vacuum pressure.
[000126] Once the sample is inside the transfer chamber, the transfer module 104 moves laterally again to align its exit hole with a hole leading to the elution chamber. The sample from the elution chamber is then moved to the transfer chamber by passing through a membrane to obtain plasma from whole blood. Once the plasma sample (which contains the antigen of interest) is back in the transfer chamber, the transfer module 104 can align with R2 and withdraw the assay buffer into the transfer chamber. Analysis buffer and plasma sample are mixed in the transfer chamber.
[000127] Once the plasma sample and the analysis buffer are mixed, the transfer module 104 moves laterally again to align its exit hole to a hole that leads to the reaction chamber 224, with the antibodies marked with way flourishing freeze-dried. The Sample + Assay Buffer Mix acts to rehydrate the fluorescently labeled antibodies within reaction chamber 224. The rehydrated fluorescent antibodies, plasma sample, and assay buffer are all combined and mixed. At this stage, if the antigen of interest is present in the mixture, the fluorescently labeled antibodies will have bound to it. In one embodiment, heating and/or mixing can be carried out to improve the reaction.
[000128] The resulting mixture is transorified from the reaction chamber 224 to each of the detection chambers 226. Again, the mixture can be gently mixed or heated in each detection chamber 226 to ensure the interaction between the antibodies of capture immobilized and the antigen within the mixture.
[000129] Once mixing is complete, the transfer module 104 lines up with RI and withdraws the wash buffer-1 into the transfer chamber. Wash buffer-1 can first be transferred to the reaction chamber and subsequently to each detection chamber containing the mixture. Wash Buffer-1 releases any unbound material. Wash buffer-1 continues through the detection chambers and passes into the waste chamber.
[000130] A second washing step can be performed. Transfer module 104 lines up with R3 and withdraws wash buffer-2 into the transfer chamber. Wash-2 buffer can first be transferred to the reaction chamber and subsequently to each detection chamber containing the mixture. Wash Buffer-2 releases any unbound material. Wash-2 buffer continues through the detection chambers and passes to the waste chamber. At this stage, any material bound to the immobilized antibodies should be the antigen of interest along with the fluorescently bound antibody bound.
[000131] The analyzer's optical measurement system can now be used for each detection chamber to quantify the amount of antigen based on the fluorescent signal received. The collected data, for example, can be plotted against a standard curve previously performed with calibrators to obtain quantitative results for the end user.
[000132] It should be noted that at the end of both protocols discussed above, the entire 100 test cartridge system can be removed from the analyzer and safely discarded. In another embodiment, the resulting solution within one or more of the detection chambers can be extracted for further analysis. As the system is self-contained, multiple test cartridges can be used with the same analyzer without concern for cross contamination or fouling between experiments.
[000133] It should be noted that the Detailed Description section, rather than the Summary and Summary sections, is intended to be used to interpret the claims. The Summary and Summary sections may be defined for one or more, but not all of the example embodiments of the present invention as contemplated by the inventors, and thus, are not intended to limit the present invention and the appended claims in any way.
[000134] Modalities of the present invention were described above with the aid of functional building blocks that illustrate the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been defined arbitrarily here for the convenience of description. Alternate boundaries can be defined as long as the specified functions and their relationships are performed properly.
[000135] The above description of the specific modalities thus will fully reveal the general nature of the invention that others can, through the application of knowledge within the art, readily modify and/or adapt such specific modalities for various applications, without going through experimentation, without deviate from the general concept of the present invention. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed modalities, based on the teaching and guidance presented here. It is to be understood that the phrase and terminology herein is for the purpose of description and not limitation, such that the terminology and phrase of the present specification is to be interpreted by the skilled person in light of the teachings and guidance.
[000136] The breadth and scope of the present invention shall not be limited by any of the exemplary embodiments described above, but shall be defined only in accordance with the following claims and their equivalents.

权利要求:
Claims (69)
[0001]
1. A test cartridge system (100), characterized in that it comprises: a cartridge housing (102) comprising: at least one sample inlet (114); a plurality of storage chambers (116); a plurality of reaction chambers (216); and, a fluid network connecting at least one sample inlet (114), at least a portion of the plurality of storage chambers (116), and at least a portion of the plurality of reaction chambers (216) with a first plurality holes (210) located in an inner surface of the cartridge housing (102); and, a hollow transfer module (104) disposed within the cartridge housing (102), comprising a second plurality of holes (312) along an outer surface of the transfer module (104) leading to a central chamber ( 316) of the transfer module (104), the transfer module (104) configured to move laterally along a length of the cartridge housing (102), wherein lateral movement of the transfer module (104) is aligns with at least a portion of the first plurality of holes (210) with at least a portion of the second plurality of holes (312).
[0002]
2. System (100) according to claim 1, characterized in that the cartridge housing (102) further comprises a plurality of processing chambers, and wherein the fluid network also connects at least a portion of the plurality of chambers process with the first plurality of holes (210).
[0003]
3. System (100) according to claim 2, characterized in that the plurality of processing chambers are located along a side surface of the cartridge housing (102).
[0004]
4. System (100) according to claim 1, characterized in that it further comprises a set of valve channels formed through an interface between the cartridge housing (102) and the hollow transfer module (104).
[0005]
5. System (100) according to claim 1, characterized in that an outer surface of the hollow transfer module (104) comprises ridges.
[0006]
6. System (100) according to claim 5, characterized in that the crests have a toroidal shape.
[0007]
7. System (100) according to claim 5, characterized in that the ridges define an area on the outer surface of the transfer module (104) that is configured to align with at least two of the first plurality of holes ( 210) and allowing fluid to flow between at least two of the first plurality of holes (210).
[0008]
8. System (100) according to claim 5, characterized in that the ridges define a plurality of valve regions coupled with the fluid network through the transfer module (104).
[0009]
9. System (100) according to claim 8, characterized in that the valve regions are configured to define a liquid sample transfer path between the sample inlet (114), the plurality of storage chambers ( 116), the plurality of reaction chambers (216), and the central chamber (316).
[0010]
10. System (100) according to claim 1, characterized in that at least one of the plurality of storage chambers (116) includes an opening configured to vent the storage chamber (116).
[0011]
11. System (100) according to claim 1, characterized in that it further comprises a plurality of premix chambers located along a side surface of the cartridge housing (102).
[0012]
12. System (100) according to claim 11, characterized in that it further comprises one or more reagents sealed within at least one of the plurality of storage chambers (116) of the plurality of reaction chambers (216) , and the plurality of premix chambers.
[0013]
13. System (100) according to claim 12, characterized in that the one or more reagents are freeze-dried.
[0014]
14. System (100) according to claim 1, characterized in that the plurality of storage chambers (116) is located along a top surface of the cartridge housing (102).
[0015]
15. System (100) according to claim 1, characterized in that the plurality of reaction chambers (216) are located along a side surface of the cartridge housing (102).
[0016]
16. System (100) according to claim 15, characterized in that the cartridge housing (102) further comprises one or more optical access windows located below the plurality of reaction chambers (216).
[0017]
17. System (100) according to claim 1, characterized in that it further comprises a first film that seals the plurality of storage chambers (116) and a plurality of films that seal the plurality of reaction chambers (216 ).
[0018]
18. System (100) according to claim 17, characterized in that the first film that seals the plurality of storage chambers (116) is in contact with a thermally controlled surface.
[0019]
19. System (100) according to claim 17, characterized in that the plurality of films that seal the plurality of reaction chambers (216) are in contact with a thermally controlled surface.
[0020]
20. System (100) according to claim 19, characterized in that a thermally controlled surface temperature is affected through a thermoelectric system.
[0021]
21. System (100) according to claim 19, characterized in that a thermally controlled surface temperature is affected through a resistive heating system.
[0022]
22. System (100) according to claim 19, characterized in that a thermally controlled surface temperature is affected by both heating and cooling the air.
[0023]
23. System (100) according to claim 1, characterized in that the at least one sample inlet (114) is sized to receive a sample through a wick.
[0024]
24. System (100) according to claim 1, characterized in that the at least one sample inlet (114) is configured to receive solid and liquid samples.
[0025]
25. System (100) according to claim 1, characterized in that the cartridge housing (102) additionally comprises at least one air inlet port.
[0026]
26. System (100) according to claim 25, characterized in that the at least one air inlet orifice is configured to connect with an external pressurized source.
[0027]
27. System (100) according to claim 27, characterized in that it further comprises a filter coupled with the at least one air inlet hole.
[0028]
28. System (100) according to claim 25, characterized in that it further comprises a buffer chamber coupled with the at least one air inlet port and configured to retain a liquid before the liquid escapes through the skin. minus one air inlet hole.
[0029]
29. System (100) according to claim 1, characterized in that the hollow transfer module (104) is configured to move laterally through a linear actuator.
[0030]
30. System (100) according to claim 29, characterized in that the linear actuator is configured to move the transfer module (104) between discrete steps.
[0031]
31. System (100) according to claim 1, characterized in that the cartridge housing (102) further comprises a means for centralizing the system within an analyzer.
[0032]
32. System (100) according to claim 1, characterized in that at least one of the second plurality of holes (312) is located at a substantially lower point in the central chamber (316).
[0033]
33. System (100) according to claim 32, characterized in that the walls of the central chamber (316) are inclined in order to properly drain a liquid into the central chamber (316) through at least one of the second plurality of holes (312).
[0034]
34. System (100) according to claim 1, characterized in that the cartridge housing (102) additionally comprises a filter coupled with the fluid network.
[0035]
35. System (100) according to claim 34, characterized in that the filter is a silicate matrix.
[0036]
36. System (100) according to claim 34, characterized in that the filter comprises a plurality of silica beads.
[0037]
37. System (100) according to claim 1, characterized in that it additionally comprises a stirring bus disposed within the central chamber (316).
[0038]
38. System (100) according to claim 1, characterized in that the cartridge housing (102) further comprises a plurality of liquid detection areas.
[0039]
39. System (100) according to claim 38, characterized in that a presence of liquid is detected in the liquid detection areas using an optical sensor.
[0040]
40. System (100) according to claim 1, characterized in that the cartridge housing (102) additionally comprises a plurality of frits coupled with the fluid network.
[0041]
41. Transfer module (104) suitable for use in the system as defined in any one of claims 1 to 40, configured to store and transport liquid samples, characterized in that it comprises: an internal housing comprising a central chamber (316) ; a jacket (108) formed around the inner housing, the jacket (108) comprising: patterned ridges along the outer surface of the jacket (108), wherein the patterned ridges are configured to define a plurality of valve regions along the outer surface of the jacket (108) when the transfer module (104) is disposed within a housing that contacts the patterned ridges; and, a plurality of holes extending through the jacket (108) and the inner housing to the central chamber (316); wherein one of the plurality of valve regions is configured to be pressurized separately from other regions in the plurality of valve regions.
[0042]
42. Transfer module (104) according to claim 41, characterized in that a fluid flow occurs both into and out of the central chamber (316) through one or more of the plurality of orifices when one of the plurality of valve regions is pressurized.
[0043]
43. Transfer module (104) according to claim 41, characterized in that the patterned ridges are further configured to define an area on the outer surface of the jacket (108) that lines up with at least two holes of a substantially housing surrounding the transfer module (104) and allowing fluid to flow between the at least two orifices.
[0044]
44. Transfer module (104) according to claim 41, characterized in that the inner housing and jacket (108) are formed as a single injection molded unit.
[0045]
45. A transfer module (104) according to claim 41, characterized in that the plurality of holes are arranged along one side of the transfer module (104) and along a top of the transfer module (104 ).
[0046]
46. Transfer module (104) according to claim 41, characterized by the fact that a plurality of patterned ridges have a toroidal shape.
[0047]
47. Transfer module (104) according to claim 41, characterized in that at least one of the plurality of holes is located at a substantially lower point in the central chamber (316).
[0048]
48. Transfer module (104) according to claim 47, characterized in that the walls of the central chamber (316) are sloped to adequately drain a liquid into the central chamber (316) through the at least one of the plurality of holes.
[0049]
49. Transfer module (104) according to claim 41, characterized in that it additionally comprises a stir bar disposed within the central chamber (316).
[0050]
50. Transfer module (104) according to claim 41, further comprising a cover configured to seal one end of the central chamber (316) and having an inclined structure within the central chamber (316).
[0051]
51. Transfer module (104) according to claim 50, characterized in that the inclined structure comprises a plurality of channels configured to direct liquid within the central chamber (316) to one or more of the plurality of holes.
[0052]
52. A method for performing fluid transfer, characterized in that it comprises: laterally translating a transfer module (104) to align a first transfer module port (104) having a central chamber (316) to a port of a first chamber; withdrawing a sample into the central chamber (316) of the first chamber through a first pressure differential applied to the sample; laterally translating the transfer module (104) to align a second hole in the transfer module (104) to a hole in a second chamber; and, withdrawing the sample into the second chamber from the central chamber (316) through a second pressure differential applied to the sample.
[0053]
53. Method according to claim 52, characterized in that it further comprises mixing the sample introduced into the first chamber with a buffer disposed within the first chamber.
[0054]
54. Method according to claim 52, characterized in that it further comprises mixing the sample taken into the central chamber (316) of the first chamber with a liquid already present in the central chamber (316).
[0055]
55. Method according to claim 52, characterized in that it further comprises introducing the sample to the first chamber through a wick that carries the sample.
[0056]
56. Method according to claim 52, characterized in that it further comprises: processing the sample in the second chamber; withdrawing the sample into the central chamber (316) from the second chamber through a third pressure differential applied to the sample; laterally translating the transfer module (104) to align the second hole in the transfer module (104) with a hole in a third chamber; withdrawing the sample into the third chamber from the central chamber (316) through a fourth pressure differential applied to the sample; and, measuring one or more qualities of the sample while in the third chamber.
[0057]
57. Method according to claim 56, characterized in that measuring comprises optically measuring a flowering signal.
[0058]
58. Method according to claim 56, characterized in that measuring comprises optically measuring an absorbance.
[0059]
59. Method according to claim 56, characterized in that it additionally comprises heating the sample both after taking the sample to the second chamber and taking the sample to the third chamber.
[0060]
60. The method of claim 52, further comprising repeating the step of laterally translating the transfer module (104) to align with the first hole of the transfer module (104) with a plurality of holes of one or more cameras.
[0061]
61. Method according to claim 60, characterized in that it further comprises withdrawing one or more liquids into the central chamber (316) from one or more chambers through one or more pressure differentials.
[0062]
62. The method of claim 52, further comprising repeating the step of laterally translating the transfer module (104) to align with the second hole of the transfer module (104) with a plurality of holes of one or more cameras.
[0063]
63. Method according to claim 62, characterized in that it further comprises withdrawing one or more liquids into the central chamber (316) from one or more chambers through one or more pressure differentials.
[0064]
64. Method according to claim 62, characterized in that it further comprises withdrawing one or more liquids into the one or more chambers from the central chamber (316) through one or more pressure differentials.
[0065]
65. Method according to claim 52, characterized in that it further comprises: processing the sample in the second chamber; withdrawing the sample into the central chamber (316) from the second chamber through a third pressure differential applied to the sample; laterally translating the transfer module (104) to align the second hole in the transfer module (104) to a hole in a third chamber; withdrawing the sample into the third chamber from the central chamber (316) through a fourth pressure differential applied to the sample; process the sample in the third chamber; laterally translating the transfer module (104) to align the second port of the transfer module (104) to a port of a fourth chamber; withdrawing the sample into the fourth chamber from the central chamber (316) through a fifth pressure differential applied to the sample; and, measuring one or more qualities of the sample while in the fourth chamber.
[0066]
66. Method according to claim 52, characterized in that removing the sample to the second chamber comprises draining the sample through a filter.
[0067]
67. Method according to claim 52, characterized in that withdrawing the sample to the second chamber comprises draining the sample through a fluid divider to one or more sub-chambers.
[0068]
68. Method according to claim 52, characterized in that it further comprises mixing the sample within the central chamber with a magnetic stirring bus.
[0069]
69. A method for performing fluid transfer, characterized in that it comprises: laterally translating a transfer module (104) within a housing to align a structure on an outer surface of the transfer module (104) with a first hole associated with a first chamber and a second hole associated with a second chamber; taking a sample from the first chamber to the second chamber through at least the structure aligned over the first hole and the second hole; and, withdrawing the sample from the second chamber into a third chamber located within the transfer module (104) through a hole through a wall of the transfer module (104).

类似技术:

---

公开号 | 公开日 | 专利标题

---

BR112014022962B1|2021-07-20|TEST CARTRIDGE SYSTEM, TRANSFER MODULE, AND METHOD FOR PERFORMING FLUID TRANSFER

---

US9855553B2|2018-01-02|Plurality of reaction chambers in a test cartridge

---

BRPI0717552A2|2013-10-22|CARTRIDGE SYSTEM, METHOD FOR FORMING A CARTRIDGE, CARTRIDGE, TEST SYSTEM, ANALYSIS METHOD FOR ONE OR MORE ANALYZES IN A SAMPLE, REAGENT COMPONENT TO STORE ONE OR MORE REAGENTS, AND, USE OF A CARTRIDGE SYSTEM, TEST AND / OR REAGENT COMPONENT

---

JP2018522241A|2018-08-09|Fluid system for performing the assay

---

US20060040311A1|2006-02-23|Integrated cartridge for sample manipulation

---

RU2767695C2|2022-03-18|Testing cassette with built-in transmitting module

同族专利:

---

公开号 | 公开日

---

EP3381558A1|2018-10-03|

---

CN104411406B|2017-05-31|

---

JP6153951B2|2017-06-28|

---

JP2020042050A|2020-03-19|

---

CN106964411A|2017-07-21|

---

HK1243724A1|2018-07-20|

---

WO2013135878A1|2013-09-19|

---

JP6347861B2|2018-06-27|

---

AU2013234281B2|2016-06-23|

---

CA2867414A1|2013-09-19|

---

US9334528B2|2016-05-10|

---

JP2017086088A|2017-05-25|

---

AU2013234281A1|2014-10-02|

---

US20150353990A1|2015-12-10|

---

ZA201500088B|2016-10-26|

---

RU2018114909A|2019-10-23|

---

US9757725B2|2017-09-12|

---

EP2825309A1|2015-01-21|

---

CN106964411B|2019-12-10|

---

CA2867414C|2021-06-01|

---

RU2018114909A3|2021-08-10|

---

CN107099445A|2017-08-29|

---

CN104411406A|2015-03-11|

---

KR20150018774A|2015-02-24|

---

KR20190109596A|2019-09-25|

---

US9914119B2|2018-03-13|

---

KR102168912B1|2020-10-23|

---

JP2015512628A|2015-04-30|

---

US20130244241A1|2013-09-19|

---

JP2018173414A|2018-11-08|

---

RU2652441C2|2018-04-26|

---

US20150352551A1|2015-12-10|

---

RU2014138186A|2016-05-20|

---

DK2825309T3|2018-07-30|

---

ES2682281T3|2018-09-19|

---

CN107099445B|2020-06-16|

---

EP2825309B1|2018-05-16|

---

CN107083319A|2017-08-22|

---

JP6838127B2|2021-03-03|

---

KR102059004B1|2019-12-24|

---

US20160288122A1|2016-10-06|

---

US9062342B2|2015-06-23|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

SE454115B|1982-09-13|1988-03-28|Wallac Oy|HOMOGENIC PHASE ANALYSIS WITH LANTANIDE KELAT AS BRAND SUBSTANCE|

---

SE8301395L|1983-03-15|1984-09-16|Wallac Oy|KELATIZING COMPOUNDS WITH FUNCTIONAL GROUPS WHICH ALLOW COVALENT COUPLING TO BIO-ORGANIC MOLECULES|

---

US4680275A|1985-02-11|1987-07-14|Becton, Dickinson And Company|Homogeneous fluorescence immunoassay using a light absorbing material|

---

WO1988000767A1|1986-06-09|1988-01-28|Kabushiki Kaisha Komatsu Seisakusho|Multi-mode narrow-band oscillation excimer laser|

---

US5144139A|1985-08-05|1992-09-01|Biotrack, Inc.|Capillary flow device|

---

WO1987002708A1|1985-10-24|1987-05-07|Siska Diagnostics, Inc.|Lanthanide chelate-tagged nucleic acid probes|

---

CA1296604C|1986-03-20|1992-03-03|Kathleen Murphy|Method for releasing rna and dna from cells|

---

US4729875A|1986-06-26|1988-03-08|Allelix Inc.|Device for performing immunochemical assays|

---

SE454781B|1986-10-17|1988-05-30|Wallac Oy|HYBRIDIZATION PROCEDURE FOR THE DETECTION OF POLYNUCLEOTIDE SEQUENCE|

---

WO1988007670A2|1987-03-27|1988-10-06|Chimerix Corporation|Time-resolved fluorescence apparatus and immunoassay|

---

US4923819A|1987-03-27|1990-05-08|Chimerix Corporation|Time-resolved fluorescence immunoassay|

---

US4855930A|1987-03-27|1989-08-08|Chimerix Corporation|Method and appartatus for improved time-resolved fluorescence spectroscopy|

---

SE8703682L|1987-09-24|1989-03-25|Wallac Oy|HOMOGENIC DETERMINATION METHOD USING AFFINITY REACTIONS|

---

WO1989004375A1|1987-10-23|1989-05-18|Siska Diagnostics, Inc.|Lanthanide chelate-tagged nucleic acid probes|

---

GB8728639D0|1987-12-08|1988-01-13|Scient Generics Ltd|Device for analytical determinations|

---

US5162237A|1988-04-11|1992-11-10|Miles Inc.|Reaction cassette for preforming sequential analytical assays by noncentrifugal and noncapillary manipulations|

---

SE8801702D0|1988-05-05|1988-05-05|Pharmacia Ab|SET FOR DETERMINATION OF ENZYMATIC ACTIVITY|

---

SE8802575D0|1988-07-08|1988-07-08|Wallac Oy|TERPYRIDINE DERIVATIVES|

---

SE8802573D0|1988-07-08|1988-07-08|Wallac Oy|MULTI-LABEL TIME-RESOLVED FLUORESCENCE ANALYSIS OF NUCLEIC ACID SEQUENCES USING LANTHANIDE CHELATES|

---

US5096669A|1988-09-15|1992-03-17|I-Stat Corporation|Disposable sensing device for real time fluid analysis|

---

US5061076A|1989-01-31|1991-10-29|Enzo Diagnostics, Inc.|Time-resolved fluorometer|

---

US5219526A|1990-04-27|1993-06-15|Pb Diagnostic Systems Inc.|Assay cartridge|

---

RU1778693C|1990-09-12|1992-11-30|Конструкторское Проектно-Технологическое Бюро Росплемобъединения|Device for placing liquid components into plate hollows|

---

EP0525181B1|1991-02-14|1997-08-06|Dade MicroScan Inc.|Novel lanthanide chelate-conjugated oligonucleotides|

---

FI88654C|1991-03-15|1993-06-10|Datacity Center Oy|Fluorescenshoejningsmetod|

---

EP0515211A3|1991-05-23|1993-04-07|Becton Dickinson And Company|Apparatus and method for phase resolved fluorescence lifetimes of independent and varying amplitude pulses|

---

ES2133312T3|1991-12-05|1999-09-16|Wallac Oy|CHELATES OF LUMINISCENT LANTANIDES.|

---

CA2082770A1|1992-02-25|1993-08-26|Denis Banville|Engineered protein chelates suitable for fluorescent lanthanide ) based time resolved fluorescence assays|

---

DE4210970C2|1992-04-02|1996-10-17|Markus Dipl Chem Sauer|Process for the simultaneous optical qualitative and quantitative detection of different molecules of a mixture marked with fluorochromes or fluorogens by means of laser spectroscopy|

---

US5223219A|1992-04-10|1993-06-29|Biotrack, Inc.|Analytical cartridge and system for detecting analytes in liquid samples|

---

US5397539A|1992-04-23|1995-03-14|Toray Industries, Inc.|Automatic analyzing apparatus|

---

AT263962T|1993-10-28|2004-04-15|I Stat Corp|DEVICE FOR TAKING AND INTRODUCING LIQUID SAMPLES|

---

US5464773A|1994-03-14|1995-11-07|Amoco Corporation|Cell disrupting apparatus|

---

AT210298T|1994-09-23|2001-12-15|Unilever Nv|MONITORING PROCEDURE AND DEVICES THEREOF|

---

US6455287B1|1995-02-23|2002-09-24|Wyeth|Mechanical disruption of bacterial cells for plasmid recovery|

---

US5856174A|1995-06-29|1999-01-05|Affymetrix, Inc.|Integrated nucleic acid diagnostic device|

---

DE69714269T2|1996-09-16|2003-03-27|Alphahelix Ab Uppsala|CARTRIDGE AND SYSTEM FOR STORING AND DISTRIBUTING REAGENTS|

---

US5744096A|1997-02-21|1998-04-28|Cholestech Corporation|Automated immunoassay cassette|

---

US6143496A|1997-04-17|2000-11-07|Cytonix Corporation|Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly|

---

AU7477398A|1997-05-09|1998-11-27|Regents Of The University Of California, The|Peltier-assisted microfabricated reaction chambers for thermal cycling|

---

US5961925A|1997-09-22|1999-10-05|Bristol-Myers Squibb Company|Apparatus for synthesis of multiple organic compounds with pinch valve block|

---

FR2768743B1|1997-09-23|2001-09-14|Bio Merieux|PROCESS FOR LYSIS OF MICROORGANISM|

---

US6036924A|1997-12-04|2000-03-14|Hewlett-Packard Company|Cassette of lancet cartridges for sampling blood|

---

US5971941A|1997-12-04|1999-10-26|Hewlett-Packard Company|Integrated system and method for sampling blood and analysis|

---

US6394952B1|1998-02-03|2002-05-28|Adeza Biomedical Corporation|Point of care diagnostic systems|

---

US6267722B1|1998-02-03|2001-07-31|Adeza Biomedical Corporation|Point of care diagnostic systems|

---

US9066695B2|1998-04-30|2015-06-30|Abbott Diabetes Care Inc.|Analyte monitoring device and methods of use|

---

FR2781500B1|1998-07-23|2000-09-08|Bio Merieux|IMPROVED DEVICE AND METHOD FOR LYSIS OF MICROORGANISMS|

---

FR2783321B1|1998-09-11|2000-11-24|Biotrol Diagnostic|REACTION CELLS, ASSEMBLY OF SUCH CELLS, IMMUNOLOGICAL ASSAY APPARATUS AND METHOD USING SUCH Cuvette assemblies|

---

US6531095B2|1999-02-11|2003-03-11|Careside, Inc.|Cartridge-based analytical instrument with optical detector|

---

US6942771B1|1999-04-21|2005-09-13|Clinical Micro Sensors, Inc.|Microfluidic systems in the electrochemical detection of target analytes|

---

WO2000065329A1|1999-04-23|2000-11-02|Surromed, Inc.|Disposable optical cuvette cartridge|

---

US20020106787A1|1999-04-29|2002-08-08|James Benn|Device for repid DNA sample processing with integrated liquid handling, thermocycling, and purification|

---

DE60014676T2|1999-05-28|2005-11-17|Cepheid, Sunnyvale|DEVICE AND METHOD FOR THE ANALYSIS OF LIQUID SAMPLES|

---

US20040200909A1|1999-05-28|2004-10-14|Cepheid|Apparatus and method for cell disruption|

---

ES2272289T5|1999-05-28|2011-10-21|Cepheid|CARTRIDGE TO PERFORM A CHEMICAL REACTION.|

---

US6818185B1|1999-05-28|2004-11-16|Cepheid|Cartridge for conducting a chemical reaction|

---

KR100675698B1|1999-08-06|2007-02-01|써모 바이오스타, 인크.|An automated point of care detection system including complete sample processing capabilities|

---

JP4627395B2|1999-08-11|2011-02-09|旭化成株式会社|Analytical cartridge and liquid feeding control device|

---

AT268477T|1999-09-03|2004-06-15|Roche Diagnostics Corp|METHOD, REAGENT AND MEASURING CARTRIDGE FOR DETERMINING THE COAGLE TIME|

---

EP1080785A1|1999-09-04|2001-03-07|F. Hoffmann-La Roche Ag|System for thermocycling of fluids in cartridges|

---

US6743399B1|1999-10-08|2004-06-01|Micronics, Inc.|Pumpless microfluidics|

---

DE60034479T2|1999-11-15|2007-12-27|I-Stat Corporation|DEVICE AND METHOD FOR DETERMINING COAGULATION IN LIQUID SAMPLES|

---

US6431476B1|1999-12-21|2002-08-13|Cepheid|Apparatus and method for rapid ultrasonic disruption of cells or viruses|

---

US6403037B1|2000-02-04|2002-06-11|Cepheid|Reaction vessel and temperature control system|

---

WO2001063270A1|2000-02-23|2001-08-30|Caliper Technologies, Inc.|Multi-reservoir pressure control system|

---

AU4917601A|2000-03-14|2001-09-24|Micronics Inc|Microfluidic analysis cartridge|

---

US7553453B2|2000-06-02|2009-06-30|Honeywell International Inc.|Assay implementation in a microfluidic format|

---

US8323564B2|2004-05-14|2012-12-04|Honeywell International Inc.|Portable sample analyzer system|

---

FR2812303B1|2000-07-27|2002-12-06|Biomerieux Sa|PROCESS FOR CELL LYSIS OF PROKARYOTS OR EUKARYOTS OR SIMULTANEOUS CELL LYSIS OF PROKARYOTS AND EUKARYOTS|

---

US6374684B1|2000-08-25|2002-04-23|Cepheid|Fluid control and processing system|

---

AU8678401A|2000-08-25|2002-03-04|Genome Therapeutics Corp|Device for rapid dna sample processing with integrated liquid handling, thermocycling, and purification|

---

FR2813207B1|2000-08-28|2002-10-11|Bio Merieux|REACTIONAL CARD AND USE OF SUCH A CARD|

---

US6349546B1|2000-09-06|2002-02-26|Wafermasters Incorporated|Liquid gas exchanger|

---

US7232109B2|2000-11-06|2007-06-19|California Institute Of Technology|Electrostatic valves for microfluidic devices|

---

US7622083B2|2002-01-28|2009-11-24|Biocal Technology, Inc.|Multi-capillary electrophoresis cartridge interface mechanism|

---

US20020168780A1|2001-02-09|2002-11-14|Shaorong Liu|Method and apparatus for sample injection in microfabricated devices|

---

CA2450676C|2001-03-09|2010-03-30|Biomicro Systems, Inc.|Method and system for microfluidic interfacing to arrays|

---

US6942169B2|2001-06-06|2005-09-13|Integrated Sensing Systems|Micromachined lysing device and method for performing cell lysis|

---

US7141058B2|2002-04-19|2006-11-28|Pelikan Technologies, Inc.|Method and apparatus for a body fluid sampling device using illumination|

---

FR2826454B1|2001-06-26|2003-10-17|Bio Merieux|ANALYSIS CARDS|

---

WO2003008636A2|2001-07-19|2003-01-30|Infectio Diagnostic Inc.|Universal method and composition for the rapid lysis of cells for the release of nucleic acids and their detection|

---

US6942836B2|2001-10-16|2005-09-13|Applera Corporation|System for filling substrate chambers with liquid|

---

US6966880B2|2001-10-16|2005-11-22|Agilent Technologies, Inc.|Universal diagnostic platform|

---

WO2003036304A1|2001-10-26|2003-05-01|Advion Biosciences, Inc.|Method and device for chemical analysis|

---

US6893613B2|2002-01-25|2005-05-17|Bristol-Myers Squibb Company|Parallel chemistry reactor with interchangeable vessel carrying inserts|

---

US8048386B2|2002-02-25|2011-11-01|Cepheid|Fluid processing and control|

---

US7419821B2|2002-03-05|2008-09-02|I-Stat Corporation|Apparatus and methods for analyte measurement and immunoassay|

---

EP1506513B1|2002-05-08|2013-09-11|Philips Intellectual Property & Standards GmbH|System for point of care diagnosis and/or analysis|

---

WO2003104770A2|2002-06-01|2003-12-18|Chempaq A/S|A disposable cartridge for characterizing particles suspended in a liquid|

---

EP1369473B1|2002-06-07|2009-01-21|Cholestech Corporation|Automated cassete module for an apparatus for conducting immunoassays and use thereof|

---

US7238519B2|2002-06-07|2007-07-03|Cholestech Corporation|Automated immunoassay cassette, apparatus and method|

---

EP1385006A3|2002-07-24|2004-09-01|F. Hoffmann-La Roche Ag|System and cartridge for processing a biological sample|

---

US7244961B2|2002-08-02|2007-07-17|Silicon Valley Scientific|Integrated system with modular microfluidic components|

---

CN1678731A|2002-08-27|2005-10-05|范德比尔特大学|Bioreactors with multiple chambers|

---

ES2402092T3|2002-09-11|2013-04-26|Temple University - Of The Commonwealth System Of Higher Education|Automated system for electrophoretic separations of high production capacity|

---

TW590982B|2002-09-27|2004-06-11|Agnitio Science & Technology I|Micro-fluid driving device|

---

WO2004040001A2|2002-10-02|2004-05-13|California Institute Of Technology|Microfluidic nucleic acid analysis|

---

WO2004042003A2|2002-11-01|2004-05-21|Promega Corporation|Cell lysis compositions, methods of use, apparatus, and kit|

---

US7842234B2|2002-12-02|2010-11-30|Epocal Inc.|Diagnostic devices incorporating fluidics and methods of manufacture|

---

US7238520B2|2002-12-04|2007-07-03|Smiths Detection Inc.|PCR sample preparation holder and method|

---

EP2711415B1|2002-12-26|2022-02-16|Meso Scale Technologies, LLC.|Assay cartridges and methods of using the same|

---

US20040176705A1|2003-03-04|2004-09-09|Stevens Timothy A.|Cartridge having an integrated collection element for point of care system|

---

DE10315074A1|2003-04-02|2004-10-14|Clondiag Chip Technologies Gmbh|Device for the duplication and detection of nucleic acids|

---

US20050019757A1|2003-06-12|2005-01-27|Stolarchuk Danylo J.|Contaminant detection apparatus|

---

US7604592B2|2003-06-13|2009-10-20|Pelikan Technologies, Inc.|Method and apparatus for a point of care device|

---

US8409528B2|2003-06-19|2013-04-02|Abbott Laboratories|Apparatus and method for handling fluids for analysis|

---

US7413712B2|2003-08-11|2008-08-19|California Institute Of Technology|Microfluidic rotary flow reactor matrix|

---

JP4146780B2|2003-10-17|2008-09-10|株式会社日立ハイテクノロジーズ|Reagent cassette and automatic analyzer using the same|

---

US7601300B2|2003-10-28|2009-10-13|BIOMéRIEUX, INC.|Compact, integrated system for processing test samples|

---

RU2265194C2|2003-11-11|2005-11-27|ФГУП "Производственное объединение "Маяк"|Transporting device|

---

EP1541991A1|2003-12-12|2005-06-15|STMicroelectronics S.r.l.|Integrated semiconductor chemical microreactor for real-time monitoring of biological reactions|

---

ES2425082T3|2003-12-16|2013-10-11|F. Hoffmann-La Roche Ag|Blood test method|

---

JP2005180983A|2003-12-17|2005-07-07|Hitachi High-Technologies Corp|Chemical analyzer and structure for chemical analysis|

---

DE10360786B4|2003-12-23|2005-12-22|Roche Diagnostics Gmbh|Handheld analyzer|

---

WO2005094981A1|2004-03-29|2005-10-13|Agilent Technologies, Inc.|Cyclic pcr system|

---

EP1745120A4|2004-04-16|2010-04-14|Spartan Bioscience Inc|System for rapid nucleic acid amplification and detection|

---

DE102004021822B3|2004-04-30|2005-11-17|Siemens Ag|Method and arrangement for DNA amplification by means of PCR using dry reagents|

---

US9101302B2|2004-05-03|2015-08-11|Abbott Diabetes Care Inc.|Analyte test device|

---

US7887750B2|2004-05-05|2011-02-15|Bayer Healthcare Llc|Analytical systems, devices, and cartridges therefor|

---

EP1963817A2|2005-12-22|2008-09-03|Honeywell International Inc.|Portable sample analyzer cartridge|

---

US7754473B2|2004-06-04|2010-07-13|Abacus Diagnostica Oy|Temperature control of reaction vessel, system with reaction vessel, software product for system and use of system|

---

EP1771786B1|2004-06-07|2017-12-20|Iquum, Inc.|Sample multiprocessing|

---

JP2008506129A|2004-07-13|2008-02-28|ラジオメーター・メディカル・アー・ペー・エス|Container containing reference gas, set of reference fluid, cassette containing reference fluid, and apparatus including reference fluid|

---

WO2006018044A1|2004-08-18|2006-02-23|Agilent Technologies, Inc.|Microfluidic assembly with coupled microfluidic devices|

---

JP4742544B2|2004-09-08|2011-08-10|凸版印刷株式会社|Gene check apparatus and method|

---

JP2008541009A|2005-04-30|2008-11-20|オークビル・ホンコン・カンパニー・リミテツド|Apparatus and methods for sample collection and analysis|

---

WO2006042907A1|2004-10-19|2006-04-27|Wallac Oy|A novel probe and its use in bioaffinity assays|

---

EP1650297B1|2004-10-19|2011-04-13|Samsung Electronics Co., Ltd.|Method and apparatus for the rapid disruption of cells or viruses using micro magnetic beads and laser|

---

US8637285B2|2004-12-31|2014-01-28|Memsflow Aps|Generation of pulsating pressure waves, E.G. for cell lysis|

---

DE102005013685A1|2005-03-18|2006-09-28|Roche Diagnostics Gmbh|Tape magazine for a hand-held device for examining a body fluid, as well as a hand-held device|

---

DE102005015005A1|2005-04-01|2006-10-05|Qiagen Gmbh|Process for treating a sample containing biomolecules|

---

WO2006122311A2|2005-05-11|2006-11-16|The Trustees Of The University Of Pennsylvania|Microfluidic chip|

---

EP1883474B1|2005-05-25|2021-03-31|Boehringer Ingelheim Vetmedica GmbH|System for the integrated and automated analysis of dna or protein and method for operating said type of system|

---

CN101252994B|2005-07-01|2011-04-13|霍尼韦尔国际公司|Microfluidic card for RBC analysis|

---

JP2007021351A|2005-07-15|2007-02-01|Yokogawa Electric Corp|Cartridge for chemical reaction and chemical reaction processing system|

---

US20070031914A1|2005-08-05|2007-02-08|Wei Zhu|Devices for analyte assays and methods of use|

---

US8220493B2|2005-08-23|2012-07-17|University Of Virginia Patent Foundation|Passive components for micro-fluidic flow profile shaping and related method thereof|

---

US20070053800A1|2005-09-02|2007-03-08|Applera Corporation|Fluid processing device comprising sample transfer feature|

---

WO2007047336A2|2005-10-12|2007-04-26|University Of Virginia Patent Foundation|Integrated microfluidic analysis systems|

---

DE102005054924B4|2005-11-17|2012-06-14|Siemens Ag|Apparatus and method for extracting a swab sample|

---

EP1951860A4|2005-11-21|2012-06-06|Life Technologies Corp|Portable preparation, analysis, and detection apparatus for nucleic acid processing|

---

EP1966366A4|2005-12-29|2011-06-15|I Stat Corp|Molecular diagnostics amplification system and methods|

---

US20070152683A1|2005-12-30|2007-07-05|Karl Werner|Electronic device for analysis of a body fluid|

---

US7888130B2|2006-01-03|2011-02-15|Dräger Safety AG & Co. KGaA|Test cassette for fluid analyses|

---

US8883490B2|2006-03-24|2014-11-11|Handylab, Inc.|Fluorescence detector for microfluidic diagnostic system|

---

KR100790880B1|2006-07-05|2008-01-02|삼성전자주식회사|A microfluidic device comprising a microchannel or microchamber bonded to a hydrophobic porous polymer having a magnetic bead therewihin at the wall thereof and method of using the same|

---

EP1878496A1|2006-07-14|2008-01-16|Roche Diagnostics GmbH|Apparatus for performing nucleic acid analysis|

---

US7888107B2|2006-07-24|2011-02-15|Nanosphere, Inc.|System using self-contained processing module for detecting nucleic acids|

---

US8807164B2|2006-08-30|2014-08-19|Semba Biosciences, Inc.|Valve module and methods for simulated moving bed chromatography|

---

US9278321B2|2006-09-06|2016-03-08|Canon U.S. Life Sciences, Inc.|Chip and cartridge design configuration for performing micro-fluidic assays|

---

GB0619008D0|2006-09-27|2006-11-08|Akubio Ltd|Cartridge for a fluid sample analyser|

---

KR20080029233A|2006-09-28|2008-04-03|삼성전자주식회사|Method and apparatus for accomplishing nucleic acid amplification and hybridization in single solid support|

---

WO2008061165A2|2006-11-14|2008-05-22|Handylab, Inc.|Microfluidic cartridge and method of making same|

---

WO2008140568A2|2006-11-15|2008-11-20|Idaho Technology, Inc.|High density self-contained biological analysis|

---

US7754148B2|2006-12-27|2010-07-13|Progentech Limited|Instrument for cassette for sample preparation|

---

US7863035B2|2007-02-15|2011-01-04|Osmetech Technology Inc.|Fluidics devices|

---

WO2008110019A1|2007-03-13|2008-09-18|The Governors Of The University Of Alberta|Clinical sample preparation on a microfluidic platform|

---

US8702976B2|2007-04-18|2014-04-22|Ondavia, Inc.|Hand-held microfluidic testing device|

---

EP2015067A1|2007-06-15|2009-01-14|Roche Diagnostics GmbH|System for measuring the analyte concentration in a body fluid sample|

---

CN103157400B|2007-06-21|2014-12-24|简·探针公司|Instrument and method for exposing container to multiple areas|

---

GB0715171D0|2007-08-03|2007-09-12|Enigma Diagnostics Ltd|Sample processor|

---

US20110212491A1|2007-08-03|2011-09-01|Enigma Diagnostics Limited|Reaction vessel|

---

US8658110B2|2007-08-13|2014-02-25|Hewlett-Packard Development Company, L.P.|Fluid delivery system|

---

EP2030567A1|2007-08-31|2009-03-04|Roche Diagnostics GmbH|Analytic device for detecting an analyte in a body fluid, cartridge for analytic device and method for creating a wound and examining the excreted body fluid|

---

WO2009027935A2|2007-08-31|2009-03-05|Koninklijke Philips Electronics N. V.|Biochemical sensor cartridge|

---

JP5413916B2|2007-09-19|2014-02-12|オプコ・ダイアグノスティクス・リミテッド・ライアビリティ・カンパニー|Liquid storage for integrated testing|

---

GB0720264D0|2007-10-17|2007-11-28|Smiths Detection Watford Ltd|Sample preparation devices and analyzers|

---

US20090104076A1|2007-10-19|2009-04-23|Los Alamos National Security Llc|Sample preparation cartridge and system|

---

EP2056114A1|2007-10-29|2009-05-06|Koninklijke Philips Electronics N.V.|Automatic detection of infectious diseases|

---

EP2077336A1|2007-12-19|2009-07-08|Koninklijke Philips Electronics N.V.|Device and method for parallel quantitative analysis of multiple nucleic acids|

---

ES2354850T3|2008-01-07|2011-03-18|F. Hoffmann-La Roche Ag|CASE OF REAGENTS.|

---

US20090215050A1|2008-02-22|2009-08-27|Robert Delmar Jenison|Systems and methods for point-of-care amplification and detection of polynucleotides|

---

WO2009137244A1|2008-04-15|2009-11-12|Charles River Laboratories, Inc.|Cartridge and method for sample analysis|

---

US8961902B2|2008-04-23|2015-02-24|Bioscale, Inc.|Method and apparatus for analyte processing|

---

WO2009131677A1|2008-04-25|2009-10-29|Claros Diagnostics, Inc.|Flow control in microfluidic systems|

---

US8404192B2|2008-04-25|2013-03-26|Ben H. Liu|Biochips and related automated analyzers and methods|

---

US8895240B2|2008-05-19|2014-11-25|E I Du Pont De Nemours And Company|Method, kit and system for collecting and processing samples for DNA and RNA detection|

---

WO2009149115A1|2008-06-04|2009-12-10|Vectrant Technologies Inc.|Cartridge for conducting biochemical assays|

---

EP2304445B1|2008-07-09|2020-06-10|Micropoint Bioscience Inc|Analytical cartridge with fluid flow control|

---

EP2143491A1|2008-07-10|2010-01-13|Carpegen GmbH|Device for analysing a chemical or biological sample|

---

US8133451B2|2008-08-28|2012-03-13|Microfluidic Systems, Inc.|Sample preparation apparatus|

---

US8201765B2|2008-09-08|2012-06-19|California Institute Of Technology|Mechanical lysis arrangements and methods|

---

US8216529B2|2008-09-15|2012-07-10|Abbott Point Of Care Inc.|Fluid-containing pouches with reduced gas exchange and methods for making same|

---

GB2464721C|2008-10-23|2013-08-14|Biosurfit Sa|Jet deflection device|

---

US7993583B2|2008-10-29|2011-08-09|Lawrence Livermore National Security, Llc|Passive microfluidic array card and reader|

---

EP2187210A1|2008-11-14|2010-05-19|Koninklijke Philips Electronics N.V.|Measurement device for body fluid analysis|

---

EP2191900B1|2008-11-28|2016-03-30|F. Hoffmann-La Roche AG|System and method for nucleic acids containing fluid processing|

---

ES2643134T3|2008-11-28|2017-11-21|F. Hoffmann-La Roche Ag|System and method for processing liquid samples|

---

JP2012511156A|2008-12-05|2012-05-17|ナノアイヴイディー，インコーポレイテッド|Microfluidic lab-on-test card for point-of-care analyzers|

---

ES2700207T3|2008-12-05|2019-02-14|Biocartis Nv|Cyclic thermal variation system comprising a transparent heating element|

---

FR2939445B1|2008-12-10|2013-05-03|Biomerieux Sa|AUTOMATED LYSE SYSTEM OF MICROORGANISMS PRESENT IN SAMPLE, NUCLEIC ACID EXTRACTION AND PURIFICATION OF MICROORGANISMS FOR ANALYSIS|

---

EP2376226B1|2008-12-18|2018-09-12|Opko Diagnostics, LLC|Improved reagent storage in microfluidic systems and related articles and methods|

---

AU2009329750C1|2008-12-23|2015-04-30|Mycartis Nv|Assay device and method for performing biological assays|

---

GB2466644B|2008-12-30|2011-05-11|Biosurfit Sa|Liquid handling|

---

ES2695039T3|2009-02-02|2018-12-28|Opko Diagnostics, Llc|Structures to control the interaction of light with microfluidic devices|

---

WO2010118427A1|2009-04-10|2010-10-14|Canon U.S. Life Sciences, Inc.|Fluid interface cartridge for a microfluidic chip|

---

CA2662546A1|2009-04-15|2010-10-15|Spartan Bioscience Inc.|Tube for dna reactions|

---

WO2010118542A1|2009-04-15|2010-10-21|Biocartis Sa|Protection of bioanalytical sample chambers|

---

EP2438016B1|2009-06-05|2021-06-02|IntegenX Inc.|Universal sample preparation system and use in an integrated analysis system|

---

US9260475B2|2009-06-26|2016-02-16|Claremont Biosolutions Llc|Capture and elution of bio-analytes via beads that are used to disrupt specimens|

---

RU2543183C2|2009-10-21|2015-02-27|Биокартис Hb|Collector for inkjet cartridge|

---

WO2011151804A1|2010-06-03|2011-12-08|Spinomix S.A.|A fluidic interfacing system and assembly|

---

CN103555558B|2010-07-23|2016-09-28|贝克曼考尔特公司|Container for real-time PCR|

---

EP2748600A4|2011-08-22|2015-06-10|Waters Technologies Corp|Analysis of dried blood spot samples in a microfluidic system with dilution of extracted samples|

---

US9075042B2|2012-05-15|2015-07-07|Wellstat Diagnostics, Llc|Diagnostic systems and cartridges|

---

KR102145639B1|2011-12-22|2020-08-19|아이씨유 메디칼 인코퍼레이티드|Fluid transfer devices and methods of use|

---

EP2814942A4|2012-02-13|2015-09-23|Neumodx Molecular Inc|Microfluidic cartridge for processing and detecting nucleic acids|

---

DK2825309T3|2012-03-16|2018-07-30|Stat Diagnostica & Innovation Sl|Sample cartridge with integrated transfer module|US8448499B2|2008-12-23|2013-05-28|C A Casyso Ag|Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method|

---

DK2825309T3|2012-03-16|2018-07-30|Stat Diagnostica & Innovation Sl|Sample cartridge with integrated transfer module|

---

DE102012222828A1|2012-12-11|2014-06-12|Agilent Technologies, Inc. - A Delaware Corporation -|Pre-filled liquid cartridge for supplying a sample separator with a working fluid|

---

US11187713B2|2013-01-14|2021-11-30|Stratec Se|Laboratory module for storing and feeding to further processing of samples|

---

CN105683751B|2013-09-06|2020-01-17|赛拉诺斯知识产权有限责任公司|Device, system, method and kit for receiving a swab|

---

ES2749925T3|2014-04-24|2020-03-24|Lucira Health Inc|Colorimetric detection of nucleic acid amplification|

---

MX2017002814A|2014-09-04|2017-08-02|Theranos Inc|Pathogen and antimicrobial resistance testing.|

---

US10413902B2|2015-07-17|2019-09-17|Stat-Diagnostica & Innovation, S.L.|Apparatus for sample separation and collection|

---

US10300486B2|2015-07-17|2019-05-28|Stat-Diagnostica & Innovation, S.L.|Dry chemistry container|

---

US10775370B2|2015-07-17|2020-09-15|Stat-Diagnostica & Innovation, S.L.|Fluidic system for performing assays|

---

EP3689466A1|2015-07-17|2020-08-05|Cue Health Inc.|System for enhanced detection and quantification of analytes|

---

EP3429752A4|2016-03-14|2019-10-30|Lucira Health, Inc.|Systems and methods for performing biological assays|

---

CA3015376A1|2016-03-14|2017-09-21|Diassess Inc.|Devices and methods for biological assay sample preparation and delivery|

---

KR102170373B1|2016-05-02|2020-10-27|인테그리컬쳐 인코포레이티드|Growth induction system, growth induction control device, growth induction control method, and growth induction control program|

---

WO2017205763A1|2016-05-27|2017-11-30|Biomerieux, Inc.|System and method for transferring specimen containers between detection instruments|

---

CN106226254B|2016-08-03|2019-06-07|天津喜诺生物医药有限公司|A kind of micro-fluidic chip and preparation method thereof for biological detection|

---

WO2018140540A1|2017-01-25|2018-08-02|Cue Health Inc.|Systems and methods for enhanced detection and quantification of analytes|

---

EP3354342A1|2017-01-26|2018-08-01|Eidgenössische Anstalt für Wasserversorgung, Abwasserreinigung und Gewässerschutz, Eawag|Device and method for producing individually processed fluid samples|

---

US11080848B2|2017-04-06|2021-08-03|Lucira Health, Inc.|Image-based disease diagnostics using a mobile device|

---

USD839447S1|2017-04-20|2019-01-29|Hemosonics Llc|Hemostasis measurement cartridge|

---

USD841184S1|2017-06-06|2019-02-19|Hemosonics Llc|Transparent hemostasis measurement cartridge|

---

US20190217292A1|2018-01-18|2019-07-18|Stat-Diagnostica & Innovation S.L.|Dry Chemistry Container|

---

USD878622S1|2018-04-07|2020-03-17|Precision Nanosystems Inc.|Microfluidic chip|

---

DE102018111834A1|2018-05-16|2019-11-21|Mildendo Gesellschaft für mikrofluidische Systeme mbH|Microfluidic device and method of using same for separating, purifying and concentrating components of fluidic media,|

---

EP3647781A1|2018-10-29|2020-05-06|EXIAS Medical GmbH|Measuring cartridge for measuring a liquid sample|

---

USD910200S1|2018-12-21|2021-02-09|Lucira Health, Inc.|Test tube|

---

WO2021219533A1|2020-04-29|2021-11-04|Boehringer Ingelheim Vetmedica Gmbh|Cartridge, system and method for amplification of at least one analyte|

法律状态:
2018-03-27| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

---

2019-09-10| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

---

2020-10-06| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|

---

2021-03-16| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|

---

2021-05-11| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

---

2021-07-20| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 15/03/2013, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

---

申请号 | 申请日 | 专利标题

---

US201261611784P| true| 2012-03-16|2012-03-16|

---

US61/611784|2012-03-16|

---

PCT/EP2013/055432|WO2013135878A1|2012-03-16|2013-03-15|A test cartridge with integrated transfer module|

---