CN108823064A - A kind of cell capture device suitable for medical test - Google Patents

A kind of cell capture device suitable for medical test Download PDF

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Publication number
CN108823064A
CN108823064A CN201810720969.4A CN201810720969A CN108823064A CN 108823064 A CN108823064 A CN 108823064A CN 201810720969 A CN201810720969 A CN 201810720969A CN 108823064 A CN108823064 A CN 108823064A
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CN
China
Prior art keywords
miniflow
protrusive board
entrance
substrate
drainage
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Granted
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CN201810720969.4A
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Chinese (zh)
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CN108823064B (en
Inventor
李劲松
侯滨
蔡宏伟
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Lejie Biotechnology Co., Ltd.
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李劲松
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS 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
    • C12M47/00Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04Cell isolation or sorting

Abstract

The present invention relates to Cell Measurement Technique field, in particular to a kind of cell capture device suitable for medical test.It is an object of the invention to overcome the problems, such as unicellular caused by structure missing is precipitated in the prior art to be not easy to be precipitated and cell stress concentration problem caused by capture mechanism design is unreasonable.A kind of cell capture device suitable for medical test of the invention, including miniflow substrate, miniflow cover board, partition is precipitated, drain entrance, culture medium entrance, drainage outlet, first fluid stopping plate, second fluid stopping plate, export opening-closing plate, miniflow substrate is arranged below miniflow cover board and is bonded integrally with miniflow cover board, partition is precipitated to be movably arranged on inside miniflow substrate, a kind of easy precipitation of captured cell is realized through the invention, reviewer is facilitated to use, the micro-current controlled cell acquisition equipment concentrated in runner without stress, farthest avoid because arresting structure it is unreasonable caused by cell dissolution, cellular damage.

Description

A kind of cell capture device suitable for medical test
Technical field
The present invention relates to Cell Measurement Technique field, in particular to a kind of cell capture device suitable for medical test.
Background technique
As the number one killer for threatening human life and health, people more and more tend to pay attention to the research of cancer, and cancer is thin The easy metastatic of born of the same parents is annoying always vast scientific research medical personnel, how fast and effeciently to divide from tissue fluid, peripheral blood Separate out the top priority that cancer cell is further research cancer metastasis and pathogenesis.At this stage, mainly using stream in industry The main path that formula analyzer is separated as cell, and finding in practical applications, that there are operating processes is complicated for flow type analyzer, Separation process influences cell activity, is difficult to the problems such as obtaining individual cells.Therefore, as academia is to MEMS research Deeply, increasingly tend in the industry use the micro-fluidic chip with specific function as cell separation, cell capture device.
Chinese patent 201611016757.5 discloses a kind of micro-fluidic chip for unicellular capture and culture, leads to Cross the upper cover plate combined, lower substrate constitutes the main structure of chip, and by setting microwell array, symmetrical crook The function of the capture and culture to individual cells is realized, however it is only micro-fluidic by overturning disclosed in its technical solution Chip realizes the precipitation of cell, and in actual operation due to the influence of atmospheric pressure, precipitation process is not smooth, directly affects thin The efficiency of born of the same parents' progress later period inspection;Similarly, Chinese patent 201210142904.9 discloses a kind of micro-fluidic battle array of cell capture Column chip, it is real by the microarray-type structures chip for etching different spacing, different size microtrabeculae volume array in microchannel The capture respectively to variety classes, different size of cell is showed, flexible structure does not design moving component, can be suitable for The capture and analysis of a variety of cancer cells, and on the other hand, the design of single runner easily causes the stress collection of fluid pressure In, the deformation of cell, or even dissolution are in turn resulted in, cell activity is caused to reduce.
It can be seen that affecting micro-fluidic chip there are still some problems in the prior art using above-mentioned patent as representative Popularization and use, for example, to cell be precipitated structure consider missing caused by be captured cell be difficult to take out or take out to have some setbacks The problem of cell activity is influenced caused by the problem of benefit, microchannel structural design are unreasonable, capture mechanism gap structure is unreasonable causes Stress concentration problem, and these problems can directly contribute that cell capture device capture rate is too low, damage capture object etc. is negative Face is rung.
Summary of the invention
It is an object of the invention to overcome the problems, such as caused by structure missing is precipitated in the prior art it is unicellular be not easy to be precipitated with And capture mechanism design it is unreasonable caused by cell stress concentration problem, to realize that a kind of captured cell is easy to be precipitated, side Just the micro-current controlled cell acquisition equipment that reviewer uses, concentrates in runner without stress, farthest avoids because of arresting structure Cell dissolution, cellular damage caused by unreasonable.
For achieving the above object, technical scheme is as follows:
A kind of cell capture device suitable for medical test, including miniflow substrate, miniflow cover board, be precipitated partition, drainage entrance, Culture medium entrance, drainage outlet, the first fluid stopping plate, the second fluid stopping plate, outlet opening-closing plate, the miniflow substrate are arranged in miniflow lid It being bonded integrally below plate and with miniflow cover board, the precipitation partition is movably arranged on inside miniflow substrate, the drainage entrance, Culture medium entrance is provided with the front side of the miniflow substrate, and the drainage outlet is provided with the rear side of the miniflow substrate, described First fluid stopping plate is movably arranged in drainage entrance, and the second fluid stopping plate is movably arranged in culture medium entrance, the outlet Opening-closing plate is movably arranged in drainage outlet.
The miniflow substrate, including upper substrate, middle layer cavity, underlying basal are provided with multiple groups on the upper substrate Lower catcher and microchannel are connected between the lower catcher by microchannel, are consolidated at the lower catcher interior inlet Surely it is provided with capture convex body, the lower catcher bottom is provided with level-one air pressure through-hole, and the depth size of the lower catcher is greater than The size of target cell cluster average diameter;The middle layer cavity is arranged on the downside of upper substrate, the middle layer cavity inside table Face is provided with nano coating;The downside substrate setting on the downside of cavity, is provided with multiple groups second level gas on the underlying basal in middle level Through-hole is pressed, the axis of the level-one air pressure through-hole on the axis and the upper substrate of the second level air pressure through-hole is in same straight line On, the radius of the level-one air pressure through-hole and second level air pressure through-hole is equal.
The microchannel, including entrance main pipeline, lateral, outlet main pipeline, the entrance main pipeline setting exist The outside of the side on the front of miniflow substrate surface, the entrance main pipeline is connected to drainage entrance and culture medium entrance, described The inside of entrance main pipeline is connected to the head end of a plurality of lateral, mutually indepedent between the lateral, and described point The end of branch pipe(tube) is connected to the inside of outlet main pipeline, and drainage outlet is provided with and communicated on the outside of the outlet main pipeline.
The capture convex body includes left valve protrusive board, mesopetalum protrusive board, right valve protrusive board, the left valve protrusive board and the right valve protrusive board Inside be provided with transverse side holes, longitudinal hole, the left valve protrusive board, mesopetalum protrusive board and right valve are provided in the middle part of the mesopetalum protrusive board There are vacant gaps between protrusive board, and the width in vacant gap is less than the size of target cell cluster mean radius, the left valve The axis of protrusive board and the right valve protrusive board is in 20 ° of settings, and the left valve protrusive board and the right valve protrusive board are positive triangular prism structure, institute State mesopetalum protrusive board inside sideline be it is arc-shaped, the level-one air pressure through-hole is located at left valve protrusive board, mesopetalum protrusive board, right valve protrusive board and encloses The height of central area out, the capture convex body is less than the depth of lower catcher.
The drainage inlet laterally offers the first interlayer cavity, and the first fluid stopping plate is set by the first interlayer cavity activity It sets in drainage inlet, the culture medium inlet laterally offers the second interlayer cavity, and the second fluid stopping plate passes through the second folder Layer chamber is movably arranged on culture medium inlet, and the drainage exit offers outlet plenum chamber, and the outlet opening-closing plate passes through Outlet plenum chamber is movably arranged on drainage exit, and the width of the drainage outlet is less than the width of drainage entrance and culture medium entrance Degree.
The partition that is precipitated is movably arranged on the outer surface setting that partition is precipitated in the middle layer cavity in the miniflow substrate There is nano coating, the length that partition is precipitated is greater than the length of the miniflow substrate mesonexine cavity.
Catcher in multiple groups, size, shape and the miniflow base of the upper catcher are offered on the miniflow cover board The lower catcher of on piece is completely the same, and is coaxially set with corresponding lower catcher, mutual between the upper catcher It is independent.
The invention has the advantages that:
1. the present invention solves in the prior art by the way that fluid stopping plate is arranged in miniflow substrate, partition, two stage atmospheric pressure through-hole is precipitated The problem of cell can not effectively be precipitated.After the present invention captures, the first fluid stopping plate of push-in, the second fluid stopping plate and outlet folding Plate later overturns acquisition equipment, and takes out and partition is precipitated to open two stage atmospheric pressure through-hole, and thus atmospheric pressure will be captured thin Born of the same parents are pressed into the upper catcher on cover board, so that cell be precipitate into upper catcher, improve precipitation efficiency.
2. capture convex body of the invention be provided with left valve protrusive board, mesopetalum protrusive board, right valve protrusive board three parts structure, three parts it Between devise the vacant gap less than target cell cluster mean radius, make acquisition equipment overcome the liquid in capture mechanism by Power concentration problem, and it is provided with interior bone on left valve protrusive board, mesopetalum protrusive board, right valve protrusive board, further reduce capture Convex body internal pressure improves the negotiability of runner, avoids the problem of cell is dissolved after by external force, damaged.
3. microchannel of the invention is provided with entrance main pipeline, lateral, outlet main pipeline three parts, and each Carry out capture work independently of one another, simultaneously between lateral, avoids in micro-fluidic chip in the prior art only by one Item or two pipelines are captured, and capture rate is improved;Middle layer cavity of the invention is provided with precipitation baffle surface and receives Rice coating, effectively prevents the leakage of culture medium, ensure that the air-tightness of acquisition equipment.
Detailed description of the invention
Fig. 1 is a kind of axonometric drawing of cell capture device suitable for medical test of the invention;
Fig. 2 is the axonometric drawing of miniflow substrate a kind of cell capture device suitable for medical test of the invention;
Fig. 3 is the top view of miniflow substrate a kind of cell capture device suitable for medical test of the invention;
Fig. 4 is the partial view A of miniflow substrate a kind of cell capture device suitable for medical test of the invention;
Fig. 5 is the three-dimensional view that convex body is captured a kind of cell capture device suitable for medical test of the invention;
Fig. 6 is the bottom view of miniflow substrate a kind of cell capture device suitable for medical test of the invention;
Fig. 7 is the axonometric drawing of miniflow cover board a kind of cell capture device suitable for medical test of the invention.
Description of symbols:
Partition is precipitated in 1- miniflow substrate, 2- miniflow cover board, 3-, and 4- drains entrance, 5- culture medium entrance, 6- drainage outlet, 7- the One fluid stopping plate, 8- the second fluid stopping plate, 9- export opening-closing plate, 11- upper substrate, the middle layer 12- cavity, 13- underlying basal, on 21- Catcher, the first interlayer cavity of 41-, the second interlayer cavity of 51-, 61- outlet plenum chamber, catcher under 111-, 112- microchannel, 113- capture convex body, 114- level-one air pressure through-hole, 131- second level air pressure through-hole, 1121- entrance main pipeline, 1122- lateral, 1123 outlet main pipelines, the left valve protrusive board of 1131-, 1132- mesopetalum protrusive board, the right valve protrusive board of 1133-, 1134- transverse side holes, 1135 is vertical To through-hole.
Specific embodiment
With reference to Fig. 1, Fig. 2, a kind of cell capture device suitable for medical test, including miniflow substrate 1, miniflow cover board 2, Partition 3, drainage entrance 4, culture medium entrance 5, the 6, first fluid stopping plate 7 of drainage outlet, the second fluid stopping plate 8, outlet opening-closing plate is precipitated 9, the miniflow substrate 1 is arranged below miniflow cover board 2 and is bonded integrally with miniflow cover board 2, and 3 activity of precipitation partition is set It sets inside miniflow substrate 1, the drainage entrance 4, culture medium entrance 5 are provided with the front side of the miniflow substrate 1, the drainage Outlet 6 is provided with the rear side of the miniflow substrate 1, and the first fluid stopping plate 7, which is movably arranged on, to be drained in 4 mouthfuls, and described second Fluid stopping plate 8 is movably arranged in culture medium entrance 5, and the outlet opening-closing plate 9 is movably arranged in drainage outlet 6.
According to fig. 2, Fig. 3, Fig. 4, Fig. 6, the miniflow substrate 1, including upper substrate 11, middle layer cavity 12, underlying basal 13, catcher 111 and microchannel 112 under multiple groups are provided on the upper substrate 11, are passed through between the lower catcher 111 Microchannel 112 is connected to, and capture convex body 113, the lower catcher are fixedly installed at lower 111 interior inlet of catcher 111 bottoms are provided with level-one air pressure through-hole 114, and the depth size of the lower catcher 111 is greater than target cell cluster average diameter Size;The setting of middle layer cavity 12 is provided with nanometer painting in 11 downside of upper substrate, 12 interior surface of middle layer cavity Layer;The setting of downside substrate 13 on the downside of cavity 12, is provided with multiple groups second level air pressure through-hole on the underlying basal 13 in middle level 131, the axis of the level-one air pressure through-hole 114 on the axis and the upper substrate 11 of the second level air pressure through-hole 131 is same On straight line, the level-one air pressure through-hole 114 is equal with the radius of second level air pressure through-hole 131.
According to fig. 2, Fig. 3, the microchannel 112, including entrance main pipeline 1121, lateral 1122, outlet supervisor The side on the front on 1 surface of miniflow substrate is arranged in road 1123, the entrance main pipeline 1121, the entrance main pipeline 1121 Outside is connected to drainage entrance 4 and culture medium entrance 5, the inside of the entrance main pipeline 1121 and a plurality of lateral 1122 Head end connection, the lateral 1122 is mutually indepedent each other, the end of the lateral 1122 and outlet main pipeline The outside of 1123 inside connection, the outlet main pipeline 1123 is provided with and communicated with drainage outlet 6.
According to Fig. 3, Fig. 4, Fig. 5, the capture convex body 113 includes left valve protrusive board 1131, mesopetalum protrusive board 1132, right valve protrusive board 1133, the inside of the left valve protrusive board 1131 and the right valve protrusive board 1133 is provided with transverse side holes 1134, the mesopetalum protrusive board 1132 middle part is provided with longitudinal hole 1135, stays between the left valve protrusive board 1131, mesopetalum protrusive board 1132 and right valve protrusive board 1133 Have a vacant gap, and the width in vacant gap is less than the size of target cell cluster mean radius, the left valve protrusive board 1131 with For the axis of the right valve protrusive board 1133 in 20 ° of settings, the left valve protrusive board 1131 and the right valve protrusive board 1133 are regular triangular prism Structure, the inside sideline of the mesopetalum protrusive board 1132 be it is arc-shaped, the level-one air pressure through-hole 114 be located at left valve protrusive board 1131, The height of the central area that mesopetalum protrusive board 1132, right valve protrusive board 1133 cross, the capture convex body 113 is less than lower catcher 111 Depth, this make in microstream it is at large obtain convex body capture cell can continue to enter next catcher complete next round Capture.
According to Fig. 1, Fig. 3, the first interlayer cavity 41 is laterally offered at the drainage entrance 4, the first fluid stopping plate 7 passes through First interlayer cavity 41 is movably arranged at drainage entrance 4, and the second interlayer cavity 51, institute are laterally offered at the culture medium entrance 5 It states the second fluid stopping plate 8 to be movably arranged at culture medium entrance 5 by the second interlayer cavity 51, be offered out at the drainage outlet 6 Mouth interlayer cavity 61, the outlet opening-closing plate 9 are movably arranged at drainage outlet 6 by outlet plenum chamber 61, the drainage outlet 6 Width be less than drainage entrance 4 and culture medium entrance 5 width, this enables microstream when being filled with miniflow substrate 1 in miniflow Loine pressure is formed in pipeline, to be full of each branch's microchannel.
With reference to Fig. 1, Fig. 2, the precipitation partition 3 is movably arranged in the middle layer cavity 12 in the miniflow substrate 1, is precipitated The outer surface of partition 3 is provided with nano coating, and the length that partition 3 is precipitated is greater than the 1 mesonexine cavity 12 of miniflow substrate Length.
According to fig. 2, Fig. 7, offers catcher 21 in multiple groups on the miniflow cover board 2, the size of the upper catcher 21, Shape and the lower catcher 111 on the miniflow substrate 1 are completely the same, and are coaxially set with corresponding lower catcher 111, institute It is mutually indepedent each other to state catcher 21.
The course of work and working principle of a kind of cell capture device suitable for medical test of the invention are as follows:
With reference to Fig. 1-Fig. 7, when work, miniflow substrate 1 is located at the horizontal down of miniflow cover board 2, pulls out the first fluid stopping plate 7 and outlet Opening-closing plate 9, the second fluid stopping plate of push-in 8 and precipitation partition 3 make to drain 6 in the open state, culture mediums of entrance 4 and drainage outlet Entrance 5 is in close state, level-one air pressure through-hole 114 and second level air pressure through-hole 131 are in close state;It will include to be captured The microstream of cell is filled into miniflow substrate 1 by draining entrance 4, and microstream successively flows into respectively by entrance main pipeline 121 A lateral 1122, then flowed into lower catcher 111 via lateral 1122.
The captured convex body 113 of individual cells captures after into lower catcher 111, micro- liquid into inside capture convex body 113 Stream is flowed out from the gap between left valve protrusive board 1131, mesopetalum protrusive board 1132, right valve protrusive board 1133, while the aperture on each protrusive board To capture 113 inner pressure relief of convex body, captured cell dissolution, damage are prevented;And the cell of capture convex body 113 is not entered then from catching 113 two sides of convex body and top is obtained to continue to flow into lower catcher 111 and enter next lower catcher through microchannel and carry out again Capture, final microstream are assembled in outlet main pipeline 1123, and pass through 6 outflow miniflow substrate 1 of drainage outlet.
After microstream is filled with, it is pushed into the first fluid stopping plate 7, closes drainage entrance 4, stopping is filled with micro- liquid containing cell Stream, and the second fluid stopping plate 8 is pulled out, to open culture medium entrance 5, while keeping drainage outlet 6 in the open state, from culture Base entrance 5 is filled with the culture medium without containing cell into miniflow substrate 1, is rinsed to miniflow substrate 1, flows into miniflow substrate 1 The cell being detained in microchannel 112 and lower catcher 111 is poured outlet main pipeline 1123 by interior culture medium, and by draining Miniflow substrates 1 are discharged in mouth 6.
It is pushed into the second fluid stopping plate 8 later, to close culture medium entrance 5, push-in outlet opening-closing plate 9 drains to close Mouth 6, and drainage entrance 4 is kept to be in off state, it is whole to overturn cell capture device, so that miniflow substrate 1 is located at miniflow cover board 2 Horizontal top, then pulls out and partition 3 is precipitated, make liquid stream in miniflow substrate 1 by level-one air pressure through-hole 114, middle layer cavity 12, Second level air pressure through-hole 131 is in communication with the outside, and under atmospheric pressure precipitate into captured cell from capture convex body 113 micro- It flows 21 in the upper catcher in cover board 2, and then completes the capture of single cell.

Claims (8)

1. a kind of cell capture device suitable for medical test, which is characterized in that including miniflow substrate, miniflow cover board, be precipitated Partition, drainage entrance, culture medium entrance, drainage outlet, the first fluid stopping plate, the second fluid stopping plate, outlet opening-closing plate, the miniflow base Piece is arranged below miniflow cover board and is bonded integrally with miniflow cover board, and the precipitation partition is movably arranged in miniflow substrate Portion, the drainage entrance, culture medium entrance are provided with the front side of the miniflow substrate, and the drainage outlet is provided with the miniflow The rear side of substrate, the first fluid stopping plate are movably arranged in drainage entrance, and the second fluid stopping plate is movably arranged on culture medium In entrance, the outlet opening-closing plate is movably arranged in drainage outlet.
2. being suitable for the cell capture device of medical test as described in claim 1, which is characterized in that the miniflow substrate, Including upper substrate, middle layer cavity, underlying basal, catcher and microchannel under multiple groups, institute are provided on the upper substrate It states and is connected between lower catcher by microchannel, be fixedly installed capture convex body at the lower catcher interior inlet, it is described Lower catcher bottom is provided with level-one air pressure through-hole, and the depth size of the lower catcher is greater than target cell cluster average diameter Size;The middle layer cavity is arranged on the downside of upper substrate, and the middle layer interior cavity surface is provided with nano coating;Under described The setting of side group piece on the downside of cavity, is provided with multiple groups second level air pressure through-hole on the underlying basal in middle level.
3. being suitable for the cell capture device of medical test as claimed in claim 2, which is characterized in that the capture convex body packet Include left valve protrusive board, mesopetalum protrusive board, right valve protrusive board, the inside of the left valve protrusive board and the right valve protrusive board is provided with transverse side holes, institute It states and is provided with longitudinal hole in the middle part of mesopetalum protrusive board, there are vacant gap between the left valve protrusive board, mesopetalum protrusive board and right valve protrusive board, And the width in vacant gap is less than the size of target cell cluster mean radius, the axis of the left valve protrusive board and the right valve protrusive board Line is in 20 ° of settings, and the left valve protrusive board and the right valve protrusive board are positive triangular prism structure, and the inside sideline of the mesopetalum protrusive board is Arc-shaped, the level-one air pressure through-hole is located at the central area that left valve protrusive board, mesopetalum protrusive board, right valve protrusive board cross, the capture The height of convex body is less than the depth of lower catcher.
4. being suitable for the cell capture device of medical test as claimed in claim 2, which is characterized in that the microchannel, Including entrance main pipeline, lateral, outlet main pipeline, on the front the one of miniflow substrate surface is arranged in the entrance main pipeline Side, the outside of the entrance main pipeline are connected to drainage entrance and culture medium entrance, the inside of the entrance main pipeline with it is a plurality of The head end of lateral is connected to, mutually indepedent between the lateral, and the end and outlet of the lateral are responsible for The inside in road is connected to, and drainage outlet is provided with and communicated on the outside of the outlet main pipeline.
5. being suitable for the cell capture device of medical test as claimed in claim 2, which is characterized in that the precipitation partition is living Dynamic to be mounted in the middle layer cavity in the miniflow substrate, the outer surface that partition is precipitated is provided with nano coating, it is described be precipitated every The length of plate is greater than the length of the miniflow substrate mesonexine cavity.
6. being suitable for the cell capture device of medical test as claimed in claim 2, which is characterized in that the second level air pressure is logical The axis of level-one air pressure through-hole on the axis in hole and the upper substrate on same straight line, the level-one air pressure through-hole and The radius of second level air pressure through-hole is equal.
7. such as the cell capture device as claimed in any one of claims 1 to 6 suitable for medical test, which is characterized in that described Drainage inlet laterally offers the first interlayer cavity, and the first fluid stopping plate is movably arranged on drainage entrance by the first interlayer cavity Place, the culture medium inlet laterally offer the second interlayer cavity, and the second fluid stopping plate is arranged by the second interlayer cavity activity In culture medium inlet, the drainage exit offers outlet plenum chamber, and the outlet opening-closing plate is living by outlet plenum chamber Dynamic setting is less than the width of drainage entrance and culture medium entrance in drainage exit, the width of the drainage outlet.
8. such as the cell capture device as claimed in any one of claims 1 to 6 suitable for medical test, which is characterized in that described Catcher in multiple groups, size, shape and the lower capture on the miniflow substrate of the upper catcher are offered on miniflow cover board Chamber is completely the same, and is coaxially set with corresponding lower catcher, mutually indepedent between the upper catcher.
CN201810720969.4A 2018-07-04 2018-07-04 A kind of cell capture device suitable for medical test Active CN108823064B (en)

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CN109837205A (en) * 2019-04-16 2019-06-04 北京龙基高科生物科技有限公司 A kind of high-throughput chip for nucleic acid sequencing
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Inventor after: Cheng Lejie

Inventor after: Hao Jianfeng

Inventor after: Li Jinsong

Inventor after: Hou Bin

Inventor after: Cai Hongwei

Inventor before: Li Jinsong

Inventor before: Hou Bin

Inventor before: Cai Hongwei

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Effective date of registration: 20190808

Address after: 712100 Free Trade Avenue Shaanxi Life Science Park, Yangling Demonstration Area, Xianyang City, Shaanxi Province

Applicant after: Lejie Biotechnology Co., Ltd.

Address before: 361000 Xiamen Zhongshan Hospital, No. 201-209 Hubin South Road, Xiamen City, Fujian Province

Applicant before: Li Jinsong

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