CN110918144A - Microfluidic chip and whole blood separation method based on microfluidic chip - Google Patents

Microfluidic chip and whole blood separation method based on microfluidic chip Download PDF

Info

Publication number
CN110918144A
CN110918144A CN201911279204.2A CN201911279204A CN110918144A CN 110918144 A CN110918144 A CN 110918144A CN 201911279204 A CN201911279204 A CN 201911279204A CN 110918144 A CN110918144 A CN 110918144A
Authority
CN
China
Prior art keywords
microfluidic chip
blood
flow resistance
unit
plasma
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201911279204.2A
Other languages
Chinese (zh)
Inventor
陈思卉
陈希
杨慧
张翊
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen Institute of Advanced Technology of CAS
Original Assignee
Shenzhen Institute of Advanced Technology of CAS
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 Shenzhen Institute of Advanced Technology of CAS filed Critical Shenzhen Institute of Advanced Technology of CAS
Priority to CN201911279204.2A priority Critical patent/CN110918144A/en
Publication of CN110918144A publication Critical patent/CN110918144A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502753Containers 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

Abstract

When whole blood flows through the branched branch passage opening, blood cells are subjected to asymmetric shearing forces on two sides, the main passage with high flow rate and low flow resistance is selected to continue to advance, and partial plasma enters the branched branch passage; when the microfluidic chip adjusts the flow resistance through the flow resistance adjusting unit 130 positioned in the branch passage, the collection efficiency of the plasma is adjusted; the microfluidic chip provides capillary driving force and realizes the functions of quantifying and collecting plasma/serum through the capillary pump unit 140 positioned at the tail end, and finally realizes on-chip self-driven whole blood separation. The microfluidic chip provided by the invention has great application potential in the field of integrated and microminiaturized bedside real-time detection.

Description

Microfluidic chip and whole blood separation method based on microfluidic chip
Technical Field
The invention relates to the technical field of micro-fluidic technology, in particular to a micro-fluidic chip and a whole blood separation method based on the micro-fluidic chip.
Background
Blood, the most popular sample in clinical diagnosis, contains a large proportion of disease markers in human body, is suitable for various tests such as immunodiagnosis, clinical biochemistry, molecular diagnosis and the like, and is the most common sample object at present. Most tests performed on blood require removal of blood cells from the blood for plasma or serum extraction, or enrichment of cells in the blood for the next relevant test, during the sample pre-treatment stage. Different from the traditional whole blood separation methods such as centrifugation, filtration, salting-out and the like, the whole blood separation method needs a corresponding novel miniaturized and high-integration whole blood separation method in the emerging in-vitro diagnosis fields such as microfluidic technology, lab-on-a-chip and the like.
The whole blood separation method based on the micro-fluidic technology can be divided into an active type and a passive type according to the existence of power provided by an external physical field. The active method is not easy to integrate with other microfluidic functional devices because of the related complex control structures of magnetism, electricity, ultrasonic waves and the like. The passive method mainly depends on fluid dynamics and a micro-channel geometric structure to realize different behavior control of blood, has relatively simple preparation process and easy integration, and shows advantages in developing microminiaturized Point-of-care instruments. According to different separation principles, the passive microfluidic whole blood separation method can be divided into three types, namely filtration, sedimentation and directional cell migration. Different from the other two methods, the cell directional migration method realizes effective plasma extraction by directionally controlling the blood cell movement track, and has advantages in the field of developing easily-controlled high-purity whole blood separation devices.
At present, the cell directional migration method is mainly used for separating whole blood and has the following two implementation schemes: 1. the deterministic lateral displacement method is characterized in that blood passes through a series of regularly ordered microstructures in the laminar flow process, and cells can generate deterministic lateral displacement according to different sizes of the cells, so that the separation of blood plasma and blood cells is realized; 2. the hydrodynamic method realizes the directional lateral migration of cells by using the modes of inertia force, viscous force, dean vortex and the like generated by a vertical or bent pipe wall on the cells, thereby achieving the purpose of separating the cells from plasma.
Because the blood has high viscosity and the plasma can be further increased after separation, the whole blood separation realized by the two methods at present needs to provide power control for the blood through a negative pressure pump or a fluid pump, and the whole separation device is not easy to be miniaturized.
Disclosure of Invention
In view of the above, it is necessary to provide a microfluidic chip with high integration and microminiaturization degree and a whole blood separation method based on the microfluidic chip, in order to overcome the defects of the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
in one aspect, the present invention provides a microfluidic chip comprising: the blood flow resistance adjusting unit is used for adjusting the flow resistance of the front end and the rear end of the bifurcation branch unit respectively, when whole blood flows through the bifurcation branch passage port, blood cells are subjected to asymmetric shearing force on two sides, the main passage with large flow rate and small flow resistance can be selected to continue to advance, and partial blood plasma can enter the bifurcation branch passage.
In some preferred embodiments, the width of the branched branch channel is 10-500 microns, and the width of the main channel is 20-1000 microns.
In some preferred embodiments, the apparatus further comprises a sample inlet unit, wherein the sample inlet unit is provided with a micro-column array on the circumferential edge, and the sample inlet unit can filter the aggregated cells with larger size and impurities from the blood.
In some preferred embodiments, the diameter of the micro-pillars is 10 to 500 micrometers, and the micro-pillars are spaced 10 to 500 micrometers apart.
In some preferred embodiments, one end of the sample inlet unit is provided with a drainage scoop through which blood can be prevented from being blocked during the filtration of the microcolumn array.
In some preferred embodiments, the flow resistance ratio of the main channel to the branch channel is 1: 2.5-1: 200.
In some preferred embodiments, the device further comprises a capillary pump unit capable of collecting blood and plasma, wherein the capillary pump unit is distributed in a micro-column array shape.
In some preferred embodiments, the microfluidic chip is a single-layer or multi-layer structure, and the depth of the microchannel of the microfluidic chip is 30-1000 microns.
In another aspect, the invention further provides a whole blood separation method based on the microfluidic chip, which includes the following steps:
adding a blood sample into a sample inlet unit of the microfluidic chip;
the flow resistance of the front end and the rear end of the branch channel are respectively regulated under the action of the flow resistance regulating units arranged at the front end and the rear end of the branch channel;
when blood flows through the branch passage, because shearing force applied to two sides is asymmetric, blood cells can be directed to flow into the main passage, and plasma can enter the branch passage;
the plasma entering the branched branch channel continues to advance under the self-driving of capillary force until entering the capillary pump unit;
the separated blood passes through the flow resistance regulating unit in the main channel until entering the capillary pump unit;
the capillary pump unit collects and measures blood and plasma.
The invention adopts the technical scheme that the method has the advantages that:
the microfluidic chip provided by the invention can realize whole blood separation without external power through the microfluidic chip constructed by a branched multi-branch structure, can regulate and control the collection efficiency of plasma/serum through the design of a liquid path, and shows great application potential in the field of integrated and microminiaturized in-bed real-time detection.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
Fig. 1 is a schematic structural diagram of a microfluidic chip according to a first embodiment of the present invention;
fig. 2 is a partially enlarged view of the branching unit 110 according to one embodiment of the present invention;
fig. 3 is a schematic process diagram of a microfluidic chip according to a second embodiment of the present invention;
fig. 4 is a flowchart of steps of a whole blood separation method based on the microfluidic chip according to a third embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example one
Referring to fig. 1, a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention includes: at least one branch branching unit 110, wherein any branch branching unit 110 comprises a main channel 111 and at least one branch branching channel 112 extending from the main channel 111, when whole blood flows through the branch branching channel 112, the blood cells are subjected to asymmetric shear forces on two sides, the main channel 111 with high flow rate and low flow resistance is selected to continue to advance, and part of blood plasma enters the branch branching channel 112.
The specific structure and the manner of connection of the respective components to each other will be described in detail below.
Please refer to fig. 1C and fig. 2, which are a schematic structural diagram and a partial enlarged view of any one of the bifurcating branch units 110 provided in this embodiment.
In the present embodiment, the branched branch channels 112 are designed to be multi-branched transversely perpendicular to the main channel 111. It will be appreciated that the connection of the bifurcated branch passage 112 to the main passage 111 is not limited to being transversely perpendicular, as long as it is cross-connected to the main passage.
In the present embodiment, the bifurcated branch passages 112 are arranged in a linear shape. It is understood that the shape arrangement of the multiple branches is not limited to a straight line, but also can be a snake shape, a spiral shape, etc., and the size is not limited to the demonstration in the embodiment, and only the Zweifach-Fung effect needs to be satisfied.
In this embodiment, the width of the branched branch channel 112 is 10 to 500 micrometers, and the width of the main channel 111 is 20 to 1000 micrometers. It can be understood that the width of the fork branch channel and the width of the main channel can be adjusted according to the situation in practice.
It can be understood that when whole blood passes through the branched branch unit 110, the blood cells can flow through the main channel 111 with a larger flow rate and a smaller flow resistance due to the asymmetric shear force, and the plasma can enter the branched branch channel 112 with a smaller flow rate and a larger flow resistance (Zweifach-warming effect), so that the blood cells can move directionally to separate the plasma.
Referring to fig. 1B, the microfluidic chip according to the embodiment of the present invention further includes a sample inlet unit 120, the sample inlet unit 120 is provided with a micro-column array 121 on a circumferential edge, and blood can filter aggregated cells and impurities with larger sizes through the sample inlet unit 120.
In this embodiment, the diameter of the micro-pillars is 10 to 500 micrometers, and the micro-pillar spacing is 10 to 500 micrometers. It is understood that the design of the microcolumn is not limited to the various sizes and shapes mentioned in the embodiment, and the microcolumn can be designed to have different sizes, intervals and spatial arrangements for the specific objects to be filtered in different biochemical solution samples, and only the characteristic size of the microcolumn is required to be not smaller than the blood cells in the blood (for example, the white blood cells with the diameter of 6-20 microns) and not larger than the aggregated cells and the impurity size to be filtered.
In some preferred embodiments, one end of the sample inlet unit 120 is provided with a drainage scoop 122, and the blood can be prevented from being blocked by the drainage scoop 122 when the micro-column array 121 is filtered.
It can be understood that the inlet of the microfluidic chip is not limited to one sample inlet unit 120, and may be designed as a plurality of inlets as required, thereby correspondingly improving the chip area utilization efficiency and the whole blood separation efficiency.
Referring to fig. 1 a, the microfluidic chip further includes flow resistance adjusting units 130 disposed at the front end and the rear end of any of the branched branch units 110, and the flow resistance adjusting units 130 respectively adjust the flow resistance of the front end and the rear end of the branched branch units 110.
In this embodiment, the flow resistance adjusting unit 130 adopts a serpentine channel as a flow resistance adjusting structure, and generates corresponding resistance to fluid by designing channels with different sizes (length, width, and depth), and at the same time, effectively saves chip area. It is understood that the structure of the flow resistance adjusting unit 130 may also be designed as a micro channel in various shapes such as a vertical shape, a spiral shape, and the like.
In the embodiment of the invention, the flow resistance ratio (characteristic ratio) of the main channel 111 and the branch channel 112 is 1: 2.5-1: 200, and the plasma separation purity is improved along with the improvement of the characteristic ratio. It will be appreciated that the choice of feature ratios can also be designed to be a broader number, as long as the Zweifach-Fung effect is satisfied.
It can be understood that the flow resistance adjusting unit is adopted in the invention, under the requirement of capillary force self-driving on the size of the microchannel, the efficiency of separating plasma/serum from whole blood is adjusted, the dependence on an external power control device in the whole blood separation process is greatly reduced, and the invention has good microminiaturization and integration potential.
Referring to fig. 1, the microfluidic chip of the present invention further includes a capillary pump unit 140, and the capillary pump unit 140 can collect and measure blood and plasma.
In this embodiment, the capillary pump units 140 are distributed in a micro-column array, and the shape, size, dimension, etc. of the micro-columns can be designed to various parameters while ensuring the characteristic dimension, as long as the characteristic dimension is not less than the separation object required by the experiment and sufficient capillary force is provided.
It is understood that the capillary pump unit 140 is not limited to the micro-column array distribution, but may also include christmas tree-like, serpentine channel-like structures, etc.
The microfluidic chip provided by the embodiment of the invention is of a single-layer structure, and the depth of the microchannel is 30-1000 microns.
It can be understood that the microfluidic chip can be expanded into a double-layer or even multilayer structure by combining different liquid path control and modules on a biochemical experiment sheet, for example, a double-layer valve structure, a double-layer cross-linking channel and the like are added; the microchannel depth is not limited to that described in the present embodiment.
When whole blood flows through the branched branch passage opening, blood cells are subjected to asymmetric shearing forces on two sides, the main passage with high flow rate and low flow resistance is selected to continue to advance, and partial plasma enters the branched branch passage; when the microfluidic chip adjusts the flow resistance through the flow resistance adjusting unit 130 positioned in the branch passage, the collection efficiency of the plasma is adjusted; the microfluidic chip provides capillary driving force and realizes the functions of quantifying and collecting plasma/serum through the capillary pump unit 140 positioned at the tail end, and finally realizes on-chip self-driven whole blood separation. The microfluidic chip provided by the invention has great application potential in the field of integrated and microminiaturized bedside real-time detection.
Example two
In this embodiment, the microfluidic chip provided by the present invention may be a material that can be manufactured by a micro-nano processing method, such as a silicon-based material, such as monocrystalline silicon, silicon oxide, silicon nitride, etc., or a glass material, such as quartz, etc., or may be a polymer material, such as Polydimethylsiloxane (PDMS), Polymethyl methacrylate (PMMA), etc. Aiming at different materials and different sizes required by channels in the chip, the preparation method comprises but is not limited to micro-nano processing methods such as laser etching, 3D printing, photoetching, plasma etching and the like.
Referring to fig. 3, a schematic process diagram of a microfluidic chip according to an embodiment of the present invention includes the following steps:
s1: and (3) coating a layer of photoresist on the substrate in a suspending way, forming a micro-channel etching window by utilizing a corresponding micro-channel mask plate through a photoetching process, and removing the part of the anode film sacrificial layer by utilizing an etching process.
In this embodiment, the substrate is glass or silicon. It is understood that the substrate includes, but is not limited to, glass materials such as quartz and silicon-based materials such as silicon oxide and silicon nitride.
In the present embodiment, the positive sacrificial layer includes, but is not limited to, photoresist (including positive photoresist, negative photoresist, and other photoresists), silicon oxide, silicon nitride, silicon carbide, or metal materials such as chrome and aluminum.
It can be understood that the above microfluidic chip preparation process is not limited to the photoresist plasma etching method in the embodiment, but can also etch a micro channel on a glass or PMMA material by means of laser etching, prepare a micro-pillar array on a glass or silicon substrate by means of photolithography, and then bond the two; or forming fluid channel patterns on the surface of glass or organic material by using a laser direct writing mode.
S2: and etching the base material of the part where the micro-channel is located by taking the anode film layer on the substrate as a mask to form a final micro-channel, and removing the residual anode film layer.
In this embodiment, the etching includes, but is not limited to, plasma etching, deep silicon etching, wet etching, and the like, and the removing process includes, but is not limited to, cleaning with concentrated sulfuric acid and hydrogen peroxide, cleaning with other organic solvents, and the like.
S3: the surface chemical treatment is carried out on the micro-fluidic chip with the micro-channel structure, the hydrophilic treatment of the surface of the micro-fluidic chip is realized, and the stability and the uniformity of the physicochemical property of the surface of the chip are improved.
The surface chemical treatment method for the micro-fluidic chip with the micro-channel structure is not limited to chemical methods such as soaking, fumigating and spraying, and can also adopt methods such as electrochemistry, thermal processing, vapor deposition and the like.
In this embodiment, the chemical treatment agents include, but are not limited to, polyethylene glycol (PEG), 3-Aminopropyltriethoxysilane (APTES), and the like, and the treatment methods include, but are not limited to, fumigation, soaking, spraying, and the like.
It is understood that the following functions of the microfluidic chip can be realized by surface chemical treatment: (1) the whole blood sample is hydrophilized, so that the capillary force driving capability of the whole blood sample on the surface is improved; (2) the uniformity and the stability of the physicochemical property of the surface of the chip are improved, so that the nonspecific adsorption of the substrate to cells and proteins in blood is blocked, and the whole blood sample is not easy to adhere and stagnate when passing through the chip.
EXAMPLE III
Referring to fig. 4, the present invention further provides a whole blood separation method based on the microfluidic chip, including the following steps:
step S110: adding a blood sample into the sample inlet unit 120 of the microfluidic chip;
it is understood that the blood sample for separating the whole blood realized by the microfluidic chip can be untreated blood, anticoagulated blood, diluted blood, etc.
Step S120: the flow resistance adjusting units 130 arranged at the front end and the rear end of the branched branch passage 112 respectively adjust the flow resistance of the front end and the rear end of the branched branch passage 112;
step S130: when blood flows through the branched branch passage 112, because the shearing force applied to the two sides is asymmetric, blood cells are directed to pass through the main passage 111, and plasma enters the branched branch passage 112;
step S140: the plasma entering the branched branch passage 112 continues to advance under the self-driving of capillary force until entering the capillary pump unit 140;
step S150: the separated blood passes through the flow resistance adjusting unit 130 in the main channel 111 until entering the capillary pump unit 140;
step S160: the capillary pump unit 140 collects and measures blood and plasma.
When whole blood flows through the branched branch passage opening, blood cells are subjected to asymmetric shearing forces on two sides, the main passage with high flow rate and low flow resistance is selected to continue to advance, and partial plasma enters the branched branch passage; when the microfluidic chip adjusts the flow resistance through the flow resistance adjusting unit 130 positioned in the branch passage, the collection efficiency of the plasma is adjusted; the microfluidic chip provides capillary driving force and realizes the functions of quantifying and collecting plasma/serum through the capillary pump unit 140 positioned at the tail end, and finally realizes on-chip self-driven whole blood separation. The microfluidic chip provided by the invention has great application potential in the field of integrated and microminiaturized bedside real-time detection.
The microfluidic chip provided by the invention is not limited to whole blood/plasma separation, and can also be used for separating and enriching biological objects of different layers in a solution system, such as circulating tumor cells of a cell layer, such as extracellular vesicles of a subcellular layer, liposomes and the like.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
Of course, the microfluidic chip positive electrode material of the present invention may have various changes and modifications, and is not limited to the specific structure of the above embodiments. In conclusion, the scope of the present invention should include those changes or substitutions and modifications which are obvious to those of ordinary skill in the art.

Claims (9)

1. A micro-fluidic chip is characterized by comprising at least one branched branch unit, wherein any branched branch unit comprises a main channel and at least one branched branch channel extending from the main channel, the front end and the rear end of any branched branch unit are respectively provided with a flow resistance adjusting unit, the flow resistance adjusting units respectively adjust the flow resistance of the front end and the rear end of the branched branch unit, when whole blood flows through the branched branch channel, the blood cells are subjected to asymmetric shearing forces on two sides, the main channel with high flow rate and low flow resistance is selected to continue to advance, and part of blood plasma enters the branched branch channel.
2. The microfluidic chip according to claim 1, wherein the width of the branched channel is 10 to 500 μm, and the width of the main channel is 20 to 1000 μm.
3. The microfluidic chip according to claim 1, further comprising a sample inlet unit, wherein the sample inlet unit is provided with a micro-column array at a circumferential edge, and the sample inlet unit can filter aggregated cells with larger size and impurities from blood.
4. The microfluidic chip according to claim 3, wherein the diameter of the micro-pillars is 10 to 500 μm, and the pitch of the micro-pillars is 10 to 500 μm.
5. The microfluidic chip according to claim 3, wherein one end of the sample inlet unit is provided with a drainage scoop through which blood can be prevented from being blocked during the filtration of the microcolumn array.
6. The microfluidic chip according to claim 1, wherein the ratio of the flow resistance of the main channel to the flow resistance of the branched channels is 1: 2.5-1: 200.
7. The microfluidic chip according to claim 1, further comprising a capillary pumping unit for collecting blood and plasma, wherein the capillary pumping unit is distributed in a micro-column array.
8. The microfluidic chip according to claim 1, wherein the microfluidic chip has a single-layer or multi-layer structure, and the depth of the microchannel of the microfluidic chip is 30 to 1000 μm.
9. A whole blood separation method based on the microfluidic chip of any one of claims 1 to 8, comprising the steps of:
adding a blood sample into a sample inlet unit of the microfluidic chip;
the flow resistance of the front end and the rear end of the branch channel are respectively regulated under the action of the flow resistance regulating units arranged at the front end and the rear end of the branch channel;
when blood flows through the branch passage, because shearing force applied to two sides is asymmetric, blood cells can be directed to flow into the main passage, and plasma can enter the branch passage;
the plasma entering the branched branch channel continues to advance under the self-driving of capillary force until entering the capillary pump unit;
the separated blood passes through the flow resistance regulating unit in the main channel until entering the capillary pump unit;
the capillary pump unit collects and measures blood and plasma.
CN201911279204.2A 2019-12-13 2019-12-13 Microfluidic chip and whole blood separation method based on microfluidic chip Pending CN110918144A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911279204.2A CN110918144A (en) 2019-12-13 2019-12-13 Microfluidic chip and whole blood separation method based on microfluidic chip

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911279204.2A CN110918144A (en) 2019-12-13 2019-12-13 Microfluidic chip and whole blood separation method based on microfluidic chip

Publications (1)

Publication Number Publication Date
CN110918144A true CN110918144A (en) 2020-03-27

Family

ID=69860383

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911279204.2A Pending CN110918144A (en) 2019-12-13 2019-12-13 Microfluidic chip and whole blood separation method based on microfluidic chip

Country Status (1)

Country Link
CN (1) CN110918144A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112481080A (en) * 2020-12-10 2021-03-12 深圳先进技术研究院 Micro-fluidic chip, micro-fluidic chip preparation method and nucleic acid extraction method
CN114260037A (en) * 2021-12-27 2022-04-01 杭州电子科技大学 3D stacked multistage inertial microfluidic sorting chip and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0269240A1 (en) * 1986-10-29 1988-06-01 Biotrack, Inc. Blood separation device under low pressure conditions
CN107702973A (en) * 2017-09-08 2018-02-16 深圳市太赫兹科技创新研究院有限公司 A kind of whole blood blood plasma piece-rate system and method
CN107999155A (en) * 2017-12-25 2018-05-08 四川蓝光英诺生物科技股份有限公司 Micro-fluidic chip and its control method, drop formation device and microballoon preparation facilities

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0269240A1 (en) * 1986-10-29 1988-06-01 Biotrack, Inc. Blood separation device under low pressure conditions
CN107702973A (en) * 2017-09-08 2018-02-16 深圳市太赫兹科技创新研究院有限公司 A kind of whole blood blood plasma piece-rate system and method
CN107999155A (en) * 2017-12-25 2018-05-08 四川蓝光英诺生物科技股份有限公司 Micro-fluidic chip and its control method, drop formation device and microballoon preparation facilities

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
MARTIN ZIMMERMANN等: "Capillary pumps for autonomous capillary systems", 《LAB ON A CHIP》 *
SUNG YANG等: "A microfluidic device for continuous, real time blood plasma separation", 《LAB ON A CHIP》 *
刘伟: "《生物高分子材料及其应用研究》", 31 March 2018, 电子科技大学出版社 *
顾月清 吴小玲: "《生物医学工程技术》", 31 July 2017, 中国医药科技出版社 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112481080A (en) * 2020-12-10 2021-03-12 深圳先进技术研究院 Micro-fluidic chip, micro-fluidic chip preparation method and nucleic acid extraction method
WO2022120994A1 (en) * 2020-12-10 2022-06-16 深圳先进技术研究院 Microfluidic chip, preparation method for microfluidic chip, and nucleic acid extraction method
CN114260037A (en) * 2021-12-27 2022-04-01 杭州电子科技大学 3D stacked multistage inertial microfluidic sorting chip and preparation method thereof
CN114260037B (en) * 2021-12-27 2023-02-03 杭州电子科技大学 3D stacked multistage inertia micro-fluidic separation chip and preparation method thereof

Similar Documents

Publication Publication Date Title
US20030226806A1 (en) Methods and devices for liquid extraction
US9404913B2 (en) Micropores and methods of making and using thereof
Sim et al. Multistage-multiorifice flow fractionation (MS-MOFF): continuous size-based separation of microspheres using multiple series of contraction/expansion microchannels
CN102513169B (en) Microfluidic device used in micron-grade particle high-flux separation, and manufacturing method thereof
AU2015200910A1 (en) Method and device for isolating cells from heterogeneous solution using microfluidic trapping vortices
CN110918144A (en) Microfluidic chip and whole blood separation method based on microfluidic chip
CN202356108U (en) Micro-current control device for high-throughput separation of nano-grade particles
US20060204400A1 (en) Process for separation of dispersions and an apparatus
WO2021115047A1 (en) Microfluidic chip and whole blood separation method based on microfluidic chip
CN104792845A (en) Sensing device
JP2004000163A (en) Cell used for treating cell
CN113042121B (en) Integrated chip for exosome nucleic acid detection, detection method and application
Park et al. On-chip whole blood plasma separator based on microfiltration, sedimentation and wetting contrast
Suriyage et al. Design and simulation of a novel MEMS based microfluidic circulating tumor cell (CTC) detection system for a lab on a chip device
WO2006056219A1 (en) Process for separation of dispersions and an apparatus
Wong et al. Size based sorting and patterning of microbeads by evaporation driven flow in a 3D micro-traps array
KR100445744B1 (en) Microchannel Array Structure Embedded In Silicon Substrate And Its Fabrication Method
US11185861B2 (en) Multistage deterministic lateral displacement device for particle separation
Berry et al. Fabrication of suspended electrokinetic microchannels from directly written sacrificial polymer fibers
KR20100048507A (en) Plasma separation device using microfluidic channel and plasma separation method using microfluidic channel
CN109967146A (en) A kind of micro-fluidic laminar flow chip and preparation method thereof
Chen et al. Surface micromachining of polydimethylsiloxane (pdms) for microfluidic biomedical applications
Shen et al. Micromachined nanofiltration modules for lab-on-a-chip applications
CN112691709B (en) Fluid driving device, preparation method of fluid driving device and surface treatment method
KR101383887B1 (en) System for trapping and releasing microparticle

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20200327