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WO2022263036A1 - Puce microfluidique - Google Patents

Puce microfluidique Download PDF

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Publication number
WO2022263036A1
WO2022263036A1 PCT/EP2022/058444 EP2022058444W WO2022263036A1 WO 2022263036 A1 WO2022263036 A1 WO 2022263036A1 EP 2022058444 W EP2022058444 W EP 2022058444W WO 2022263036 A1 WO2022263036 A1 WO 2022263036A1
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WO
WIPO (PCT)
Prior art keywords
sample
channel
layer
inlet
test sections
Prior art date
Application number
PCT/EP2022/058444
Other languages
German (de)
English (en)
Inventor
Max Sonnleitner
Original Assignee
Genspeed Biotech Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Genspeed Biotech Gmbh filed Critical Genspeed Biotech Gmbh
Publication of WO2022263036A1 publication Critical patent/WO2022263036A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • 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
    • 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
    • B01L3/502707—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 manufacture of the container or its components
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • 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
    • 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
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0325—Cells for testing reactions, e.g. containing reagents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0346—Capillary cells; Microcells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N2021/752—Devices comprising reaction zones
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7756—Sensor type
    • G01N2021/7763—Sample through flow
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7756—Sensor type
    • G01N2021/7766—Capillary fill
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • G01N21/763—Bioluminescence

Definitions

  • the present invention relates to a microfluidic chip for a measuring arrangement for the quantitative optical evaluation of a chemical reaction, comprising a sample carrier with a carrier layer and a
  • sample layer has an analysis side and, opposite this, a light exit side, and wherein a plurality of test sections are arranged spaced apart from one another in a longitudinal direction of the sample layer on the analysis side of the sample layer,
  • a first inlet is arranged on the carrier layer, which is connected to a first receiving reservoir by means of microfluidics via a first channel, and the sample layer is arranged with the analysis side on the carrier layer in such a way that a first row of test sections corresponds to the volume of the first channel is directed, according to the preamble of claim 1, and a method for the quantitative optical evaluation of a chemical reaction using a microfluidic chip according to the invention according to the preamble of claim 4.
  • Microfluidic chips per se are already known in the prior art.
  • AT 510750 B which is understood here as the closest prior art, discloses a measuring arrangement for the quantitative optical evaluation of a chemical reaction, comprising a microfluidic chip, which comprises an inlet for a sample as well as a channel and a reservoir.
  • the abandoned Sample is drawn from the inlet through the channel by capillary action and collected in the reservoir.
  • the microfluidic chip comprises a sample carrier with a carrier layer and a sample layer, the carrier layer being arranged on the sample layer and the sample layer having an analysis side and, opposite this, a light exit side.
  • test sections for the analytes to be examined are arranged at a distance from one another on the analysis side of the sample sheet in a longitudinal direction of the sample sheet and face the volumes of the microfluidic channels of the carrier sheet.
  • the sample thus passes through the spaced test sections one after the other as it passes through the channel, with the electromagnetic signal emanating from the relevant test section in the event of a chemical reaction, which is mostly in the visible wavelength range, serving as quantifiable evidence of a reactant in the sample.
  • the electromagnetic signal is measured by photodetectors of a measuring arrangement into which the microfluidic chip was inserted.
  • a line of photodiodes (also referred to as a photodiode array) running in the longitudinal direction of the sample position in the area of the test sections is used, which forms a largely uninterrupted, strip-shaped measurement area that enables a one-dimensional, spatially resolved measurement of the signal.
  • the distance between the test sections and the photodetectors is less than 700pm, so that at least 99.5% of the electromagnetic radiation emanating from a test section falls on a maximum of three photodetectors, so that the electromagnetic signal can be localized as precisely as possible .
  • Further designs of microfluidic chips were described in US 2005/106066 A1, WO 2012/080339 A1, US 2002/123059 A1, US 2019/039060 A1 and WO 2005/070546 A1.
  • the detector In order to accurately quantify reactants, the detector must be calibrated with a known amount of sample. For this purpose, the signal size of the detector for a reactant is compared with that of a standard for each quantitative evaluation. Ideally, the comparison is made under constant analysis conditions, but this is sometimes difficult to achieve. Especially with decreasing concentration of the reactants and the associated weakness of the electromagnetic signal, constant analysis conditions and the current status of the measuring system must be taken into account. On the other hand, there is an increasing need for automated measurement arrangements in order to obtain measurement results quickly and to accelerate sample throughput.
  • a microfluidic chip for a measuring arrangement for the quantitative optical evaluation of a chemical reaction comprising a sample carrier with a carrier layer and a sample layer,
  • the sample layer has an analysis side and, opposite this, a light exit side and wherein a plurality of test sections are arranged spaced apart from one another in a longitudinal direction of the sample layer on the analysis side of the sample layer,
  • a first inlet is arranged on the carrier layer, which is connected to a first receiving reservoir by means of microfluidics via a first channel, and the sample layer is arranged with the analysis side on the carrier layer in such a way that a first row of test sections corresponds to the volume of the first channel is facing.
  • the carrier layer has a second inlet which is separate from the first inlet and which is connected to a second receiving reservoir by means of microfluidics via a second channel, the first channel having an analysis channel section which bears against an analysis channel section of the second channel and running parallel to it and the first row of test sections faces the volume of the analysis channel section of the first channel and a second row of test sections faces the volume of the analysis channel section of the second channel.
  • the microfluidic chip according to the invention is suitable or provided for use in a suitable measuring arrangement for the quantitative optical evaluation of a chemical reaction.
  • a drop or part of a drop of a sample is applied to the first inlet, the sample material being brought to the first receiving reservoir by the capillary effect of the first channel connected to this first inlet.
  • the sample passes through the first row of spaced apart test sections on the sample layer, which have immobilized analytes, also referred to as scavenger molecules.
  • the microfluidic chip usually has a number of test sections, which serve to ensure that the sample introduced into the test system by means of the inlet is present when a specific reactant is present
  • Test section provided analytes react chemically by coupling the reactants present in the sample mixture to the capture molecules present on the test section.
  • Various parameters or biomarkers are generally understood as reactants.
  • the chemical reaction will preferably be a bio- or chemiluminescence reaction, which can be detected and evaluated by an appropriate measuring device.
  • a chemical reaction can also result in a color change or a change in transmission as a result of the reaction. It is also possible that electromagnetic radiation is emitted as a result of the chemical reaction, or that fluorescence properties are used for the measurement.
  • a corresponding standard can be applied to the second inlet.
  • the standard passes through the second row of test sections arranged at a distance from one another on the sample layer, which in this application are identical to those of the first row. Since, according to the invention, the first channel has an analysis channel section that is adjacent to an analysis channel section of the second channel and runs parallel to it, the reactions of the sample and those of the standard take place in close proximity and can be detected by the same detector under approximately identical conditions Analysis conditions are measured.
  • the comparative measurements using the standard can also be carried out very close in time to the analysis of the sample, which means that the analysis conditions can be assessed as constant and the current status of the measurement system is taken into account.
  • the quality of the quantitative measurement can be significantly improved because it is possible to have a sample and an associated standard among practically the same almost simultaneously measuring conditions.
  • the measurement of a sample taken together with a standard is of particular interest in the field of quality control in the chemical/pharmaceutical industry.
  • the limited shelf life of the reagents to be used must also be taken into account. Signal fluctuations due to limited durability and associated intensity losses in the intensity of the electromagnetic radiation can be reduced with a structure according to the invention and calculated out by knowing the concentration of the standard.
  • the microfluidic chip according to the invention can also be used to measure two different samples.
  • Different samples are understood to mean, for example, the samples from two different patients or two samples taken from one patient independently of one another or at different times.
  • no standard is applied to the second inlet, but a second sample.
  • the advantageous arrangement according to the invention with two inlets enables a faster throughput than in conventional test systems because two different samples can be tested in quick succession. This is particularly advantageous when the largest possible contingent of samples has to be analyzed in the shortest possible time. Also, unlike the prior art, it is possible to prevent contamination by applying the two samples through the same inlet.
  • test sections which extend along the first and the second channel either have the same sequence of immobilized capture molecules, which is recommended when using a standard or when measuring two different samples.
  • the test sections along the first channel can also have completely different immobilized capture molecules than the test sections along the second channel, which makes it possible to determine even more different parameters or biomarkers. However, this will only make sense if the same sample is applied to the first and second inlet.
  • the arrangement of the test sections is preferably such that the test sections of one row are spaced apart from one another when viewed in the longitudinal direction of the sample layer, and the test sections of the first and second rows are arranged in alignment when viewed in the transverse direction.
  • the microchip according to the invention can therefore also be used in particular in connection with the detection of viral diseases or allergies.
  • the analytes used i.e. capture molecules
  • the test sections can include immobilized capture molecules in the form of antibodies as analytes for generating a chemical reaction in order to be able to carry out antigen tests in particular.
  • the use of antibodies as scavenger molecules in the chip according to the invention enables a rapid determination of parameters with regard to antigens, the formation of which can be triggered by viral infections, among other things.
  • the advantageous arrangement according to the invention with at least two inlets enables faster throughput than in conventional test systems because testing of two different samples is possible. This is particularly advantageous when the largest possible contingent of samples has to be analyzed in the shortest possible time.
  • the channels usually have a length of 30-50 mm, a width of 1-4 mm and a height of 10-200 ⁇ m.
  • the channels or the carrier layer, which comprises the channels can be produced cost-effectively by injection molding of the carrier layer.
  • the channels usually have a very small volume, so that the consumption of sample chemicals or sample material is minimized, which in turn is advantageous for the efficiency and acceptance of the method.
  • a configuration of the channel with a length of 40 mm, a width of 2 mm and a height of 100 ⁇ m is preferred.
  • it must be ensured that the cross section of the channels is designed in such a way that a capillary effect of the channels is ensured.
  • the first channel also has an analysis channel section, which rests against an analysis channel section of the second channel and runs parallel to it.
  • "Adjacent" is understood here to mean that the analysis channel section of the first channel and the analysis channel section of the second channel must be at least so close together that they pass through the measuring range of the same photodetector, in particular the measuring range of the same photodiode line (also known as photodiode called array) as they are already known in the field of quantitative analysis of chemical reactions.
  • the analysis channel section of the first channel and the analysis channel section of the second channel are preferably as close together as possible, as far as this is technically possible while ensuring a structurally stable separation of the two channel sections.
  • the chip has 5 to 15 test sections in each analysis channel section.
  • 20 different parameters or analytes can be tested.
  • the use of 20 different parameters or biomarkers will be used and will be advantageous in particular when the microfluidic chip is used to detect the presence of specific allergies.
  • first inlet and the second inlet are arranged one behind the other, viewed in the longitudinal direction of the sample layer.
  • This measure enables compact structural designs in connection with the measuring arrangement provided for the chip according to the invention, which is basically known from AT 510750 B, as will be explained in more detail below.
  • the object is further achieved by a method for the quantitative optical evaluation of a chemical reaction using a microfluidic chip according to the invention with a measuring arrangement having an optical detector, comprising the steps that follow one another in terms of time
  • the microfluidic chip is placed in a suitable measuring device and a sample is applied to the first inlet and, depending on the requirement, the same or another sample or a standard is applied to the second inlet. Due to the capillary action of the channels, the samples are guided through the channels and, if the corresponding parameter/biomarker is present, this is bound by the corresponding analyte in the test section.
  • different reagents can also be added automatically by the measuring device, if necessary, which are required to achieve the desired chemical reactions or to terminate them.
  • a washing solution for example, after measuring a first sample in the first channel and before measuring a second sample in the second channel, it is possible to run a washing solution through the first channel in order to stop any chemical reaction in the test sections of the first row and thus eliminate interfering signals to avoid when measuring the second sample.
  • several Actuation elements may be present via which the reagents or the sample to be analyzed can be dispensed in the correct order and in the specified quantity.
  • a control module can be provided which, in operative connection with the actuating elements, automatically and in the correct order dispenses the samples and any reagents.
  • the control module can also be designed to evaluate the measured signals of the photodetector, to process them accordingly and to make them available at a communication connection.
  • the chemical reaction is a bio- or chemiluminescence reaction in order to be able to detect a positive result particularly well and subsequently to be able to prove it.
  • a microfluidic chip according to the invention has more than two inlets and associated channels and receiving reservoirs, for example three, four or five.
  • FIG. 1 shows a perspective view of a microfluidic chip according to the invention
  • FIG. 2 shows a perspective view of a carrier layer of a microfluidic chip according to the invention
  • 3 shows a view from above of a microfluidic chip according to the invention
  • the microfluidic chip 1 shows a perspective view of a microfluidic chip 1 according to the invention.
  • the microfluidic chip 1 preferably has a length of 75 mm and a width of 25 mm and a thickness of approximately 1.5 mm.
  • the chip 1 is preferably designed to be completely transparent. It goes without saying that it cannot be ruled out that the chip 1 has different dimensions and is designed to be partially non-transparent.
  • the microfluidic chip 1 comprises a sample carrier 2 with a carrier layer 3 and a sample layer 4 .
  • the carrier layer 3 is arranged on the sample layer 4 .
  • the sample layer 4 has an analysis side 5 and a light exit side 6 lying opposite thereto.
  • the analysis side 5 is required to be able to analyze an applied sample, while the light exit side 6 is required at the same time to be able to detect optical effects generated by the chemical reaction when chemical reactions occur, also using a suitable measuring device.
  • the microfluidic chip 1 is placed in a measurement arrangement (not shown in FIGS. 1-3).
  • the microfluidic chip 1 further comprises a first inlet 8 and a second inlet 9 separate from the first inlet 8.
  • the first inlet 8 is connected to a first channel 10, which has a volume, and to a first receiving reservoir 12.
  • the second inlet 9 is connected to a second channel 11 having a volume and a second receiving reservoir 13 .
  • the first and second channel 10 , 11 are formed by the sample layer 4 and the carrier layer 3 .
  • the inlets 8, 9 are located on the backing layer 3, being recesses in the backing layer 3 form.
  • the sample layer 4 has several test sections 7 on its analysis side 5, the test sections 7 being arranged in such a way that they face the volumes of the channels 10,11 so that the sample can come into contact with the capture molecules immobilized on the test sections 7.
  • the sample After being applied to the inlets 8 , 9 , the sample is conveyed through the channels 10 , 11 by the capillary effect, with possible parameters or biomarkers contained in the sample being able to react with the analytes of the test sections 7 .
  • the sample solution is then stored in the receiving reservoir 12,13.
  • Further required reagents can then be added via the inlets 8.9 at the time intervals required in each case in order to obtain desired bio- or chemiluminescent reactions or to terminate them. These reagents are then also stored in the receiving reservoir 12,13.
  • the volumes of the samples and the other reagents are of course selected or adjusted according to the volume of the receiving reservoirs 12,13.
  • the microfluidic chip according to the invention has test sections 7, in the present case 18 test sections 7, which are arranged spaced apart from one another along a longitudinal direction L of the sample layer 4.
  • test sections 7, in the present case 18 test sections 7, which are arranged spaced apart from one another along a longitudinal direction L of the sample layer 4.
  • antibodies are immobilized as so-called scavenger molecules on the test sections 7, with each test section having a different antibody as a scavenger molecule, so that it is possible to measure 18 different parameters in a sample.
  • the microfluidic chip 1 according to the embodiment of FIG. 1 further comprises a connecting element 14, whereby the microfluidic chip 1 can be detachably connected to a suitable measuring arrangement in order to measure the to allow microfluidic chip 1 or the samples applied therein.
  • Fig. 2 only shows the carrier layer 3 of the embodiment of the microfluidic chip 1 according to the invention as shown in FIG. 1.
  • the carrier layer 3 is part of the sample carrier 2.
  • the carrier layer 3 comprises the first and second inlet 8, 11 and the first and second receiving reservoirs 12,13, the channels 10,11 and the receiving reservoirs 12,13 being formed by the carrier layer 3.
  • the support sheet 3 and the sample sheet 4 sandwich the channels 10,11 with the test portions 7 of the sample sheet 4 located on the analysis side 6 of the sample sheet 4 in contact come with the volumes of channels 10,11.
  • FIG. 3 shows a plan view of the embodiment of the microfluidic chip according to the invention as shown in FIG. 1.
  • FIG. 3 shows the sample carrier 2 including the carrier layer 3 and the sample layer 4.
  • the carrier layer 3 is arranged on the sample layer 4 and forms the inlets 9 out. Furthermore, the two separate channels 10,11 can be seen.
  • the first channel 10 is connected to the first inlet 8 and opens into the first receiving reservoir 12.
  • the second channel 11 is connected to the second inlet 9 and opens into the second receiving reservoir 13.
  • FIG which the microfluidic chip 1 can be detachably connected to a suitable measuring device.
  • Fig. 3 also shows that the test sections 7 are arranged in two rows, namely in the form of a first row of test sections 7a along the analysis channel section of the first channel 10, and in the form of a second row of test sections 7b along the analysis channel section of the second channel 11.
  • the first row of test sections 7a is thereby facing the volume of the analysis channel section of the first channel 10 and the second row of test sections 7b the volume of the analysis channel section of the second channel 11.
  • the analysis channel section of the first channel 10 is adjacent to the analysis channel section of the second channel 11 and parallel running towards him.
  • the chip according to the invention can be used with a measurement arrangement as is known in principle from AT 510750 B.
  • the sample carrier 2 can be detachably arranged in a receiving device of the measuring arrangement, so that the light exit side 6 of the sample layer 4 is arranged facing a photodetector.
  • the photodetector is in turn arranged in a base body, with the photodetector being covered by a transparent cover layer.
  • the receiving device is designed, for example, in such a way that the sample carrier 2 is placed in a stationary part of the receiving device and is held fixed by a second, movable and/or foldable part of the receiving device.
  • the photodetector of the measuring arrangement is arranged in the base body in such a way that the test sections 7 are arranged along the channels 10, 11 with their light exit side above the photodetector. If the foldable part is pivoted into the measuring position, the interior space, in particular the sample carrier 2 and the photodetector, is sealed off light-tight from the environment by a sealing element.
  • the sample carrier 2 has the inlets 8, 9 into which the sample to be analyzed is released, which is automatically moved from the respective inlet 8, 9 to the receiving reservoir 12, 13 assigned to it due to the dimensioning of the channels 10, 11 and the microfluidics .
  • sample material is delivered at the inlet 8, 9, however, this is the case ensure that on the one hand the quantity to be dispensed is adhered to as precisely as possible and on the other hand that the order in which sample chemicals are dispensed is observed.
  • a feed device is provided in the foldable part, which contacts the respective inlet 8, 9 for liquid-tight dispensing of the sample material and also ensures the light-tight closure of the sample carrier 2 from the environment.
  • the sample carrier 2 can be placed in the receiving device of the measuring arrangement and the foldable part can then be closed without sample material or sample chemistry already being in the microfluidic, which ensures that no chemical reaction in the test sections 7 is triggered prematurely. Only when the sample carrier 2 is closed and after a light-tight seal has been reliably produced are the reagents or the sample to be analyzed released at the feed device and forwarded by it to the respective inlet 8 , 9 of the sample carrier 2 . Since additional reagents can also be required to carry out the sample analysis, the measuring arrangement can also have a dispensing device for reagents.
  • the dispensing device preferably comprises an actuating element and a removable depot which can be coupled and which is designed, for example, as a blister and has a number of closed containers in which reagents are arranged.
  • a blister as a depot
  • the seal of the reagent chamber is broken and the reagent is transferred to the respective inlet 8, 9 via the feed device.
  • several actuating elements can also be present, via which the reagents or the sample to be analyzed can be delivered in the correct order and in the specified quantity.
  • the depot can also specify an activation direction, for example by the depot being rotatably accommodated in the dispensing device and after each Reagent delivery is turned on manually or automatically.
  • a control module can be provided which, in operative connection with the actuating elements, dispenses the reagents automatically and in the correct sequence.
  • the control module can also be designed to evaluate the measured signals of the photodetector, to process them accordingly and to make them available at a communication connection.
  • This communication connection is preferably formed by a USB communication connection, although other wired or wireless communication connections from the field of data transmission are possible.
  • the invention overcoming the disadvantages of the prior art, thus provides a microfluidic chip with which it is possible to increase the accuracy of quantitative measurements and at the same time to speed up the measurements.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • General Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Plasma & Fusion (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Clinical Laboratory Science (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne une puce microfluidique (1) pour un dispositif de mesure destiné à l'évaluation quantitative et optique d'une réaction chimique, comprenant un support d'échantillon (2) avec une couche de support (3) et une couche d'échantillon (4), plusieurs sections de test (7) étant disposées à distance les unes des autres sur le côté d'analyse (5) de la couche d'échantillon (4) dans un sens longitudinal (L) de la couche d'échantillon (4), et une première entrée (8) étant disposée sur la couche de support (3), laquelle est reliée à un premier réservoir de réception (12) au moyen de la microfluidique par un premier canal (10) avec des sections de test (7). Selon l'invention, la couche de support (3) présente une seconde entrée (9) séparée de la première entrée (8), qui est reliée à un second réservoir de réception (13) par voie microfluidique par le biais d'un second canal (11) avec des sections de test (7), le premier canal (10) présentant une section de canal d'analyse qui est conçue de manière adjacente à une section de canal d'analyse du second canal (11) et qui s'étend parallèlement à celle-ci.
PCT/EP2022/058444 2021-06-15 2022-03-30 Puce microfluidique WO2022263036A1 (fr)

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ATA50481/2021A AT525192A1 (de) 2021-06-15 2021-06-15 Mikrofluidischer chip

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EP2523004A1 (fr) * 2004-01-26 2012-11-14 President and Fellows of Harvard College Procédé pour déterminer un analyte et test immunologique
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US20170197212A1 (en) * 2014-06-30 2017-07-13 Siemens Healthcare Diagnostics Inc. Microfluidic test cartridge with no active fluid control
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Publication number Priority date Publication date Assignee Title
US20020123059A1 (en) 2001-03-05 2002-09-05 Ho Winston Z. Chemiluminescence-based microfluidic biochip
US20050106066A1 (en) 2003-01-14 2005-05-19 Micronics, Inc. Microfluidic devices for fluid manipulation and analysis
WO2005070546A1 (fr) 2004-01-12 2005-08-04 Applera Corporation Procede et dispositif servant a detecter des sequences d'acides nucleiques
EP2523004A1 (fr) * 2004-01-26 2012-11-14 President and Fellows of Harvard College Procédé pour déterminer un analyte et test immunologique
WO2012080339A1 (fr) 2010-12-14 2012-06-21 Greiner Bio - One Gmbh Système de mesure pour l'évaluation optique quantitative d'une réaction chimique
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US20180356393A1 (en) * 2017-06-09 2018-12-13 Optimum Imaging Diagnostics LLC Novel Universal Testing System for Quantitative Analysis
US20190039060A1 (en) 2017-08-03 2019-02-07 The Board Of Trustees Of The Leland Stanford Junior University Massive microfluidics for multiplexed counting

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