WO2015106932A1 - Procédé pour faire fonctionner une puce microfluidique et puce microfluidique - Google Patents

Procédé pour faire fonctionner une puce microfluidique et puce microfluidique Download PDF

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Publication number
WO2015106932A1
WO2015106932A1 PCT/EP2014/078971 EP2014078971W WO2015106932A1 WO 2015106932 A1 WO2015106932 A1 WO 2015106932A1 EP 2014078971 W EP2014078971 W EP 2014078971W WO 2015106932 A1 WO2015106932 A1 WO 2015106932A1
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Prior art keywords
reaction
chamber
array
reactants
array chamber
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Application number
PCT/EP2014/078971
Other languages
German (de)
English (en)
Inventor
Jochen Hoffmann
Original Assignee
Robert Bosch Gmbh
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Filing date
Publication date
Application filed by Robert Bosch Gmbh filed Critical Robert Bosch Gmbh
Publication of WO2015106932A1 publication Critical patent/WO2015106932A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
    • 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
    • B01L3/50273—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 the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers

Definitions

  • the present invention relates to a method for operating a microfluidic chip and to a microfluidic chip.
  • Microfluidic chips can be used to reproducibly run standardized processes using fluids.
  • a sample can be examined for ingredients in a microfluidic chip.
  • biological properties of the sample can be detected.
  • reactions between reactants occur within one or more
  • Reaction chambers off.
  • a sample can be taken out of the reaction chamber and in a
  • Analysis chamber are analyzed. If the reaction produces a detectable result within the reaction chamber, the analysis can also be done directly inside the reaction chamber. Then a sampling is unnecessary.
  • the unconsumed reactants can be removed from the reaction chamber during the analysis and in another
  • Reaction chamber be stored.
  • a method for operating a microfluidic chip is presented, wherein the microfluidic chip has a fluidically coherent
  • Reaction space comprises at least one reaction chamber and an array chamber containing a microarray for detecting reaction products of the reaction, the method comprising the following steps:
  • a microfluidic chip having the following features: a reaction space for a reaction, which is subdivided into an array chamber and at least one reaction chamber, wherein the array chamber and the
  • Reaction chambers are fluidically interconnected and in the
  • Array chamber a microarray for detecting reaction products of the reaction is arranged, wherein the array chamber has a transparent wall for reading the microarray; and means for displacing configured to displace the reaction reactants from the array chamber in response to a displacement signal.
  • a microfluidic chip can be understood as meaning a microfluidic system. Similarly, a microfluidic chip may be part of a
  • a reaction space may consist of several chambers and intermediate channels. Valves may be arranged in the channels.
  • a reaction chamber may be a single cavity for carrying out the reaction.
  • An array chamber may be a single cavity for carrying out the reaction.
  • Different partial reactions of the reaction can take place on a microarray.
  • the microarray may comprise a matrix of different reactants of partial reactions of the reaction.
  • the reactants of the partial reactions may be fixed to the microarray.
  • reaction products of the partial reactions can be fixed to the microarray.
  • the reaction products may be detectable through the transparent wall.
  • the array chamber may have approximately the same volume as the reaction chamber.
  • the reaction chamber and the array chamber can be connected to each other via a channel.
  • a means for displacing may be adapted to a pressure gradient between the
  • the chip may include a means for rearrangement, which is adapted, in response to a Umlagerungssignal the reactants from the
  • the method can be a
  • Step of rearranging the reactants within the reaction space wherein the reactants are rearranged in particular between the reaction chamber and the array chamber to perform the reaction.
  • the reactants can be reduced by decreasing a volume of
  • Reaction chamber to be relocated. By displacing and rearranging the reactants are moved within the reaction space. The reactants are mixed so that unreacted reactants can react with each other.
  • the means for displacing may be pneumatically actuated
  • the Device for repositioning may be formed as a pneumatically actuated displacer within the reaction chamber.
  • the displacement body can in particular by a flexible membrane
  • the reactants can be displaced from the array chamber by reducing a volume of the array chamber.
  • the reactants can be displaced from the reaction chamber by reducing a volume of the reaction chamber.
  • the reactants can be squeezed out of the respective chamber, if in the other chamber, a lower internal pressure prevails. The reactants then flow along the pressure gradient.
  • the chip may include means for purging the array chamber using a purging fluid.
  • the microarray can be prepared using the
  • Rinsing fluids are rinsed. In this case, for example, by a
  • volume flow of the flushing fluid through the array chamber unconsumed reactants are flushed out of the microarray.
  • the reactants can be displaced from the array chamber by a flushing fluid pressed into the array chamber.
  • the purge fluid may purge unconsumed reactants from the microarray that would corrupt readout of the microarray.
  • the flushing fluid may in particular be a liquid.
  • the flushing fluid can be used as a single
  • the flushing fluid may be stored in sufficient quantity on the chip.
  • the means for purging may include a pumping chamber to build up sufficient purging pressure in the array chamber.
  • the reaction space can at least two reaction chambers and the
  • the reactants can be displaced from the array chamber into the reaction chamber.
  • the analysis can be carried out after the displacement when at least a major part of the reactants has been displaced from the array chamber into the reaction chamber.
  • the analysis can also be done if a small residual amount of the reactants remain in the array chamber.
  • the method may include a further step of displacing, in which the injected flushing fluid by reducing a volume of the
  • Array chamber is displaced from the array chamber.
  • the array chamber can therefore first be reduced in size in order to displace the reactants into the at least one reaction chamber. Then, the array chamber may be flushed with the rinse fluid to rinse out the remainder of the reactants. In this case, the volume of the array chamber can be increased again.
  • the volume of the array chamber can be reduced again to squeeze out the flushing fluid from the array chamber.
  • the microarray can be read out particularly well because components of the
  • Reactants that can reduce the quality of reading are removed from the array chamber by the rinse step.
  • the steps of rearrangement and analysis may be repeated, particularly until the reaction has reached a predetermined termination criterion.
  • By repeating the reaction in intermediate stages can be analyzed.
  • a polymerase chain reaction can be carried out.
  • the at least one reaction chamber and the array chamber can be kept at different temperature levels.
  • the reactants can each in the step of repositioning for predetermined residence times in the
  • Reaction chamber and the array chamber are held. Each of its own chamber for a single temperature level, the reaction can be accelerated because a time for repeated heating and / or cooling of the entire reaction space can be omitted.
  • the microarray may be passed through the wall of the substrate using a transmitted light method or an incident light method
  • Incident light methods are simple and fast analysis methods that are simple and fast analysis methods that are
  • the approach presented here also provides a control unit which is designed to implement the steps of a variant of a method presented here
  • a control device can be understood as meaning an electrical device which processes sensor signals and outputs control and / or data signals in dependence thereon.
  • the control unit may have an interface, which may be formed in hardware and / or software. In a hardware training, the interfaces may for example be part of a so-called system ASICs, the various functions of the
  • Control unit includes.
  • the interfaces are their own integrated circuits or at least partially consist of discrete components.
  • the interfaces may be software modules that are present, for example, on a microcontroller in addition to other software modules.
  • An advantage is also a computer program product with program code, which on a machine-readable carrier such as a semiconductor memory, a
  • Hard disk space or an optical storage can be stored and used to carry out the method according to one of the embodiments described above, when the program product is executed on a computer or a device.
  • Fig. 1 is a sectional view of a microfluidic chip in a first
  • FIG. 2 is a sectional view of a microfluidic chip in a second state according to an embodiment of the present invention
  • FIG. 3 is a flowchart of a method for operating a
  • FIG. 4 shows a representation of a microfluidic chip with a device for the
  • FIG. 1 shows a sectional view of a microfluidic chip 100 in a first state according to an embodiment of the present invention.
  • the microfluidic chip 100 has a reaction space 102 and a
  • the reaction space 102 is provided to perform a reaction therein.
  • the reaction space 102 is subdivided into an array chamber 106 and at least one reaction chamber 108.
  • the array chamber 106 and the reaction chamber 108 are fluidly connected to each other via a channel.
  • Arranged in the array chamber 106 is a microarray 110 for detecting reaction products of the reaction.
  • the array chamber 106 has a transparent wall 1 12 for reading out the microarray 110.
  • the transparent wall 1 12 can be referred to as a viewing window 1 12.
  • the displacement means 104 is configured to displace the reactants 1 14 of the reaction from the array chamber 106 in response to a displacement signal.
  • the chip has a repositioning device 16, which is designed to relocate the reactants 1 14 from the reaction chamber 108 into the array chamber 106 in response to a repositioning signal.
  • the reactants 114 can be moved back and forth between the array chamber 106 and the reaction chamber.
  • the displacing means 104 and / or the reloading means 16 are pneumatically actuatable
  • Displacement body 104, 1 16 formed within the array chamber 106 and / or the reaction chamber 108.
  • a volume of the array chamber 106 and / or the reaction chamber 108 can be reduced.
  • Reaction chamber 108 is pushed out.
  • the displacer 104, 16 is formed by a flexible membrane. On one side of the membrane, the array chamber 106 and / or the reaction chamber 108 is arranged. On the other side a fillable and emptied cavity is arranged. A higher pressure in the cavity than in the array chamber 106 and / or the reaction chamber 108 directs the membrane in the direction of the array chamber 106 and / or the
  • Reaction chamber 108 and reduces the volume of the array chamber 106 and / or the reaction chamber 108th
  • the membrane 104 is black to build the chip 100 by laser welding. With a black membrane 104, the microarray 1 10 can be read from below. But it can also be used a transparent membrane.
  • means 104 for displacing is formed as a transparent, deflectable membrane 104.
  • Microarrays 110 can therefore also be read out through the membrane 104.
  • the microfluidic system 100 includes a
  • Reaction chamber 106 Reaction chamber 106, an auxiliary chamber 108 and a device 104 for displacing.
  • a microarray 1 10 is arranged in the reaction chamber 106.
  • the microarray 1 10 is located on a transparent wall 1 12 of
  • the Reaction chamber 106 on.
  • the auxiliary chamber 108 is fluidic with the
  • Reaction chamber 106 connected.
  • the displacing means 104 is configured to relocate a content 114 of the reaction chamber 106 into the auxiliary chamber 108 in response to a displacement signal.
  • the device 104 In the first state, the device 104 is disabled for displacement.
  • the reaction chamber 106 In the reaction chamber 106, at least one reactant 1 14 of a reaction to be carried out is arranged.
  • means 104 for displacing is disposed in reaction chamber 106.
  • the device 104 for displacing is designed as a pneumatically actuable displacement body 104, 1 16.
  • the displacer 104, 16 is formed by a flexible membrane 104, 16.
  • the membrane 104, 16 separates the reaction chamber 106 from an air chamber which can be filled and emptied via an air duct 118.
  • the system 100 includes a microfluidic channel 120 in the reaction chamber 106.
  • the channel 120 can be shut off by a valve 122.
  • the system 100 has another one
  • microfluidic channel 124 from the auxiliary chamber 108.
  • the further channel 124 can be shut off by a further valve 126.
  • FIG. 1 shows a section through an embodiment of the present invention.
  • a layer structure of the system 100 consists of a first polymer substrate 128 with perforations 1 18 on the underside of which the deflectable polymer membranes 104, 16 are mounted. Plan parallel to this structure is a second polymer substrate 130, the
  • PCR reaction chamber 106 Polymerase chain reaction (PCR) reaction chamber 106 with a
  • Deoxyribonucleic acid (DNA) microarray 10 and an auxiliary chamber 108 On the microarray 1 10 different oligonucleotides are immobilized in the form of individual spots.
  • a microfluidic channel 120, 124 is connected to the chambers 106, 108 in each case. Both channels 120, 124 each have a controllable valve 122, 126 to keep the chambers 106, 108 filled with a reaction mix for an amplification reaction and sealed during the reaction.
  • Amplification reaction such as a polymerase chain reaction, PCR
  • certain DNA motifs of a template DNA are amplified and simultaneously fluorescently labeled. These amplification products can be combined with the
  • Oligonucleotides of the microarray 1 10 interact during the amplification reaction and are thus bonded to the surface of the array 1 10.
  • the Fluorescence signals can be measured during the course of the reaction by the reaction volume 1 14 of the reaction chamber 106 is displaced by deflection of the polymer membrane 104 in the auxiliary chamber 108.
  • reaction volume / reaction solution 1 14 is first displaced fluidically with a solution before the mechanical displacement and then expressed only.
  • reaction space 102 is limited to an array chamber 106 that is used to analyze the microarray 110 through the array
  • Rinsing solution is rinsed.
  • the reaction space 102 is limited to two chambers 106, 108. In this case, the reaction volume is displaced into the reaction chamber 108 and then rinsed the microarray 1 10 for analyzing.
  • reaction liquid is removed from the chamber 106 containing the array 110. This happens, for example, by displacement by means of deflection of a membrane or direct displacement with a washing solution. Thereafter, the located above the array 1 10
  • Displaced washing solution and the microarray 1 10 read by optical methods.
  • the approach presented here has the advantage that the molecules in the reaction solution, such as fluorophores, which would interfere with the readout of the microarray 10, are removed from the microarray 10 not only mechanically but also fluidically by the displacement solution. This results in lower background fluorescence, thereby increasing the sensitivity of the microarray-based detection system 100.
  • the polymer substrate 128, 130 is made of a thermoplastic, such as polycarbonate (PC), polypropylene (PP), polyethylene (PE),
  • the polymer membrane 104, 16 can be made of an elastomer or a thermoplastic elastomer, such as thermoplastic urethane-based TPU, styrene block copolymer TPS, Polyurethane PU, thermoplastics, hot-melt adhesive films, sealing films for microtiter plates, latex.
  • a thermoplastic elastomer such as thermoplastic urethane-based TPU, styrene block copolymer TPS, Polyurethane PU, thermoplastics, hot-melt adhesive films, sealing films for microtiter plates, latex.
  • the polymer substrate 128, 130 has a thickness of 0.5 millimeter to 5 millimeters.
  • the channels 120, 124 have channel diameters of 10 microns to 3 millimeters.
  • the polymer membrane 104, 16 has a thickness of 5 microns to 500 microns.
  • Polymer substrates 128, 130 each have a volume of 1 cubic millimeter to 1000 cubic millimeters.
  • the polymer membrane 104, 1 16 is deflected at a pressure of 0.2 bar to 2 bar.
  • FIG. 2 shows a sectional view of a microfluidic chip 100 in a second state according to an embodiment of the present invention.
  • the microfluidic chip 100 corresponds to the microfluidic system in FIG. 1.
  • the device 104 is activated for displacement.
  • the flexible membrane 104, 1 16 is characterized by an overpressure in the air chamber in the
  • Array chamber 106 is pressed. As a result, at least the major part of the contents 1 14 of the array chamber 106 has been pressed into the auxiliary chamber 108. The reactant is now the content 200 of the auxiliary chamber 108. In the second state, the microarray 110 is analyzed by a detector 202.
  • the system 100 includes means 1 16 for restoring.
  • the means 1 16 for restoring is adapted to the content 200 of the auxiliary chamber 108 adoptedlieagern in the reaction chamber 106 in response to a wastewatershedssignal.
  • the device 16 is disposed in the auxiliary chamber 108 for storage.
  • the device 1 16 for restoring is formed as a further pneumatically actuated displacement body 1 16.
  • the further displacement body 1 16 is formed by the flexible membrane 1 16.
  • the membrane 1 16 separates the auxiliary chamber 108 from an air chamber which can be filled and emptied via an air duct.
  • the polymer membrane 1 16 is actuated and the reaction volume 200 is transferred again into the reaction chamber 106.
  • FIG. 3 shows a flow chart of a method 300 for operating a microfluidic chip according to an embodiment of the present invention.
  • the method 300 presented here can be implemented on a microfluidic chip, as shown in FIGS. 1 and 2.
  • the microfluidic chip has a fluidic
  • the reaction space comprises at least one reaction chamber and an array chamber containing a microarray for detecting reaction products of the reaction.
  • the method 300 includes a step 302 of displacing and a step 304 of analyzing.
  • step 302 of the suppression the
  • Reactants displaced from the array chamber can also be displaced into a waste chamber if they are no longer usable and / or should not be used further.
  • the microarray is analyzed by a wall of the array chamber.
  • step 302 of the displacement the reactants are displaced from the array chamber into the reaction chamber.
  • the analyzing 304 occurs after displacement when at least a majority of the reactants have been displaced from the array chamber into the reaction chamber. The reactants remain in the system and can therefore be used further.
  • the reactants are displaced from the array chamber by reducing a volume of the array chamber. By reducing an internal pressure in the array chamber increases. The reactants flow out of the array chamber in the direction of lower pressure.
  • the step of suppression in the step of suppression, the
  • Reactants displaced from the array chamber by a flushing fluid pressed into the array chamber Reactants displaced from the array chamber by a flushing fluid pressed into the array chamber.
  • the flushing fluid is forced into the array chamber at an elevated pressure.
  • the flushing fluid replaces the reactants.
  • the microarray is selected in step 302 of FIG.
  • the flushing fluid flows through the drainage channel from the array chamber.
  • the method 300 includes a step 308 of rearranging the reactants within the reaction space.
  • the reactants are in particular between the reaction chamber and the
  • Analyzing 304 the reactants are rearranged into the array chamber to continue the reaction.
  • Reactants rearranged by reducing a volume of the reaction chamber can be done analogously to displace.
  • the reactants are displaced from the reaction chamber in step 308 of the rearrangement by rinsing fluid introduced into the reaction chamber.
  • the repositioning and analyzing steps 308, 304 are repeated, particularly until the reaction has reached a predetermined abort criterion.
  • a polymerase chain reaction is performed as a reaction.
  • the at least one reaction chamber and the array chamber are kept at different temperature levels.
  • Reactants are held in the reaction chamber and the array chamber for predetermined residence times, respectively, in step 308 of the rearrangement.
  • the microfluidic system comprises at least one reaction chamber, an auxiliary chamber and a device for displacing.
  • a microarray is arranged in the reaction chamber.
  • the method comprises a step of initiating, a step of displacing, and a step of analyzing.
  • the step of introducing at least one reactant of a reaction is introduced into the reaction chamber to stop the reaction at the
  • Microarray to start In the step of displacing at least a major part of the reactant from the reaction chamber into the auxiliary chamber of the
  • the microarray is analyzed through a wall of the reaction chamber.
  • the method includes a step of backing up. At this time, the reactant is stored in the reaction chamber after the step of analyzing to continue the reaction.
  • the steps are repeated until the reaction has reached a predetermined termination criterion.
  • the termination criterion is achieved when the reactants reach a predetermined concentration of waste.
  • the abort criterion is reached when a predetermined result on the microarray is read in step 304 of the analysis.
  • a predetermined reaction time is awaited between the initiating step and the displacing step.
  • the predetermined reaction time is awaited between the step of storing back and the step of displacing. By waiting for the reaction time, the reaction in predetermined
  • the reactant in the initiating step, is introduced to at least one further reactant bound to the microarray.
  • the microarray in the step of analyzing, is read out through the wall of the reaction chamber using a transmitted light method or an incident light method.
  • the approach presented here introduces a method and an apparatus for the real-time readout of microarrays in a microfluidic system.
  • LoC Lab on Chip
  • Labeled fluorescent molecules These molecules then bind to specific binding sites or spots on the microarray and can be detected there, for example, fluorometrically.
  • Fluorescence signals may be measured in step 306 of analyzing, for example, by transmitted or reflected light methods.
  • the fluorescence signals of the solution in the fluorophore also referred to as background fluorescence, in a microarray experiment in
  • SPR Surface Plasmon Resonance Spectroscopy
  • Fluorescence signals in a microfluidic LoC system containing unbound fluorophores in the reaction solution Fluorescence signals in a microfluidic LoC system containing unbound fluorophores in the reaction solution.
  • Reaction chamber a DNA microarray and an elastic membrane are located.
  • the reaction liquid located above the array is displaced by deflection of the membrane into an auxiliary chamber. This removes the fluorophores in the liquid from the microarray.
  • the microarray can thus be read out with simple optical methods.
  • the method presented here allows
  • FIG. 4 shows a representation of a microfluidic chip 100 having a
  • the chip 100 has as
  • Reaction space 102 an array chamber 106, a first reaction chamber 108 and a second reaction chamber 402 on.
  • the chambers 106, 108, 402 are arranged in a row and fluidly coupled together by fluid channels 404.
  • controllable valves for closing or opening the channels 404 are arranged between the chambers 106, 108, 402.
  • the purging device 400 includes a rinse fluid storage chamber 406 and a pumping chamber 408.
  • the storage chamber 406 the rinse fluid storage chamber 406 and a pumping chamber 408.
  • the chambers 406, 408 of the device 400 for rinsing and the array chamber 106 are arranged in the illustrated example in a row and fluidly connected to each other by further fluid channels 404. Between the storage chamber 406 and the pumping chamber 408, a first controllable valve 410 for closing or opening the channel 404 is arranged. Between the pumping chamber 408 and the array chamber 106 is a second controllable valve 412 for closing or
  • a third controllable valve 414 for closing or opening the channel 404 is arranged on an opposite side of the array chamber 106 for flushing.
  • the chip 100 includes means 400 for
  • the means 400 for purging is adapted to the flushing fluid in the
  • Array chamber 106 initiate.
  • the flushing fluid can be introduced if the reactants are still arranged in the array chamber 106.
  • the flushing fluid may be introduced into the array chamber 106 when the reactants have already been displaced from the array chamber 106.
  • the flushing fluid may be removed after it has been introduced from the array chamber 106.
  • the reaction space 102 has at least two reaction chambers 108, 402 and the array chamber 106. In one embodiment, the reaction space 102 is split into three chambers 106, 108, 402. As a result, no additional auxiliary chamber is necessary because the reaction volume can be displaced into one of the two other reaction chambers 108, 402.
  • the reaction volume for performing a PCR between the three chambers 106, 108, 402 is pushed back and forth. Whenever the reaction volume is in the array chamber 106, here the lowermost chamber, the second valve 412 and the third valve 414 are closed. When the reaction volume is displaced from the chamber 106 in which the microarray 110 is located, in this embodiment the lowest, by means of the pump 408, which here consists of the pumping chamber 408 and the first valve 410 and the second valve 412, a
  • the reaction space 102 is on three chambers 106,
  • reaction chambers 108, 402 divided.
  • the reaction proceeds in the reaction chambers 108, 402 while the microarray 110 in the array chamber 106 is purged and analyzed.
  • the embodiments described and shown in the figures are chosen only by way of example. Different embodiments may be combined together or in relation to individual features. Also, an embodiment can be supplemented by features of another embodiment.
  • an exemplary embodiment includes a "and / or" link between a first feature and a second feature, this is to be read such that the
  • Embodiment according to an embodiment both the first feature as well as the second feature and according to another embodiment, either only the first feature or only the second feature.

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Abstract

L'invention concerne un procédé (300) pour faire fonctionner une puce microfluidique (100), qui comporte un espace de réaction (102) en communication fluidique destiné à des réactifs (114) intervenant dans une réaction. L'espace de réaction (102) comprend au moins une chambre à microréseau (106), renfermant un microréseau (110) permettant l'identification des produits de la réaction, et une chambre de réaction (108). Le procédé (300) comprend une étape (302) de déplacement et une étape (304) d'analyse. Lors de l'étape (302) de déplacement, les réactifs (114) sont déplacés de la chambre à microréseau (106). Lors de l'étape (304) d'analyse, le microréseau (110) est analysé à travers une paroi (112) de la chambre à microréseau (106).
PCT/EP2014/078971 2014-01-14 2014-12-22 Procédé pour faire fonctionner une puce microfluidique et puce microfluidique WO2015106932A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102014200483.7 2014-01-14
DE102014200483.7A DE102014200483B4 (de) 2014-01-14 2014-01-14 Verfahren zum Betreiben eines mikrofluidischen Chips und mikrofluidischer Chip

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