EP4363607A1 - Procédé de mise en place d'une cohorte de compartiment d'un échantillon microfluidique, en particulier biologique - Google Patents

Procédé de mise en place d'une cohorte de compartiment d'un échantillon microfluidique, en particulier biologique

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Publication number
EP4363607A1
EP4363607A1 EP22732972.9A EP22732972A EP4363607A1 EP 4363607 A1 EP4363607 A1 EP 4363607A1 EP 22732972 A EP22732972 A EP 22732972A EP 4363607 A1 EP4363607 A1 EP 4363607A1
Authority
EP
European Patent Office
Prior art keywords
partition
partitions
uncertainty
measure
sample
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
EP22732972.9A
Other languages
German (de)
English (en)
Inventor
Manuel Loskyll
Daniel Sebastian Podbiel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Robert Bosch GmbH
Original Assignee
Robert Bosch 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 Robert Bosch GmbH filed Critical Robert Bosch GmbH
Publication of EP4363607A1 publication Critical patent/EP4363607A1/fr
Pending legal-status Critical Current

Links

Classifications

    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6851—Quantitative amplification
    • 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
    • B01L2200/12—Specific details about manufacturing devices
    • 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
    • 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
    • B01L2300/0893—Geometry, shape and general structure having a very large number of wells, microfabricated wells

Definitions

  • Microfluidic analysis systems allow automated, reliable, fast, compact and cost-effective processing of patient samples for medical diagnostics.
  • complex molecular diagnostic test sequences can be carried out on a lab-on-chip cartridge.
  • each of these partitions an end point amplification of the specific DNA target takes place independently of one another, which results in an increase in fluorescence if at least one target was located in the respective partition at the beginning of the amplification reaction.
  • the target concentration in the analyzed sample can be deduced by using Poisson statistics.
  • the general recommendation is to reduce the partitioning error by using the largest possible number of partitions in order to increase the dynamic measuring range of the analysis system.
  • the subsampling error is generally negligible and, according to the literature, only plays a significant role if the proportion of the volume analyzed is below 30% or 50%, depending on the application (Jacobs et al., BMC Bioinformatics 15, 283 (2014), https https://doi.org/10.1186/1471-2105-15-283).
  • the advantage of the highest possible number of partitions is emphasized.
  • the invention relates to a method for designing a partitioning of a microfluidic sample into partitions on a partition surface.
  • the invention also relates to a method for partitioning, dividing or aliquoting such a sample into partitions or subsets of the sample.
  • the method can be used in particular for determining a concentration of an analyte in the sample, in particular in combination with a digital PCR in the case of nucleic acid sections as analytes.
  • a partitioning of a sample can thus be understood as a division or aliquoting of a sample into sample parts, in a preferred embodiment an actual placement of the sample in the form of sample parts on the partition area.
  • the sample can in particular be a biological sample, for example comprising a body fluid such as blood, urine, sputum or a smear.
  • the sample can also contain other substances, for example in the form of a mixture of the body fluid with a transport medium such as eNATTM or UTMTM.
  • the analyte, also called target can be a molecule in the sample, in particular a nucleic acid segment, for example part of a DNA or RNA of a pathogen or a specific body cell, in particular a tumor cell.
  • the analyte can also be cells, in particular protozoa or animal or human body cells, for example one or more of what are known as circulating tumor cells (CTC for short).
  • CTC circulating tumor cells
  • the method according to the invention can thus be part of or a prerequisite for a partition-based quantitative detection method for analytes in the sample, for example with the aid of a digital PCR, with such a detection method being used in the case of microfluidic samples preferably with a microfluidic device, in particular a lab-on-chip system, can be carried out.
  • a partitioning of the sample can advantageously be implemented for a statistical estimation of a concentration of the analyte in the sample with a low relative error.
  • the method for designing a partitioning comprises a partitioning of the sample on the partition area according to the invention.
  • the partition surface can generally be part of a microfluidic device, preferably part of a microfluidic cartridge.
  • the partition surface can be a surface on a substrate in a chamber of the microfluidic device.
  • a geometric shape of the partitions, a shape of the partition area and a total volume of the sample are defined.
  • the partition area can, for example, have a square or rectangular shape and optionally be surrounded by a delimiting wall.
  • the partitions can preferably be in the form of droplets or chambers. In the case of the droplets, these are present in particular as an emulsion, for example as water-based droplets in an oil emulsion, it being possible for the droplets to be stabilized preferably by adding surface-active substances, so-called surfactants.
  • the chambers can have a round or angular base, preferably a hexagonal base.
  • the chambers are separated from one another by walls, the walls preferably being made as thin as possible in order to block as little surface as possible. The walls are preferably taken into account in the geometric shape of the chambers.
  • a minimum partition measure of the partitions is determined.
  • a minimum partition size is a size, that is to say a representative and preferably unique value, for the size of the partition, in particular for the volume of the partition.
  • the partition dimension can be the diameter of the partition in the case of a spherical or teardrop-shaped partition or the width of the chamber in the case of partitioning into chambers with an angular, for example square or hexagonal, base area.
  • the partition dimension is the distance between two opposite corners, preferably the minimum center distance of the partitions.
  • a maximum number of partitions with a minimum partition size that can be arranged on the partition area results implicitly from the minimum partition size.
  • This maximum number is also referred to below as the first number of partitions and is a measure of a minimum value of the partitioning error because the statistical inaccuracy of the concentration determination of the entire partitioned volume of the sample decreases with an increasing number of partitions.
  • a partitioning design with as many partitions as possible and a correspondingly small partition size is referred to below as a minimal variant.
  • a second partition measure of the partitions and thus a second number of partitions is determined under the condition that a maximum possible proportion of the total volume can be partitioned on the partition area and under this condition the maximum possible proportion on as many partitions as possible on the Partition area is divided.
  • This second partition size is also referred to below as the maximum partition size d max and, however, represents the smallest possible partition size given the maximum partitioned total volume.
  • the number of partitions at the maximum partition size is also referred to below as the second designated.
  • a design of a partitioning in which the complete total volume of the sample is partitioned as far as possible and a correspondingly larger partition size is selected, is referred to as the maximum variant in the following as a distinction from the minimum variant.
  • this step can also be carried out before the previous step.
  • a first uncertainty of a measurable concentration of the analyte is determined when using a partition measure from a first range around the minimum partition measure and a second uncertainty of the measurable concentration is determined Using a partition measure from a second range around the second partition measure.
  • the first and second uncertainties can preferably be relative uncertainties. These determinations advantageously determine whether a design according to the minimum or maximum variant is better with regard to the smallest possible measurement error of the concentration.
  • the first range is preferably defined such that the first range includes the minimum partition metric, preferably as the lower end of the first range, and does not include the second partition metric.
  • the second range is preferably defined such that the second range includes the second partition measure, preferably as the upper end of the second range, and does not include the minimum partition measure.
  • the first area and the second area can be two mutually non-overlapping areas, ie in particular disjunctive areas.
  • the first uncertainty of a measurable concentration of the analyte is determined when using the first partition number of partitions with the minimum partition measure and the second uncertainty of the measurable concentration is determined when using the second partition number of partitions with the second partition measure.
  • the first uncertainty and/or the second uncertainty are determined at a value from the maximum theoretical range for a measurement of the concentration of the analyte. This maximum theoretical range is from -log(11 /A max )/V par to -log(1-( A max -1)/A max )/V par, where A max is the first partition number, V par is the capacity/volume of a single partition and log denotes the natural logarithm.
  • the center point of this range on a logarithmic scale is selected as the value, which is at (log(ll/A max ) * log(l-( A max -l)/A max )) A 0.5 /V Par lies.
  • the partitions are designed with a partition measure from the first range, preferably with the minimum partition measure, if a measurement of a concentration of the analyte at a predetermined concentration value is carried out when the Partitions with a partition size from the second range, in particular with the second partition size, is not possible.
  • the predetermined concentration value can preferably be a value from the maximum theoretical range described above, preferably around the midpoint of this range on a logarithmic scale, described above.
  • the partitions are designed from the first area or from the second area depending on a comparison of the first uncertainty with the second uncertainty.
  • the minimum variant or maximum variant can be selected on the basis of these ascertained uncertainties.
  • the partitions are designed with a partition measure not equal to the maximum partition measure if the first uncertainty is less than the second uncertainty, and the partitions are designed not equal to the minimum partition measure if the first uncertainty is greater than or equal to the second uncertainty is big.
  • the first area thus includes all feasible partition dimensions with the exception of the second/maximum partition dimension and the second area thus includes all feasible partition dimensions with the exception of the minimum partition dimension.
  • the partitions are designed with a partition measure from the first range if the first uncertainty is smaller than the second uncertainty, and the partitions are designed with a partition measure from the second range if the first uncertainty is greater than the second uncertainty or equal.
  • a range (optionally modified compared to the previous step of the method) can preferably be selected as the first range in such a way that the range only includes partition dimensions whose associated, preferably relative, uncertainty of the measurable concentration is smaller than the preferably relative uncertainty of the measurable concentration Choice of second/maximum partition measure.
  • a range (optionally modified compared to the previous step) can preferably be selected as the second range in such a way that the range only includes partition dimensions whose associated, preferably relative, uncertainty of the measurable concentration is smaller than the preferably relative uncertainty of the measurable concentration when selecting the minimum partition size.
  • the partitions are designed as a first partition number of partitions with the minimum partition measure if the first uncertainty is smaller than the second uncertainty, or as a second partition number of partitions with the second/maximum partition measure if the first uncertainty is greater than or equal to the second uncertainty.
  • the method can be part of an analysis method for detecting an analyte in a microfluidic sample.
  • the subject matter of the invention is therefore also such an analysis method, in which the sample is divided into partitions according to the invention and in which at least one partition is examined for the presence of the analyte.
  • the analysis method preferably includes carrying out a digital PCR with at least some of the partitions.
  • the subject matter of the invention is also a method for producing a partitioning of a microfluidic sample.
  • a partition area is provided and the sample is partitioned according to the design method according to the invention.
  • the manufacturing method may preferably include manufacturing compartments for partitioning on the partition surface.
  • FIG. 1 shows a flowchart of an exemplary embodiment of the method according to the invention for designing a partitioning
  • FIGS. 2a, 2b show a schematic representation of a partitioning of a sample onto a partition surface in the form of droplets or in the form of chambers filled with sample parts
  • FIG. 4 shows a flowchart of an exemplary embodiment of the analysis method according to the invention for detecting an analyte in a microfluidic sample
  • FIG. 5 shows a flow chart of an exemplary embodiment of the manufacturing method according to the invention for a partitioning of a microfluidic sample.
  • FIG. 1 shows a flowchart 500 of an exemplary embodiment of the method 500 according to the invention for designing a partitioning of a microfluidic sample.
  • the partitioning can in particular be part or a prerequisite of a partition-based quantitative detection method for analytes in the sample, with such a detection method for microfluidic samples preferably having a microfluidic device, in particular a lab-on-chip system, can be performed.
  • the method described below is part of a quantitative detection of nucleic acid segments of pathogens or tumor cells in a biological sample comprising a body fluid (e.g. blood, sputum or a smear), the quantitative detection using a digital PCR with the partitioning of the sample designed according to the invention he follows.
  • a body fluid e.g. blood, sputum or a smear
  • a first step 510 of the method 500 the volume of the sample and an area available for the partitioning, partition area for short, are determined.
  • FIG. 2a schematically shows an arrangement of droplets 110 with a diameter d on a partition surface 101 with a width L, the partition surface 101 being able to be, for example, square or rectangular and delimited by a wall 102 as illustrated.
  • the partition surface 101 can be arranged in particular in a chamber of a microfluidic cartridge.
  • FIG. 1a schematically shows an arrangement of droplets 110 with a diameter d on a partition surface 101 with a width L, the partition surface 101 being able to be, for example, square or rectangular and delimited by a wall 102 as illustrated.
  • the partition surface 101 can be arranged in particular in a chamber of a microfluidic cartridge.
  • the chambers 120 have, for example, as shown, a hexagonal base area 121 with a width d, a wall height D, which corresponds to a chamber depth, and a wall thickness w between each two chambers, with the wall thickness w preferably being selected as small as possible in order to minimize the area of the partition surface 101 by walls 122 of chambers 120 to block.
  • a minimum wall thickness and maximum wall height for maximizing the volume of the chambers 120 can also be limited, in particular, by manufacturing requirements.
  • the partition area 101 can in particular be a surface of a substrate, for example a substrate made of silicon, plastic or a combination of both materials.
  • the chambers 120 in particular the walls 122, can also be made of silicon, plastic or a combination of both materials.
  • a hydrophilic configuration of the partition surface 101 or of the chambers 120 is advantageous.
  • a minimum partition size d m/n is defined, with a size of this minimum partition size d m/n being determined by manufacturing limitations, also mentioned above depending on the individual case, and a resolution of a detection optics to be used for the analysis of the partitions can.
  • a fourth step 540 it is calculated how many partitions can be accommodated on the partition area 101, possibly while maintaining the minimum wall thickness w.
  • the first partition number A max also defines the maximum theoretical range for a measurement of the concentration of the analyte (with cp/pL as units of copies per microliter), which is from -log(II /A max )/V par to -log(l- ( A max - 1)/A max )/V par , where log denotes the natural logarithm.
  • log denotes the natural logarithm.
  • according to one fifth step 550 halves this maximum measurement range on a logarithmic scale.
  • the resulting center point l is then at (log(ll /A max ) * log(l-( A max -l)/A max )) A 0.5/V par and in this example corresponds to about 431 cp/pL.
  • concentration value l from this measurement range can also be selected, particularly if there are reasons for preferring measurement at lower or higher concentrations.
  • a preferred alternative to as many partitions as possible is to choose the dimensions of the partitions in such a way that the entire volume ⁇ Z sys is also partitioned. If the partition area and a height that is filled by the partitions are large enough, it is basically always possible to accommodate the entire volume ⁇ Z sys on the partition area 101, and in extreme cases in just a single partition. However, in order to keep the partitioning error as low as possible, when using the maximum possible volume, the volume should be divided into as many partitions as possible. Therefore, according to the sixth step 560 of the method 500, a second partition measure d max must first be found, which under the given conditions maximizes the partitionable and thus analyzable volume V ana and at the same time implies as many partitions as possible.
  • This second partition size is also referred to as the maximum partition size d max and, however, represents the smallest possible partition size given the maximum partitioned total volume.
  • d max is 128.52 pm with a maximum partitionable volume V ana of 24.999 pL, i.e. practically the entire volume ⁇ Z sys of 25 pL.
  • the partitionable volume V ana is divided into 6132 partitions, this number being referred to below as the second partition number A mm .
  • the sixth step 560 can also be carried out earlier, in particular before or in parallel with one of the preceding steps, provided that the first step 510 and the second step 520 have taken place.
  • the maximum theoretical range for a measurement of the concentration of the analyte is determined when using the second partition number A mm of partitions with the maximum partition size d max , this range being analogous to above from -log(ll/ A min )lVp ar _2 extends to -log(l-( A min -1)/ A min )/Vp ar _2 and where V par _2 corresponds to the volume of a partition with partition size d max .
  • the partitioning is preferably designed according to the first number of partitions A max with a minimum partition measure d m/n . If the calculated center point I falls within this range, the method 500 according to this embodiment continues as follows.
  • a first uncertainty of a measurable concentration of the analyte when using the first partition number A max of partitions with a minimum partition measure d m/n (hereinafter referred to as minimum variant) and a second uncertainty of the measurable concentration calculated using the second number of partitions A m/n of partitions with maximum partition size d max (referred to below as maximum variant for short).
  • the relative uncertainties can preferably be determined using the following approach.
  • An uncertainty based on the confidence interval of the following probability distribution P ⁇ C ⁇ H) can be used to calculate the partitioning error: where C is the number of targets in the analyzed sample volume V ana , H is the number of partitions containing at least one analyte, A is the available number of partitions, and S is the Stirling number of the second kind.
  • C, p) can be used: where C stands for the number of targets in the analyzable sample volume V ana , C tot for the number of targets in the partitionable volume ⁇ Z sys and p for the fraction of the analyzable volume in the partitionable volume V ana /V sys .
  • the confidence interval can be calculated directly from the variance s. In the case of a 95% confidence interval, this is m ⁇ 1.96 Vs, where m represents the expected value.
  • the standard deviation s of a Gaussian distribution can be calculated from the probability at the expected value, i.e. the maximum probability:
  • P ⁇ C tot ⁇ H, p) is calculated via: This calculation is advantageous in terms of the time required. This approximation allows for a qualitative comparison and the quantitative results are within about 10% of the true, exact value of the uncertainty.
  • the first relative uncertainty of the measurement result s at the center point l when using the minimum variant of about 0.0566 or 5.66% results.
  • the second relative uncertainty at midpoint l is about 0.0254 or 2.54%, i.e. less than half the relative uncertainty
  • a ninth step 590 of the method 500 the two relative uncertainties are now compared and an interpretation of the partitioning is determined as a function of this comparison.
  • a partitioning according to the minimum variant 591 or according to the maximum variant 592 can be implemented, so that the relative uncertainty is preferably as low as possible.
  • several approaches are advantageous, which were explained above in particular.
  • that interpretation can then be selected which provides the lower uncertainty in the middle of the maximum theoretical measuring range.
  • the sample is distributed into 6132 hexagonal partitions with the partition measure of 128.52 pm.
  • the chambers 120 can be covered with (transparent) oil in a particular embodiment before subsequent processing or analysis, for example as part of a digital PCR, takes place.
  • FIG. 3 shows, by way of example, relative uncertainties s calculated according to the approach described above as a function of the partition measure d for various concentrations of the analyte in the sample (10, 50, 100 and 500 analytes per microliter, respectively) when using chambers 120 and the same values for volume, edge length, chamber depth/wall height and wall thickness.
  • a design with large partition dimensions is usually associated with a lower relative error, with a design with the smallest possible partition dimension being disadvantageous, especially in the case of low concentrations. This is due to the fact that in these cases the subsampling error dominates over the partitioning error due to the significantly smaller partitionable volume with a very small partition size.
  • smaller relative errors for designs with a small partition size compared to designs according to the maximum variant can also result for certain concentrations.
  • the total dividable volume ⁇ Z sys is increased to 30 pl_.
  • the minimum partition dimension d mm , the edge length L of the partition surface 101, the wall height/chamber depth D and the wall thickness w remain unchanged at 10 pm, 10 mm, 380 pm and 25 pm, respectively.
  • the center l of the logarithmic measuring range is around 431 cp/pL.
  • FIG. 4 shows a flow chart of an exemplary embodiment of the analysis method 600 according to the invention.
  • a sample can preferably be divided into partitions according to the method according to the invention for designing a partitioning, for example according to the method 500 described above for FIG in a second step 620 at least one partition, preferably all partitions as far as possible, are examined for the presence of the analyte and a conclusion is drawn from this as to a concentration of the analyte in the divided sample.
  • This determination of Concentration is preferably carried out by carrying out a digital PCR, for which the partitions form the basis.
  • FIG. 5 shows a flowchart of an exemplary embodiment of the production method 700 according to the invention.
  • a partition area is provided. This can be done, for example, by providing a substrate, with a surface of the substrate forming the partition area.
  • the partition surface or the substrate can be part of a microfluidic cartridge or can be arranged or fixed in the cartridge in the course of the manufacturing method 700 .
  • the partitioning is designed according to the method according to the invention for designing a partitioning, for example according to the method 500 described above for FIG

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Abstract

L'invention concerne un procédé (500) pour placer une cohorte de compartiment d'un échantillon microfluidique, en particulier biologique, dans des compartiments (110, 120) sur une surface de compartiment (101), en particulier pour déterminer une concentration d'un analyte dans l'échantillon. L'invention concerne en outre un procédé d'analyse (600) pour la détection d'un analyte dans un échantillon microfluidique et un procédé (700) pour préparer une cohorte de compartiment d'un échantillon microfluidique.
EP22732972.9A 2021-06-29 2022-06-03 Procédé de mise en place d'une cohorte de compartiment d'un échantillon microfluidique, en particulier biologique Pending EP4363607A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102021206717.4A DE102021206717A1 (de) 2021-06-29 2021-06-29 Verfahren zur Auslegung einer Partitionierung einer mikrofluidischen, insbesondere biologischen Probe
PCT/EP2022/065161 WO2023274662A1 (fr) 2021-06-29 2022-06-03 Procédé de mise en place d'une cohorte de compartiment d'un échantillon microfluidique, en particulier biologique

Publications (1)

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EP4363607A1 true EP4363607A1 (fr) 2024-05-08

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EP22732972.9A Pending EP4363607A1 (fr) 2021-06-29 2022-06-03 Procédé de mise en place d'une cohorte de compartiment d'un échantillon microfluidique, en particulier biologique

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EP (1) EP4363607A1 (fr)
CN (1) CN117897499A (fr)
DE (1) DE102021206717A1 (fr)
WO (1) WO2023274662A1 (fr)

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US20160310949A1 (en) * 2015-04-24 2016-10-27 Roche Molecular Systems, Inc. Digital pcr systems and methods using digital microfluidics

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CN117897499A (zh) 2024-04-16
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