CN104689860B - A kind of screening anti-tumor medicine micro-fluidic chip for single ball level and application - Google Patents
A kind of screening anti-tumor medicine micro-fluidic chip for single ball level and application Download PDFInfo
- Publication number
- CN104689860B CN104689860B CN201310655993.1A CN201310655993A CN104689860B CN 104689860 B CN104689860 B CN 104689860B CN 201310655993 A CN201310655993 A CN 201310655993A CN 104689860 B CN104689860 B CN 104689860B
- Authority
- CN
- China
- Prior art keywords
- chip
- micro
- cell
- fluidic chip
- tumor medicine
- 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.)
- Active
Links
Abstract
A kind of screening anti-tumor medicine micro-fluidic chip for single ball level and application, steps of the method are the SU after utilizing hot melt 8 template construct PDMS channel chip template；One-step method can make the depression aperture of multiple sizes, for forming the tumour microballoon that varies in size.Micro-fluidic chip is 2 layers of chip, containing 12 parallel microfluidic cell, this chip may be used for the screening anti-tumor medicine of single ball level of tumour cell, the method is without expensive etching apparatus, having simple to operate, quick, experimental cost is cheap, is not related to organic reagent, environmental friendliness, can be with the advantage of other Integration ofTechnology.
Description
Technical field
The invention belongs to the processing of polymer chip, make, modify and application, specifically
Relate to a kind of screening anti-tumor medicine micro-fluidic chip for three-dimensional list ball level and application.
Background technology
Monolayer cell culture is the main method of Cell culture invitro, and it is simple, easily that it has cultivation
Operation, expense is low, the advantage that can widely apply, is widely used as the research of external pharmacological toxicology
Experimental model.But the cultured in monolayer in vitro method of routine is not provided that tissue normal growth grows institute
The environmental condition needed, and growing environment has important impact to cellular gene expression and behavior,
The genome of internal each cell is identical, but its phenotype and function knot in different organ and tissue
Structure is different, as embryonic cell heterotopic transplantation can make cell deterioration develop into teratoma, and in uterus
In can develop into fetal tissues；Equally, teratocarcinoma cell can be converted into normal cell in embryo.
In monolayer cell culture, cell is attached in substrate plane growth, because lacking three-dimensional bracket, only
Can develop to two dimension, can not cellulation epimatrix.Owing to lacking internal specificity growth factor
And differentiation factor effect, cell can not break up and lose substance in time solid shape.Therefore,
The biological character that monolayer cell culture is reflected, differs greatly with in-vivo tissue cell.Therefore
There is provided and internal similar mounting system for cell, create the growing environment similar with in substance,
Promote cell proliferation, break up and present similar in-vivo tissue 26S Proteasome Structure and Function proterties be external carefully
The development trend that born of the same parents cultivate.Three-dimensional cell cultivation is namely based on These characteristics, special by some
The external stereoscopic culture method set up of culture technique.Dimensional culture system provides class for cell
Like support or the matrix of tumor growth environment, cell is connected by compact siro spinning technology and gap connection etc.
Mode sets up contacting between iuntercellular and cell and extracellular matrix, forms certain three-dimensional structure.
Dimensional culture cellular gene expression, matrix secretion and cell function are movable equal with single-layer culturing cell
There is notable difference, and increasingly similar with internal cell.Therefore Three-dimensional cell culture can retention body
The structure of matter basis of inner cell microenvironment, intuitive and the condition that can embody again cell cultivation can
Controlling, external acellular and monolayer cell culture system and histoorgan and holistic approach connection
System gets up.
Clinical cancer therapy would generally occur that MDR (multidrug resistance, MDR) is existing
As, i.e. tumour cell cross resistance raw to Treated with Chemotherapeutic Drugs produce.Although in recent years to its machine
System has carried out numerous studies, but does not the most also have this many of feasible method suppression tumour cell
Medicine drug resistance.Drug-resistant Journal of Sex Research generally uses monolayer cell culture model in vitro, should
The elementary cell of model is single oncocyte, have ignored tumour as a special heterogeneous population
Its cell growth microenvironment and intercellular interaction, the result obtained the most on this basis
The biggest difference is often had with experiment in vivo result.There are some researches show the knot of dimensional culture tumour cell
Structure function is significantly different with monolayer cultivation tumour cell, and similar and internal solid tumor, by three-dimensional
The tumour cell cultivated carries out biomedical research and can more truly reflect situation in tumour body.?
In the research of dimensional culture tumour cell screening anti-tumor medicine, tumour cell many cells microballoon big
The little meeting directly image tumour cell resistance to the action of a drug to medicine.
Utilize making arc-shaped recess micro-structural to form three-dimensional cell structure in recent years and study cell
Behavior and function are increasingly paid close attention to by people.The micro-structural of report forms three-dimensional cell structure now
On the one hand can be that cultured cell in vitro provides raw to its tissue-derived the most identical similar cell
Long microenvironment and cell communication, thus not only improve the differentiation directional induction of various types of cells, again
Be conducive to maintenance and the propagation of cell phenotypic differentiation；On the other hand it is expected to build in vitro with all kinds of
Tissue, organ corresponding cell three-dimensional growth analog or equivalent.And its application also relates to
And stem cell differentiation, islet cell function regeneration, the resistance to the action of a drug of tumour cell, vitro in organ
All many-sides such as reconstruction.Along with the demand of biomedical sector, make arc-shaped recess micro-structural side
Method is also developing rapidly, and main method has: ice etches, and Soft lithograph, electron beam lithography are former
Position synthetic method, pneumatics etc. (1, Park, J.Y.；Hwang,C.M.；Lee,S.-H.,
Ice-lithographic fabrication of concave microwells and a microfluidic
network.Biomedical Microdevices 2008,11(1),129-133；2、Xu,Y.；Xie,
F.；Qiu,T.；Xie,L.；Xing,W.；Cheng,J.,Rapid fabrication of a
microdevice with concave microwells and its application in embryoid
body formation.Biomicrofluidics 2012,6(1),016504)。
Although it is more ripe that said method has developed, but still has several factors to limit
It is more widely applied: the precision that the technology such as Soft lithograph, electron beam lithography is modified is high, but its
Need specialized expensive instrument and operate complexity；Although in-situ synthesis is simple to operate, but
Its molecule system that is expensive and that synthesize being used for fabricated in situ is used sometimes to be had in a large number
Machine reagent；Pneumatic mode technology is simple, quick, with low cost, but required passage template
Being to require the penetrating template with small structure, preparation method is loaded down with trivial details, operation is complicated.Above-mentioned side
In method, can be only formed the aperture of the depression of unified size, it is impossible to form multiple size by one-step method
Depression aperture, and in the drug screening of tumour cell, the size of tumour microballoon is for anti-swollen
Tumor medicine screening has directly impact.
In sum, invention is a kind of simple, quickly, controllability strong and cheap one
Footwork makes the antineoplastic sieve for three-dimensional single ball level making arc of multiple sizes
Micro-fluidic chip is selected to be of great significance.
Summary of the invention
It is an object of the invention to provide the screening anti-tumor medicine for single ball level micro-fluidic
Chip and application, to solve, complex operation step present in conventional manufacture craft is complicated, price
Costliness, quickly forms tumour microballoon and the high flux of antineoplastic thereof and the drug sieve of high intension
Choosing.
The invention provides a kind of screening anti-tumor medicine micro-fluidic chip for single ball level,
This chip is 2 layers of integral chip, and upper strata is fluid chamber, long 700 microns, wide 700 microns,
High 80 microns, there is the microfluidic cell that parallel 12 group are parallel, each unit different-diameter
The depression aperture of size and fluid passage, carry out the antineoplastic sieve of parallel three-dimensional single ball level
Choosing experiment；
The preparation method of this chip is as follows:
(1) optical lithography is utilized to make the SU-8 polymerization of the aperture containing multiple diameter dimensions
Thing template；
(2) SU-8 polymer template is carried out hot melt in 5 minutes at 85 degrees Centigrade, make
The shape of aperture is become umbilicate type from square；
(3) the SU-8 polymer template after hot melt is carried out overall uv-exposure 90 seconds；
(4) by uncured PDMS polymer solution (monomer and silane coupler volume proportion
For 10:1) pour on SU-8 polymer template, 85 degrees Centigrade solidification PDMS gather
Polymer solution 40 minutes, peels off solidification PDMS polymer chip, obtains PDMS polymer
Reverse chip；
(5) by uncured PDMS polymer solution (monomer and silane coupler volume proportion
For 10:1) pour on above-mentioned PDMS polymer reverse chip, 85 degrees Centigrade
Solidification PDMS polymer solution 40 minutes, peels off solidification PDMS polymer chip, obtains
There is the PDMS polymer chip of the different depression aperture of diameter；
(6) the PDM S polymer chip that Soft lithograph fabrication techniques contains flow path channel is utilized；
(7) the PDMS polymerization that the irreversible sealing-in of plasma instrument contains flow path channel is utilized
The PDMS polymer chip of the depression aperture that thing chip is different with there being diameter；
(8) above-mentioned integral chip is carried out surface modification, obtain micro-fluidic chip of the present invention；
Wherein, surface is modified condition and is: 0.2%PF-127 processes 4 hours, rear with aseptic
Water and PBS solution respectively rinse 2 times.
The screening anti-tumor medicine micro-fluidic chip for single ball level that the present invention provides, the party
The shrinkage pool of the micron level formed in method, the width of this micropore and structure are fixing for design, micro-
The diameter in hole is set as successively: 200,300,400,500,600,700,800 is micro-
Rice；The degree of depth of concave shape aperture by regulation ethyl lactate development SU-8 polymer template time
Between control, the time is 5 minutes, the curvature shapes of concave shape aperture by heating plate regulate
The heat time of hot melt controls, and the heat time is 5 minutes.
Present invention also offers the application of described micro-fluidic chip, this chip is used for forming diameter not
The three-dimensional bead of same U87 cell and the screening of antineoplastic thereof.
The application of the micro-fluidic chip that the present invention provides, the first PDMS to arc-shaped recess aperture
Polymer chip carries out surface modification, to reach the effect of cell not wall-attached surface, inoculates U87
Thin osteocyte suspension, under conditions of gravity, the formation three-dimensional microballoon that U87 cell can be spontaneous,
During forming microballoon, due to the difference of hole diameter, the quantity of cell settlement is different,
The U87 cell microsphere varied in size can be formed.
The application of the micro-fluidic chip that the present invention provides, the screening technique of described antineoplastic
For: in each functional unit of micro-fluidic chip, inoculate U87 cell suspension, cultivate 20-24
After hour, U87 cell forms the single microballoon of three-dimensional；After U87 cell microsphere is cultivated 4-5 days,
Add antineoplastic to process 24-30 hour.
The application of the micro-fluidic chip that the present invention provides, described antineoplastic is resveratrol
With PI3K inhibitor PI-103, concentration respectively 200 is micro-rubs/liter and 1.5 receive rub/liter.
It is an advantage of the current invention that:
1, one-step method the aperture of multiple size can be formed, micro-for forming the tumour varied in size
Ball；
2, also have 12 functional units, can carry out fluid-operated；
3, without expensive instrument, simple to operate, quick；
4, experimental cost is cheap；
5, it is not related to organic reagent, environmental friendliness；
6, can be with other Integration ofTechnology.
Accompanying drawing explanation
Fig. 1 is the screening anti-tumor medicine micro-fluidic chip design drawing for single ball level；(1)
For upper strata chip, (2) are lower layer chip.
Fig. 2 is the screening anti-tumor medicine micro-fluidic chip Experimental equipment for single ball level；
(1) being overall chip design, (2) are single microfluidic cell.
Fig. 3 is the depression aperture of the screening anti-tumor medicine micro-fluidic chip formation of single ball level
Deep statistical figure；(1) the depression aperture pictorial diagram of screening anti-tumor medicine micro-fluidic chip,
(2) be screening anti-tumor medicine micro-fluidic chip cave in little hole depth statistical chart.
Fig. 4 is that the screening anti-tumor medicine micro-fluidic chip of single ball level cultivates U87 cell four
The U87 microsphere diameter statistical chart of diverse location after it；(1) this screening anti-tumor medicine miniflow
Control chip cultivates U87 cell pictorial diagram after four days, and (2) are that this screening anti-tumor medicine is micro-
Fluidic chip cultivates U87 after tetra-days, the statistical chart of cell ball diameter.
Fig. 5 is that U87 cell cultivates 4 at the screening anti-tumor medicine micro-fluidic chip of single ball level
After it, add the design sketch after 200 μm ol/L resveratrol effect 24 hours；(1) this resists
Tumor drug screening micro-fluidic chip cultivates U87 cell pictorial diagram after four days before dosing, (2)
After cultivating U87 cell four days for this screening anti-tumor medicine micro-fluidic chip and to add 200 micro-
Rub/liter resveratrol medicament processes the pictorial diagram of 24 hours, the instruction of figure open arrow is straight
The cell ball that footpath diminishes, the cell ball that the diameter of white arrow instruction increases, and markd be not
Unconverted cell ball.
Fig. 6 is that U87 cell cultivates 4 at the screening anti-tumor medicine micro-fluidic chip of single ball level
After it, add the design sketch after 1.5 μm ol/L PI-103 effect 24 hours.(1) this is anti-swollen
Tumor medicine screening micro-fluidic chip cultivates U87 cell pictorial diagram after four days before dosing, (2)
After cultivating U87 tetra-days for this screening anti-tumor medicine micro-fluidic chip and add 1.5 micro-rub/liter
The PI-103 drug-treated pictorial diagram of 24 hours, the instruction of figure open arrow is that diameter diminishes
Cell ball, white arrow instruction diameter increase cell ball, do not have markd for unchanged
Cell ball.
Detailed description of the invention
The present invention will be further described by the following examples, but the most therefore limit
The present invention.
Embodiment 1
Utilizing optical etching technology to make SU-8 polymer template, template is 12 groups of parallel containing
The micropore that 7 kinds of diameters are different, diameter is respectively 200, and 300,400,500,600,700,
800 microns.Parallel 6 groups of same size.Conventional optical etching technology is used to make SU-8
Template: SU-8 photoengraving glue is applied on clean sheet glass, 95 degrees Celsius of front baking heating 1
After hour, remove organic reagent, after SU-8 photoresist cools down；Put the mask designed
After exposing 90 seconds under ultraviolet, after 95 degrees Celsius, dry heating 15 minutes.It is different from routine
Method, SU-8 template developing time of the present invention is 5 minutes, for not exclusively development, dries up aobvious
After shadow agent, hot melt 5 minutes at 85 DEG C, make the structure of micropore in SU-8 template by right angle
Become arc；After cooling, SU-8 template is exposed 90 seconds under uviol lamp completely, form tool
There is the SU-8 template of multiple diameter dimension arc-shaped recess micropore.By uncured PDMS (body
Long-pending than 10:1) it is poured on the SU-8 polymer template made, and simultaneously at 85 DEG C
It is heating and curing 40 minutes.After device cooling, peel off upper strata PDMS chip and form reverse.Will
Uncured PDMS is poured on PDMS polymer reverse chip, and simultaneously at 85 DEG C
It is heating and curing 40 minutes, after device cooling, peels off upper strata PDMS polymer and can form arc
The PDMS polymer chip of depression aperture.Conventional lithographic technique is utilized to make containing of upper strata
There is the PDMS polymeric layer of stream, utilize plasma technology, irreversible sealing-in to contain arc
The PDMS layer of depression aperture and the PDMS layer chip (as illustrated in fig. 1 and 2) having stream.
Meanwhile, the aperture height (as shown in Figure 3) of the PDMS layer containing arc-shaped recess aperture is investigated.
This method one-step method can form the depression micropore of multiple size, and with different curvature.
Embodiment 2
The PDMS polymer chip of sealing-in carries out U87 cell microsphere cultivate such as Fig. 4 institute
Show.First PDMS polymer chip carries out sterilization treatment, and ultraviolet irradiation overnight, then uses
The PF-127 solution of 0.2% carries out surface and modifies 4 hours, respectively rushes by sterilized water and PBS solution
After washing 2 times, inoculating U87 cell suspending liquid, cell under gravity, can be deposited to
Bottom the aperture of chip surface, spontaneous formation three-dimensional cell ball.Owing to devising different size
The micropore result of size, U87 cell defines different size of many cells microballoon.
Embodiment 3
The screening anti-tumor medicine micro-fluidic chip of single ball level is for the anticarcinogen of U87 cell
The research of the screening of thing.Fig. 5 shows the U87 cell PDMS at different size depression aperture
After polymer chip is cultivated four days, then add the 200 white lamb's-quarters of μm ol/L by the fluid passage layer on upper strata
Reed alcohol medicine, to U87 cell microsphere effect, the diameter of part many cells microballoon diminishes, carefully
Cytoactive reduces, but apoptotic situation does not occur.Fig. 6 shows that U87 cell exists
After the PDMS polymer chip of different size depression aperture is cultivated four days, then pass through upper strata
Fluid passage layer add 1.5 μm ol/L PI-103 medicines, the diameter of part many cells microballoon diminishes,
Cytoactive reduces, and has apoptotic situation to occur.
Claims (11)
1. the screening anti-tumor medicine micro-fluidic chip for single ball level, it is characterized in that: this chip is 2 layers of integral chip, there are 12 groups of parallel microfluidic cell, each unit has depression aperture and the fluid passage of different-diameter size, carries out the screening anti-tumor medicine experiment of parallel three-dimensional single ball level；
The preparation method of this chip is as follows:
(1) optical lithography is utilized to make the SU-8 polymer template of the aperture containing multiple diameter dimensions；
(2) SU-8 polymer template is carried out hot melt, make the shape of aperture be become umbilicate type from square；
(3) the SU-8 polymer template after hot melt is carried out the uv-exposure of entirety；
(4) being poured on SU-8 polymer template by uncured PDMS polymer solution, be heating and curing PDMS polymer solution, peels off solidification PDMS polymer chip, obtains PDMS polymer reverse chip；
(5) being poured into by uncured PDMS polymer solution on above-mentioned PDMS polymer reverse chip, be heating and curing PDMS polymer solution, peels off solidification PDMS polymer chip, obtains the PDMS polymer chip with the different depression aperture of diameter；
(6) the PDMS polymer chip that Soft lithograph fabrication techniques contains flow path channel is utilized；
(7) the PDMS polymer chip of the depression aperture that the PDMS polymer chip that utilizes the irreversible sealing-in of plasma instrument to contain flow path channel is different with there being diameter；
(8) above-mentioned integral chip is carried out surface modification, obtain micro-fluidic chip；
Wherein, surface is modified condition and is: 0.2%PF-127 process 4 hours, respectively rinses 2 times by sterilized water and PBS solution afterwards.
2. according to the screening anti-tumor medicine micro-fluidic chip for single ball level a kind of described in claim 1, it is characterised in that: in described step (1), the diameter of aperture is set as successively: 200,300,400,500,600,700,800 microns.
3. according to the screening anti-tumor medicine micro-fluidic chip for single ball level a kind of described in claim 1, it is characterised in that: in described step (2), the condition of hot melt is: 85 degrees Centigrade 5 minutes.
4. according to the screening anti-tumor medicine micro-fluidic chip for single ball level a kind of described in claim 1, it is characterized in that: in described step (2), the curvature shapes of concave shape aperture is by controlling in the heat time of heating plate regulation hot melt, and the heat time is 5 minutes；The degree of depth of concave shape aperture was controlled by the time of regulation ethyl lactate development SU-8 polymer template, and the time is 5 minutes.
5. according to the screening anti-tumor medicine micro-fluidic chip for single ball level a kind of described in claim 1, it is characterised in that: in described step (3), the uv-exposure time is 90 seconds.
6. according to the screening anti-tumor medicine micro-fluidic chip for single ball level a kind of described in claim 1, it is characterized in that: in described step (4) and (5), uncured PDMS polymer solution is PDMS monomer and silane coupler volume proportion is 10:1.
7. according to the screening anti-tumor medicine micro-fluidic chip for single ball level a kind of described in claim 1, it is characterised in that: in described step (4) and (5), the condition being heating and curing is: 85 degrees Centigrade solidify 40 minutes.
8. the application of micro-fluidic chip described in claim 1, it is characterised in that: this chip is for forming three-dimensional bead and the screening of antineoplastic thereof of the different U87 cell of diameter.
9. according to the application of micro-fluidic chip described in claim 8, it is characterized in that: first the PDMS polymer chip of arc-shaped recess aperture is carried out surface modification, to reach the effect of cell not wall-attached surface, inoculation U87 thin osteocyte suspension, under conditions of gravity, the formation three-dimensional microballoon that U87 cell can be spontaneous, during forming microballoon, due to the difference of hole diameter, the quantity of cell settlement is different, can form the U87 cell microsphere varied in size.
10. according to the application of micro-fluidic chip described in claim 8, it is characterized in that: the screening technique of described antineoplastic is: in each functional unit of micro-fluidic chip, inoculate U87 cell suspension, after cultivating 20-24 hour, U87 cell forms the single microballoon of three-dimensional；After U87 cell microsphere is cultivated 4-5 days, add antineoplastic and process 24-30 hour.
11. according to the application of micro-fluidic chip described in claim 10, it is characterised in that: described antineoplastic is 200 micro-rub/liter resveratrol and 1.5 micro-/liter PI3K inhibitor PI-103 that rub.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310655993.1A CN104689860B (en) | 2013-12-04 | 2013-12-04 | A kind of screening anti-tumor medicine micro-fluidic chip for single ball level and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310655993.1A CN104689860B (en) | 2013-12-04 | 2013-12-04 | A kind of screening anti-tumor medicine micro-fluidic chip for single ball level and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104689860A CN104689860A (en) | 2015-06-10 |
| CN104689860B true CN104689860B (en) | 2016-09-07 |
Family
ID=53337631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310655993.1A Active CN104689860B (en) | 2013-12-04 | 2013-12-04 | A kind of screening anti-tumor medicine micro-fluidic chip for single ball level and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104689860B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107916224A (en) * | 2016-10-11 | 2018-04-17 | 中国科学院大连化学物理研究所 | A kind of micro-fluidic chip formed for cell micro-assembly robot and preparation method and application |
| CN108117986A (en) * | 2016-11-26 | 2018-06-05 | 中国科学院大连化学物理研究所 | It is a kind of based on method and its application of the micro-fluidic chip cell without stent self assembly |
| CN108117969A (en) * | 2016-11-28 | 2018-06-05 | 中国科学院大连化学物理研究所 | Single celled micro-fluidic chip of a kind of high throughput automatic capture and preparation method thereof |
| CN108148751A (en) * | 2016-12-06 | 2018-06-12 | 中国科学院大连化学物理研究所 | A kind of integrated drug screening and dyeing micro-fluidic chip and preparation method thereof |
| CN112264115B (en) * | 2020-10-26 | 2022-03-11 | 南京鼓楼医院 | Fishbone microfluidic chip carrying molecular imprinting inverse opal structure microspheres and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101750488A (en) * | 2008-12-17 | 2010-06-23 | 中国科学院大连化学物理研究所 | Beta 2-adrenergic receptor stimulant detection method based on microfluidic chip |
| CN102008983A (en) * | 2010-11-01 | 2011-04-13 | 武汉大学 | Microfluidic chip suitable for producing microcapsules |
| 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 |
| CN103266050A (en) * | 2013-06-04 | 2013-08-28 | 上海市东方医院 | Microfluidic chip for sorting and application thereof |
| EP1838442B1 (en) * | 2005-01-18 | 2013-09-11 | Biocept, Inc. | Cell separation using microchannel having patterned posts |
-
2013
- 2013-12-04 CN CN201310655993.1A patent/CN104689860B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1838442B1 (en) * | 2005-01-18 | 2013-09-11 | Biocept, Inc. | Cell separation using microchannel having patterned posts |
| CN101750488A (en) * | 2008-12-17 | 2010-06-23 | 中国科学院大连化学物理研究所 | Beta 2-adrenergic receptor stimulant detection method based on microfluidic chip |
| CN102008983A (en) * | 2010-11-01 | 2011-04-13 | 武汉大学 | Microfluidic chip suitable for producing microcapsules |
| 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 |
| CN103266050A (en) * | 2013-06-04 | 2013-08-28 | 上海市东方医院 | Microfluidic chip for sorting and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104689860A (en) | 2015-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104689860B (en) | A kind of screening anti-tumor medicine micro-fluidic chip for single ball level and application | |
| Xue et al. | Projection-based 3D printing of cell patterning scaffolds with multiscale channels | |
| Ling et al. | Bioprinting-based high-throughput fabrication of three-dimensional MCF-7 human breast cancer cellular spheroids | |
| Sodunke et al. | Micropatterns of Matrigel for three-dimensional epithelial cultures | |
| CN105861309B (en) | A kind of super-hydrophobic micro-pit array chip and preparation method and application | |
| Bian et al. | Mesoscopic hydrogel molding to control the 3D geometry of bioartificial muscle tissues | |
| Khademhosseini et al. | Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment | |
| Yang et al. | Rapid fabrication of hydrogel microstructures using UV-induced projection printing | |
| Weiß et al. | Two‐photon polymerization of biocompatible photopolymers for microstructured 3D biointerfaces | |
| US20100129908A1 (en) | Spaced projection substrates and devices for cell culture | |
| Yanagawa et al. | Directed assembly of cell‐laden microgels for building porous three‐dimensional tissue constructs | |
| Shen et al. | Recent advances in three-dimensional multicellular spheroid culture and future development | |
| CN102978110B (en) | Preparation method and application of PDMS polymer chip of arc-shaped concave aperture | |
| Underhill et al. | Bioengineering methods for analysis of cells in vitro | |
| CN107916224A (en) | A kind of micro-fluidic chip formed for cell micro-assembly robot and preparation method and application | |
| Cha et al. | A novel cylindrical microwell featuring inverted-pyramidal opening for efficient cell spheroid formation without cell loss | |
| CN102787364B (en) | Manufacturing method and application of PDMS (Polydimethylsiloxane) polymer chip with arc sunk holes | |
| Zhang et al. | Fabrication of agarose concave petridish for 3D-culture microarray method for spheroids formation of hepatic cells | |
| Taebnia et al. | Dual-material 3D-printed intestinal model devices with integrated villi-like scaffolds | |
| US20130029422A1 (en) | Composite Substrate for 3D Cell Culture | |
| CN106591127A (en) | Cell culture device with three-dimensional surface microstructure, and manufacturing method thereof | |
| Chen et al. | Liver-lobule-mimicking patterning via dielectrophoresis and hydrogel photopolymerization | |
| Tan et al. | Investigating PEGDA and GelMA microgel models for sustained 3D heterotypic dermal papilla and keratinocyte co-cultures | |
| Jiang et al. | Construction of in vitro 3-D model for lung cancer-cell metastasis study | |
| Wei et al. | Dot extrusion bioprinting of spatially controlled heterogenous tumor models |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |