WO2019047498A1 - Système et procédé de séparation de plasma de sang total - Google Patents

Système et procédé de séparation de plasma de sang total Download PDF

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Publication number
WO2019047498A1
WO2019047498A1 PCT/CN2018/079015 CN2018079015W WO2019047498A1 WO 2019047498 A1 WO2019047498 A1 WO 2019047498A1 CN 2018079015 W CN2018079015 W CN 2018079015W WO 2019047498 A1 WO2019047498 A1 WO 2019047498A1
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WIPO (PCT)
Prior art keywords
blood
plasma
array
microcolumn
microfluidic chip
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Application number
PCT/CN2018/079015
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English (en)
Chinese (zh)
Inventor
刘荣跃
韩琳
丁庆
冯军正
Original Assignee
深圳市太赫兹科技创新研究院有限公司
深圳市太赫兹科技创新研究院
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Publication of WO2019047498A1 publication Critical patent/WO2019047498A1/fr

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    • 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
    • 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
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B01L3/50255—Multi-well filtration
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • 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

Definitions

  • the embodiments of the present invention belong to the field of biomedical technology, and in particular, to a whole blood plasma separation system and method.
  • the blood is composed of blood cells and plasma.
  • the blood is closely related to the tissues and organs of various systems. Under normal physiological conditions, the quality and quantity of various components in the blood directly reflect the normal metabolism of the body and the environment inside and outside the body. In the pathological condition, in addition to directly reflecting the diseases of the human hematopoietic system, the blood can directly or indirectly reflect the lesions of the whole body or local tissues and organs. Therefore, blood can not only serve as the main basis for the diagnosis, differential diagnosis, therapeutic observation and prognosis of primary hematopoietic diseases, but also provide important information for the diagnosis and treatment of other systemic diseases that cause secondary blood changes. Normally, blood testing requires separation of blood cells from the blood because its presence can interfere with the spectral analysis of blood tests.
  • the invention can quickly separate a very small amount of blood sample, can directly connect the blood detecting device, improve the detection efficiency of the blood sample, has small volume and simple structure, and can meet the requirements of complete and rapid blood testing.
  • An embodiment of the present invention provides a whole blood plasma separation system including a first blood separation device and a second blood separation device, the first blood separation device including a blood collection unit and at least one first microfluidic chip.
  • the microfluidic array is disposed in the first microfluidic chip, the minimum column spacing of the microcolumn array is greater than or equal to the diameter of the red blood cells, and the second blood separation device comprises a second microfluidic chip, a plasma recovery unit, and a waste liquid recovery unit, wherein the second microfluidic chip is provided with a micro flow channel;
  • the blood collection unit, the at least one first microfluidic chip and the two microfluidic chips are sequentially arranged along the blood flow direction and sequentially connected end to end through a fluid conduit, and the plasma recovery unit passes through the fluid conduit and the microfluid a plasma outlet connection of the channel, the waste liquid recovery unit being connected to the waste liquid outlet of the micro flow channel through a fluid conduit;
  • the blood collected by the blood collection unit sequentially flows into the at least one first microfluidic chip, and the at least one first microfluidic chip intercepts blood cells in the blood to obtain platelets containing less than a preset amount
  • the plasma of the red blood cells the second microfluidic chip performs inertial focusing treatment on the plasma to obtain high purity plasma, platelets, and lower than a predetermined amount of red blood cells, and the high purity plasma flows into the plasma recovery unit,
  • the platelets and lower than a predetermined amount of red blood cells flow into the waste liquid recovery unit.
  • the microcolumn array comprises at least one sub-microcolumn array arranged in sequence along the blood flow direction, the column spacing of each of the sub-microcolumn arrays is different, and the column spacing of each sub-microcolumn array is in accordance with The arrangement order of the at least one sub-microcolumn array is sequentially reduced, and the micro-pillar array comprises at least an array of the most end red blood cell intercepting microcolumns, wherein the column spacing of the red blood cell intercepting microcolumn array is greater than or equal to the diameter of the red blood cells;
  • the array of red blood cell intercepting microcolumns intercepts blood cells in the blood to filter blood cells in the blood.
  • the micro-pillar array is any one of a cylindrical array, an elliptical cylinder array, or a polygonal cylinder array, and the micro-columns in the micro-column array have a diameter ranging from 10 micrometers to 200 micrometers.
  • the height of the microcolumns ranges from 10 microns to 200 microns.
  • the whole blood plasma separation system further includes a micropneumatic valve, the inlet of the micropneumatic valve is connected to a constant pressure gas source, and the outlet of the micropneumatic valve is connected to the inlet of the blood collection unit. ;
  • a constant pressure air source is outputted to the blood collection unit, and blood in the blood collection unit is pushed into the first microfluidic chip by gas pressure.
  • the whole blood plasma separation system further includes a plasma buffer pool, the inlet of the plasma buffer pool being connected to the outlet of the first microfluidic chip arranged at the extreme end by a fluid conduit, the blood An outlet of the buffer pool is connected to an inlet of the second microfluidic chip through a fluid conduit;
  • Plasma outputted from the first microfluidic chip arranged at the extreme end flows into the plasma buffer pool, and the plasma buffer pool stores the plasma, and when the plasma exceeds the storage capacity of the plasma buffer pool, the inflow The second microfluidic chip.
  • the micro flow channel includes a plurality of micro flow channel units that are periodically arranged, the plurality of micro flow channel units are connected end to end in sequence, and the micro flow channel unit includes a first semicircular micro flow channel and The second semi-annular microchannel, the outlet of the first semi-annular microchannel and the inlet of the second semi-circular microchannel are seamlessly docked.
  • the difference between the outer diameter and the inner diameter of the first semi-annular microchannel is equal to the circumscribed diameter at any one of the first semi-annular microchannels, and the second semi-circular microchannel
  • the difference between the outer diameter and the inner diameter is smaller than the maximum circumscribed diameter of the second semi-annular microchannel, and the outer diameter of the first semi-annular microchannel is smaller than the inner diameter of the second semi-annular microchannel.
  • the number of the micro flow channel units ranges from 1 to 50, and the first half annular micro flow channel and the second semicircular micro flow channel have a circumscribed diameter ranging from 1 micrometer to 200 micrometers. .
  • the plasma outlet is disposed above the waste liquid outlet.
  • Another aspect of the present invention provides a method for separating whole blood plasma, comprising:
  • Blood cells in the blood are at least once trapped by a microcolumn array having a minimum column spacing greater than or equal to the diameter of the red blood cells to obtain plasma containing platelets and less than a predetermined amount of red blood cells;
  • the platelets and the lower than a predetermined amount of red blood cells are simultaneously recovered.
  • the system provided by the embodiment of the present invention performs preliminary separation of blood cells in blood by a first blood separation device including a microcolumn array having a column spacing greater than or equal to the diameter of red blood cells, and performs blood on the blood through a second blood separation device including a micro flow channel.
  • Inertial focusing treatment, further separation of blood platelets and residual red blood cells can achieve rapid separation of blood cells and platelets in a very small amount of blood samples, can be directly connected to blood testing equipment, improve the detection efficiency of blood samples, small size, simple structure It can meet the requirements of complete and rapid blood testing.
  • FIG. 1 is a schematic structural view of a whole blood plasma separation system provided by an embodiment of the present invention.
  • FIG. 2 is a top plan view of a first microfluidic chip according to an embodiment of the present invention
  • FIG. 3 is a front view of a second microfluidic chip according to an embodiment of the present invention.
  • Figure 4 is a front elevational view of a microchannel provided by an embodiment of the present invention.
  • FIG. 5 is a schematic structural view of a whole blood plasma separation system according to another embodiment of the present invention.
  • FIG. 6 is a schematic structural view of a whole blood plasma separation system according to still another embodiment of the present invention.
  • FIG. 7 is a schematic flow chart of a method for separating whole blood plasma provided by an embodiment of the present invention.
  • one embodiment of the present invention provides a whole blood plasma separation system 100 that includes a first blood separation device 10 and a second blood separation device 20.
  • the first blood separation device is mainly used for pretreating blood, separating and trapping blood cells in the blood, and the blood cells in the blood mainly include red blood cells, and also including monocytes and white blood cells.
  • the blood cells in the blood mainly include red blood cells, and also including monocytes and white blood cells.
  • Tumor cells may also be included in the blood. Diameter of tumor cells > diameter of monocytes > diameter of leukocytes > diameter of red blood cells.
  • the first blood separation device 10 includes a blood collection unit 11 and at least one first microfluidic chip 12, and the first microfluidic chip 12 is provided with a microcolumn array 13 and micro The minimum column spacing of the column array 13 is greater than or equal to the diameter of the red blood cells.
  • the number of the first microfluidic chips can be set according to actual needs. The more the number of the first microfluidic chips, the better the separation and filtration effect on blood cells, but the excessive number can also cause the separation speed of blood cells to decrease. , thereby reducing the overall blood detection efficiency, therefore, should be based on the separation and filtration requirements of blood cells and blood detection efficiency requirements to comprehensive analysis, select the appropriate number of the first microfluidic chip, while ensuring the separation and filtration effect, To ensure separation efficiency.
  • Two first microfluidic chips are exemplarily shown in FIG.
  • the number of first microfluidic chips ranges from 1 to 10.
  • the smallest diameter cell in the blood cell is red blood cells, it is only necessary to make the minimum column spacing of the microcolumn array greater than or equal to the diameter of the red blood cell, so that filtration of all blood cells in the blood can be achieved.
  • the column spacing refers specifically to the width of the gap between any two adjacent micro-pillars in the direction perpendicular to the flow direction of the blood in the micro-column array, and the column spacing in the embodiment specifically refers to Horizontal column spacing.
  • the width of the gap between any two adjacent microcolumns (ie, the longitudinal column spacing) can be set according to actual needs, and the longitudinal column spacing can be Equal to the horizontal column spacing.
  • the microcolumns in the microcolumn array have a diameter ranging from 10 micrometers to 200 micrometers, and the microcolumnars have a height ranging from 10 micrometers to 200 micrometers.
  • the microcolumns have a diameter of 30 microns and the micropillars have a height of 40 microns.
  • the micropillar array can be any of a cylindrical array, an elliptical cylinder array, or a polygonal cylinder array.
  • a top view of the microcolumn array is exemplarily shown in Fig. 1, and the microcolumn array shown in Fig. 1 is a cylindrical array.
  • the column spacing cannot be made smaller than the size of all red blood cells, so some red blood cells cannot be effectively trapped.
  • the size of the preset amount can be determined by the number of microcolumn arrays and the column spacing. The smaller the column spacing, the smaller the preset amount.
  • the second blood separation device 20 includes a second microfluidic chip 21, a plasma recovery unit 22, and a waste liquid recovery unit 23, and the second microfluidic chip 21 is provided with a microflow. Road 24.
  • the plasma recovery unit specifically refers to a container for collecting and storing high-purity plasma output by the second blood separation device
  • the waste liquid recovery unit specifically refers to collecting and storing platelets and lower than a predetermined amount.
  • the container of red blood cells the size of which is determined by the amount of blood sample to be blood tested, can be selected according to actual needs.
  • the micro flow path may be a curved S-shaped micro flow channel, a linear micro flow channel or a micro flow channel of other shapes.
  • the shape of the micro flow channel is not particularly limited.
  • the micro flow channel is exemplarily shown in Fig. 1 as a curved S-shaped micro flow channel.
  • connection relationship between the components in the whole blood plasma separation system 100 provided in this embodiment is as follows:
  • the blood collection unit 11, at least one first microfluidic chip 12 (only two first microfluidic chips are exemplarily shown in FIG. 1) and two microfluidic chips 21 are sequentially arranged in the blood flow direction and through the fluid conduit 30.
  • the plasma recovery unit 22 is connected to the plasma outlet of the second microfluidic chip 21 through the fluid conduit 30, and the waste liquid recovery unit 23 is connected to the waste liquid outlet of the second microfluidic chip 21 through the fluid conduit 30.
  • a fluid conduit specifically refers to a universal microchannel for achieving a connection between an outlet and an inlet of two adjacent components so that blood can flow from one component to another, which may be glass micro.
  • the blood collected by the blood collection unit sequentially flows into the two first microfluidic chips, and the two first microfluidic chips respectively intercept the blood cells in the blood to obtain plasma containing platelets and lower than a predetermined amount of red blood cells;
  • the microfluidic chip performs inertial focusing treatment on plasma to obtain high-purity plasma, platelets and less than a predetermined amount of red blood cells, high-purity plasma flows into the plasma recovery unit, platelets and less than a predetermined amount of red blood cells through the inflow waste recovery unit .
  • the inertial focusing process specifically refers to: filtering the small-sized cells or particles remaining in the plasma by inertial focusing, and when the cells and the like flow in the micro-flow channel, in addition to being driven by the mainstream driving force, they are still in the vertical direction. Shear force caused by the difference in velocity gradient of the fluid and wall lift caused by the closed channel wall (Wall Effect Lift Force), shear force and wall lift are combined into inertial force. Under the action of inertial force, the cells will migrate at a fixed position in the microchannel, so they can be used to separate platelets and a small amount of red blood cells in plasma to obtain high-purity plasma.
  • the plasma outlet is disposed above the waste liquid outlet. Based on the principle of inertial force focusing treatment, it can be seen that the platelets and a small amount of red blood cells in the plasma after separation are discharged by gravity from the waste liquid outlet below, and the high-purity plasma for blood detection is from above. Plasma outlets flow out.
  • At least one microcolumn array is arranged by sequentially arranging at least one microcolumn array including an array of red blood cell intercepting microcolumns for trapping and filtering red blood cells along the blood flow direction, and making the column spacing of each microcolumn array different.
  • the column spacing is sequentially decreased in accordance with the arrangement order of the at least one microcolumn array, so that blood flows in from the inlet of the blood separation pretreatment chip, sequentially passes through the interception and filtration of the at least one microcolumn array, and the content is lower than the preset.
  • the amount of red blood cells and platelets of plasma flow out from the outlet of the blood separation pretreatment chip, which can achieve rapid separation of a very small amount of blood samples and improve the detection efficiency of blood samples.
  • the microcolumn array 13 includes at least one sub-microcolumn array arranged in sequence along the blood flow direction, and the column spacing of each sub-microcolumn array is different, and each sub-microcolumn array The column spacing is sequentially decreased in accordance with the arrangement order of at least one sub-microcolumn array, and the micro-column array 13 includes at least the last-end red blood cell-retaining micro-column array 131, and the column spacing of the red blood cell-retaining micro-column array 131 is greater than or equal to that of the red blood cells. diameter.
  • the number of sub-microcolumn arrays included in the microcolumn array can be set according to actual needs. Since the smallest blood cell in the blood is red blood cells, it is only necessary to ensure that the red blood cell interceptor microcolumn array can be realized. Interception and filtration of all blood cells in the blood.
  • the microcolumn array 13 includes a tumor cell interceptor microcolumn array 134, a mononuclear remnant microcolumn array 133, a white blood cell remnant microcolumn array 132, and a blood cell flow direction.
  • the number and type of sub-microcolumn arrays can be set according to actual needs. Multiple sub-microcolumn arrays of the same type can be placed at the same time to enhance the entrapment filtering effect.
  • FIG. 2 exemplarily shows a top view of the micro-pillar array 13 when the micro-pillar array 13 is a cylindrical array, and any two adjacent rows of micro-pillars are misaligned.
  • the misalignment arrangement specifically means that the adjacent two rows of microcolumns are not disposed opposite each other, but are arranged offset from each other by a certain distance, so that the entire microcolumn array constitutes an oblique array, and the inclination of the oblique array is Can be set according to actual needs.
  • each row of microcolumns in the microcolumn array can also be positioned facing up.
  • each row of microcolumns in the microcolumn array is arranged directly to form a rectangular array, the blood cells can easily flow out along a straight gap without occlusion, thereby reducing the interception and filtering effect on blood cells.
  • the diameter of the tumor cells is usually 17 microns to 52 microns. Therefore, the column spacing of the tumor cell interceptor microcolumn array should be less than or equal to 17 microns or slightly larger than 17 microns to achieve the majority of tumor cells. Interception. For example, the column spacing of the tumor cell interceptor microcolumn array can range from 17 microns to 25 microns.
  • the tumor cell interceptor microcolumn array has a column spacing of 20 microns and the tumor cell entrapment microcolumn diameter is 20 microns.
  • the cross-sectional size and height of each microcolumn in the tumor cell interceptor microcolumn array can be set according to actual needs, for example, the height can be greater than 52 microns; when the tumor cell intercepts the microcolumn width in the microcolumn array The range is 10 ⁇ 30 microns, for example, 10 microns, 15 microns, 20 microns, 25 microns or 30 microns; when the microcolum is cylindrical, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square column, the microcolumn Width refers to the square side length of the square column.
  • the column spacing of the mononuclear interceptor microcolumn array is less than or equal to the diameter of the monocytes and greater than the diameter of leukocytes, red blood cells, and platelets in the blood.
  • the diameter of monocytes is usually 15 microns to 25 microns. Therefore, the column spacing of the mononuclear interceptor microcolumn array should be less than or equal to 15 microns or slightly larger than 15 microns to achieve most Interception of nuclear cells. For example, the column spacing of the mononuclear interceptor microcolumn array can range from 15 microns to 17 microns.
  • the mononuclear interceptor microcolumn array has a column spacing of 15 microns and the monocyte trapped microcolumn has a diameter of 18 microns.
  • the cross-sectional size and height of each microcolumn in the mononuclear interceptor microcolumn array can be set according to actual needs, for example, the height can be greater than 25 microns; when the mononuclear cells are in the microcolumn array
  • the width of the column ranges from 10 micrometers to 30 micrometers, for example, 10 micrometers, 15 micrometers, 20 micrometers, 25 micrometers, or 30 micrometers; when the microcolumn is a cylinder, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square pillar The microcolumn width refers to the square side length of the square column.
  • the column spacing of the leukocyte-retaining micro-pillar array is less than or equal to the diameter of the white blood cells and greater than the diameter of the red blood cells and platelets in the blood.
  • the diameter of white blood cells is usually 7 micrometers to 10 micrometers, 12 micrometers to 20 micrometers, or 14 micrometers to 20 micrometers. Therefore, the column spacing of the white blood cell interceptor microcolumn array should be less than or equal to 7 micrometers or slightly larger than 7 micrometers. To achieve the interception of most white blood cells. For example, the column spacing of the white blood cell interceptor microcolumn array can range from 7 microns to 14 microns.
  • the column spacing of the leukocyte-retaining micro-pillar array is 10 microns and the diameter of the leukocyte-retaining micro-column is 12 microns.
  • the cross-sectional size and height of each microcolumn in the array of white blood cell intercepting micropillars can be set according to actual needs, for example, the height can be greater than 20 micrometers;
  • the microcolumn width in the array of white blood cell intercepting microcolumns is 5 Micron ⁇ 25 microns, for example, 5 microns, 10 microns, 15 microns, 20 microns or 25 microns; when the microcolumns are cylindrical, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square column, the microcolumn width is Refers to the square side length of the square column.
  • the diameter of the red blood cells is usually 6 micrometers to 8 micrometers. Therefore, the column spacing of the red blood cell interceptor microcolumn array should be less than or equal to 6 micrometers or slightly larger than 6 micrometers to achieve the retention of most red blood cells.
  • the column spacing of the erythrocyte interceptor microcolumn array can range from 4 microns to 7 microns.
  • the red blood cell trap micropillar array has a column spacing of 5 microns and the red blood cell trapped microcolumn has a diameter of 10 microns.
  • the cross-sectional size and height of each microcolumn in the red blood cell intercepting microcolumn array can be set according to actual needs, for example, the height can be greater than 8 micrometers; the microcolumn width in the red blood cell intercepting microcolumn array ranges from 5 Micron ⁇ 25 microns, for example, 5 microns, 10 microns, 15 microns, 20 microns or 25 microns; when the microcolumn is a cylinder, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square column, the microcolumn Width refers to the square side length of the square column.
  • the working principle of the micro-pillar array 13 provided in this embodiment is as follows:
  • the tumor cell interceptor microcolumn array intercepts tumor cells in the blood to filter tumor cells in the blood;
  • the monocyte interceptor microcolumn array intercepts monocytes in the blood to filter monocytes in the blood
  • the white blood cell interceptor microcolumn array intercepts white blood cells in the blood to filter white blood cells in the blood;
  • the blood flows from the inlet of the first microfluidic chip, in turn through the tumor cell interceptor microcolumn array, the mononuclear truncation microcolumn array, the leukocyte truncated microcolumn array, and the red blood cell interceptor microcolumn array, for tumors in the blood After the cells, monocytes, white blood cells, and red blood cells are intercepted and filtered, plasma containing less than a predetermined amount of red blood cells and platelets is allowed to flow out from the outlet of the first microfluidic chip.
  • the first blood separation device comprises four first microfluidic chips arranged in sequence along the blood flow, wherein the first microfluidic chip comprises a tumor cell interceptor microcolumn array, a second microfluidic
  • the control chip comprises a mononuclear truncated micropillar array, the third microfluidic chip comprises a white blood cell remnant microcolumn array, and the fourth microfluidic chip comprises a red blood cell interceptor microcolumn array.
  • blood cells in the blood are sequentially intercepted and filtered by a microcolumn array including a plurality of sub-microcolumn arrays, thereby enabling efficient separation of blood cells in the blood and obtaining plasma of higher purity.
  • the micro flow channel 24 includes a plurality of micro flow channel units 241 that are periodically arranged, and the plurality of micro flow channel units 241 are connected end to end in sequence, and the micro flow channel unit
  • the 241 includes a first semi-annular microchannel 2411 and a second semi-annular microchannel 2412.
  • the outlet of the first semi-annular microchannel 2411 and the inlet of the second semi-annular microchannel 2412 are seamlessly butted.
  • the number of microchannel units can be set according to actual needs.
  • Speed which reduces blood detection efficiency. Therefore, the separation effect and separation speed requirements of platelets and residual red blood cells should be comprehensively considered according to actual needs, and an appropriate number of microchannel units should be set.
  • the number of microchannel units ranges from 1 to 50.
  • the number of microchannel units ranges from 18.
  • the micro-pipe 24 is exemplarily shown to include five micro-pipe units 241.
  • the difference between the outer diameter R3 of the microchannel and the inner diameter R4 is smaller than the maximum circumscribed diameter L2 of the second semicircular microchannel, that is, R3-R4 ⁇ L2; the outer diameter R1 of the first semicircular microchannel is smaller than the second half ring
  • the inner diameter R4 of the microchannel, that is, R1 ⁇ R4; the circumscribed diameter L1 at any position on the first semicircular microchannel is smaller than the maximum secant diameter L2 of the second semicircular microchannel, that is, L1 ⁇ L2.
  • the first semi-annular microchannel and the second semi-annular microchannel have a circumscribed diameter ranging from 1 micron to 200 microns.
  • the second half-annular microchannel has a maximum circumscribed diameter L2 of 30 microns.
  • the first semi-annular microchannel has a width M1 of 280 microns and the first semi-annular microchannel has an outer diameter R1 of 300 microns.
  • the second semi-annular microchannel has a width M2 of 550 microns and the second semi-annular microchannel has an outer diameter R3 of 980 microns.
  • the residual platelets and blood cells in the plasma can be effectively separated, and high-purity plasma is obtained, thereby improving the accuracy of blood detection.
  • the whole blood plasma separation system 100 further includes a micro pneumatic valve 40.
  • the air inlet of the micro pneumatic valve 40 is connected to a constant pressure air source, and the air outlet of the micro pneumatic valve 40 is connected.
  • the micropneumatic valve specifically refers to a microvalve that is equivalent to the volume of the first microfluidic chip for opening when a gas having a constant pressure is connected, and driving the gas output by gas pressure.
  • the constant pressure origin specifically means that the pressure of the gas required to be kept constant during one blood separation process, so that the blood can be pushed into the first microfluidic chip at a constant speed. In different blood separation processes, depending on the blood concentration and the blood flow rate requirements, the pressure of the gas can be adjusted according to actual needs.
  • the blood can be prevented from being contaminated, and the blood separation speed can be controlled by controlling the pressure and flow rate of the gas.
  • the whole blood plasma separation system 100 further includes a plasma buffer pool 50 through which the inlet of the plasma buffer pool 50 passes through the fluid conduit 30 and the first microfluidic array arranged at the extreme end.
  • the outlet of the chip 12 is connected, the outlet of the blood buffer pool 50 is connected to the inlet of the second microfluidic chip 21 through the fluid conduit 30; the plasma outputted from the first microfluidic chip 12 arranged at the extreme end flows into the plasma buffer pool 50, plasma
  • the buffer pool 50 stores plasma, and when the plasma exceeds the storage capacity of the plasma buffer pool 50, it flows into the second microfluidic chip 21.
  • the plasma buffer pool refers specifically to a container for collecting and storing the blood plasma containing platelets and red blood cells below a predetermined amount, which is output by the first blood separation device, and the volume of the container is specifically determined by blood detection.
  • the amount of blood sample is determined and can be selected according to actual needs.
  • an embodiment of the present invention provides a method for separating whole blood plasma, comprising:
  • Step S101 collecting blood, the blood including whole blood plasma.
  • blood can be collected by any feasible blood collection method, such as blood collection through a blood collection tube and a matching hose and needle.
  • the blood usually refers to the arterial or venous blood of the human body, and of course can also be animal blood.
  • the manner of collecting blood is not particularly limited.
  • step S101 is performed by the blood collection unit of any of the above embodiments.
  • Step S102 At least one entrapment of blood cells in the blood is performed by a microcolumn array having a minimum column spacing greater than or equal to the diameter of the red blood cells, thereby obtaining plasma containing platelets and less than a predetermined amount of red blood cells.
  • the retention of blood cells is mainly to filter out blood cells such as white blood cells, monocytes, and red blood cells that interfere with the spectral analysis of plasma in the blood.
  • step S102 is performed by the first microfluidic chip in any of the above embodiments, and the red blood cells in the blood and other blood cells larger than the red blood cells are intercepted by the microcolumn array to realize blood cells in the blood. Filtering.
  • the step of filtering the blood may be performed by filtering the blood by the same first microfluidic chip at least once.
  • the first microfluidic chip may also be sequentially used. Filter the blood to achieve multiple filtration of the blood.
  • Step S103 performing inertial focusing treatment on the plasma by a microfluidic chip provided with a micro flow channel, further filtering the platelets and the lower than a predetermined amount of red blood cells to obtain high purity plasma.
  • step S103 is performed by the second microfluidic chip of any of the above embodiments.
  • Step S104 recovering the high-purity plasma separately
  • Step S105 simultaneously recovering the platelets and the lower than a predetermined amount of red blood cells.
  • different recovery containers can be used to recover high-purity plasma and platelets and less than a predetermined amount of red blood cells, respectively, because platelets and lower than a predetermined amount of red blood cells are mixed by inertial force. Together, therefore, platelets and lower than a predetermined amount of red blood cells are simultaneously recovered, and high purity plasma is separately recovered for subsequent blood testing.
  • step S104 is performed by the plasma recovery unit of any of the above embodiments
  • step S105 is performed by the waste liquid recovery unit of any of the above embodiments.
  • the method further includes the following steps:
  • the plasma is buffered.
  • the buffer specifically refers to a step of buffering and storing the plasma so that the blood enters the inertial force after a short storage.
  • plasma can be buffered by any plasma storage container.
  • the step of buffering the plasma described above may be specifically performed by the plasma buffer pool of the above embodiment.
  • the whole blood plasma processing method provided by the method embodiments of the present invention can be achieved by the whole blood plasma separation system provided by any of the above system examples.
  • the blood cells in the blood are intercepted by the microcolumn array, and the blood cells in the blood can be initially separated, and the blood is subjected to inertial focusing treatment to further separate the blood platelets and residual red blood cells, thereby achieving a very small amount of blood samples.
  • the rapid separation of blood cells and platelets improves the detection efficiency of blood samples.

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Abstract

L'invention concerne un système et un procédé de séparation de plasma de sang total. Le système comprend : un premier appareil de séparation de sang et un second appareil de séparation de sang. Le premier appareil de séparation de sang comprend une unité de collecte de sang et au moins une première puce de commande de micro-écoulement, un réseau de micro-colonnes est disposé dans la première puce de commande de micro-écoulement, et un intervalle de colonne minimum du réseau de micro-colonnes est supérieur ou égal au diamètre d'un érythrocyte. Le second appareil de séparation de sang comprend une seconde puce de commande de micro-écoulement, une unité de récupération de plasma et une unité de récupération de fluide résiduel, et un passage de micro-écoulement est situé sur la seconde puce de commande de micro-écoulement. L'unité de collecte de sang, lesdites premières puces de commande de micro-écoulement et la seconde puce de commande de micro-écoulement sont agencées le long de la direction d'écoulement du sang et sont successivement reliées par l'intermédiaire de tuyaux de fluide d'une manière tête-bêche ; l'unité de récupération de plasma est reliée à une sortie de plasma du passage de micro-écoulement par l'intermédiaire d'un tuyau de fluide ; et l'unité de récupération de fluide résiduel est reliée à une sortie de fluide résiduel du passage de micro-écoulement par l'intermédiaire d'un tuyau de fluide. La solution permet de réaliser une séparation rapide d'hémocytes et de thrombocytes dans une petite quantité d'échantillon de sang, ce qui améliore l'efficacité de détection de l'échantillon de sang.
PCT/CN2018/079015 2017-09-08 2018-03-14 Système et procédé de séparation de plasma de sang total WO2019047498A1 (fr)

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