CN103571738A - Micro-fluidic chip device based on chemotactic factor enriching effect and preparation method thereof - Google Patents
Micro-fluidic chip device based on chemotactic factor enriching effect and preparation method thereof Download PDFInfo
- Publication number
- CN103571738A CN103571738A CN201310274879.4A CN201310274879A CN103571738A CN 103571738 A CN103571738 A CN 103571738A CN 201310274879 A CN201310274879 A CN 201310274879A CN 103571738 A CN103571738 A CN 103571738A
- Authority
- CN
- China
- Prior art keywords
- sample
- micro
- module
- fluidic chip
- chemokine
- 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
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/04—Cell isolation or sorting
Abstract
The invention provides a micro-fluidic chip device based on a chemotactic factor enriching effect and a preparation method thereof. The micro-fluidic chip device consists of a PDMS (Polydimethylsiloxane) substrate layer, two corresponding micro-fluidic chip modules A and B, a semipermeable membrane arranged between the two micro-fluidic chip modules, a top cover plate and corresponding sample inlet and outlet pipelines. The micro-fluidic chip module A is used for injecting, enriching and sorting a to-be-treated cell sample, and a sample pool in the module A is connected with a sample inlet 2 and a sample outlet 2 so as to inject the to-be-treated cell sample and sort tissue stem cells enriched on the semipermeable membrane. The module B is used for injecting the chemotactic factor so as to form a chemotactic effect in an area of the module A close to the semipermeable membrane by means of the semipermeable membrane. Various tissue stem cells in the cell sample injected into the module A move toward the semipermeable membrane under the chemotactic effect and are separated from other cells. The separated stem cells and other cell samples are collected through different sample outlets.
Description
Technical field
The present invention relates to stem cell biology, Transplanted cells and drug screening technology field, be specifically related to the micro fluidic device for stem cell enrichment sorting.
Background technology
Stem cell is the original undifferentiated cell that a class has multi-lineage potential and the of self-replication capacity; The research of nearly more than ten years has confirmed to have adult tissue stem cell in Various Tissues organ, and they have self and directed differentiation potential, is the seed cell that tissue upgrades and damage rear Regeneration and Repair.The research of stem cell has very important meaning to the control of regenerative medicine and some histoorgan degenerative diseases, is one of focus of current life science and medical science.Different tissues stem cell is carried out to the basic fundamental that isolation and purification culture also becomes this field.
Stroma cell derivative chemokine SDF-1(stromal cell-derived factor-1) belong to respectively CXC class chemokine and CXCR class g protein coupled receptor superfamily with its receptor CXCR 4 (CXC chemokine receptor4), they are high conservative during evolution.Research in the recent decade shows, SDF-1 is except by the lasting generations such as marrow stromal cell, endotheliocyte, at the stem cell microenvironment of Various Tissues high expression level in some low oxygen areas particularly; Its chemotaxis is mediated by receptor CXCR 4, and both are in conjunction with rear common startup target cell downstream signal path.
CXCR4 is familiar with by the mankind as the co-receptor of HIV (human immunodeficiency virus) (HIV) infection attack target cell, thereafter research find it Various Tissues stem cell as mescenchymal stem cell (MSC), hemopoietic stem cell (HSC), epidermal stem cells and skeletal muscle stem Cells etc. also present high expression level, the Various Tissues stem cell just of interacting fast between chemokine SDF-1 and target cell CXCR4 acceptor moves the important drive shaft of chemotactic.As studied, find to upgrade at skin histology, in wound repair, SDF-1 has very strong chemotaxis for epidermal stem cells after wound, CXCR4 acceptor is the highest in the cellular expression levels near stratum basale, by the phosphorylation of inducement signal albumen PKC-ζ, SDF-1 affects polarization and the directional migration thereof of epidermal stem cells Actin muscle.Use SDF-1 can promote mesenchymal stem cells MSCs migrating to tissues such as Spinal Cord; From promote vascular endothelial cell proliferation and vascularization under body anaerobic environment.
In addition research in recent years confirms, application CXCR4 antagonist AMD3100 etc. can significantly increase HSCs mobilization to peripheral blood from marrow (HSC because of high expression level CXCR4 attached in a large number bone marrow microenvironment), thereby contribute to gather HSC by peripheral blood, also further support the keying action of SDF-1/CXCR4 axle in the migration chemotactics such as HSCs.
Various Tissues stem cell under isolated culture condition often need to carry out purifies and separates, and a class stem cell self also exists the heterogeneous population of difference in functionality phenotype simultaneously; More existing animal implant tests textured are as demonstration stronger stem cell colonies of transfer ability such as hematopoietic stem cell transplantation, and after its functionally active and implantation, survival is better.Therefore the specific tissue stem cell composition of sorting purifying, particularly there is good function state stem cell colony significant to function and relevant transplantation experiments etc.
To the grouping system of different tissues stem cell, be at present mainly to use to take the means that flow cytometer is representative and carry out, principle is some differential protein tagged molecule (antigen) of expressing based on stem cell, apply corresponding fluorescent-labeled antibody and carry out antigen-antibody combination, final grouping system goes out to express the specific stem cell composition of differential protein; The deficiency of these class methods is that material installation is relatively costly and consuming time, the reflection of one or more protein labeling molecules be only the phenotype of cell but not functional status, due to through antigen-antibody combination, follow-up application is comprised to cultivation, transplanting etc. cause uncertain impact simultaneously.
Patents is as follows both at home and abroad:
CN200480004361.8,2005 Nian， Effie Hackett Cell Institute Co., Ltd (Japan), golden rugged scholar is bright
CN200580025365.9,2005 Nian， Cleveland Clinic Foundation (U.S.), mark S Penn etc.
CN200680007351.9,2008 Nian， Emory University (U.S.), H executes; DC Ray Liotta etc.
CN200810229391.9,2008 Nian， Dalian Inst of Chemicophysics, Chinese Academy of Sciences, Qin Jianhua etc.
CN201010252513.3,2010 Boao Biological Co., Ltd of Nian， Tsing-Hua University, Xie Lan etc.
Summary of the invention
The invention provides a kind of isolated liver cell micro flow control chip device based on chemokine enrichment effect, is a kind of tissue stem cell enrichment sorting platform based on stem cell functional performance (specificity chemotactic).It is by the micro fluidic device of integrated suitable dimension on chip, specific chemokines generation migration effect in the liquid cell that stem cell composition in sample (cell) pond and connected passage can be separated semi-permeable membranes, thus certain space apart from the effective enrichment of particular organization stem cell in realizing mixing sample with separated.Different from the grading principle of classical flow cytometer antigen-antibody combination, this micro-fluidic system can realize the sorting of moving chemotactic ability based on stem cell function.
Concrete technical scheme of the present invention is as follows:
A micro flow control chip device based on chemokine enrichment effect, it comprises:
One stratum basale.
One micro-fluidic chip modules A, be positioned on stratum basale, micro-sample pool, cell mixing sample sample intake passage and injection port, pressure current control sample intake passage and injection port, cell mixing sample sample output passage and outlet and hemopoietic stem cell sample output passage and outlet of being processed to form in micro-fluidic chip modules A, above-mentioned each injection port and outlet respectively sample introduction or the sample output passage by are separately communicated with sample pool, described sample pool design is leaned on position on one side at the middle part of micro-fluidic chip modules A, its side of keeping to the side opens wide, and passes to modules A edge.
One micro-fluidic chip module B, be positioned on stratum basale, relative side by side with micro-fluidic chip modules A, micro-chemokine sample storage pond, chemokine damping fluid sample intake passage and injection port, chemokine damping fluid sample output passage and the outlet of being processed to form of micro-fluidic chip module B; Above-mentioned each injection port and outlet respectively sample introduction or the sample output passage by are separately communicated with chemokine sample storage pond, and the design of described chemokine sample storage pond is at the middle part of micro-fluidic chip module B by position on one side, and its side of keeping to the side opens wide, and passes to module B edge; The position, chemokine sample storage pond of the sample pool of described micro-fluidic chip modules A and micro-fluidic chip module B is over against also adjacent, and the length in chemokine sample storage pond is less than the length of corresponding sample pool.
One semi-permeable membranes, is sandwiched between micro-fluidic chip modules A and B, separates sample pool and chemokine sample storage pond, forms the barrier film between two ponds, and semi-permeable membranes lower end is connected with stratum basale and seals.
One top layer cover plate, is placed on micro-fluidic chip modules A and B, has sample introduction and the sample outlet hole corresponding with sample introduction on modules A and module B and outlet, and sample introduction is housed and goes out sample pipe on it, and described semi-permeable membranes upper end is connected and seals with top layer cover plate.
Assembling between described stratum basale, micro-fluidic chip modules A and B, top layer cover plate adopts contraposition and bonding technology.
In operation, first in the chemokine sample storage pond of micro-fluidic chip module B, inject chemokine SDF-1, then to cell sample pond, add to fill and use acellular damping fluid, reinject and treat sorting cell mixing sample thereafter, for guaranteeing that stem cell colony is in the abundant enrichment of semi-permeable membranes sample pool one side, except suitable SDF-1 concentration (being 10～50ng/ml according to bibliographical information), adopt the time in convenient pressure 1cm length sample storage pond so that individual cells is flowed through not to be shorter than 1 minute, finally make the enrichment of most HSC composition next-door neighbour semi-permeable membranes chemotactic, and collect through the sample output passage in downstream.
The stem cell that the present invention proposes divides that to select microfluidic system be the motion chemotactic characteristic based on stem cell in principle, is different from the grading principle of traditional flow cytometer antigen-antibody combination.In design, between cell pool and flow duct and liquid cell, use suitable semi-permeable membranes to separate, by application specific chemokines, can realize the chemotactic of Various Tissues stem cell composition in cell mixing sample is attracted and sorting, can be repeatedly used containing chemokine liquid, the active stem cell colony that collect in cell harvesting pond can be further used for immunostaining checking, cultivate and in researchs such as body transplanting.Therefore, this installs not only simple and efficient, can, for the sorting of multiple mixed cell population stem cell, obtain the stem cell composition of high functionally active; Chip itself is reusable simultaneously, in conjunction with suitable cleaning-sterilizing means, can meet the aseptic requirement under culture condition, can be widely used in the research fields such as stem cell biology, Transplanted cells and drug screening.
Accompanying drawing explanation
Fig. 1 is the profile schematic diagram of this device;
Fig. 2 is the structure assembling schematic diagram of this device;
Fig. 3 is the structural representation of micro-fluidic chip modules A;
Fig. 4 is the structural representation of micro-fluidic chip module B.
Embodiment
Below in conjunction with accompanying drawing, describe structure of the present invention in detail:
Referring to Fig. 1 and Fig. 2, this device is on forming, placement for the ease of semi-permeable membranes 4, micro-fluidic chip be take PDMS(polydimethylsiloxane polydimethylsiloxane) be stratum basale 1, by micro-fluidic chip modules A 2 and two module compositions of B3, modules A 2 has sample pool 14, cell mixing sample sample intake passage 11 and injection port 10, pressure current is controlled sample intake passage 16 and injection port 15, cell mixing sample sample output passage 13 and outlet 12 and hemopoietic stem cell sample output passage 17 and outlet 18 respectively.Module B3 has chemokine sample storage pond 21, chemokine damping fluid sample intake passage 20 and injection port 19, chemokine damping fluid sample output passage 22 and outlet 23, be mainly used in injecting chemokine, after A, micro-the machining of B two modules, assemble, between sample pool and chemokine sample storage pond, insert semi-permeable membranes 4, use PDMS make its sealing bonding and add top layer cover plate 5, on stratum basale and top layer cover plate, be provided with semi-permeable membranes length and mate, width is the rectangular opening of 0.2mm, lower end and the upper end of semi-permeable membranes are inserted wherein respectively, and sealing is fixing.It is the PDMS material of 2～5mm that above micro-fluidic chip modules A and micro-fluidic chip module B adopt thickness, and stratum basale and top layer cover plate are that thickness is the PDMS material of 3～5mm.
In order to realize the sorting of hemopoietic stem cell in cell mixing sample, migration speed according to HSC under chemokine effect (the tens of microns of per minute), chemokine sample storage pond 21 Design of length relative with semi-permeable membranes 4 are at 0.5～1cm, the corresponding length of sample pool 14 is longer to guarantee that sample liquids stream is stable and stem cell is separated, the wide 200 μ m of cell sample access way, dark 50 μ m, can meet the injection of the various mixed cell populations of body and flow, and in certain flowing time (minute) to realize HSC close to the chemotactic of semi-permeable membranes.
Specifically as shown in Figure 3 and Figure 4, in the horizontal plane direction of the sample pool 14 of micro-fluidic chip modules A, shape approximation is trapezoidal, and long edge lengths is 1～3cm, and bond length is 0.5～2cm, width (long limit is to the distance of minor face) is 2～5mm, and this length limit is the side that opens wide that passes to modules A edge.The diameter of its injection port 10,15 and outlet 12,18 is 1mm, and the width of sample output passage 13,17 and sample intake passage 11,16 is 200 μ m, and the degree of depth is 50 μ m.
In the horizontal plane direction in the chemokine sample storage pond 21 of micro-fluidic chip module B, shape is also trapezoidal, long edge lengths is 0.5～1cm, bond length is 0.2～0.6cm, and width (long limit is to the distance of minor face) is 100～300 μ m, passes to the side that opens wide at module B edge described in described long limit is.The diameter of its injection port 19 and outlet 23 is 400 μ m, and the width of sample output passage 22 and sample intake passage 20 is 100 μ m, and the degree of depth is 50 μ m.
The semi-permeable membranes 4 that forms chemokine concentration gradient for building selects molecular weight cut-off to be greater than the Mierocrystalline cellulose dialysis membrane of 8KD, as adopt commercial regenerated cellulose film, this is a kind of uncharged homogeneous membrane, membrane pore size is less than 1 μ m, according to the molecular size range of SDF-1 (8KD), selecting molecular retention amount is the semi-permeable membranes (MWCO8000 that is greater than 8KD, Yuan Ye bio tech ltd, Shanghai etc.), can form chemokine SDF-1 concentration gradient in sample pool one side near semi-permeable membranes like this, can prevent again its too fast loss.
Embodiment 1:
Referring to Fig. 1, Fig. 2, a kind of micro flow control chip device based on chemokine enrichment effect by PDMS stratum basale 1, corresponding micro-fluidic chip modules A 2 and the module B3 arranging in two left and right, be placed in semi-permeable membranes 4 between two micro-fluidic chip modules, top layer cover plate 5 and correspondingly into and out of sample pipeline 6, form.
Each functional component and module and assembling process are as follows:
1, semi-permeable membranes 4 lower ends are inserted in the rectangular opening 7 of PDMS stratum basale 1, and use PDMS from bottom the fixing gap of 7 of semi-permeable membranes 4 and shutoff semi-permeable membranes and rectangular openings, avoid the cell in sample storage pond 14 to flow to opposite side sample storage pond 21, or the rapid diffusion of chemokine in sample storage pond 21.
2, adopt plasma treatment stand-by the PDMS stratum basale 1 and modules A 2, module B3, the PDMS top layer cover plate 5 that fix semi-permeable membranes 4.
3, modules A 2 and module B3 being close to semi-permeable membranes 4 is placed on PDMS stratum basale 1, the sample storage pond of module B3 is over against the centre of the sample pool of modules A 2, and from two ends extruding module A2 and module B3, make two module close contacts, make semi-permeable membranes 4, modules A 2, module B3 and the each other tight bonding of PDMS stratum basale 1, and utilize PDMS to fix.
4, PDMS top layer cover plate 5 is inserted to modules A 2 and module B3 upper, semi-permeable membranes 4 upper ends need be passed by the rectangular opening 8 of cover plate 5, and use PDMS sealing, avoid the cell in sample storage pond 14 to flow to opposite side sample storage pond 21, or the rapid diffusion of chemokine in sample storage pond 21.Meanwhile, on PDMS top layer cover plate 5, sample introduction/sample outlet hole 9 is corresponding one by one with modules A 2 and the upper sample introduction/ sample outlet hole 15,10,19/12,18,23 of module B3, makes tight bonding between each module.
5, sample introduction, produce kinds of pipeline 6 are inserted on PDMS cover plate 5 in sample introduction and sample outlet hole 9, use gap between PDMS sealing sample introduction, produce kinds of pipeline 6 and sample introduction and sample outlet hole 9.
Sample screening process is as follows:
From injection port 19, inject chemokine damping fluid, through sample intake passage 20, enter chemokine damping fluid sample storage pond 21, and through sample output passage 22 and outlet 23, flow out under mobilization force effect, can form successive loops by peripheral conduits.Due to the difference of semi-permeable membranes 4 both sides chemokine concentration, chemokine can be spread by high density (sample storage pond 21) side direction lower concentration one side (sample storage pond 14), and then forms concentration gradient.Meanwhile, from injection port 10, use micro pump to inject cell mixing suspension, from injection port 15, inject damping fluid; When cell suspending liquid enters cell mixing sample storage pond 14 through cell mixing sample intake passage 11, mix with the damping fluid entering through sample intake passage 15, due to the impact of Laminar Flow, cell will mainly flow near injection port 10 1 sides (away from semi-permeable membranes 4); The formed concentration gradient of chemokine affect Xia， particular organization stem cell will be under the effect of chemotactic effect to semi-permeable membranes 4 directions (high chemokine concentration range) motion, and then near semi-permeable membranes 4 formative tissue stem cell enrichment districts, region; The cell of enrichment, under the drive of the damping fluid injecting from injection port 15, flows out from stem cell sample output passage 17, and collects at stem cell outlet 18; In cell mixing sample storage pond 14, all the other cells flow out from sample output passage 13, collect, thereby reach the object of utilizing chemotactic effect separation and concentration tissue stem cell at outlet 12.
Claims (8)
1. the micro flow control chip device based on chemokine enrichment effect, is characterized in that it comprises:
One stratum basale;
One micro-fluidic chip modules A, be positioned on stratum basale, micro-sample pool, cell mixing sample sample intake passage and injection port, pressure current control sample intake passage and injection port, cell mixing sample sample output passage and outlet and hemopoietic stem cell sample output passage and outlet of being processed to form in micro-fluidic chip modules A, above-mentioned each injection port and outlet respectively sample introduction or the sample output passage by are separately communicated with sample pool, described sample pool design is leaned on position on one side at the middle part of micro-fluidic chip modules A, its side of keeping to the side opens wide, and passes to modules A edge;
One micro-fluidic chip module B, be positioned on stratum basale, relative side by side with micro-fluidic chip modules A, micro-chemokine sample storage pond, chemokine damping fluid sample intake passage and injection port, chemokine damping fluid sample output passage and the outlet of being processed to form of micro-fluidic chip module B; Above-mentioned each injection port and outlet respectively sample introduction or the sample output passage by are separately communicated with chemokine sample storage pond, and the design of described chemokine sample storage pond is at the middle part of micro-fluidic chip module B by position on one side, and its side of keeping to the side opens wide, and passes to module B edge; The position, chemokine sample storage pond of the sample pool of described micro-fluidic chip modules A and micro-fluidic chip module B is over against also adjacent, and the length in chemokine sample storage pond is less than the length of corresponding sample pool;
One semi-permeable membranes, is sandwiched between micro-fluidic chip modules A and B, separates sample pool and chemokine sample storage pond, forms the barrier film between two ponds, and semi-permeable membranes lower end is connected with stratum basale and seals;
One top layer cover plate, is placed on micro-fluidic chip modules A and B, has sample introduction and the sample outlet hole corresponding with sample introduction on modules A and module B and outlet, and sample introduction is housed and goes out sample pipe on it, and described semi-permeable membranes upper end is connected and seals with top layer cover plate;
Assembling between described stratum basale, micro-fluidic chip modules A and B, top layer cover plate adopts contraposition and bonding technology.
2. the micro flow control chip device based on chemokine enrichment effect according to claim 1, is characterized in that: described semi-permeable membranes selects molecular weight cut-off to be greater than the Mierocrystalline cellulose dialysis membrane of 8KD.
3. the micro flow control chip device based on chemokine enrichment effect according to claim 1 and 2, is characterized in that: it is the PDMS material of 2～5mm that described micro-fluidic chip modules A and micro-fluidic chip module B adopt thickness.
4. the micro flow control chip device based on chemokine enrichment effect according to claim 1 and 2, is characterized in that: stratum basale and top layer cover plate are that thickness is the PDMS material of 3～5mm.
5. the micro flow control chip device based on chemokine enrichment effect according to claim 3, it is characterized in that: the injection port of described micro-fluidic chip modules A and the diameter of outlet are 1mm, the width that goes out sample and sample intake passage is 200 μ m, and the degree of depth is 50 μ m; The injection port of micro-fluidic chip module B and the diameter of outlet are 400 μ m, and the width that goes out sample and sample intake passage is 100 μ m, and the degree of depth is 50 μ m.
6. the micro flow control chip device based on chemokine enrichment effect according to claim 3, it is characterized in that: in the horizontal plane direction of the sample pool of described micro-fluidic chip modules A, shape approximation is trapezoidal, long edge lengths is 1～3cm, bond length is 0.5～2cm, width (long limit is to the distance of minor face) is 2～5mm, passes to the side that opens wide at modules A edge described in described long limit is; In the horizontal plane direction in the chemokine sample storage pond of described micro-fluidic chip module B, shape is also trapezoidal, long edge lengths is 0.5～1cm, bond length is 0.2～0.6cm, width (long limit is to the distance of minor face) is 100～300 μ m, passes to the side that opens wide at module B edge described in described long limit is.
7. the micro flow control chip device based on chemokine enrichment effect according to claim 4, it is characterized in that: on described stratum basale and top layer cover plate, be provided with semi-permeable membranes length and mate, width is the rectangular opening of 0.2mm, and lower end and the upper end of semi-permeable membranes are inserted wherein respectively, and sealing is fixing.
8. the preparation method of the micro flow control chip device described in any one of claim 1-7, is characterized in that: the assembling of device adopts contraposition and bonding technology, and preparation process is as follows:
A. semi-permeable membranes lower end is inserted in the rectangular opening of PDMS stratum basale, and use PDMS from bottom the fixing gap between semi-permeable membranes and shutoff semi-permeable membranes and rectangular opening, avoid the damping fluid leakage in two ponds and mutual buffer-exchanged;
B. adopt plasma treatment stand-by the PDMS stratum basale and modules A, module B, the PDMS top layer cover plate that fix semi-permeable membranes;
C. modules A and module B being close to semi-permeable membranes is placed in PDMS substrate, the sample storage pond of module B, over against the centre of the sample pool of modules A, from two ends extruding modules A and module B, makes two module close contacts, make the each other tight bonding of modules A, module B and PDMS basic unit, and utilize PDMS to fix;
D. PDMS top layer cover plate is placed on modules A and module B, semi-permeable membranes upper end is through the rectangular opening of top layer cover plate, and use PDMS sealing, avoid the damping fluid leakage in two ponds and mutual buffer-exchanged, make on PDMS top layer cover plate sample introduction and sample outlet hole and modules A and the upper sample introduction of module B and sample outlet hole corresponding one by one, make tight bonding between each module;
E. sample introduction and produce kinds of pipeline are inserted on PDMS top layer cover plate in sample introduction and sample outlet hole, use PDMS sealing sample introduction and produce kinds of pipeline.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310274879.4A CN103571738A (en) | 2013-07-02 | 2013-07-02 | Micro-fluidic chip device based on chemotactic factor enriching effect and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310274879.4A CN103571738A (en) | 2013-07-02 | 2013-07-02 | Micro-fluidic chip device based on chemotactic factor enriching effect and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103571738A true CN103571738A (en) | 2014-02-12 |
Family
ID=50044454
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310274879.4A Pending CN103571738A (en) | 2013-07-02 | 2013-07-02 | Micro-fluidic chip device based on chemotactic factor enriching effect and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103571738A (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103913486A (en) * | 2014-04-12 | 2014-07-09 | 太原理工大学 | Method for preparing AuNPs-PDMS composite micro film biosensor |
| CN103952300A (en) * | 2014-03-31 | 2014-07-30 | 大连医科大学 | Micro-fluidic chip and cell chemotaxis movement research method |
| CN103981094A (en) * | 2014-05-07 | 2014-08-13 | 大连理工大学 | Micro-fluidic chip for screening hepatoenteral circulation drugs |
| CN104830683A (en) * | 2015-04-30 | 2015-08-12 | 大连医科大学附属第二医院 | Bionic micro-fluidic chip for simulating in vivo tumor cells and metastasis microenvironment |
| CN105420106A (en) * | 2015-11-23 | 2016-03-23 | 大连医科大学附属第一医院 | Bionic glomerulus chip and chipset composed of bionic glomerulus chips |
| CN107058081A (en) * | 2017-04-11 | 2017-08-18 | 宁波美晶医疗技术有限公司 | A kind of biochip for being used to screen rare cell in positioning and detection blood |
| CN108893411A (en) * | 2018-06-15 | 2018-11-27 | 杭州电子科技大学 | Micro-fluidic chip and its manufacturing method based on photocuring printing |
| CN109187463A (en) * | 2018-08-31 | 2019-01-11 | 哈尔滨工业大学 | Micro-fluidic type radiation injury biological dose analysis and detection device and its determination method based on photobacteria |
| CN110747111A (en) * | 2019-09-29 | 2020-02-04 | 山东大学 | Exosome filter equipment |
| CN110918140A (en) * | 2018-09-20 | 2020-03-27 | 北京怡天佳瑞科技有限公司 | Microfluidic chip, device containing same and method for separating particles |
| CN111212900A (en) * | 2017-10-03 | 2020-05-29 | Nok株式会社 | Cell capturing device |
| CN113941379A (en) * | 2021-10-15 | 2022-01-18 | 重庆大学 | Micro-fluidic chip and method for sorting, enriching and detecting bacteria and fungi |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101914435A (en) * | 2010-05-24 | 2010-12-15 | 博奥生物有限公司 | Microtube device and using method thereof |
| CN102174369A (en) * | 2011-01-28 | 2011-09-07 | 南京大学 | Micro-slit-structure-based full PDMS (polydimethylsiloxane) micro-fluidic cell capturing chip and manufacturing method thereof |
| CN103087912A (en) * | 2011-10-27 | 2013-05-08 | 中国科学院大连化学物理研究所 | Micro-fluidic chip capable of producing stable concentration gradient and cell co-culture method |
-
2013
- 2013-07-02 CN CN201310274879.4A patent/CN103571738A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101914435A (en) * | 2010-05-24 | 2010-12-15 | 博奥生物有限公司 | Microtube device and using method thereof |
| CN102174369A (en) * | 2011-01-28 | 2011-09-07 | 南京大学 | Micro-slit-structure-based full PDMS (polydimethylsiloxane) micro-fluidic cell capturing chip and manufacturing method thereof |
| CN103087912A (en) * | 2011-10-27 | 2013-05-08 | 中国科学院大连化学物理研究所 | Micro-fluidic chip capable of producing stable concentration gradient and cell co-culture method |
Non-Patent Citations (4)
| Title |
|---|
| JONATHAN W. SONG ET AL.: "Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells", 《PLOS ONE》, vol. 4, no. 6, 1 June 2009 (2009-06-01), XP055196313, DOI: doi:10.1371/journal.pone.0005756 * |
| SEOK CHUNG ET AL.: "Microfluidic Platforms for Studies of Angiogenesis, Cell Migration, and Cell–Cell Interactions", 《ANNALS OF BIOMEDICAL ENGINEERING》, vol. 38, no. 3, 30 March 2010 (2010-03-30) * |
| 蒋丽莉等: "浓度梯度微流控芯片技术研究进展", 《国际检验医学杂志》, vol. 33, no. 11, 30 June 2010 (2010-06-30) * |
| 蔡绍皙等: "微流控与细胞迁移技术的研究进展", 《生物技术通报》, 31 December 2010 (2010-12-31) * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103952300A (en) * | 2014-03-31 | 2014-07-30 | 大连医科大学 | Micro-fluidic chip and cell chemotaxis movement research method |
| CN103913486B (en) * | 2014-04-12 | 2016-06-08 | 太原理工大学 | The preparation method of AuNPs-PDMS compound mems thin film biosensor |
| CN103913486A (en) * | 2014-04-12 | 2014-07-09 | 太原理工大学 | Method for preparing AuNPs-PDMS composite micro film biosensor |
| CN103981094A (en) * | 2014-05-07 | 2014-08-13 | 大连理工大学 | Micro-fluidic chip for screening hepatoenteral circulation drugs |
| CN104830683A (en) * | 2015-04-30 | 2015-08-12 | 大连医科大学附属第二医院 | Bionic micro-fluidic chip for simulating in vivo tumor cells and metastasis microenvironment |
| CN105420106A (en) * | 2015-11-23 | 2016-03-23 | 大连医科大学附属第一医院 | Bionic glomerulus chip and chipset composed of bionic glomerulus chips |
| CN107058081A (en) * | 2017-04-11 | 2017-08-18 | 宁波美晶医疗技术有限公司 | A kind of biochip for being used to screen rare cell in positioning and detection blood |
| CN111212900A (en) * | 2017-10-03 | 2020-05-29 | Nok株式会社 | Cell capturing device |
| CN111212900B (en) * | 2017-10-03 | 2023-09-29 | Nok株式会社 | Cell capturing device |
| CN108893411A (en) * | 2018-06-15 | 2018-11-27 | 杭州电子科技大学 | Micro-fluidic chip and its manufacturing method based on photocuring printing |
| CN108893411B (en) * | 2018-06-15 | 2024-03-08 | 杭州电子科技大学 | Microfluidic chip based on photo-curing printing and manufacturing method thereof |
| CN109187463A (en) * | 2018-08-31 | 2019-01-11 | 哈尔滨工业大学 | Micro-fluidic type radiation injury biological dose analysis and detection device and its determination method based on photobacteria |
| CN110918140A (en) * | 2018-09-20 | 2020-03-27 | 北京怡天佳瑞科技有限公司 | Microfluidic chip, device containing same and method for separating particles |
| CN110747111A (en) * | 2019-09-29 | 2020-02-04 | 山东大学 | Exosome filter equipment |
| CN113941379A (en) * | 2021-10-15 | 2022-01-18 | 重庆大学 | Micro-fluidic chip and method for sorting, enriching and detecting bacteria and fungi |
| CN113941379B (en) * | 2021-10-15 | 2023-02-17 | 重庆大学 | Micro-fluidic chip and method for sorting, enriching and detecting bacteria and fungi |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103571738A (en) | Micro-fluidic chip device based on chemotactic factor enriching effect and preparation method thereof | |
| Xie et al. | h-FIBER: Microfluidic topographical hollow fiber for studies of glomerular filtration barrier | |
| AU2008236529B2 (en) | Improved bioreactor surfaces | |
| US8911995B2 (en) | Culture system and method for immunogenicity and immunofunction testing in vitro | |
| US20140335496A1 (en) | Human conducting airway model comprising multiple fluidic pathways | |
| CN103952300B (en) | A kind of micro-fluidic chip and cell chemotaxis motion study method | |
| US8389277B2 (en) | Forming cell structure with transient linker in cage | |
| CN108289914B (en) | Systems and methods for producing platelets | |
| CA3045796A1 (en) | In vitro epithelial models comprising lamina propria-derived cells | |
| Zhang et al. | Recent Advances in Microfluidic Platforms for Programming Cell‐Based Living Materials | |
| EP2321405A1 (en) | Microfluidic continuous flow device | |
| CN108587902A (en) | Cell sorting devices based on dielectrophoresis and its screening technique | |
| CN108277198A (en) | A kind of liver micro-fluidic chip and its application for realizing that two dimension, three dimensional intersection co-culture | |
| US20230365906A1 (en) | Recirculating bioreactor | |
| Lin et al. | From model system to therapy: scalable production of perfusable vascularized liver spheroids in “open-top “384-well plate | |
| CN103877631A (en) | Bioartificial liver system | |
| Shito et al. | Efficacy of an extracorporeal flat-plate bioartificial liver in treating fulminant hepatic failure | |
| CN114317272B (en) | Culture device for multicellular co-culture and cell culture method | |
| CN103170021A (en) | Deflector-type micro-capsule suspension type fluidized bed bioreactor for artificial liver | |
| US20130236972A1 (en) | Liver Sinusoid Model | |
| JP7023938B2 (en) | Systems and methods for cell transduction | |
| CN114574540A (en) | Novel coronavirus intestinal infection model construction method based on microfluidic chip | |
| CN203244625U (en) | Flow guiding type minitype capsule suspension fluidized bed bioreactor for artificial liver | |
| CN115554469A (en) | Bionic bioartificial liver chip and preparation method and application thereof | |
| CN219174512U (en) | Plug-in tissue culture chip |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140212 |