巴西专利BR112014027737B1 fluidic testing system, and, method for filling a chamber

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专利摘要:
FLUIDIC TEST SYSTEM, E, METHOD FOR FILLING A CHAMBER. A fluidic test system is presented that includes a plurality of test chambers, a plurality of inlet channels, and a fluidic network that connects the inlet channels in one or more other chambers. Each plurality of test chambers is characterized by a length and a hydraulic diameter. The length of each test chamber is aligned substantially parallel to a gravity vector. Each of the test chambers has only one opening arranged along the length of the corresponding test chamber. Additionally, each of the test chambers is coupled through its respective opening to only one of the plurality of input channels.
公开号:BR112014027737B1
申请号:R112014027737-0
申请日:2013-05-09
公开日:2021-05-11
发明作者:Rafael Bru Gibert；Jordi Carrera Fabra；Anna Comenges Casas；José Antonio García Sánchez
申请人:Stat-Diagnostica & Innovation, S.L；
IPC主号:

专利说明:

FIELD OF THE INVENTION
[0001] Modalities of the present invention refer to the field of clinical diagnostic tools. FUNDAMENTALS OF THE INVENTION
[0002] Given the complexity of automating molecular testing and immunoassay techniques, there is a lack of products that provide adequate performances to be clinically usable in nearby patient testing environments. Typical molecular testing includes several processes involving correct dosage of reagents, sample introduction, lysis of cells to extract DNA or RNA, purification steps, and amplification for their subsequent detection. Although central laboratory robotic platforms exist that automate some of these processes, for many tests that require a short process 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 expense. 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 experienced high entry barriers for clinical diagnostic applications due to background generated by exogenous DNA sources. 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, for example, from: improper disposal of agents that inhibit Polymerase Chain Reaction (PCR) such as hemoglobin, urine or sputum; 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 concentrations lower than previous reference methods makes it very difficult to obtain clinically relevant conclusions, while avoiding erroneous calls with false positives. To minimize this problem, especially for the detection of pathogen micro-organisms, tests should be capable of quantification. Therefore, it has become increasingly necessary to perform multiplex test matrices and assays to consolidate enough data to draw confident conclusions. As an example, one of the main limitations of existing PCR-based assays is the inability to perform amplifications of different target genes simultaneously. Although techniques such as microarrays provide very high multiplexing capability, their main limitation is the slow speed in obtaining results, which often have no positive impact on patient control. SUMMARY OF THE INVENTION
[0005] A fluidic test system that includes a plurality of test chambers is presented. Simultaneous fluid control of each test site can reduce testing time and increase the likelihood of getting reproducible results across multiple test sites.
[0006] In one embodiment, a single orifice fluidic test system includes a plurality of test chambers, each characterized by a length and a hydraulic diameter. Each of the plurality of test chambers has only one opening disposed along the length of the corresponding test chamber. The fluidic test system additionally includes a first inlet channel and a plurality of fluid dividing elements. The fluid dividing elements divide an initial liquid flowing down the first inlet channel to a plurality of second inlet channels. Each of the plurality of test chambers is coupled via its respective aperture to only one of the plurality of second input channels.
[0007] An example method is described. The method includes flowing an initial amount of liquid down a first inlet channel of a single-port fluidic testing system. The initial amount of liquid is divided into a plurality of second inlet channels, each second inlet channel coupled to a plurality of test chambers, each of the plurality of test chambers having only one opening disposed along a length. of the camera. The method further includes filling each of the test chambers with a final amount of liquid, the final amount being substantially equal in each of the test chambers and summing all the test chambers to equal the initial amount of liquid.
[0008] In another embodiment, a fluidic test system includes a plurality of test chambers, a plurality of input channels, and a fluidic network that connects the input channels in one or more other chambers. The test chambers each have a length and a hydraulic diameter. The length of each test chamber is aligned substantially parallel to a gravity vector. Each of the test chambers has only one opening arranged along the length of the corresponding test chamber. Additionally, each of the test chambers is coupled through its respective opening to only one of the plurality of input channels.
[0009] Another example method is described. The method includes flowing liquid through a plurality of inlet channels, each inlet channel coupled to a plurality of test chambers. A length of each test chamber is aligned substantially parallel to a gravity vector, and each of the test chambers has only one opening disposed along the length of the chamber. The method further includes filling each of the plurality of test chambers with liquid to a threshold amount. The method further includes extracting liquid from each of the test chambers through the inlet channels to leave a predetermined amount of liquid within each test chamber.
[00010] Another example method is described. The method includes flowing a first liquid through a first inlet channel coupled to a first opening disposed along a length of a test chamber at a first height. The length of the test chamber is aligned substantially parallel to a gravity vector. The method additionally includes filling the test chamber with the first liquid up to a first threshold amount. The first liquid is drawn from the test chamber through the first inlet channel, and leaves a first predetermined amount of the first liquid inside the test chamber. The method further includes flowing a second liquid through a second inlet channel coupled to a second opening disposed along the length of the test chamber at a second height. The second height is greater than the first height. The method additionally includes filling the test chamber with the second liquid to a second threshold amount. The second liquid is drawn from the test chamber through the second inlet channel, and leaves a second predetermined amount of the second liquid within the test chamber.
[00011] Another example method is described. The method includes flowing liquid through each of a plurality of channels to a liquid detection area disposed in each channel, thereby establishing a predetermined amount of liquid in each of the plurality of channels. The method further includes flowing only the predetermined amount of liquid in each of the plurality of channels to respective chambers coupled in each of the channels. BRIEF DESCRIPTION OF DRAWINGS / FIGURES
[00012] 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 enable those skilled in the pertinent art to produce and use the invention .
[00013] Figure 1 is a graphical representation of a test cartridge system, according to an embodiment.
[00014] Figure 2 shows a side view of the test cartridge system, according to an embodiment.
[00015] Figure 3 illustrates a test chamber, according to a modality.
[00016] Figures 4A to 4C illustrate operation of the test chamber, according to a modality.
[00017] Figure 5 illustrates a plurality of test chambers, according to an embodiment.
[00018] Figures 6A to 6C illustrate another operation of the test chamber, according to an embodiment.
[00019] Figure 7 illustrates another test chamber, according to a modality.
[00020] Figure 8 illustrates another plurality of test chambers, according to an embodiment.
[00021] Figure 9 illustrates another plurality of test chambers, according to an embodiment.
[00022] Figure 10 illustrates the test cartridge system in an analyzer, according to a modality.
[00023] Figures 11 to 14 illustrate methods of filling the example chamber, according to modalities.
[00024] Embodiments of the present invention will be described with reference to the accompanying drawings. DETAILED DESCRIPTION OF THE INVENTION
[00025] Although specific configurations and arrangements are discussed, it should be understood that this is done for illustrative purposes only. Those skilled in the pertinent art will appreciate that other configurations and arrangements can be used without departing from the spirit and scope of the present invention. It will be apparent to those skilled in the pertinent art that this invention can also be employed in a variety of other applications.
[00026] Note that references in the specification to "a particular modality", "any modality", "an example modality", etc., indicate that the described modality may include a particular feature, structure or characteristic, but each modality may not necessarily include the particular feature, structure, or feature. Furthermore, such phrases do not necessarily refer to the same modality. Additionally, when a particular feature, structure or feature is described in relation to a modality, it would be within the knowledge of those skilled in the art to realize such feature, structure or feature in relation to other modalities, whether or not explicitly described.
[00027] Modalities described herein refer to a test cartridge system for performing a variety of molecular tests, such as immunoassays, PCR hybridization, DNA, etc. 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 by an external measurement system that provides data related to the reactions taking place within the test cartridge. In one embodiment, the test cartridge includes a plurality of test chambers with a transparent window to perform optical detection with each test chamber.
[00028] In one example, a single test cartridge can be used to perform an array of immunoassays with a given sample. The test cartridge contains all the necessary buffers, reagents and markers held in sealed chambers integrated into the cartridge to perform immunoassays.
[00029] In another example, a single test cartridge can be used to perform PCR. DNA can be purified from the rest of a sample by means of a filter incorporated into the test cartridge. The sample can be extruded through the filter while a separately stored elution liquid can remove the DNA and bind it in another chamber to initiate the temperature cycling process.
[00030] 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 in the instrument.
[00031] In one embodiment, the test cartridge provides a self-contained liquid sealed during the manufacturing process. Reagents and sample do not come into contact with the environment or any part of the instrument. This test cartridge feature is also important for many laboratories and hospitals to safely dispose of products after use.
[00032] In order to carry out a test matrix, the test cartridge contains a plurality of test chambers designed to facilitate measurement of the optical properties of the contents within each test chamber, according to a modality. For example, the test chambers each contain a transparent window to allow both fluorescence and absorbance studies of the contents in them. Additionally, the fluidic arrangement design for each test chamber can allow each chamber to be filled at the same level while using a single pump source.
[00033] Additional details relating to the components of the test cartridge system, including the test chambers, are described here with references made to the figures. It should be understood that the illustrations of each physical component should not be limiting, and that those versed in the relevant technique(s) given the description here would find ways to rearrange or otherwise change any of the components without running away from the scope or spirit of the invention.
[00034] Figure 1 illustrates a test cartridge system of example 100 with an array of test chambers, according to an embodiment. While reference will be made here to example test cartridge system structure 100, those skilled in the art will appreciate that test chamber modalities described herein can be used with any number of test system types and configurations.
[00035] Test cartridge system 100 includes a cartridge housing 102. Other components may also be considered for inclusion in test cartridge system 100, such as an analyzer module or various active components such as pumps or heaters.
[00036] Cartridge housing 102 includes a variety of channels, chambers, and fluidic 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 filled with various liquids so that the end user will not need to pre-fill storage chambers 116 before placing the test cartridge system 100 into an analyzer. In another example, reagents are lyophilized prior to being placed in storage chambers 116. Cartridge housing 102 may additionally include one or more processing chambers 124a-b connected to fluid channels along one side of cartridge housing 102 Processing chambers 124a-b can be used for a variety of processing and/or waste applications.
[00037] Samples are introduced into the cartridge housing 102 through sample port 114, according to a modality. In one example, sample port 114 receives solid, semi-solid, or liquid samples. In another embodiment, cartridge housing 102 includes more than one inlet for introducing samples.
[00038] The various chambers and channels around the cartridge housing 102 can be sealed through the use of caps 118, 126, 127, and 128. The caps may be films capable of sealing the fluid in the cartridge housing 102. another example, the covers can be plastic panels. In one example, one or more of the covers are transparent. Additionally, one or more of the covers may be thermally controlled to heat portions of housing 102.
[00039] The integrated test cartridge system 100 allows a user to place a sample, for example, in sample port 114, and then place the test cartridge system 100 into an analyzer. In embodiments, the reaction steps to be carried out including, for example, purification, lysis, mixing, binding, labeling and/or detection can all be carried out in the test cartridge system 100 via interaction with the analyzer without any need for the end user intervenes. Additionally, since all liquids remain sealed in 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.
[00040] Figure 2 illustrates a side view of the cartridge housing 102, according to an embodiment. The description of cartridge housing 102 is presented to describe features that may be present in cartridge housing 102, but should not be limiting to the placement or dimensional properties of the features.
[00041] Figure 2 illustrates a fluidic network and a series of holes extending in the cartridge housing 102. The fluidic network can connect into one or more of the storage chambers 116 and/or processing chambers 124a-b of the housing. cartridge 102. These chambers may be disposed on the opposite side of the cartridge housing 102 from the side illustrated in Figure 2. In one embodiment, the fluidic network also connects in a series of test chambers 216.
[00042] Each fluidic channel may also be designed to terminate in an orifice that will interface with orifice or valve regions in a movable transfer module (not shown) in housing 102. A plurality of orifices 210 allow fluid to flow to any housing chamber 102, according to an embodiment. The plurality of holes 210 can act both as inlet holes for liquid to be extracted to an inner chamber in cartridge housing 102, and as outlet holes for liquid to be expelled from the inner chamber to the fluid network of cartridge housing 102. For example, the liquid can be pressurized to flow through the second hole to the right hole of the liquid holes 210 and down to the rightmost test chamber 216. In addition, the liquid can be extracted again from the most test chamber. right 216 and to the second orifice to the right orifice of the liquid orifices 210 by means of an applied vacuum pressure.
[00043] Test chambers 216 can be modeled similarly, for example, to a centrifuge tube. In one embodiment, liquid can be drawn into test chambers 216 to mix with reagents that have been preloaded into each test chamber. For example, each test chamber can be loaded with different oligonucleotide primers and probes for a PCR process, and liquid can be drawn into each test chamber to create distinct mixtures in each chamber. Reagents can be lyophilized before being loaded into test chambers 216. In another embodiment, test chambers 216 are also used for sample detection. Detection can occur using an external optical source and photodetector coupled to an analyzer in which the test cartridge system 100 is placed. Thus, any wall or lids of test chambers 216 may be transparent to allow optical detection. In one example, the photodetector measures the absorbance through the liquid inside the test chamber at one or more wavelengths. In another example, the photodetector measures a fluorescence signal generated from a fluorescent compound within the test chamber. In one embodiment, fluorescence measurements are taken from the test chambers below 216. The test chambers 216 can be adapted for other means of detection, for example, electrochemical, electromechanical, surface plasmon resonance, etc.
[00044] A set of minor channel widenings 214 is observed upstream of the test chambers 216, according to an embodiment. Channel flares 214 can act as liquid sensing areas. As such, 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 functions of test cartridge system 100. in another embodiment, channel widenings 214 may include integrated sensors, such as a standard resistive sensor, to indicate the presence or flow of fluid. Additionally, optical signal detected at a particular channel widening 214 monitors the presence of liquid within a corresponding test chamber 216.
[00045] Liquid sensing areas in channel enlargements 214 can be used to set predetermined amounts of liquid to be metered into each test chamber 216. For example, liquid can be pressurized in each channel separately or simultaneously until liquid reaches the liquid sensing areas in each channel. In this way, each channel can contain substantially the same amount of liquid filling the channel up to channel widening 214. Then, each channel can be separate or simultaneously pressurized to force the predetermined amount of liquid down into each test chamber 216, from according to some modalities.
[00046] A plurality of premix chambers 231 may also be arranged upstream of the test chambers 216, according to an embodiment. Premix chambers 231 can include dry chemicals, such as frozen or lyophilized analyte. In another example, premix chambers 231 include dry chemical microspheres or biological samples. Biological samples can be lyophilized within premix chambers 231. Such biological or chemical compounds can be stored in premix chambers 231 for extended periods of time before use. The dimensions of premix chambers 231 can be specifically designed to adjust the size of a dry chemical microsphere, typically on the order of a few millimeters in diameter, according to a modality. In one example, fluid drawn into reaction chambers 216 mixes with samples stored in premix chambers 231.
[00047] At the bottom of the cartridge housing 102 in figure 2, an optical access area 240 is arranged below the test chambers 216, according to an embodiment. Optical Access Area 240 is designed to be substantially transparent at all wavelengths used during the optical detection process. In one example, each individual test chamber 216 has its own optical access area. In another example, a single optical access area extends across multiple test chambers 216.
[00048] Also illustrated on the side of the cartridge housing 102 are a pressure port 236 and an exhaust port 234, according to an embodiment. Pressure port 236 can be connected to an external pressure source to apply both positive and negative pressure differentials throughout the system, according to a modality. Exhaust port 234 can be either open to atmosphere or connected to another pressure source. For example, a positive pressure difference can be applied in one orifice while a negative pressure difference is applied in the other orifice to force faster movement of liquid through the coupled channels of the system.
[00049] A film or plurality of films can be placed over the series of test chambers 216. The films can be thin enough to still provide adequate sealing while also allowing easier heating and/or cooling of the contents inside the chambers test 216 through an external source. For example, films can have a surface that is thermally controlled by any of thermoelectric devices, resistive and forced air heaters, or a combination of these. In one example, the films are polymeric films with a thickness of less than 100 microns. In one example, the thermal conductivity of films is greater than 1 W/mK.
[00050] Figure 3 illustrates a more detailed view of the test chamber 216, according to an embodiment. Test chamber 216 includes a single aperture 304 disposed along a length of test chamber 216 that couples to an inlet channel 302. Test chamber 216 also has a curved base wall 306. The curved base wall 306 it can be transparent to allow optical detection of the test chamber 216 underneath. Test chamber 216 has a hydraulic diameter large enough for gravity to influence the flow of fluid within test chamber 216. Thus, test chamber 216 is aligned so that its length is substantially parallel to a gravity vector. Due to this alignment, the liquid is influenced by the forces of gravity and fills the chamber from the bottom upwards.
[00051] Test chamber 216 may contain 308 reagents. Any number of reagents may be present in 308 reagents. 308 reagents may be present in liquid form or as a lyophilized globule. Reagents 308 are resuspended within the liquid that flows into test chamber 216. In another example, reagents 308 are stored in premix chamber 231 for mixing with fluid upstream of test chamber 216.
[00052] An input channel 302 couples into the test chamber 216 through the opening 304. The input channel 302 may be a channel of a plurality of channels integrated within the cartridge housing 102. The input channel 302 provides a path of fluid to liquid to flow into the test chamber 216 and to extract from the test chamber 216.
[00053] In one embodiment, the opening 304 is wider than the width of the inlet channel 302. The wider opening provides a more controlled entry of liquid into the test chamber 216 and also reduces the droplet size created by the liquid to as it enters test chamber 216 through opening 304. Each of these factors reduces the likelihood that liquid will form a meniscus between the two side walls of test chamber 306. Meniscus formation makes it difficult to control the amount of liquid inside the chamber and causes bubbles to form. Bubbles can interrupt any biological process that occurs within the test chamber 216 and cause errors in optical measurements.
[00054] An example operation of the test chamber 216 is illustrated in figures 4A to 4C, according to an embodiment. In Fig. 4A, a predetermined amount of liquid is disposed within inlet channel 302. The predetermined amount of liquid is dispensed through opening 304 and into test chamber 216 as shown in Fig. 4B. Liquid can be dispensed, for example, by means of a pressure difference generated.
[00055] In one example, the amount of liquid to be metered into the test chamber 216 is chosen so that the resulting liquid level is both at a height h and below it, where H is the distance of the opening 304 from from the bottom of the test chamber 216. The resulting liquid 402 is illustrated in Figure 4C. As a result, any gas in the top portion of test chamber 216 is free to escape through opening 304.
[00056] Dosing a predetermined amount of liquid into the test chamber 216 allows the procedure to occur through a single pressurization event. As such, coordination of filling multiple test chambers in parallel is simplified.
[00057] Figure 5 illustrates an example arrangement for a plurality of test chambers 216, according to an embodiment. A single connecting inlet (or orifice) 502 is illustrated for coupling the various test chambers 216 in the fluidic network of, for example, test cartridge system 100. In one embodiment, a single inlet 502 is coupled to a single orifice where the single orifice is the only external opening for the fluidic system.
[00058] In the example shown, since only a single inlet 502 is provided for dosing liquid in the multiple test chambers 216, the fluid channels include multiple channel dividers 504a-c. The geometry of channel dividers 504a-c can be chosen so that half of the incoming liquid flows down in one path, while the other half flows down in the other path. Alternatively, the geometry can be chosen to create any liquid split ratio between the two resulting channels. The plurality of test chambers 216 need not be directly aligned as illustrated, but may be arranged in any way that keeps the total path lengths between the single input 502 and each of the test chambers 216 equal. Equal path lengths simplify the procedure for dosing controlled amounts of liquid into each test chamber 216.
[00059] Channel dividers 504a-c assist in providing an equal amount of liquid for dosing into each of the test chambers 216. For example, 80 µL of liquid can be introduced via a single connection port 502. passing through the channel divider 504a, 504b and 504c in succession, 10 µL of liquid would be metered into each test chamber 216. Although this example assumes that each channel divider 504a-c is a 50/50 fluid divider, this need not be the case, and any ratio of resulting fluid amounts could be performed between the test chambers 216.
[00060] The channel arrangement illustrated in figure 5 represents a closed fluidic system that allows dosing to be more easily implemented through a single pressurization event. For example, a positive pressure applied to a single connection port 502 can be used to dose a predetermined amount of liquid into each of the test chambers 216 as previously described with respect to Figures 4A-C.
[00061] Figures 6A to 6C depict an example operation of the test chamber 216, according to an embodiment. In Figure 6A, test chamber 216 is filled with liquid to a height greater than height H. Positive pressure can be applied to fill chamber 216 to this point. In one embodiment, a pressure sensor and/or regulator may be included with the system to control the pressure and direction applied when the liquid has reached a threshold amount.
[00062] In figure 6B, a negative pressure is applied and the liquid is extracted from the test chamber 216 through the inlet channel 302. The negative pressure can be applied so that the fluid is extracted faster than when it flowed into the test chamber 216.
[00063] In Fig. 6C, liquid is withdrawn until the liquid level inside the test chamber 216 falls below height H. A predetermined amount 602 of liquid remains inside the test chamber 216 after the negative pressure is removed. The exact volume of the predetermined quantity 602 depends on the height H of the opening 304, the hydraulic diameter of the test chamber 216 and the pressure applied during the extraction of the liquid. Using this procedure, a calculated amount of liquid can be metered into the test chamber 216 only through the single inlet channel 302. For example, the amount of liquid left in the chamber can be determined by the point at which the gravitational force and surface tension on the liquid overcome the negative pressure applied in the channel. In one example, liquid is drawn from test chamber 216 fairly quickly so that any reagents that may be present within test chamber 216 are drawn through inlet channel 302. Height H can be adjusted for various designs of the test chamber. test 216 to adjust the amount of liquid left inside the test chamber 216.
[00064] Figure 7 illustrates an embodiment of a multi-channel chamber 702. Two input channels 704a-b are coupled in the multi-channel chamber 702 through openings 706a-b respectively. Each of the openings 706a-b is arranged along a length of multi-channel chamber 702 at a height H1 and H2, respectively.
[00065] Multichannel chamber 702 can be used to dose multiple controlled levels of different liquids within the same chamber. For example, with inlet channel 704b closed to atmosphere, a first liquid can flow into multichannel chamber 702 through inlet channel 704a. A predetermined amount of liquid may be metered into multichannel chamber 702 via inlet channel 704a and 704b in succession using a process similar to that described with respect to Figure 4A to 4C. In another embodiment, a quantity of the first and second liquids is left in the multi-channel chamber 702 using a process similar to that described with respect to Figures 6A to 6C. The amount of first liquid left can correspond to the height H1 of the first opening 706a. Then, inlet channel 704a is closed to atmosphere while a second liquid flows into multichannel chamber 702 through inlet channel 704b. Again, using a similar process already discussed, a predetermined amount of second liquid is left in multichannel chamber 702. The amount of second liquid left can correspond to a difference between the height H2 and H1 of opening 706b and 706a respectively.
[00066] It should be noted that although only two inlet channels are illustrated, any number of inlet channels can be realized to distribute liquids at various heights along the length of the multichannel chamber 702.
[00067] Figure 8 illustrates a plurality of test chambers 216 as may be arranged in cartridge housing 102, according to another embodiment. Each test chamber 216 of the plurality includes an input channel 302. Each input channel 302 may additionally connect into a fluidic network, such as, for example, the fluidic network around the test cartridge 102.
[00068] A single pressure source (not shown) can be coupled in the system to flow liquid down each of the plurality of inlet channels 302. Thus, each of the plurality of test chambers 216 can be filled with the same source depression. Additionally, during the application of a negative pressure, the same predetermined amount of fluid can be left in each of the plurality of test chambers 216. The same amount of fluid can be left in each test chamber 216 regardless of any geometric difference between the various input channels 302, since each test chamber 216 is similarly pressurized. In another example, liquid may be pressurized in each channel until a liquid sensing area disposed in each channel establishes a predetermined amount of liquid in each channel, before dosing the liquid below into test chambers 216.
[00069] Figure 9 illustrates a plurality of test chambers, according to another embodiment. Instead of each inlet channel 901 coupling into a single chamber, each inlet channel 901 includes a fluidic divider 902 for dividing the liquid flow into at least two divided channels 903a-b. At least two split channels 903a-b can then mate in at least two test chambers 904a-b. Although each input channel is shown in Fig. 9 as splitting into two split channels 903a-b, those skilled in the relevant art in possession of the description herein will understand how to split any of the input channels 901 into any number of other channels. Each of the split channels 903a-b can engage respective test chambers 904a-b via aperture 906a-b disposed along a length of the respective test chamber. In one example, each input channel 901 can additionally connect in a fluidic network.
[00070] Feeding multiple test chambers through a smaller number of inlet channels helps ensure that each test chamber contains the same concentrations of compounds present in the liquid. In addition, using a single inlet channel to dose multiple test chambers reduces the complexity of coupling a single pressure source to control fluid flow to each chamber.
[00071] Figure 10 illustrates an analyzer 1001 that operates to perform optical detection of compounds in the test cartridge system 100, according to an embodiment. Analyzer 1001 includes an optical probe 1002, a temperature control element 1004, a fan 1006, and a photodetection unit 1008 that includes a 1010 objective.
[00072] The optical probe 1002 can be aligned on the channel widening 214 to detect the presence of liquid within the respective channel chamber. Optical probe 1002 can use infrared or visible light wavelengths and include any number of detector and transmitter components. Additionally, data collected from optical probe 1002 can be used to control other components of analyzer 1001. For example, after optical probe 1002 has detected that liquid has been present for a certain threshold time, a signal can be sent to interrupt application of a positive pressure to the liquid and/or initiate heating of the contents of the test chambers of the test cartridge system 100, using temperature control element 1004.
[00073] The temperature control element 1004 may be disposed close to the test chambers along the bottom portion of the test cartridge system 100. Temperature control element 1004 may contain components to heat and/or cool the contents of the test chambers. For example, temperature control element 1004 may be a Peltier device that applies thermoelectric heating or cooling. In another example, temperature control element 1004 is a resistive heater. Current can pass through coils of wire or metal tape printed on a surface to heat the surrounding area. In yet another example, temperature control element 1004 provides forced air to both heat and cool the test chambers. Forced air can be provided by fan 1006. In one mode, the analyzer 1001 has temperature control elements on both sides of the test chambers. One temperature control element can be used for heating, while the other is used for cooling, for example.
[00074] Photodetection unit 1008 may contain any type of optical detector known to those skilled in the relevant art(s) including, but not limited to, CCD arrays, photodiodes, and CMOS sensors. In one embodiment, the photodetection unit 1008 supplies an excitation wavelength of light to the test chambers and collects the fluorescence light emitted through the objective 1010. In another embodiment, the excitation wavelength is supplied by an other source (not shown). The emitted fluorescence escapes from the test chambers via optical access area 240 along the bottom portion of the test chambers.
[00075] Figure 11 is a flowchart illustrating a method of filling the chamber 1100, according to an embodiment.
[00076] In block 1102, an initial amount of liquid flows down into a first inlet channel. The first input channel can be, for example, connection input 502 illustrated in figure 5.
[00077] In block 1104, the initial amount of liquid is divided into a plurality of second input channels, with each of the second input channels coupled to a plurality of test chambers. In one embodiment, each of the plurality of test chambers has only one opening disposed along a length of the chamber to receive one of the second input channels. A length of each test chamber can be aligned substantially parallel to a gravity vector.
[00078] In block 1106, each of the plurality of test chambers is filled with a final amount of liquid that is substantially equal in each of the test chambers. Additionally, the sum of the final amount of liquid in each of the test chambers is equal to the initial amount of liquid.
[00079] Other actions can be considered, as well as part of the method of filling chamber 1100. For example, the method of filling chamber 1100 may include resuspension of one or more reagents disposed in one or more of the plurality of test chambers in the final amount of liquid dosed in each of the test chambers. Another exemplary action includes heating the contents in at least one of the plurality of test chambers. Heating can be carried out, for example, by a Peltier device, a resistive heating element, and/or forced air. One or more optical properties of the contents in at least one of the plurality of test chambers can also be detected during the filling method of chamber 1100.
[00080] Figure 12 is a flowchart illustrating a method of filling the chamber 1100, according to an embodiment.
[00081] In block 1202, liquid is drained through a plurality of inlet channels. Each of the input channels is coupled to a plurality of test chambers, according to a modality. A length of each test chamber is aligned substantially parallel to a gravity vector. In one embodiment, each of the plurality of test chambers has only one opening disposed along the length of the chamber. In one example, flow through the plurality of inlet channels is carried out by means of a single pump source.
[00082] In block 1204, each of the plurality of test chambers is filled with liquid up to a threshold amount. In one example, the threshold quantity is equal to or greater than a height at which the opening is arranged along the length of each of the test chambers.
[00083] In block 1206, liquid is drawn from each of the plurality of test chambers through the inlet channels, leaving a predetermined amount of liquid within each test chamber. The predetermined amount of liquid can be an amount of liquid that is below the height at which the opening is disposed along the length of each of the test chambers. For example, the amount of liquid left in the chamber can be determined by the point at which the gravitational force and surface tension in the liquid overcome the negative pressure applied to the channel.
[00084] Other actions may also be considered as part of the method of filling chamber 1200. For example, the method of filling chamber 1200 may include resuspending one or more reagents disposed in one or more of the plurality of test chambers in the amount of liquid left inside one or more test chambers. If the reagents are resuspended, then the liquid extraction in block 1206 is carried out fairly quickly such that the extracted liquid does not contain the reagents. Another exemplary action includes heating the contents in at least one of the plurality of test chambers. Heating can be carried out, for example, by a Peltier device, a resistive heating element, and/or forced air. One or more optical properties of the contents in at least one of the plurality of test chambers may also be detected during the filling method of chamber 1200.
[00085] Figure 13 is a flowchart illustrating another method of filling the chamber 1200, according to an embodiment.
[00086] In block 1302, a first liquid flows through a first inlet channel. In one embodiment, the first input channel is coupled to a first opening disposed along a length of a test chamber at a first height. The length of the test chamber is aligned substantially parallel to a gravity vector. As the first liquid flows through the first inlet channel in block 1302, a second inlet channel coupled to the test chamber is closed to atmosphere. In one example, both the first and second input channels are open to the atmosphere to begin with.
[00087] In block 1304, the test chamber is filled with the first liquid up to a first threshold amount. In one example, the first threshold quantity is equal to or greater than the first height of the first opening of the test chamber.
[00088] In block 1306, the first liquid is drawn from the test chamber through the first inlet channel, leaving a first predetermined amount of liquid inside the test chamber. The first predetermined amount of liquid can be an amount of liquid that corresponds to the first height of the first opening of the test chamber. For example, the amount of liquid left in the chamber can be determined by the point at which the gravitational force and surface tension in the liquid overcome the negative pressure applied in the first channel.
[00089] In block 1308, the first inlet channel is closed to atmosphere and the second inlet channel is opened, according to a modality. The switching of the active channel can be performed by means of one or more valves coupled to the fluidic network.
[00090] In block 1310, a second liquid flows through a second inlet channel. In one embodiment, the second input channel is coupled into a second opening disposed along the length of the test chamber at a second height that is greater than the first height. In one example, the flow of both the first liquid in block 1302 and the second liquid in block 1308 is accomplished via a single pump source.
[00091] In block 1312, the test chamber is filled with the second liquid up to a second threshold amount.
[00092] In block 1314, the second liquid is drawn from the test chamber through the second inlet channel, leaving a second predetermined amount of liquid inside the test chamber. In one example, the second predetermined amount of liquid is an amount of liquid that corresponds to the difference between the second height of the second opening and the first height of the first opening of the test chamber. In another example, the amount of liquid left in the chamber can be determined by the point at which the gravitational force and surface tension in the liquid overcome the negative pressure applied in the second channel.
[00093] Similar to the method of filling chamber 1200, other actions can be considered part of the method of filling chamber 1300. For example, method filling chamber 1300 may include resuspending one or more reagents disposed within the test chamber in the predetermined amount of first and second liquid left in the test chamber. Alternatively, one or more reagents can be resuspended only in the first liquid left in the test chamber. In one example, any reagent that may be present within the test chamber is not re-extracted to either the first or second input channels in blocks 1306 and 1314 respectively. The method of filling the chamber 1300 may additionally include heating the contents of the test chamber and/or detecting one or more optical properties of the contents of the test chamber as described previously with respect to the method of filling the chamber 1200. input are described in the filling method of chamber 1300, it should be understood that the filling method of chamber 1300 can be expanded to include any number of input channels for one or more chambers.
[00094] Figure 14 is a flowchart illustrating another method of filling the chamber 1400, according to an embodiment.
[00095] In block 1402, a liquid flows through each of a plurality of channels to a liquid sensing area disposed in each channel, according to a modality. Liquid can be pressurized to flow down each channel, and it can be drained down each channel separately or simultaneously. Flow of liquid to the sensing area establishes a predetermined amount of liquid in each of the plurality of channels, according to an embodiment.
[00096] In block 1404, the predetermined amount of liquid in each of the plurality of channels flows into respective chambers coupled in each of the channels, according to a modality. Each channel can be separate or simultaneously pressurized to force the predetermined amount of liquid down into each corresponding chamber.
[00097] Method 1400 may also include resuspending one or more reagents disposed in one or more channels of the plurality of channels. Reagents can be disposed within premix chambers coupled to each of the channels.
[00098] The above description of the specific modalities will thus fully reveal the general nature of the invention that others can, applying the knowledge of those skilled in the art, easily modify and/or adapt such specific modalities for various applications, without undue experimentation, without departing from the concept of the present invention. Therefore, such adaptations and modifications must be DAC. The meaning and range of equivalents of the described modalities, based on the precept and guideline presented here. It is to be understood that the phraseology or terminology herein is for the purpose of description and not limitation, such that the terminology or phraseology in the present specification is to be interpreted by those skilled in the art in light of the precepts and guideline.
[00099] The summary and summary sections may present one or more, but not all, of the exemplary embodiments of the present invention contemplated by the inventor(s) and, thus, are not intended to limit the present invention and claims in any way. attached.
[000100] The scope 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 (73)
[0001]
1. Fluidic test system (100), characterized in that it comprises: a plurality of test chambers (216), each distinguished by a length and a hydraulic diameter, each of which of the plurality of test chambers (216 ) has only one opening (304) disposed along the length of the corresponding test chamber (216), wherein the length of each test chamber is configured to be aligned parallel to a gravity vector; a first inlet channel (502) configured to drain an initial amount of liquid from an inlet port, the inlet port being the only external opening to the fluidic testing system (100); and a plurality of fluid dividing elements (504) configured to divide the initial liquid flowing down the first inlet channel to a plurality of second inlet channels (302), each of the plurality of test chambers (216 ) is coupled via its respective opening (304) to only one of the plurality of second input channels (302).
[0002]
2. Fluid testing system (100) according to claim 1, characterized in that it further comprises a plurality of liquid sensing areas disposed along the plurality of second inlet channels (302).
[0003]
3. Fluid testing system (100) according to claim 2, characterized in that each of the plurality of liquid sensing area (214) is configured to monitor the presence of liquid within a test chamber (216 ) corresponding.
[0004]
4. Fluid testing system (100) according to claim 2, characterized in that each of the plurality of liquid sensing areas (214) is configured to dose a predetermined amount of liquid into a test chamber (216 ) corresponding.
[0005]
5. Fluidic test system (100) according to claim 1, characterized in that at least one of the plurality of test chambers (216) includes one or more reagents (308).
[0006]
6. Fluidic test system (100) according to claim 5, characterized in that one or more reagents (308) are lyophilized globules arranged inside the test chambers (216).
[0007]
7. Fluid testing system (100) according to claim 1, characterized in that it further comprises a plurality of premix chambers (231) arranged along the plurality of second inlet channels (704a-b).
[0008]
8. Fluid testing system (100) according to claim 7, characterized in that the plurality of premix chambers (231) comprises one or more reagents (308).
[0009]
9. Fluidic test system (100) according to claim 1, characterized in that a curved base wall (306) of each of the plurality of test chambers (216) has a curved geometry.
[0010]
10. Fluidic test system (100) according to claim 1, characterized in that the curved base wall (306) of each of the plurality of test chambers (216) is transparent to allow optical interrogation.
[0011]
11. Fluidic test system (100) according to claim 1, characterized in that a single pump is configured to force an initial amount of liquid through the first inlet channel and fill each of the plurality of test chambers ( 216) with an equal portion of the initial amount of liquid.
[0012]
12. Fluid test system (100) according to claim 1, characterized in that one or more walls of the plurality of chambers (216) is in contact with a thermally controlled housing (102).
[0013]
13. Fluidic test system (100) according to claim 12, characterized in that one or more walls are polymeric films with a thickness less than 100 microns.
[0014]
14. Fluidic test system (100) according to claim 12, characterized in that one or more walls have a thermal conductivity greater than 1 W/mK.
[0015]
15. Fluid test system (100) according to claim 12, characterized in that the thermally controlled housing (102) comprises a Peltier device.
[0016]
16. Fluid test system (100) according to claim 12, characterized in that the thermally controlled housing (102) comprises electrical resistive heating elements.
[0017]
17. Fluid test system (100) according to claim 12, characterized in that the thermally controlled housing (102) is heated by means of forced air.
[0018]
18. A method (1100) for filling a chamber, characterized in that it comprises: draining (1102) an initial amount of liquid down into a first inlet channel (502) of a single-port fluidic test system (100); dividing (1104) the initial amount of liquid from the first inlet channel (502) into a plurality of second inlet channels (302), each second inlet channel (302) coupled in a test chamber into a plurality of test chambers ( 216, wherein each of the plurality of test chambers (216) has only one opening (304) disposed along a length of the chamber, wherein the length of each test chamber (216) is configured to be aligned parallel to a gravity vector; and filling (1106) each of the plurality of test chambers (216) with a final amount of liquid, the final amount being equal in each of the test chambers (216) and the sum of all the test chambers (216) equal to the initial amount of liquid.
[0019]
19. The method (1100) of claim 18, further comprising resuspending one or more reagents (308) disposed in one or more of the plurality of test chambers (216) in the final amount of liquid.
[0020]
20. The method (1100) according to claim 18, characterized in that it further comprises resuspending one or more reagents (308) disposed in one or more of a plurality of premix chambers (231) in the final amount of liquid .
[0021]
21. The method (1100) of claim 18, further comprising heating the contents in at least one of the plurality of test chambers (216).
[0022]
22. Method (1100) according to claim 21, characterized in that heating comprises heating with a Peltier device.
[0023]
23. Method (1100) according to claim 21, characterized in that the heating comprises heating with resistive heating elements.
[0024]
24. Method (1100) according to claim 21, characterized in that the heating comprises forced air heating.
[0025]
25. The method (1100) of claim 18, further comprising detecting one or more optical properties of the contents in at least one of the plurality of test chambers.
[0026]
26. Method (1100) according to claim 18, characterized in that the flow, division, and filling are carried out by means of a single pump source.
[0027]
27. Fluidic test system (100), characterized in that it comprises: a plurality of test chambers (216), each defined by a length and a hydraulic diameter, wherein the length of each test chamber (216) is configured to be aligned parallel to a gravity vector, and wherein each of the plurality of test chambers (216) has only one opening disposed along the length of the corresponding test chamber (216); a plurality of input channels (302), each of the plurality of test chambers (216) being coupled via its respective aperture to only one of the plurality of input channels (302); and a fluidic network configured to connect the plurality of input channels (302) in one or more other chambers.
[0028]
28. Fluid testing system (100) according to claim 27, characterized in that it further comprises a plurality of liquid sensing areas (214) disposed along the plurality of inlet channels (302).
[0029]
29. Fluid testing system according to claim 28, characterized in that each of the plurality of liquid sensing areas (214) is configured to monitor the presence of liquid within a corresponding test chamber (216).
[0030]
30. Fluid testing system (100) according to claim 28, characterized in that each of the plurality of liquid sensing areas (214) is configured to dose a predetermined amount of liquid into a test chamber (216 ) corresponding.
[0031]
31. Fluid testing system (100) according to claim 27, characterized in that the position of the single opening (304) along the length of the corresponding test chamber (216) controls the amount of liquid that remains within the respective chamber (216) after the remainder of the liquid is extracted from the opening through the respective inlet channel (302).
[0032]
32. Fluid testing system (100) according to claim 27, characterized in that the width of the single opening (304) is greater than the width of the respective inlet channel (302).
[0033]
33. Fluidic test system (100) according to claim 27, characterized in that at least one of the plurality of test chambers (216) includes one or more reagents (308).
[0034]
34. Fluidic test system (100) according to claim 33, characterized in that one or more reagents (308) are lyophilized globules arranged within the test chambers (216).
[0035]
35. Fluid testing system (100) according to claim 27, characterized in that it further comprises a plurality of premix chambers (231) disposed along the plurality of inlet channels (302).
[0036]
36. Fluidic testing system (100) according to claim 35, characterized in that the plurality of premix chambers (231) comprises one or more reagents (308).
[0037]
37. Fluidic test system (100) according to claim 27, characterized in that a curved base wall (306) of each of the plurality of test chambers (216) has a curved geometry.
[0038]
38. Fluidic test system (100) according to claim 27, characterized in that the curved base wall (306) of each of the plurality of test chambers (216) is transparent to allow optical interrogation.
[0039]
39. Fluid testing system (100) according to claim 27, characterized in that a single pump is used to force liquid through the plurality of inlet channels (302).
[0040]
40. Fluid testing system (100) according to claim 27, characterized in that one or more walls of the plurality of chambers (216) is in contact with a thermally controlled housing (102).
[0041]
41. Fluid test system (100) according to claim 40, characterized in that one or more walls are polymeric films with a thickness less than 100 microns.
[0042]
42. Fluidic test system (100) according to claim 40, characterized in that one or more walls have a thermal conductivity greater than 1 W/mK.
[0043]
43. Fluid test system (100) according to claim 40, characterized in that the thermally controlled housing comprises a Peltier device.
[0044]
44. Fluid test system (100) according to claim 40, characterized in that the thermally controlled housing comprises electrical resistive heating elements.
[0045]
45. Fluid test system (100) according to claim 40, characterized in that the thermally controlled housing is heated by means of forced air.
[0046]
46. Fluid testing system (100) according to claim 27, characterized in that at least one of the plurality of inlet channels (302) is coupled in more than one opening (906).
[0047]
47. Method (1200) for filling a chamber, characterized in that it comprises: draining (1202) the liquid through a plurality of inlet channels (302), each inlet channel coupled to a plurality of test chambers (216 ), wherein a length of each test chamber (216) is configured to be aligned parallel to a gravity vector, and wherein each of the plurality of test chambers (216) has only one opening (304) disposed along the length. the length of the chamber (216); filling (1204) each of the plurality of test chambers (216) with liquid to a threshold amount; extracting (1206) liquid from each of the plurality of test chambers (216) through the inlet channels (302), the extraction (1206) leaving a predetermined amount of liquid within each test chamber (216).
[0048]
48. The method (1200) according to claim 47, further comprising resuspending one or more reagents (308) arranged in one or more of the plurality of test chambers (216) in the amount of liquid left in one or more test chambers (216).
[0049]
49. The method (1200) according to claim 48, characterized in that the extraction (1206) extracts liquid that does not contain the reagents (308).
[0050]
50. Method (1200) according to claim 47, characterized in that filling (1204) to the threshold amount comprises filling each of the test chambers (216) to a height equal to or greater than a height at which the opening (304) is arranged along the length of each of the test chambers (216).
[0051]
51. The method (1200) according to claim 50, characterized in that leaving a predetermined amount of liquid comprises leaving an amount of liquid that is below the height at which the opening (304) is disposed along the length of each which of the test chambers (216).
[0052]
52. The method (1200) of claim 47, further comprising heating the contents in at least one of the plurality of test chambers (216).
[0053]
53. Method (1200) according to claim 52, characterized in that heating comprises heating with a Peltier device.
[0054]
54. Method (1200) according to claim 52, characterized in that the heating comprises heating with resistive heating elements.
[0055]
55. Method (1200) according to claim 52, characterized in that the heating comprises forced air heating.
[0056]
56. The method (1200) of claim 47, further comprising detecting one or more optical properties of the contents in at least one of the plurality of test chambers (216).
[0057]
57. Method (1200) according to claim 47, characterized in that the flow (1202) is performed by means of a single pump source.
[0058]
58. Method (1300) for filling a chamber, characterized in that it comprises: draining (1302) a first liquid through a first inlet channel (704a) coupled to a first opening (706a) arranged along a length of a test chamber (702) at a first height, the length of the test chamber (702) being configured to be aligned parallel to a gravity vector; filling (1304) the test chamber (702) with the first liquid to a first threshold amount; extracting (1306) the first liquid from the test chamber (702) through the first inlet channel (704a), wherein the extraction (1306) leaves a first predetermined amount of the first liquid within the test chamber (702); flow (1310) a second liquid through a second inlet channel (704b) coupled in a second opening (706b) arranged along the length of the test chamber (702) at a second height, the second height being greater than the first height; filling (1312) the test chamber (702) with the second liquid to a second threshold amount; extracting (1314) the second liquid from the test chamber (702) through the second inlet channel (704b), wherein the extraction leaves a second predetermined amount of the second liquid within the test chamber (702).
[0059]
59. The method (1300) of claim 58, characterized in that leaving a first predetermined amount of the first liquid comprises leaving an amount of the first liquid that corresponds to the first height of the first opening (706a).
[0060]
60. The method (1300) of claim 59, characterized in that leaving a second predetermined amount of the second liquid comprises leaving an amount of the second liquid that corresponds to a difference between the second height of the second opening (706b) and the first height of the first opening (706a).
[0061]
61. The method (1300) of claim 58, further comprising resuspending one or more reagents (308) disposed in the test chamber (702) in the predetermined amount of the first and second liquid left within the test chamber (702).
[0062]
62. The method (1300) of claim 58, further comprising resuspending one or more reagents (308) disposed in the test chamber (702) in the predetermined amount of only the first liquid left inside the test chamber ( 702).
[0063]
63. The method (1300) according to claim 62, characterized in that the extraction (1306, 1314) of both the first and second liquid extracts liquid that does not contain any of the reactants (308).
[0064]
64. The method (1300) of claim 58, further comprising heating the contents within the test chamber (702).
[0065]
65. Method (1300) according to claim 64, characterized in that heating comprises heating with a Peltier device.
[0066]
66. Method (1300) according to claim 64, characterized in that heating comprises heating with resistive heating elements.
[0067]
67. Method (1300) according to claim 64, characterized in that the heating comprises forced air heating.
[0068]
68. The method (1300) of claim 58, further comprising detecting one or more optical properties of the contents within the test chamber (702).
[0069]
69. The method (1300) according to claim 58, characterized in that the flow (1302, 1310) of the first and second liquid is carried out by means of a single pump source.
[0070]
70. The method (1300) of claim 58, further comprising, after extraction (1306) of the first liquid, closing (1308) the first inlet channel (704a) from the atmosphere.
[0071]
71. Method (1400) for filling a chamber, characterized in that it comprises: flowing (1402) liquid through each of a plurality of channels (302) to a liquid sensing area (214) disposed in each channel ( 302, thereby establishing a predetermined amount of liquid in each of the plurality of channels (302); flow (1404) only the predetermined amount of liquid in each of the plurality of channels (302) to the respective chambers (216) coupled in each of the channels (302), wherein a length of each of the respective chamber (216) configured to be aligned parallel to a gravity vector.
[0072]
72. The method (1400) of claim 71, further comprising resuspending one or more reagents (308) disposed in one or more channels of the plurality of channels (302).
[0073]
73. The method (1400) according to claim 72, characterized in that resuspending one or more reagents (308) comprises resuspending one or more reagents disposed within premix chambers coupled in one or more channels (302).

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同族专利:

公开号 | 公开日

RU2644476C2|2018-02-12|

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CA2871856C|2020-12-29|

ES2834461T3|2021-06-17|

US9063121B2|2015-06-23|

US10099216B2|2018-10-16|

JP6585119B2|2019-10-02|

US10092900B2|2018-10-09|

RU2014144122A|2016-07-10|

JP2015516085A|2015-06-04|

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KR20190128257A|2019-11-15|

AU2013258002B2|2016-08-11|

US20150284771A1|2015-10-08|

EP2846911B1|2020-09-30|

US9855553B2|2018-01-02|

BR112014027737A2|2017-06-27|

KR20190062620A|2019-06-05|

US20150284772A1|2015-10-08|

AU2016208331B2|2018-08-02|

US9968928B2|2018-05-15|

CN104582849B|2016-08-17|

ZA201600473B|2017-04-26|

JP6375291B2|2018-08-15|

US20150284773A1|2015-10-08|

CN104582849A|2015-04-29|

US20150283542A1|2015-10-08|

KR20150016313A|2015-02-11|

AU2016208331A1|2016-08-11|

ZA201500089B|2017-07-26|

KR20200143742A|2020-12-24|

US20130302809A1|2013-11-14|

CN105642378A|2016-06-08|

AU2013258002A1|2014-11-13|

WO2013167716A3|2014-01-09|

US10159972B2|2018-12-25|

US20150284774A1|2015-10-08|

EP2846911A2|2015-03-18|

KR102127231B1|2020-06-29|

WO2013167716A2|2013-11-14|

JP2017142271A|2017-08-17|

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法律状态:
2018-03-06| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

2018-03-13| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

2018-03-20| B06I| Publication of requirement cancelled [chapter 6.9 patent gazette]|Free format text: ANULADA A PUBLICACAO CODIGO 6.6.1 NA RPI NO 2462 DE 13/03/2018 POR TER SIDO INDEVIDA. |

2019-09-17| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

2020-09-29| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|

2021-02-23| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

2021-05-11| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 09/05/2013, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

申请号 | 申请日 | 专利标题

US201261644858P| true| 2012-05-09|2012-05-09|

US61/644858|2012-05-09|

US13/837,007|US9063121B2|2012-05-09|2013-03-15|Plurality of reaction chambers in a test cartridge|

US13/837007|2013-03-15|

PCT/EP2013/059692|WO2013167716A2|2012-05-09|2013-05-09|Plurality of reaction chambers in a test cartridge|

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