WO2024259905A1 - Dispositif microfluidique et procédé d'extraction de plasma sanguin à partir de sang total - Google Patents

Dispositif microfluidique et procédé d'extraction de plasma sanguin à partir de sang total Download PDF

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Publication number
WO2024259905A1
WO2024259905A1 PCT/CN2023/136201 CN2023136201W WO2024259905A1 WO 2024259905 A1 WO2024259905 A1 WO 2024259905A1 CN 2023136201 W CN2023136201 W CN 2023136201W WO 2024259905 A1 WO2024259905 A1 WO 2024259905A1
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blood sample
plasma
microfluidic device
separation membrane
sample inlet
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English (en)
Chinese (zh)
Inventor
陈定璿
陈根气
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City University of Hong Kong CityU
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City University of Hong Kong CityU
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Priority claimed from US18/490,160 external-priority patent/US20240183765A1/en
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Publication of WO2024259905A1 publication Critical patent/WO2024259905A1/fr
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    • 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

Definitions

  • Plasma separation and extraction (BPSE) devices and methods are known (see Mielczarek, et al., “Microfluidic blood plasma separation for medical diagnostics: Is it worth it?”, Lab Chip, vol. 16, pp. 3441, 2016, and Gao, et al., “A simple and rapid method for blood plasma separation driven by capillary force with an amplification in protein detection”, anal. Met., vol. 12, pp. 2560-70, 2020); however, such methods typically require, for example, long extraction times, low plasma extraction volumes, blood sample pretreatment, etc.
  • manual or powered devices have significant disadvantages, such as consistency of use and the need for a power source, respectively.
  • manual pump powered devices require a trained professional to operate, while powered devices may require a power outlet, batteries, etc.
  • Ordered discharge is known (see Olanrewaju and Juncker, "Autonomous microfluidic capillaric circuits replicated from 3D-printed molds", Lab Chip, vol. 16, p. 19, 2016) for providing an automatically regulated liquid discharge system.
  • microfluidic devices are described, for example, in Wang et al., Portable microfluidiv device with thermometer-like display for real-time visual quantitation of Cadmium(II)contamination in drinking water, Analytica Chimica Acta, Volume 1160, 338444, 2021, https://doi.org/10.1016/j.aca.2021.338444 ; Wu et al., Cascade-Amplified Microfluidic Particle Accumulation Enabling Quantification of Lead Ions through Visual Inspection, Sens & Actuators: B.Chemical, Volume 324, 128727, https://doi.org/10.1016/j.snb.2020.128727 ; Jiang et al., Microfluidic particle accumulation for visual quantification of copper ions, Microchimica Acta,Volume 188,176,2021, https://doi.org/10.1007/s00604-021-04822-0 ; Wu et al., Visual quantification of silver contamination in fresh water via
  • the microfluidic device comprises a blood sample inlet, a separation membrane, a manifold inlet in fluid communication with the blood sample inlet at a joint, a capillary pump in fluid communication with the joint and located downstream of the joint, and a vent in fluid communication with the capillary pump.
  • the separation membrane comprises a top layer adjacent to the sample inlet. and a bottom layer away from the sample inlet.
  • the top layer has an average pore size of about 1 ⁇ m to about 50 ⁇ m in diameter; or a diameter of about 3 ⁇ m to about 20 ⁇ m; or a diameter of about 7 ⁇ m to about 13 ⁇ m.
  • the bottom layer has an average pore size of about 0.05 ⁇ m to about 20 ⁇ m in diameter; or a diameter of about 0.1 ⁇ m to about 7 ⁇ m; or a diameter of about 1 ⁇ m to about 3 ⁇ m.
  • the separation membrane is disposed between the blood sample inlet and the connector.
  • typical biomarkers are smaller than, for example, red blood cells and white blood cells (e.g., including phagocytes). Therefore, the present invention can separate, for example, red blood cells, white blood cells, etc. from, for example, whole blood samples, while allowing blood plasma and desired biomarkers to flow downstream to a connector and a capillary pump through a separation membrane.
  • the present invention provides a new blood separation device and method, which utilizes a pressure difference to pass through a membrane/porous material to separate blood plasma from whole blood.
  • the pressure difference can be utilized using various devices, such as a syringe pump, a hydrostatic pump, a peristaltic pump, etc.
  • the core structure of these devices can also be in different forms, such as a syringe and its additional components, and an elastic tube, which is equipped with a membrane/porous material that helps to separate or purify blood plasma from a whole blood sample.
  • a capillary pump can be used herein to draw blood downstream from a blood sample inlet.
  • a method for separating plasma from a blood sample comprises the following steps: providing a microfluidic device according to the present application; providing a blood sample comprising a plurality of red blood cells and plasma; if the vent is initially closed, opening the vent before or after the blood sample is added to the blood sample inlet; adding the blood sample to the blood sample inlet, then adding the working fluid to the manifold inlet, and extracting the plasma by orderly discharge of the manifold inlet and the blood sample inlet.
  • the orderly discharge allows the blood sample to flow preferentially downstream from the blood sample inlet to the separation membrane, thereby filtering out the red blood cells from the blood sample, and finally extracting the plasma separated by the separation membrane.
  • the vent can be closed with a vent cover such as a removable seal, patch, plastic plug, etc.
  • the methods herein provide a simple, easy and easily operable method for separating plasma and any biomarkers therein from RBCs, WBCs, contaminants, etc. that may cause clogging and/or complicate further analysis.
  • the methods of the invention may be designed for use in a simple test kit, or may, for example, be scaled up for larger scale blood sample purification and/or biomarker separation and/or identification.
  • FIG1A shows a circuit diagram simulating the flow resistance of an embodiment of the device of the present invention
  • FIG. 1B shows a top perspective view of an embodiment of a microfluidic device of the present invention
  • FIG. 1C shows a side view of the embodiment of FIG. 1B ;
  • FIG2 shows a schematic partially exploded view of an embodiment of a microfluidic device of the present invention
  • Figure 3A shows a photograph of erythrocytes stained with DiD
  • FIG3B shows a photograph of leukocytes stained with CMFDA green.
  • FIG4 shows photographs, phase contrast images, and Cy5, TXRED, and FITC fluorescence images of the microfluidic device at specific time points during the plasma extraction process
  • FIG5A is a graph showing the relative fluorescence intensity of Cy5 dye labeled in whole blood in an embodiment of the present invention.
  • FIG5B is a graph showing the relative fluorescence intensity of Cy5 dye labeled in plasma in an embodiment of the present invention.
  • FIG6 shows the average relative fluorescence intensity of TXRED and FITC channels, indicating that plasma was extracted without leakage and rupture of red blood cells (RBC) and white blood cells (WBC) in the reaction chamber at different concentrations of labeled plasma; and
  • FIG. 7 is a graph comparing extracted plasma volumes between plasma and whole blood samples at different expected plasma volumes.
  • downstream is a relative term, meaning in the direction toward the air outlet. up.
  • upstream is a relative term meaning in a direction away from the air outlet, typically toward the blood sample inlet and/or the manifold inlet.
  • the microfluidic device includes a blood sample inlet, a separation membrane, a manifold inlet connected to the blood sample inlet fluid at a joint, a capillary pump connected to the joint fluid and located downstream of the joint, and a vent connected to the capillary pump fluid.
  • the separation membrane comprises a top layer adjacent to the sample inlet and a bottom layer away from the sample inlet.
  • the top layer has an average pore size of about 1 ⁇ m to about 50 ⁇ m in diameter; or a diameter of about 3 ⁇ m to about 20 ⁇ m; or a diameter of about 7 ⁇ m to about 13 ⁇ m.
  • the bottom layer has an average pore size of about 0.05 ⁇ m to about 20 ⁇ m in diameter; or a diameter of about 0.1 ⁇ m to about 7 ⁇ m; or a diameter of about 1 ⁇ m to about 3 ⁇ m.
  • the separation membrane is disposed between the blood sample inlet and the joint.
  • typical biomarkers are smaller than, for example, red blood cells and white blood cells (e.g., including phagocytes). Therefore, the present invention can separate, for example, red blood cells, white blood cells, etc. from, for example, a whole blood sample, while allowing plasma and desired biomarkers to pass through the separation membrane and flow downstream to a connector and a capillary pump.
  • Capillary pump herein is by such as wicking, capillary action etc. fluid is sucked through device.
  • Capillary pump herein can be selected from capillary pump based on porous material, single microchannel with hydrophilic surface, multiple microchannel with hydrophilic surface, chamber with hydrophilic microstructure and group of combination thereof.
  • capillary pump based on porous material comprises filter, such as filter paper.Useful filter paper material comprises such as cellulose, cotton linter derivative material etc.
  • source or capillary pump based on porous material is made of porous material, and it is by capillary action fluid flow to downstream suction.Therefore, in the embodiment herein, electric power or active pump is not needed.Not limited by theory, this feature can help reduce or avoid the potential blockage of capillary pump based on porous material in use.
  • the capillary pumps herein may comprise microstructures that facilitate pumping fluid through the device.
  • the microstructures may comprise, for example, microchannels; or a plurality of microchannels, with or without a plurality of microstructures.
  • the capillary pump is unpowered, meaning that it is self-propelled, and No electricity is consumed or an external power source is required to draw fluid through the device.
  • the top layer of the separation membrane has an average pore size of about 7 ⁇ m to about 13 ⁇ m in diameter
  • the bottom layer has an average pore size of about 1 ⁇ m to about 3 ⁇ m in diameter.
  • these pore sizes are optimized to effectively filter out RBC, WBC, etc. from the plasma in a typical human blood sample.
  • the separation membrane further comprises an additional layer located near the sample inlet and above the top layer.
  • the average pore size of the additional layer may be, for example, about 20 ⁇ m to about 100 ⁇ m in diameter; or about 30 ⁇ m to about 75 ⁇ m in diameter; or about 40 ⁇ m to about 50 ⁇ m in diameter.
  • additional filters may remove larger contaminants in the blood sample, such as, for example, dirt, aggregated platelets, skin cells, tissue, microorganisms/bacteria, etc., which would otherwise reduce the effectiveness of the top filter and/or clog the top filter.
  • the microfluidic device further comprises a reaction chamber in fluid communication with the separation membrane, wherein the reaction chamber is downstream of the separation membrane.
  • the function of the reaction chamber may be to provide a location for a chemical reaction or a physical reaction, such as detecting a biomarker and, for example, a reactant for a reaction, wherein the reaction is selected from the group consisting of: a color reaction, an antibody reaction, an enzyme reaction, an electrochemical reaction, fluorescence, chemiluminescence, and a combination thereof; or a color reaction, an antibody reaction, an enzyme reaction, and a combination thereof.
  • the reaction chamber may detect a biomarker from plasma.
  • Such a biomarker may be selected from the group consisting of: biological cells, protein biomarkers, organic molecules, metal ions, and a combination thereof.
  • the biomarker may be, for example, lead ions, alpha-fetoprotein, SARS CoV-2 antibodies, SARS CoV-2 antigens, serum albumin, prostate-specific antigen, blood creatinine, blood cystatin C, glycosylated hemoglobin, and a combination thereof.
  • the microfluidic device in particular the reaction chamber, can further comprise a capture mechanism, such as an immobilized antibody, an immobilized antigen, an immobilized microparticle, and combinations thereof, to facilitate the capture of the biomarker.
  • the capture mechanism can be, for example, a reversible capture mechanism that can release the captured biomarker, for example, when a release solution is provided and added to the reaction chamber.
  • the release solution can achieve the release of such a biomarker by, for example, utilizing an ionic strength, pH, etc. different from that of the original blood sample.
  • the reaction chamber may be between the separation membrane and the capillary pump, or may even be contained within the capillary pump.
  • the reaction chamber is comprised within the capillary pump.
  • the reaction chamber protrudes from the microfluidic device downstream of the separation membrane, for example, after or parallel to the capillary pump, or directly downstream of the separation membrane.
  • embodiments of the present invention relate to a blood separation device and method that utilizes the pressure difference between the blood sample inlet, the manifold inlet and the capillary pump to separate plasma from whole blood across a separation membrane.
  • various devices can be used to utilize the pressure difference, such as syringe pumps, hydrostatic pumps, peristaltic pumps, etc., and in particular capillary pumps.
  • the core structure can also be in different forms, such as a syringe and its accessories, and an elastic tube equipped with a separation membrane that helps separate or purify plasma from a whole blood sample.
  • Embodiments of the present invention relate to a kind of microfluidic device, it has the pressure difference of the capillary drive across the separation membrane.
  • Microfluidic device can include microchannel or multiple microchannels for fluid, and the fluid is based on the wettability of capillary pump and moves downstream along the path by fluid wicking mechanism.
  • Typical fluid wicking material includes hydrophilic material, such as hydrophilic polymer (PDMS, acrylic acid) and ceramic (glass).
  • PDMS hydrophilic polymer
  • the pressure difference of capillary drive device may come from fluid interface.Such as porous membrane (filter paper, cotton, fiber membrane, the particulate of accumulation) allows this material of micro-size interface to produce pressure gradient, and this pressure gradient allows fluid to flow through channel/path when combined with separation porous membrane.Therefore, it can drive fluid to pass through separation porous membrane, separate plasma from whole blood, and large particles in whole blood such as RBC, WBC etc. are captured on separation membrane.
  • the microfluidic device herein provides plasma separation using a capillary-induced pressure differential across a separation membrane, which ensures automatic, unpowered, and nearly complete separation and extraction of plasma from a whole blood sample by utilizing ordered discharge.
  • Device components such as the blood sample inlet/channel, manifold inlet/channel, and reaction chamber have specially designed dimensions that have their own pressure and resistance when these channels are filled with fluid.
  • the pressure differential between the blood sample inlet/channel, manifold inlet/channel, and reaction chamber is designed so that the liquid meniscus from the blood sample inlet will be discharged first, while the liquid at the manifold inlet will remain stationary. The liquid meniscus from the manifold inlet will only move when the liquid in the blood sample inlet is completely discharged.
  • the device may include a channel layer made of block copolymer PDMS (polydimethylsiloxane) and a sealing layer made of glass (such as a glass slide).
  • PDMS polydimethylsiloxane
  • a sealing layer made of glass such as a glass slide.
  • the slide is particularly useful because it allows the user to directly observe the microfluidic device at work (e.g., see Figure 4).
  • the channel layer mold is first designed using AutoCAD with reference to the dimensions measured from the ordered emission calculation data.
  • the mold is made using a 3D printer (Phrozen Sonic Mini 8K, Hsinchu City, Taiwan, 30091) and a standard UV photosensitive resin (ANYCUBIC, Shenzhen, Guangdong, China).
  • HMDS hexamethyldisilane
  • CVD chemical vapor deposition
  • the block copolymer PDMS device and the glass slide were then plasma treated (Harrick Plasma PDC-001, New York, USA) at 700mTorr for 3 minutes and then bonded by light compression to produce a closed device.
  • the closed device was then heated at 95°C for 5 minutes to ensure a tighter bond and remove the plasma hydrophilic effect on the block copolymer PDMS and the glass slide.
  • a filter paper was then inserted into the outlet slot to act as a capillary pump for the device (see Figure 1).
  • a method for separating plasma from a blood sample includes the following steps: providing a microfluidic device according to the present application; providing a blood sample containing a plurality of red blood cells and plasma; if the vent is initially closed, opening the blood sample inlet before adding the blood sample, or opening the vent after adding the blood sample to the blood sample inlet, adding the blood sample to the blood sample inlet, and then adding the working fluid to the manifold inlet, extracting plasma through the orderly discharge of the manifold inlet and the blood sample inlet.
  • the orderly discharge allows the blood sample to flow preferentially downstream from the blood sample inlet to the separation membrane, and the plasma separated by the separation membrane is extracted.
  • the microfluidic device may be in a closed state.
  • the vent is closed with a vent cover, such as a removable seal, patch, plastic plug, etc.
  • the vent is opened to allow the blood sample to flow through the device.
  • the methods herein provide a simple, easy and easily operable method for separating plasma and any biomarkers therein from RBCs, WBCs, contaminants, etc. that may cause clogging and/or complicate further analysis.
  • the methods of the invention may be designed for use in a simple test kit, or may, for example, be scaled up for larger scale blood sample purification and/or biomarker separation and/or identification.
  • plasma flows downstream from the separation membrane to a capillary pump where the plasma can be collected, among other things.
  • FIG. 1A shows a circuit diagram simulating the flow resistance of an embodiment of the device of the present invention.
  • the blood sample inlet has a pressure P1 of -48.6Pa
  • the manifold inlet has a pressure P2 of -196.7Pa.
  • the resistance R1 from the blood sample inlet and the membrane is 83.5M ⁇
  • the resistance R2 from the manifold inlet is 5M ⁇ .
  • This provides a joint pressure Pj of -189.2Pa at the joint, and satisfies the condition P1>Pj>P2.
  • the reaction chamber provides a resistance Rrc of 20G ⁇
  • the capillary pump provides a pressure Pc of -4kPa.
  • Fig. 1B shows a top perspective view of an embodiment of a microfluidic device 10 of the present invention.
  • Microfluidic device 10 comprising a blood sample inlet 12 connected to a separation membrane 14.
  • a separate manifold inlet 16 is located at the distal end of the blood sample inlet 12, and is in fluid communication with the blood sample inlet 12 at a joint 18 through the separation membrane 14.
  • a reaction chamber 20 is located downstream of the joint 18, and a capillary pump 22 is in fluid communication with the reaction chamber 20 and the joint 18 and is located downstream of the reaction chamber 20 and the joint 18.
  • a vent 24 is in fluid communication with the capillary pump 22 downstream, and a vent cover 26 (a patch in this example) is shown peeled off from the vent 24.
  • the vent can be opened all the time or kept closed before use.
  • the vent cover 26 will usually cover and seal the vent 24, and after the blood sample is added to the blood sample inlet 12, the vent cover 26 can be removed.
  • a working fluid may be added to the manifold inlet 16 in order to extract plasma from the separation membrane 14 .
  • the separation membrane 14 is located downstream of the blood sample inlet 12, and the connector 18 is located downstream of the separation membrane 14. Similarly, the connector 18 is located downstream of the manifold inlet 16. Conversely, the manifold inlet 16 is located upstream of the connector 18.
  • FIG1C shows a side view of the embodiment of FIG1B .
  • the microfluidic device 10 has a blood sample inlet 12, a separation membrane 14, a manifold inlet 16, a connector 18, a reaction chamber 20, a capillary pump 22, and a vent 24.
  • the separation membrane 14 includes a top layer 28 adjacent to the blood sample inlet 12.
  • the separation membrane 14 also includes a bottom layer 30 away from the blood sample inlet 12.
  • the top layer 28 is in fluid communication with the bottom layer 30, and in this embodiment, the top layer 28 is directly upstream of the bottom layer 30. Upstream of the top layer 28 is an optional additional layer 32, which can further help remove unwanted materials, such as larger particles, before the blood sample flows to the top layer 28.
  • FIG2 shows a schematic partially exploded view of an embodiment of a microfluidic device 10 of the present invention.
  • the microfluidic device 10 is oriented in the opposite direction to that of FIG1B and includes a blood sample inlet 12, a separation membrane 14, a manifold inlet 16, a reaction chamber 20, and a capillary pump 22.
  • the separation membrane 14 is separated from the microfluidic device 10, and a top layer 28 with different pore sizes of 10 ⁇ m and a bottom layer 30 with a pore size of 2 ⁇ m are shown in close-up.
  • FIG2 also shows a glass slide 34 that can be fixed to the microfluidic device 10.
  • FIG. 3A shows a photograph of erythrocytes stained with DiD, wherein the red color indicates the presence of erythrocytes.
  • FIG. 3B shows a photograph of leukocytes stained with CMFDA green, wherein the green color indicates the presence of leukocytes.
  • the first (left) column of all rows indicates the zero time point; that is, 0 minutes after the working fluid is released to contact the capillary pump.
  • the second column of all rows represents the 1 minute time point after the working fluid contacts the capillary pump.
  • the third column of all rows represents the 9 minute time point after the working fluid contacts the capillary pump.
  • the fourth (right) column of all rows represents the 15 minute time point after the working fluid contacts the capillary pump.
  • FIG. 4 shows that the blood plasma of Cy5 dyeing has passed through reaction chamber completely and all accumulates in capillary chamber, and does not have RBC or WBC to pass through reaction chamber or accumulate in capillary chamber.
  • FIG. 4 photos therefore illustrate that blood plasma flows through blood sample inlet, separation membrane, joint and reaction chamber quickly and completely in 15 minutes, and accumulates in capillary pump.
  • RBC and WBC do not pass through separation membrane, therefore never enter joint, reaction chamber or capillary pump.
  • the RBCs and WBCs captured in the separation membrane do not hinder the flow of plasma downstream because they are all captured in the capillary pump.
  • Fig. 5A is a graph showing the relative fluorescence intensity of Cy5 dye labeled in whole blood in an embodiment of the present invention. This shows that the peak fluorescence intensity of Cy5-stained whole blood is about 6 minutes, and staining can be easily detected even after 15 minutes.
  • Fig. 5 B is a diagram showing the relative fluorescence intensity of the Cy5 dye labeled in the plasma after separation in an embodiment of the present invention. This shows that the peak fluorescence intensity of the plasma dyed with Cy5 is about 6.5 minutes, and the standardized fluorescence intensity of plasma is higher than the standardized fluorescence intensity of whole blood (Fig. 5 A).
  • FIG. 6 shows the average relative fluorescence intensity of TXRED and FITC channels, indicating that plasma was extracted without leakage and rupture of RBCs and WBCs in the reaction chamber at different concentrations of labeled plasma.
  • FIG. 7 is a graph comparing extracted plasma volumes at different expected plasma volumes between plasma and whole blood samples.
  • Red blood cells red blood cells
  • WBC white blood cells
  • DiD lipophilic dye carbocyanine 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate solid (DiD; Lumiprobe, Hunt Valley, Maryland, USA) for RBC and 1 ⁇ g/mL CellTracker TM Green (5-chloromethylfluorescein diacetate (aka, CMFDA, Lumiprobe, Hunt Valley, Maryland, USA) for WBC, in a volume ratio of 1:1, and incubated with continuous mixing at room temperature for 30 minutes.
  • DiD lipophilic dye carbocyanine 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate solid (DiD; Lumiprobe, Hunt Valley, Maryland, USA) for RBC and 1 ⁇ g
  • the stained blood cells were washed again 3 times with 1 ⁇ PBS buffer, and the plasma separated from the centrifugation step was reintroduced into the stained blood cells at a hematocrit (HCT) fraction of 50%.
  • HCT hematocrit
  • RBCs stained with DiD were detected with the Texas Red/TXRED channel (see Figure 3A)
  • WBCs stained with CMFDA green were detected with the FITC Green channel (see Figure 3B).
  • Plasma was labeled with cyanine 5 amine (Cy5; Lumiprobe) fluorescent dye at different concentrations (0, 10, 20, 50, 100 ⁇ g/ml).
  • Cy5 cyanine 5 amine
  • the labeled whole blood samples were then observed under bright field and fluorescence microscopy to ensure that all components were properly stained.
  • a time-lapse study was performed by injecting 10 ⁇ L of whole blood sample (Hct 50%) into the device and then injecting 20 ⁇ L of buffer through the manifold inlet. Images were taken of bright field, Cy5 red, FITC green, and TXRED channels every 30 seconds for 20 minutes to monitor the flow of plasma extracted by orderly discharge and the possibility of leakage or rupture of red and white blood cells during filtration. Referring to Figure 4, time-lapse images were then processed in ImageJ (National Institute of Health (NIH), Bethesda, Maryland, USA) to obtain the fluorescence image intensity in the reaction chamber. The intensity values were normalized by dividing the raw intensity values by the background value. The intensity of Cy5 determined the extraction volume of plasma versus time. DiD and CMFDA green intensities were used together with bright field images to observe RBC and WBC leakage and rupture.
  • the density of the whole blood sample, separated plasma and manifold buffer was calculated by weighing the known volume using a balance.
  • the experimental group injected the whole blood sample or separated plasma at the blood sample inlet, and the manifold was injected with the buffer working fluid.
  • the control group only injected the manifold buffer into the device.
  • each porous membrane used for the capillary pump was weighed.
  • the above experimental group weighing value was subtracted from the weight value of the control group.
  • the subtracted weight value was then converted to volume using the density of the corresponding fluid.

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  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical & Material Sciences (AREA)
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  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne un dispositif microfluidique (10), comprenant une entrée d'échantillon de sang (12), une membrane de séparation (14), une entrée de collecteur (16) en communication fluidique avec l'entrée d'échantillon de sang (12) au niveau d'un joint (18), une pompe capillaire (22) en communication fluidique avec le joint (18) et située en aval du joint (18) et un trou d'évent (24) en communication fluidique avec la pompe capillaire (22). La membrane de séparation (14) comprend une couche supérieure (28) adjacente à l'entrée d'échantillon (12) et une couche inférieure (30) distante de l'entrée d'échantillon (12). La couche supérieure (28) possède une taille de pore moyenne comprise dans la plage allant d'environ 1 µm à environ 50 µm. La couche inférieure (30) possède une taille de pore moyenne comprise dans la plage allant d'environ 0,05 µm à environ 20 µm. La membrane de séparation (14) est agencée entre l'entrée d'échantillon de sang (12) et le joint (18).
PCT/CN2023/136201 2023-06-20 2023-12-04 Dispositif microfluidique et procédé d'extraction de plasma sanguin à partir de sang total Ceased WO2024259905A1 (fr)

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US63/509,110 2023-06-20
US18/490,160 2023-10-19
US18/490,160 US20240183765A1 (en) 2022-12-02 2023-10-19 Microfluidic device and method for extracting blood plasma from whole blood

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KR20080051011A (ko) * 2006-12-04 2008-06-10 한국전자통신연구원 혈장 분리용 마이크로 필터 소자
CN101965225A (zh) * 2008-03-11 2011-02-02 皇家飞利浦电子股份有限公司 用于过滤流体的过滤装置
CN105050720A (zh) * 2013-01-22 2015-11-11 华盛顿大学商业化中心 顺序递送流体体积和相关的设备、系统和方法
CN109925884A (zh) * 2019-04-27 2019-06-25 南京岚煜生物科技有限公司 一种全血过滤的方法及用于全血过滤的滤膜结构
CN113167785A (zh) * 2018-09-06 2021-07-23 卡皮台内尔公司 微流体装置

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KR20080051011A (ko) * 2006-12-04 2008-06-10 한국전자통신연구원 혈장 분리용 마이크로 필터 소자
CN101965225A (zh) * 2008-03-11 2011-02-02 皇家飞利浦电子股份有限公司 用于过滤流体的过滤装置
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