CN104388299A - Micro-fluidic chip for cell capture - Google Patents
Micro-fluidic chip for cell capture Download PDFInfo
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- CN104388299A CN104388299A CN201410605526.2A CN201410605526A CN104388299A CN 104388299 A CN104388299 A CN 104388299A CN 201410605526 A CN201410605526 A CN 201410605526A CN 104388299 A CN104388299 A CN 104388299A
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- 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
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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Abstract
The invention discloses a micro-fluidic chip for cell capture. The micro-fluidic chip comprises an upper substrate and a lower substrate which are matched with each other, wherein a runner is engraved in the surface of the lower substrate and comprises an inlet and an outlet; a dam-shaped structure is arranged in the runner; the height from the dam-shaped structure to the bottom of the runner is less than the depth of the runner; the dam-shaped structure consists of a plurality of bent structures which are connected one another; one end of the dam-shaped structure is connected with one side of the runner, and the other end of the dam-shaped structure is connected with the other side of the runner. According to the micro-fluidic chip, the cell capture capacity of the chip is greatly increased, the chip processing process is simple, and the requirement on a chip processing platform is greatly reduced; the number of the bent structures in the dam-shaped structure, the depth of the bent structures along a liquid flowing direction and the height between the dam-shaped structure and the upper substrate can be correspondingly adjusted by the micro-fluidic chip so as to meet different requirements.
Description
Technical field
The invention belongs to micro fluidic chip technical field, especially relate to the micro-fluidic chip that a kind of structure of dam type by back and forth bending realizes Large Copacity cell capture.
Background technology
Early 1990s, Manz and Widmer proposes the concept of micro-total analysis system, this system is for the purpose of " the individualizing " and " family expenses " in Realization analysis laboratory, be widely used in analyzing, detecting each relevant research field, as unicellular research, gene sequencing, medical diagnosis on disease, environment measuring etc.Micro-fluidic chip is the important component part of micro-total analysis system, utilizes micro-processing technology, on the chip of micro volume, carves the microcavity body and fluid channel with certain function.Have fast, the advantage such as efficient, low-material-consumption, high-throughput.
The behavior utilizing micro-fluidic chip to study cell is direction more popular in recent years, from the various biological fluid samples of complicated component, isolated cell is an important biomedical engineering technology, all has great importance in medical research and clinical application.Such as can be applied to the circulating tumor cell detected in tumour patient blood.At present, existing multiple scheme of carrying out cell capture based on micro-fluidic chip, main is all be less than the structural unit of cell size by cell " card " firmly by design, these structures comprise compact arranged columnar structure unit, the structural unit of similar capitalization English letter " U ", is less than or equal to the microtubule structural unit etc. of cell dia.These micro-fluidic chips all can realize catching operation to object cell well.But these schemes have common deficiency, the course of processing is complicated, and cell-volume is limited.For compact arranged columnar structure, first add the micron-sized size of number and fix microtrabeculae and just need micro-fluidic chip processing platform to realize larger depth-to-width ratio, the cell being less than microtrabeculae quantity can be caught at the most simultaneously; The structural unit of similar " U " type needs processing platform to realize larger depth-to-width ratio equally, and the structural unit of each " U " only can catch a cell, and capture rate is low.When sample to be detected be blood etc. containing more cellulous biological liquid sample time, using said structure as the micro-fluidic chip of cell capture unit will very fast because capture ability exhausts lost cell capture ability.
No matter existing be the cell capture micro-fluidic chip of micro-column structure, " U " structure or microtube structure, there is the problem that cell-volume is limited without exception, and these microstructures needs larger depth-to-width ratio mostly, very high to the requirement of chip manufacture.
Summary of the invention
Goal of the invention: for current cell capture micro-fluidic chip cell capture finite capacity, the present situation of chip manufacture complex process, the invention provides in a kind of runner the micro-fluidic chip with back and forth bending dam shape structure, micro-fluidic chip of the present invention improves the cell capture capacity of chip greatly, and chip manufacture technique is simple, significantly reduces the requirement to chip manufacture platform.
Summary of the invention: for solving the problems of the technologies described above, the technology used in the present invention means are:
A kind of micro-fluidic chip for cell capture, comprise the upper substrate and hypocoxa that cooperatively interact, runner is carved with on the surface of described hypocoxa, described runner includes an inlet and an outlet, dam shape structure is provided with in described runner, height bottom described dam shape structure distance runner is less than the degree of depth of described runner, described dam shape structure is made up of multiple interconnective bending structure, one end of described dam shape structure connects a side of described runner, and the other end of described dam shape structure connects another side of described runner.
Wherein, can be consistent with the height of described upper substrate bottom described runner, also can be inconsistent.
Wherein, in described dam shape structure, each bending part can be consistent with the height of described upper substrate, also can be inconsistent.The height of dam shape structure and upper substrate is close or be less than at least one target cell size.
Wherein, the bending angle of the bending part of described dam shape structure linearly bends or curved bending, and dam shape structure back and forth bends the useful length that can increase and catch cell along liquid flow direction.
Wherein, the bending part of described dam shape structure can be identical along the degree of depth of liquid flow direction, also can not be identical.
Beneficial effect: compared to prior art, micro-fluidic chip of the present invention improves the cell capture capacity of chip greatly, and chip manufacture technique is simple, significantly reduces the requirement to chip manufacture platform; Micro-fluidic chip of the present invention is provided with dam shape structure in runner, thus utilize the height of dam shape structure and upper substrate to be less than target cell diameter catching of realize target cell, dam shape structure is reciprocal bending, the dam shape structure of reciprocal bending significantly can improve the useful length of runner for cell capture, and the capacity making chip can catch cell significantly promotes; In addition, micro-fluidic chip of the present invention does not need larger depth-to-width ratio, and processing is simple, therefore requires lower to the platform for making of micro-fluidic chip; Finally, micro-fluidic chip of the present invention can carry out corresponding adjustment along the degree of depth of liquid flow direction and dam shape structure to the height of upper substrate to the quantity of bending structure in dam shape structure and bending structure as required.
Accompanying drawing explanation
Fig. 1 is the structural representation of micro-fluidic chip of the present invention;
Fig. 2 is the partial enlarged drawing of micro-fluidic chip A-A face of the present invention sectional view;
Fig. 3 is the partial enlarged drawing of shape structure in dam in micro-fluidic chip of the present invention;
Fig. 4 is the partial enlarged drawing of dam shape structures capture cell in micro-fluidic chip of the present invention;
Wherein, upper substrate 1, hypocoxa 2, flow channel entry point 3, runner exit 4, dam shape structure 5, bending structure 6, runner 7.
Embodiment
Below in conjunction with accompanying drawing, the present invention is further described.
A kind of micro-fluidic chip for cell capture, comprise the upper substrate and hypocoxa that cooperatively interact, runner is carved with on the surface of described hypocoxa, described runner includes an inlet and an outlet, dam shape structure is provided with in described runner, height bottom described dam shape structure distance runner is less than the degree of depth of described runner, described dam shape structure is made up of multiple interconnective bending structure, one end of described dam shape structure connects a side of described runner, and the other end of described dam shape structure connects another side of described runner.
Wherein, can be consistent with the height of described upper substrate bottom described runner, also can be inconsistent.
Wherein, in described dam shape structure, each bending part can be consistent with the height of described upper substrate, also can be inconsistent.The height of dam shape structure and upper substrate is close or be less than at least one target cell size.
Wherein, the bending angle of the bending part of described dam shape structure linearly bends or curved bending, and dam shape structure back and forth bends the useful length that can increase and catch cell along liquid flow direction.
Wherein, the bending part of described dam shape structure can be identical along the degree of depth of liquid flow direction, also can not be identical.
As shown in Fig. 1 ~ 2, micro-fluidic chip for cell capture of the present invention, comprise the upper substrate 1 and hypocoxa 2 that cooperatively interact, runner 7 is carved with on the surface of hypocoxa 2, upper substrate 1 and hypocoxa 2 are bonded together, sealing runner 7, runner 7 comprises entrance 3 and outlet 4, dam shape structure 5 is provided with in runner 7, dam shape structure 5 is less than the degree of depth (being the degree of depth of runner 7 with the height of upper substrate 1 bottom runner 7) of runner 7 apart from the height bottom runner 7, dam shape structure 5 is made up of multiple interconnective bending structure 6, a side of shape structure 5 one end, the dam connecting passage 7 be made up of multiple interconnective bending structure 6, another side of the other end connecting passage 7 of dam shape structure 5, micro-fluidic chip by the distance between dam shape structure 5 and upper substrate 2 close to or be less than target cell and catch cell, micro-fluidic chip extends the useful length of catching cell by the bending structure 6 of dam shape structure 5.
In whole piece runner 7, each point bottom runner 7 can be consistent with the height of upper substrate 1, also can be inconsistent; In dam shape structure 5, each bending part 6 can be consistent with the height of upper substrate 1, also can be inconsistent, the height of dam shape structure 5 and upper substrate 1 close to or be less than the size of at least one target cell; The bending angle of the bending part 6 of dam shape structure 5 linearly bends or curved bending, and dam shape structure 5 back and forth bends the useful length that can increase and catch cell along liquid flow direction; The bending part 6 of dam shape structure 5 can be identical along the degree of depth of liquid flow direction, also can not be identical.
Micro-fluidic chip of the present invention is adopted to catch human leukemia cell line K562 cell:
K562 clone is human leukemia cell line, cell dia is about 10 microns, utilize photolithography preparation chip as shown in Figure 1, runner 7 is engraved on hypocoxa 2, upper substrate 1 and hypocoxa 2 are PDMS, upper substrate 1 and hypocoxa 2 pass through together with chemical bonding, the degree of depth of runner 7 is 30 microns, dam shape structure 5 is 23 microns apart from the height bottom runner 7, gap between dam shape structure 5 and upper substrate 1 is 7 microns, in dam shape structure 5, the bending angle of each bending part 6 is straight line bends (bending angle is rectangular), as shown in Figure 3, in bending structure 6, the width a of each straight line is 50 microns, the width l of each bending structure 6 is 200 microns, bending part 6 is 1000 microns along the degree of depth d of liquid flow direction, dam shape structure 5 is having 11 bending structures 6 along liquid flow direction upper left side, there are 10 bending structures 6 on right side, therefore its useful length of catching cell much larger than dam shape structure 5 linearly structure time effectively catch length (when dam shape structure 5 linearly structure time, effectively catch length and be distance between two sides being connected with dam shape structure 5 respectively in runner 7).
Suspension with K562 cell enters runner 7 from flow channel entry point 3, when liquid stream is to dam shape structure 5, K562 cell is because diameter is greater than 7 microns and be blocked in the left side of dam shape structure 5, cell suspension passes through the gap between dam shape structure 5 and upper substrate 1 smoothly, thus successfully by K562 cell capture (as shown in Figure 4).
Micro-fluidic chip of the present invention is provided with the dam shape structure 5 that has reciprocal bending structure in runner 7, and then can capture the target cell that cell dia is greater than gap between dam shape structure 5 and upper substrate 1.Runner 7 is partitioned into two regions by the dam shape structure 5 of reciprocal bending, reciprocal bending structure 6 adds the cell capture useful length of chip with can becoming the order of magnitude, when the liquid containing cell flows to opposite side from the side of runner, cell will be trapped in dam shape structure 5 any one, and fluid can normal through the gap between dam shape structure 5 and upper substrate 1, until the target cell that all surface of the sample introduction side of dam shape structure 5 is all captured to is paved with and the flowing of obstruct fluid flow.
Micro-fluidic chip of the present invention can also carry out corresponding adjustment to meet different needs along the degree of depth of liquid flow direction and dam shape structure 5 from the height of upper substrate 1 to the quantity of bending structure 6 in dam shape structure 5 and bending structure 6 neatly; If need to catch comparatively many cells, can realize along the degree of depth of liquid flow direction by increasing the quantity of bending structure 6 and bending structure 6, more bending structure 6 and darker bending structure 6 can increase the useful length that target cell is caught; By the size in gap between adjustment dam shape structure 5 and upper substrate 1, catching different diameter target cell can be realized.
Claims (5)
1. the micro-fluidic chip for cell capture, it is characterized in that: comprise the upper substrate and hypocoxa that cooperatively interact, runner is carved with on the surface of described hypocoxa, described runner includes an inlet and an outlet, dam shape structure is provided with in described runner, height bottom described dam shape structure distance runner is less than the degree of depth of described runner, described dam shape structure is made up of multiple interconnective bending structure, one end of shown dam shape structure connects a side of described runner, and the other end of described dam shape structure connects another side of described runner.
2. the micro-fluidic chip for cell capture according to claim 1, is characterized in that: can be consistent with the height of described upper substrate bottom described runner, also can be inconsistent.
3. the micro-fluidic chip for cell capture according to claim 1, is characterized in that: in described dam shape structure, each bending part can be consistent with the height of described upper substrate, also can be inconsistent.
4. the micro-fluidic chip for cell capture according to claim 1, is characterized in that: the bending angle of the bending part of described dam shape structure linearly bends or curved bending.
5. the micro-fluidic chip for cell capture according to claim 1, is characterized in that: the bending part of described dam shape structure can be identical along the degree of depth of liquid flow direction, also can not be identical.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410605526.2A CN104388299B (en) | 2014-10-30 | 2014-10-30 | A kind of micro-fluidic chip for cell capture |
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| CN201410605526.2A CN104388299B (en) | 2014-10-30 | 2014-10-30 | A kind of micro-fluidic chip for cell capture |
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| CN104388299A true CN104388299A (en) | 2015-03-04 |
| CN104388299B CN104388299B (en) | 2016-03-16 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105176816A (en) * | 2015-10-30 | 2015-12-23 | 东南大学 | Micro-vessel liver chip based on cell clusters and making method and using method thereof |
| CN109652287A (en) * | 2019-01-03 | 2019-04-19 | 京东方科技集团股份有限公司 | A kind of micro-control substrate and preparation method thereof and micro-fluidic chip |
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| US20080169192A1 (en) * | 2007-01-11 | 2008-07-17 | Korea Advanced Institute Of Science And Technology | AC electro-osmosis micro-fluidic device for pumping and mixing liquids and method for pumping and mixing liquids |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105176816A (en) * | 2015-10-30 | 2015-12-23 | 东南大学 | Micro-vessel liver chip based on cell clusters and making method and using method thereof |
| CN109652287A (en) * | 2019-01-03 | 2019-04-19 | 京东方科技集团股份有限公司 | A kind of micro-control substrate and preparation method thereof and micro-fluidic chip |
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| CN104388299B (en) | 2016-03-16 |
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