WO2023016916A1 - Dispositif microfluidique et procédé pour son fonctionnement - Google Patents

Dispositif microfluidique et procédé pour son fonctionnement Download PDF

Info

Publication number
WO2023016916A1
WO2023016916A1 PCT/EP2022/071956 EP2022071956W WO2023016916A1 WO 2023016916 A1 WO2023016916 A1 WO 2023016916A1 EP 2022071956 W EP2022071956 W EP 2022071956W WO 2023016916 A1 WO2023016916 A1 WO 2023016916A1
Authority
WO
WIPO (PCT)
Prior art keywords
filter
microfluidic device
cells
suction chamber
flow rate
Prior art date
Application number
PCT/EP2022/071956
Other languages
German (de)
English (en)
Inventor
Hannah Bott
Christian GRUMAZ
Tanja Maucher
Astrid LUX
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 WO2023016916A1 publication Critical patent/WO2023016916A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/18—Apparatus therefor
    • 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
    • B01L3/502753—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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • 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
    • B01L3/502761—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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1017—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by filtration, e.g. using filters, frits, membranes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N15/0272—Investigating particle size or size distribution with screening; with classification by filtering
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G01N15/0606—Investigating concentration of particle suspensions by collecting particles on a support
    • G01N15/0618—Investigating concentration of particle suspensions by collecting particles on a support of the filter type
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2311/00—Details relating to membrane separation process operations and control
    • B01D2311/14—Pressure control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2311/00—Details relating to membrane separation process operations and control
    • B01D2311/16—Flow or flux control
    • B01D2311/165—Cross-flow velocity control
    • 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
    • B01L2300/0681—Filter
    • 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
    • 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
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
    • G01N2001/4088—Concentrating samples by other techniques involving separation of suspended solids filtration

Definitions

  • the present invention relates to a method for operating a microfluidic device. Furthermore, the present invention relates to a microfluidic device that is set up to be operated by means of the method.
  • transport media for biological samples are established as clinical standards in diagnostics, which make it possible to transport patient swabs or patient samples to a diagnostic laboratory.
  • Transport media are used for molecular-biological or biochemical analyzes of the samples, the main task of which is to ensure a stabilizing environment for nucleic acids and other analytes so that the sample is not altered. In these media, pathogens are also completely or partially destroyed, nucleic acids are released and degrading proteins are inhibited.
  • the transport media must not be lysing, because intact living cells are required for a wide variety of proofs.
  • cells which contain pathogens, for example, are first accumulated on a retaining element, such as a filter frit.
  • a retaining element such as a filter frit.
  • pathogens such as bacteria (e.g. mycoplasma), parasites (e.g. Trichomonas or Plasmodium sp.) or viruses (e.g. influenza or SARS-CoV-2).
  • the accumulation is followed by a mechanical, chemical or thermal lysis directly at the site of accumulation, i.e. on the filter frit, in order to carry out a concentration in the pathogens to be detected molecular-biologically or biochemically in the next step. It is important that the accumulated cells on the retaining element remain intact before lysis.
  • the method for operating a microfluidic device provides that a medium containing human cells is transported through a filter at a flow rate that is selected or set such that damage to the cells is avoided.
  • the flow rate is preferably adjusted via at least one suction chamber and/or pump.
  • a medium can be understood to mean a fluid, in particular a liquid.
  • the medium can be a body fluid, in particular sputum, urine or blood.
  • the medium can preferably be a transport medium, in particular a non-lysing transport medium, for example a phosphate-buffered saline solution or UTM®, wherein the transport medium can also contain body fluid depending on a sampling.
  • This method is based on the finding that human cells tend to lyse even at low shear stress.
  • a low flow rate or a low flow rate range reduces this shear stress, so that damage to the cells can be avoided.
  • the flow rate is thus selected or adjusted in such a way, in particular at least by adjusting the suction chamber and/or pump, that the highest possible proportion of the cells are accumulated intact on the filter.
  • the flow rate can preferably be selected or adjusted taking into account the microfluidic conditions of the microfluidic device, i.e. in particular taking into account the fluidic resistance of the filter, the viscosity of the medium and/or a fluidic resistance of a channel through which the medium with the cells to filter is transported.
  • the fluidic resistance of the channel can depend in particular on the geometry, in particular a width and length of the channel, and/or on an inner surface of the channel.
  • Avoiding damage to the cells can thus be understood in particular as meaning that at least 30%, preferably at least 40%, particularly preferably at least 50%, very particularly preferably at least 60% of the cells contained in the transport medium are accumulated intact on the filter. It is preferably taken into account that due to a condition, in particular a pore size of the filter and due to a pressure acting on the filter due to the flow rate, a proportion of intact cells can also pass through the filter and that a further proportion of intact cells due to the microfluidic nature of the microfluidic device can be lost during transport.
  • avoiding damage to the cells can also be understood to mean that the flow rate is selected in such a way that essentially no damage to the cells occurs. “Substantially no damage” can preferably be understood to mean that less than 40%, preferably less than 30%, very preferably less than 20% of the cells are damaged by transport to the filter.
  • the flow rate is preferably at most 300 pl/s and particularly preferably at most 200 pl/s. This flow rate is particularly suitable for preventing damage to human cells as far as possible. In addition, with such flow rates, it is avoided as far as possible that cells are pushed through the filter and are therefore no longer available for later analysis.
  • the transport is preferably carried out by sucking the medium.
  • microfluidic devices that press a medium through a filter by means of excess pressure usually work at high pressures, such as a pressure of 260 kPa, and thus generate high flow rates of, for example, 500 pl/s
  • microfluidic devices are in Usually set up to perform suction with only slight suppression, as a result of which lower flow rates can be realized.
  • the method can also be implemented by pumping medium if the pumping takes place with such a low overpressure that the required low flow rates can be implemented.
  • the suction is preferably performed by setting a pressure on a downstream side of the filter which is at most 90 kPa. Most preferably the pressure is in the range of 30 kPa to 40 kPa. Since atmospheric pressure usually prevails in a microfluidic device in which no active pumping or suction processes take place, these pressure ranges cause only a slight negative pressure during the suction process, which enables gentle filtration of the cells contained in the medium, in particular in the transport medium.
  • the suction is preferably performed by means of a suction chamber located downstream of the filter. It is particularly preferably arranged immediately downstream of the filter. “Immediately downstream” is understood to mean that the filter and the suction chamber are only connected to one another by a line, without further microfluidic elements being arranged in this line. Using such a suction chamber enables a vacuum to be applied very precisely downstream of the filter and thus to precisely control the flow rate.
  • the suction chamber can also be a pump which can be operated in such a way that it sucks in fluids, in particular liquids.
  • the microfluidic device is set up to be operated using the method. This setup takes place in particular in that the method steps are implemented as a computer program on a computing unit or control unit of the microfluidic device.
  • the microfluidic device has a filter, which is designed in particular as a filter frit.
  • a number-average pore diameter of the filter is preferably in the range of 0.5 ⁇ m to 10.0 ⁇ m. Since human cells usually have a diameter of more than 10 ⁇ m to 20 ⁇ m, This ensures that the cells are retained safely, while at the same time other particles contained in the transport medium can be separated from the cells.
  • a suction chamber is preferably located downstream of the filter. It is particularly preferably arranged immediately downstream of the filter.
  • the suction chamber has a membrane that divides it into a first part and a second part.
  • the first part lies in a fluidic layer of the microfluidic device through which the medium is transported.
  • the second part is in a pneumatic layer in which an overpressure or a negative pressure can be generated.
  • a suction chamber differs from a pumping chamber in that its second part is connected to a channel of the pneumatic layer arranged to create a negative pressure therein, while the second part of a pumping chamber is connected to a channel of the pneumatic layer arranged to so that an overpressure is generated in it. If a negative pressure is generated in the second part of the suction chamber, the membrane is deflected into the pneumatic layer, as a result of which a negative pressure is also created in the first part of the suction chamber.
  • the membrane In order to enable the membrane to be easily deflected, it preferably consists of an elastomer.
  • Particularly preferred elastomers are thermoplastic polyurethane or polydimethylsiloxane (PDMS).
  • the thickness of the membrane is preferably in the range from 50 ⁇ m to 300 ⁇ m. It is particularly preferably in the range from 75 ⁇ m to 125 ⁇ m. Furthermore, it is preferred that the radius of the membrane is in the range from 1 mm to 10 mm. It is particularly preferably in the range from 2.5 mm to 3.5 mm.
  • the suction chamber is connected to the filter via a channel, the channel cross section of which is preferably in the range from 0.1 mm 2 to 0.4 mm 2 and particularly preferably in the range from 0.22 mm 2 to 0.26 mm 2 .
  • This cross section advantageously allows the desired flow rates through the channel to be set.
  • FIG. 1 schematically shows elements of a microfluidic device according to the prior art.
  • FIG. 2 schematically shows elements of a microfluidic device according to an embodiment of the invention.
  • FIG. 3 schematically shows a suction chamber of a microfluidic device according to an embodiment of the invention.
  • FIG. 4 shows in a diagram a comparison of RNA recovery from human cells in a comparative example and an example of the method according to the invention.
  • FIG. 5 shows in a diagram a comparison of the RNA recovery in three examples of the method according to the invention.
  • a prior art microfluidic device for example Vivalytic®, Robert Bosch GmbH, Germany
  • FIG. 1 has a fluidic layer 100 and a pneumatic layer 200 .
  • An inlet 110 is arranged in the fluidic layer 100, via which a medium, in particular a transport medium, can be introduced into a channel system.
  • the transport medium is, for example, the UTM® RT medium (Universal Transport Medium Room Temperature, COPAN Diagnostics, USA).
  • This cell-stabilizing transport medium contains salts to buffer a neutral pH and sugar compounds to stabilize human cells.
  • the transport medium which in the present exemplary embodiment contains human cells, is pumped through the channel system by means of a pump chamber 210 at a pressure of 260 kPa.
  • the pump chamber 210 has a membrane 211 which divides it into a first part in the fluidic layer 100 and a second part in the pneumatic layer 200 .
  • a first reservoir 120 which has a valve 121
  • a second reservoir 130 which has a valve 131 branches off from the channel system downstream of the pump chamber 210 .
  • Reagents can be metered into the channel system from the two reservoirs 120, 130.
  • a filter 140 is located downstream of the pumping chamber 210 and the second reservoir 130 in the duct system. It is designed as a filter frit with a number-average pore diameter of 5 ⁇ m.
  • a third reservoir 150 branches off from the channel system with a valve 151, through which reagents can also be metered into the channel system.
  • a collection vessel 160 which has a valve 161, collects the transport medium, which was pumped through the filter 140, downstream of the third reservoir 150. Flow rates of up to 500 pl/s occur during this pumping process.
  • FIG. 2 shows an embodiment of a microfluidic device according to the invention.
  • This device differs from the device according to FIG. 1 in that downstream of the filter 140 and upstream of the third reservoir 150 a suction chamber 220 with a membrane 221 is arranged in the channel system.
  • the transport of the medium, in particular the transport medium, through the filter 140 does not take place using the pump chamber 210, which generates an overpressure upstream of the filter 140, but using the suction chamber 220, which generates a negative pressure downstream of the filter 140.
  • the membrane 221 of the suction chamber 220 has a thickness d of 100 ⁇ m. Their radius r is 3.0 mm.
  • the circular channel cross-section a in a channel 222 of the channel system between the filter 140 and the suction chamber 220 is 0.24 mm 2 .
  • 4 shows the comparison of a comparative example VB1 and an example B1 according to the invention of the accumulation of human cells on the filter 140. In both cases, 10,000 cells were introduced into an exemplary embodiment of the microfluidic device according to FIG. 2 using the transport medium. After the end of the accumulation, these were lysed and the mass m of the recovered RNA was determined. This mass m represents a measure of the number of cells accumulated intact.
  • example VB1 the device according to FIG. 1 was used and the transport medium was pumped by means of the pump chamber 210 with a pressure of 260 kPa.
  • example B1 according to the invention the device according to FIG. 2 was used and the transport medium was sucked in by means of the suction chamber 220 at a pressure of 35 kPa. While only 1.8 ng of RNA could be recovered in comparative example VB1, it was possible to recover 10.1 ng of RNA in example B1 according to the invention. This shows that suction according to the invention resulted in a low flow rate and low shear stress on the human cells, thereby destroying only a few cells on the filter 140.
  • FIG. 5 shows the recovery of RNA from 10,000 human cells in each case in three further examples B2 to B4 according to the invention.
  • a different exemplary embodiment of the microfluidic device according to FIG. 2 was used in all examples and the transport medium was sucked in by means of the suction chamber 220 .
  • the pressure adjusted by the suction chamber 220 downstream of the filter 140 was 70 kPa in the second example B2, 50 kPa in the third example B3, and B435 kPa in the fourth example. It can be seen that the pressures set in these examples B2 to B4 according to the invention lead to a lower RNA recovery than in the first example B1 according to the invention, but this is still higher than in comparative example VB1.
  • RNA recovery The lower the set pressure, the lower the RNA recovery.
  • Lower pressures in the suction chamber 220 result in a greater pressure difference compared to the inlet of the filter 140, which is at ambient pressure, so that the flow rate through the filter 140 increases and thus more cells are destroyed.
  • a pressure of 35 kPa ensures that compared to the use of non-inventive Device only a few cells are destroyed.
  • a lower average RNA recovery was achieved at this pressure in example B4, this was more reproducible and showed less scatter than in examples B2 and B3.

Abstract

L'invention concerne un procédé de fonctionnement d'un dispositif microfluidique où un milieu de transport contenant des cellules humaines est transporté à travers un filtre (140) à un certain débit. Le débit est choisi de manière à ce que les cellules ne soient essentiellement pas endommagées. L'invention concerne également un dispositif microfluidique comprenant au moins un filtre (140), le dispositif étant conçu de manière à pouvoir être actionné par le procédé selon l'invention.
PCT/EP2022/071956 2021-08-12 2022-08-04 Dispositif microfluidique et procédé pour son fonctionnement WO2023016916A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102021208831.7A DE102021208831A1 (de) 2021-08-12 2021-08-12 Mikrofluidische Vorrichtung und Verfahren zu ihrem Betrieb
DE102021208831.7 2021-08-12

Publications (1)

Publication Number Publication Date
WO2023016916A1 true WO2023016916A1 (fr) 2023-02-16

Family

ID=83112986

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2022/071956 WO2023016916A1 (fr) 2021-08-12 2022-08-04 Dispositif microfluidique et procédé pour son fonctionnement

Country Status (2)

Country Link
DE (1) DE102021208831A1 (fr)
WO (1) WO2023016916A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011079217A1 (fr) * 2009-12-23 2011-06-30 Cytovera, Inc. Système et procédé pour filtration de particules
US20120178097A1 (en) * 2010-05-28 2012-07-12 California Institute Of Technology Methods and design of membrane filters
WO2013052951A2 (fr) * 2011-10-07 2013-04-11 The Trustees Of Columbia University In The City Of New York Dispositifs, procédés et systèmes de séparation de composants de fluide
US20160158428A1 (en) * 2013-01-11 2016-06-09 The Charles Stark Draper Laboratory, Inc. Systems and methods for increasing convective clearance of undesired particles in a microfluidic device
US20160186167A1 (en) * 2013-08-07 2016-06-30 Robert Bosch Gmbh Method and Device for Processing a Sample of Biological Material Containing Target Cells and Companion Cells in Order to Extract Nucleic Acids of the Target Cells
WO2016172675A1 (fr) * 2015-04-24 2016-10-27 The Regents Of The University Of California Séparation de plasma sanguin sans hémolyse
WO2019049944A1 (fr) * 2017-09-07 2019-03-14 Sony Corporation Chambre de capture de particules, puce de capture de particules, procédé de capture de particules, appareil et système d'analyse de particules

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011079217A1 (fr) * 2009-12-23 2011-06-30 Cytovera, Inc. Système et procédé pour filtration de particules
US20120178097A1 (en) * 2010-05-28 2012-07-12 California Institute Of Technology Methods and design of membrane filters
WO2013052951A2 (fr) * 2011-10-07 2013-04-11 The Trustees Of Columbia University In The City Of New York Dispositifs, procédés et systèmes de séparation de composants de fluide
US20160158428A1 (en) * 2013-01-11 2016-06-09 The Charles Stark Draper Laboratory, Inc. Systems and methods for increasing convective clearance of undesired particles in a microfluidic device
US20160186167A1 (en) * 2013-08-07 2016-06-30 Robert Bosch Gmbh Method and Device for Processing a Sample of Biological Material Containing Target Cells and Companion Cells in Order to Extract Nucleic Acids of the Target Cells
WO2016172675A1 (fr) * 2015-04-24 2016-10-27 The Regents Of The University Of California Séparation de plasma sanguin sans hémolyse
WO2019049944A1 (fr) * 2017-09-07 2019-03-14 Sony Corporation Chambre de capture de particules, puce de capture de particules, procédé de capture de particules, appareil et système d'analyse de particules

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
S. J. TANH. PHANB. M. GERRYA. KUHNL. Z. HONG ET AL.: "A microfluidic device for preparing next generation DNA sequencing libraries and for automating other laboratory protocols that require one or more column chromatography steps", PLOS ONE, vol. 8, 2013, pages e64084

Also Published As

Publication number Publication date
DE102021208831A1 (de) 2023-02-16

Similar Documents

Publication Publication Date Title
EP1160573A2 (fr) Plaque de microtitrage et dispositif de pipetage multivoies couplé à celui
EP2322277B1 (fr) Puce microfluidique
EP2695655A1 (fr) Dispositif en plusieurs parties destiné à obtenir du plasma à partir de sang total
DE102018004909A1 (de) Modulares Prozessiersystem und Verfahren zum modularen Aufbau eines Prozessiersystems
EP1161995B1 (fr) Procédé et dispositif pour absorber un milieu dans un dispositif capillaire
WO2015018707A1 (fr) Procédé et dispositif pour traiter un échantillon de matière biologique contenant des cellules cibles et des cellules chaperons, de manière à extraire des acides nucéliques desdites cellules cibles
WO2015018647A1 (fr) Procédé et dispositif pour traiter un échantillon de matière biologique contenant des cellules cibles et des cellules chaperons, de manière à extraire des acides nucéliques desdites cellules cibles
WO2015144345A1 (fr) Dispositif microfluidique et procédé pour analyser un échantillon de matière biologique
WO2023016916A1 (fr) Dispositif microfluidique et procédé pour son fonctionnement
WO2003033096A2 (fr) Procede et module de separation pour separer des particules d'une dispersion, notamment pour separer des corpuscules sanguins contenu dans le sang
WO2014117908A1 (fr) Dispositif d'extraction de liquides organiques préstockés à sec dans un prélèvement, cartouche et procédé
EP2486313B1 (fr) Structure microfluidique et procédé pour le positionnement d'un volume de liquide dans un système microfluidique
EP3973288B1 (fr) Système d'analyse microfluidique pour l'analyse d'échantillons de sang
WO2022037912A1 (fr) Dispositif microfluidique
EP3610013B1 (fr) Désorption d'acides nucléiques
DE10340012A1 (de) Vorrichtung zur Gas-oder Flüssigkeitsabscheidung aus mikrofluidischen Durchflusssystemen
DE102019215029A1 (de) Filterabfolge, Spritzenaufsatz und Verfahren zur Separierung von Partikeln aus einer Körperflüssigkeit
DE102014200467A1 (de) Mikrofluidisches System sowie Verfahren zum Analysieren einer Probe biologischen Materials
EP1397483B1 (fr) Systeme microfluidique
DE102022114873A1 (de) System zum Analysieren eines Analyten in einer Probe
WO2022137162A1 (fr) Dispositif microfluidique avec système d'actionneur d'entrée
DE102016123658B4 (de) Filtrationsvorrichtung und Verfahren zur Anreicherung von Targets und der nachfolgenden Freisetzung biogener Agenzien
DE102021212645A1 (de) Vorrichtung und Verfahren zur Durchführung mikrofluidischer Prozessschritte
DE102022209415A1 (de) Mikrofluidisches Ventil und mikrofluidische Vorrichtung
WO2021013595A1 (fr) Système de laboratoire sur puce comportant au moins une partie fonctionnalisée

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22760974

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE