EP2624954B1 - Procédé de nettoyage d'une cavité microfluidique - Google Patents

Procédé de nettoyage d'une cavité microfluidique Download PDF

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Publication number
EP2624954B1
EP2624954B1 EP11764212.4A EP11764212A EP2624954B1 EP 2624954 B1 EP2624954 B1 EP 2624954B1 EP 11764212 A EP11764212 A EP 11764212A EP 2624954 B1 EP2624954 B1 EP 2624954B1
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EP
European Patent Office
Prior art keywords
cavity
liquid
gas
chamber
section
Prior art date
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EP11764212.4A
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German (de)
English (en)
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EP2624954A1 (fr
Inventor
Wolfgang Stoeters
Ying Yu
Silke Knoll
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Boehringer Ingelheim Microparts GmbH
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Boehringer Ingelheim Microparts GmbH
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Priority to EP11764212.4A priority Critical patent/EP2624954B1/fr
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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B08—CLEANING
    • B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
    • B08B3/00—Cleaning by methods involving the use or presence of liquid or steam
    • B08B3/04—Cleaning involving contact with liquid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L13/00—Cleaning or rinsing apparatus
    • B01L13/02—Cleaning or rinsing apparatus for receptacle or instruments
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/141—Preventing contamination, tampering
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/0318—Processes
    • Y10T137/0402—Cleaning, repairing, or assembling
    • Y10T137/0419—Fluid cleaning or flushing
    • Y10T137/0424—Liquid cleaning or flushing

Definitions

  • the invention relates to a microfluidic component: according to claim 1 for washing a cavity in the microfluidic component.
  • a basic task of this technology is the detection of biological molecules such as DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), proteins, polypeptides, etc.
  • biological molecules such as DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), proteins, polypeptides, etc.
  • DNA deoxyribonucleic acid
  • RNA ribonucleic acid
  • proteins proteins
  • polypeptides etc.
  • molecules in which genetic information is encoded are of particular interest. Their detection, for example in a blood sample from a patient, enables pathogens to be detected, which makes it easier for the doctor to make a diagnosis.
  • microfluidic components or microfluidic cartridges are increasingly used.
  • Microfluidic cartridges are used in a variety of ways in the form of single-use tests, with so-called lateral flow cartridges being used as a rule, the components of which have length and width measurements that are a few millimeters to centimeters.
  • an analysis fluid to be tested e.g. blood, urine or saliva
  • a cartridge equipped with a biosensor The sample is added to the cartridge before or after the cartridge is inserted into an analysis device.
  • the analyte is added in an opening in the cartridge, with the liquid being fed through microchannels to corresponding sample preparation chambers and sample examination chambers.
  • micro is intended to imply that the channels and / or cavities (chambers) have a dimension on the micrometer scale at least in one geometrical direction of extent, ie. H. the dimensions in at least one dimension are less than one millimeter.
  • microfluidic is understood to mean that a pressure-induced and / or capillary liquid flow occurs through and in the microchannels and / or microcavities.
  • microfluidic component is understood to mean a component which has at least such microchannels or microcavities for the storage and transport of liquids or fluids and gases.
  • microfluidic cartridge is understood to mean a device (possibly consisting of several microfluidic components) for the analysis of liquids.
  • microfluidic cartridges The detection of low concentrations of biological and inorganic substances in biological samples is often difficult.
  • the tests (assays) for this type of detection in microfluidic cartridges are usually associated with several process steps, which include the binding of a primary antibody, multiple washing steps, the binding of a second antibody, further washing steps, and (depending on the type of detection system ) If necessary, also include enzymatic and washing measures.
  • microfluidic cartridges The number of steps that are usually required when using such microfluidic cartridges to obtain a desired, specific signal are time-consuming and labor-intensive.
  • the need for modern microfluidic cartridges aims to shorten the measurement time between the application of the sample liquid and ultimately the appearance of the measured value. This time is lengthened by frequent washing steps, which, however, are mostly desirable and necessary in order to increase the sensitivity and reduce background values.
  • a liquid previously introduced into the chamber for example reaction liquid
  • a washing liquid introduced into the chamber immediately thereafter.
  • a quantity of washing liquid is passed through the chamber, the liquid to be washed from the chamber mixing with the washing liquid (diffusion) and being removed from the chamber with the washing liquid.
  • washing process in a microfluidic system usually takes place in the form of a laminar flow with no significant turbulent component, the liquid to be washed away is not sufficiently captured by the washing liquid, especially in the corner areas of chambers. This leaves residues in the chamber. This usually requires a multiple repetition of washing steps, which, however, is counterproductive in terms of achieving the shortest possible measurement time. This also drives demand Washing liquid and thus also the space required for reservoir and waste increase, which is undesirable in a volume-minimized microfluidic system.
  • the US 2008/0069739 A1 describes a software control for chemical process systems in which internal elements are automatically cleaned with solvents or drying gases, which means that devices can be reused.
  • One focus here is on flexible, re-configurable, reusable multi-purpose "lab-on-a-chip" systems that can be reconfigured using software.
  • Schematically controllable valve subsystems are discussed, by means of which reactants can be selected and directed to controlled reaction chambers, whereby the reaction chambers and transport lines can be cleaned of solvents and gases by pumping through them. For example, valve complexes with several inlets (e.g. for two sample liquids / reactants, liquid solvent and gas) and one outlet are presented.
  • valves in such a complex are, for example, two-way valves and are formed by microvalve structures.
  • selected reactants, cleaning solvents and gas for drying are released from the outlet of the valve complex.
  • gas can be used both for the final drying and for a "clearing" between the passage of a reactant and a flushing solvent.
  • the US 2007/0207063 A1 shows a device for controlling a fluid sequence running into (and out of) an integrated work area.
  • the device comprises a base plate on which a first fluid channel with an inlet and an outlet is arranged.
  • a plurality of valve elements are arranged in the channel in order to divide it into several segments.
  • the segments for their part are connected to injection tanks and the valve elements to venting tanks, these tanks being "open-type" in contrast to the duct and valves, ie having a side that is open at the top.
  • the individual working fluids are each injected into an inlet tank connected to the inlet and the injection tanks and flow by capillary force to the valve elements, which form a pressure barrier.
  • the injection tanks and the ventilation tanks are closed and the pressure barriers of the valves are overcome by pressure at the inlet tank or by negative pressure at the outlet, excess air trapped in the duct is pressed into the ventilation tanks and the flow of the fluid sequence in the duct into or through the work area is started.
  • the US 2004/0063217 A1 shows a fluidic miniature cassette made of plastic, which contains a reaction chamber with a multiplicity of immobilized species, a capillary channel and a pump structure with an external actuator.
  • Various reservoirs one for washing liquid, one for rinsing air, one for solution and one for an antibody conjugate
  • the pump structure so that the contents can be pumped from the connected reservoir into the reaction chamber.
  • the US 2008/038839 A1 shows a method of sequentially feeding liquid or gaseous fluids (reagents, solvents, reactants) to a chemical, biological or biochemical process or a reaction site (specific example: immunoassay method).
  • Rinsing liquids can be used intermittently to remove unwanted reactant residues or to prepare the reaction site.
  • Different fluids are stored in the same vessel, a third fluid separating a first from a second fluid.
  • a tube (or tube) is given, which sequentially contains a reagent, an air cushion, a rinsing liquid, a further air cushion and a second rinsing liquid, the respective fluids regionally depending on the size and material of the tube or are arranged one behind the other like a plug and the air cushions prevent the liquids from contacting one another.
  • a vessel with plug-like fluid sections is fluidically connected to a reaction site (for example a microfluidic immunoassay) and the fluids are pressed to the reaction site by means of a pump, syringe or other pressure source or drawn to the reaction site by means of negative pressure.
  • the invention is based on the object of providing a microfluidic component for washing a cavity in the microfluidic component.
  • a gas is supplied to the cavity before the washing liquid is supplied.
  • This “prewashing” makes it possible to significantly reduce the need for washing liquid to be subsequently supplied, which is necessary in order to bring about a desired reduction in the residual concentration of the liquid to be washed out in the cavity.
  • the need for washing liquid can therefore be reduced and, under certain circumstances, a reduction in the washing time or washing steps is also possible.
  • the gas is passed through the cavity in the form of a bubble, that is to say with a defined volume.
  • This enables the method to be implemented in a microfluidic component or a microfluidic cartridge even without an external gas connection, so that, for example, the gas bubble with a defined volume can be provided in a cavity of the microfluidic component itself.
  • the gas bubble has a volume which is smaller than the volume of the cavity.
  • the volume should still be large enough for efficient washing.
  • the gas bubble spreads continuously when it is introduced into the cavity to be washed by means of excess pressure and immediately becomes so wide that it touches the side walls of the cavity. It can thus displace a large part of the liquid to be washed out, located in the cavity, through an outlet opening to be provided in the cavity. Subsequent washing liquid in turn displaces the gas bubble in the direction of the outlet opening.
  • the gas bubble works like a barrier layer between the first liquid to be washed out and the subsequent washing liquid. Finally, the gas bubble is pressed completely out of the cavity by the washing liquid.
  • the washing liquid can easily absorb any remaining, small residual portion of liquid to be washed out by diffusion and carry it out of the cavity as it is transported further. Under certain circumstances, a single washing step is sufficient to achieve a desired residual concentration.
  • the invention would also like to provide a microfluidic component for carrying out the washing process.
  • the invention is based on a microfluidic component containing at least one first cavity which is filled with a liquid for washing at least one second cavity and means for establishing a fluidic connection between the at least one first and the at least one second cavity.
  • At least one further cavity which is filled with a gas, is now arranged between the first and the second cavity, viewed in the direction of flow of the liquid.
  • the washing liquid flows in the direction of the cavity containing the gas and, if necessary, only pushes the gas bubble into the cavity to be washed after releasing a corresponding fluidic connection (for example by means of corresponding valves) .
  • the at least one further cavity filled with gas has a volume which is smaller than the volume of the at least one second cavity to be washed. This is because it has been shown that a significantly smaller gas volume than the volume of the cavity to be washed is already sufficient to achieve the desired effect.
  • At least one valve is connected upstream and at least one valve is connected downstream of the gas-filled cavity. In this way, undesired gas or liquid flows can be excluded. It is very advantageous if the valves can be controlled. As a result, the flow of the liquid or gas can be controlled even better, which among other things can also reduce the risk of undesired bubble or foam formation. Control can preferably be carried out by means of electrical signals or pulses.
  • the cavity to be washed in such a way that it has a first section in the direction of flow in which its cross section continuously expands and a second section in which the cross section of the cavity tapers again continuously.
  • a section with a constant cross section is then expediently arranged between these sections with a changing cross section.
  • the first section should expediently be arranged in the area of the inlet opening and the second section in the area of the outlet opening, viewed in the direction of flow.
  • a controllable valve can expediently be provided for releasing or interrupting a fluidic connection.
  • Air is expediently used as the gas here, too, and the ambient air can be used as a further gas reservoir.
  • a section of a microfluidic component 1 can be seen.
  • the microfluidic functional group 90 comprises a first, preferably circular, chamber 10 filled with washing liquid F2.
  • a second, approximately rectangular chamber 20 can be seen, which is filled with a liquid F1.
  • the liquid F1 has triggered a specific detection reaction in the chamber 20. Some of the biomolecules contained in F1 are bound in the chamber 20. The remainder of F1 is now to be washed out of the chamber 20 with the washing liquid F2.
  • PCR polymerase chain reaction
  • air instead of air, other gases, for example nitrogen or the like, can of course also be used.
  • the chambers 10, 20 and 30 are fluidly connected to one another by means of microchannels 40, with a preferably electrically controllable valve 50a or 50b being provided between the chambers 10 and 30 or 30 and 20, with which the fluidic connection can be released or interrupted .
  • microchannel 80 is provided with which the fluidic connection from the chamber 20 to other, not shown microfluidic functional elements, e.g. a waste area can be produced.
  • the air-filled chamber 30 is connected to a microchannel 60.
  • the microchannel 60 establishes a fluid connection between the chamber 30 and a further gas reservoir.
  • the fluidic connection can be interrupted or released by means of a preferably electrically controllable valve 70.
  • the mentioned gas reservoir itself can be realized by one or more further cavities or chambers (not shown).
  • a film, preferably bonded to the component 1, for covering or sealing the aforementioned chambers and channels is not shown or numbered.
  • the component 1 itself is a plastic plate, which is preferably manufactured by injection molding.
  • the chamber 10 in the application example is now subjected to a pressure of approximately 0.4 bar to 0.8 bar. This is preferably done by means of suitable actuators of a microfluidic cartridge into which the component 1 is installed (not shown).
  • the valves 50a and 50b are activated, which thus release the fluidic connection between the chambers 10, 20 and 30.
  • the washing liquid F2 is now pressed in the flow direction S into the chamber 30 and also pushes the air L located in the chamber 30 in front of it in the flow direction S, in the direction of the chamber 20 first the air L is pressed in in the form of a defined air bubble.
  • a large part of the liquid F1 located in the chamber 20 is already displaced by the air L, so that the washing liquid F2 following the air bubble L only contains the remaining liquid F1 must remove from the chamber 20.
  • valve 50a is closed again for this purpose.
  • the valve 70 is then opened and a fluidic connection between the chamber 30 and the air reservoir mentioned is released.
  • the chamber 30 can be filled with air L again, for example by a pump.
  • valve 70 is closed, valve 50a is opened again and pressure is built up on chamber 10, as already described. If necessary, the size and shape of the chamber 10 can be varied as required.
  • Several chambers 10 are also conceivable, each of which is assigned to a washing step.
  • FIG. 2 Another embodiment 1 'of a microfluidic component according to the invention is now shown in principle.
  • the microfluidic component 1 ′ has a plurality of microfluidic functional groups 90 (as in FIG Fig. 1 described).
  • several further microchannels 80 are also provided. For example, they can be connected to a shared waste area.
  • This embodiment 1 'can serve, for example, to combine the reaction and washing steps to be carried out in the functional groups 90, to cascade them or to run several assays at the same time.
  • FIG. 3 two possible geometries of the chamber 20 to be washed are shown, although other geometries are of course also conceivable.
  • the chamber geometry according to Figure 3b represents according to the geometry Fig. 3a represents an improvement in terms of washing efficiency and can expediently be combined with the method according to the invention.
  • FIG. 3a it can be seen that the chamber 20 as in FIG Fig. 1 shown, is formed. It thus has an approximately rectangular plan in plan view, the inlet (microchannel 40) and the outlet (microchannel 80) also being recognizable. The chamber 20 is already penetrated by washing liquid F2 in the flow direction S here.
  • the diagonal arrangement of the inlet and outlet (40 and 80) in the direction of flow S can improve the washing efficiency somewhat, but significant residues of liquid F1 are unavoidable in the corner areas not assigned to the inlet or outlet, since this method of washing diagonally leaves out the opposite corners.
  • a chamber 20 ′ can be seen therein, which has an inlet opening 21 and an outlet opening 22 in the direction of flow S.
  • the chamber geometry is thereby optimized with regard to the flow course of the washing liquid F2. Nevertheless, certain residues of liquid F1 to be washed away in the corner areas are unavoidable here as well.
  • FIG. 4 now shows in detail how the process leads to a significant improvement in washing efficiency:
  • the chamber 20 ' is initially filled with the liquid F1 to be washed away ( Figure 4a ).
  • the air bubble L previously driven by the washing liquid F2 is first pressed into the chamber 20 ', specifically in the area of the inlet opening 21 ( Figure 4b ), until the entire air bubble L has been pushed into the chamber 20 '( Figure 4c ). It can be seen that the air bubble L spreads outward very quickly in the direction of the side walls of the chamber 20 ′ and forms contact areas 26 with them.
  • the washing liquid F2 following the air bubble L penetrates into the chamber 20 '( Figure 4d ). Due to the air bubble L or the contact areas 26, there is on the one hand a very good displacement of the liquid F1 in the direction of the outlet opening 22 and, on the other hand, a very good separation between the liquid F1 and the subsequent liquid F2.
  • the size of the air bubble L in no way has to correspond to the volume of the chamber 20 '. It should only be ensured that the defined amount of air L in the chamber 30 is so large that an air bubble L can be generated which is so large that they form the mentioned contact areas 26 with the chamber 20 'and thus quasi as a barrier layer between the liquid F1 and the subsequent liquid F2 can serve.
  • good results could be achieved with a chamber geometry of the chamber 20 'of approximately 32 mm 2 in plan, combined with a height of a few hundred ⁇ m at volume flows of approximately 4 ⁇ l / sec. Volume flows from 2 ⁇ l / sec to around 10 ⁇ l / sec could be achieved.
  • a pressure of approximately 0.4 bar has proven to be extremely useful as the initial pressure for triggering the washing process, although significantly higher pressures of up to approximately 0.8 bar have also been used.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Cleaning By Liquid Or Steam (AREA)

Claims (6)

  1. Composant (1, 1') microfluidique contenant au moins une première cavité (10), laquelle est remplie d'un liquide (F2) pour laver au moins une deuxième cavité (20, 20') et des moyens (40, 50a, 50b) pour établir une communication fluidique entre l'au moins une première (10) et l'au moins une deuxième cavité (20, 20'), dans lequel au moins une autre cavité (30), laquelle (30) est remplie d'un gaz (L), vue dans la direction d'écoulement (S) du liquide (F2), est disposée entre la première (10) et la deuxième cavité (20, 20'),
    dans lequel la cavité (20') à laver présente dans la direction d'écoulement (S) une première section (23), dans laquelle la section transversale de la cavité (20') s'élargit en continu, et une deuxième section (25), dans laquelle la section transversale de la cavité (20') se rétrécit en continu, et dans lequel une section (24) avec une section transversale constante est disposée entre les sections (23 et 25) avec une section transversale qui varie, et
    dans lequel l'au moins une autre cavité (30) remplie de gaz (L) présente un volume, lequel est inférieur au volume de l'au moins une deuxième cavité (20, 20') à laver,
    caractérisé en ce que la première cavité (10) peut être soumise à l'action d'une pression de sorte que le liquide (F2) pour laver la deuxième cavité (20, 20') s'écoule en direction de l'autre cavité (30) contenant le gaz et pousse le gaz en tant que bulle de gaz devant lui à l'intérieur de la cavité (20') à laver, dans lequel la bulle de gaz est si grande qu'elle peut former des zones de contact (26) avec les parois latérales de la cavité (20') à laver dans la section (24) avec une section transversale constante lorsqu'elle est poussée à l'intérieur de la cavité (20') à laver, et
    que respectivement au moins une soupape (50a) est disposée en amont de la cavité (30) remplie de gaz (L) ou au moins une soupape (50b) est disposée en aval de celle-ci, vues dans la direction d'écoulement (S) du liquide (F2), dans lequel les soupapes (50a, 50b) sont pilotables.
  2. Composant (1, 1') microfluidique selon la revendication 1, caractérisé en ce que la cavité (30) remplie de gaz (L) peut être mise en communication fluidique avec au moins un autre réservoir de gaz.
  3. Composant (1, 1') microfluidique selon la revendication 2, caractérisé en ce que la communication fluidique peut être établie par une soupape (70) pilotable.
  4. Composant (1, 1') microfluidique selon l'une quelconque des revendications 1 à 3, caractérisé en ce que le gaz (L) est de l'air.
  5. Composant (1, 1') microfluidique selon l'une quelconque des revendications 1 à 4, caractérisé en ce que le volume de la bulle de gaz est d'environ 40 % à 60 % du volume de la deuxième cavité (20, 20') à laver.
  6. Composant (1, 1') microfluidique selon l'une quelconque des revendications 1 à 5, caractérisé en ce qu'un liquide à éliminer par lavage se trouve dans la deuxième cavité (20, 20').
EP11764212.4A 2010-10-07 2011-10-04 Procédé de nettoyage d'une cavité microfluidique Active EP2624954B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP11764212.4A EP2624954B1 (fr) 2010-10-07 2011-10-04 Procédé de nettoyage d'une cavité microfluidique

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP10186833 2010-10-07
PCT/EP2011/067341 WO2012045754A1 (fr) 2010-10-07 2011-10-04 Procédé de lavage d'une cavité microfluidique
EP11764212.4A EP2624954B1 (fr) 2010-10-07 2011-10-04 Procédé de nettoyage d'une cavité microfluidique

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EP2624954A1 EP2624954A1 (fr) 2013-08-14
EP2624954B1 true EP2624954B1 (fr) 2020-08-26

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US (1) US9089883B2 (fr)
EP (1) EP2624954B1 (fr)
JP (1) JP6015659B2 (fr)
DK (1) DK2624954T3 (fr)
ES (1) ES2821373T3 (fr)
WO (1) WO2012045754A1 (fr)

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WO2017141362A1 (fr) * 2016-02-17 2017-08-24 株式会社 日立ハイテクノロジーズ Appareil d'analyse
US10046322B1 (en) 2018-03-22 2018-08-14 Talis Biomedical Corporation Reaction well for assay device
US11008627B2 (en) 2019-08-15 2021-05-18 Talis Biomedical Corporation Diagnostic system

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US9089883B2 (en) 2015-07-28
DK2624954T3 (da) 2020-11-23
EP2624954A1 (fr) 2013-08-14
JP2013539044A (ja) 2013-10-17
WO2012045754A1 (fr) 2012-04-12
JP6015659B2 (ja) 2016-10-26
US20140150890A1 (en) 2014-06-05

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