CN102115738B - Gold nanoparticle template for promoting cell growth and preparation method thereof - Google Patents
Gold nanoparticle template for promoting cell growth and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a gold nanoparticle template for promoting cell growth and a preparation method thereof. The preparation method of the gold nanoparticle template comprises the following the steps of: printing a micro-nano gold array pattern on a substrate by using ink-jet water-soluble ink which contains gold nanoparticles through an ink-jet printer; and performing calcination or laser etching on the substrate with the array pattern and removing a high polymer protective agent on the surfaces of the gold nanoparticles to obtain the gold nanoparticle template. A preparation method of the ink-jet water-soluble ink which contains the gold nanoparticles comprises the following steps of: ultrasonically mixing the gold nanoparticles, a water-soluble cosolvent, a high polymer dispersing agent, a surfactant and secondary distilled water; and pre-dispersing and concentrating to obtain the ink-jet water-soluble ink. The gold nanoparticle template can be co-cultured with cells to obtain a cell biological chip. By adopting the method for preparing a functional template, the prepared chip has the advantages of low cost, simple preparation process, easiness in grasping, quick detection, remarkable performance and price advantages, no pollution to the environment, and the like.
Description
Technical field
The present invention relates to a kind of gold nano grain template that promotes the cell growth and preparation method thereof.
Background technology
The biochip template mainly refers to the microarray that the biologically active substance (comprising cell, nucleic acid, protein and small tissue etc.) assembled at solid substrate constitutes, with realize to compound (comprising medicine), protein, nucleic acid, cell and other biological components accurately, fast, selective growth, enrichment, screening or the detection of large information capacity.
Arranging of a large amount of cells is extremely important for research cell and intercellular interaction, such as two cell masses (or two unicellular) can being positioned two zones of certain microspur that are separated by respectively, and then study interaction and exchange of substance situation between them.The meaning that cell is arranged also is embodied in and is easy to observation that a large amount of cells physiological situations are walked abreast, is easy to realize the quick counting to a large amount of cells, and is easy to realize biosensor based on cell etc.In addition, the array of cell grouping research and the high-flux parallel cell analysis of arranging for cell is a tool technique that has Practical significance.Simultaneously a kind of in the cell chip biochip for gene functional research provides a kind of high-throughput instrument, except the purposes with organization chip, also has the irreplaceable purposes of organization chip.
Jing Tang etc. are at Patterning of HeLa Cells on a Microfabricated Au-Coated ITO Substrate.Langmuir, mention the template for preparing cellular array with electrochemical method in 2009,25,5380.But wherein need to use template and prepare chip earlier, and then with electrochemical method gold is appeared in the ITO substrate selectively, adding can only have the routine of adsorption function and block cell absorption to hate cell reagent at Au---and have the polyethylene glycol polymer of sulfydryl end, grown cell prepares cell chip in the above then.
The above method requires all very high in the preparation of biomass cells chip template, as the substrate of special use, and special biotechnological formulation, special facilities for observation, or prepare template in advance and hate cell or close cell processing etc.Therefore develop a kind of simple, cost is low, feasible, and conveniently realize producing a kind of preparation method of the cell biological chip template of cell growth that can promote at same chip on a large scale and be significant.
Continuous development along with electronics technology, make the relative merits of ink-jet printer product constantly outstanding, its major advantage is that price is low, noise is low, change print cartridge or irritate black convenient, with low cost, can provide good panchromatic be printing quality, and can directly print on the first-class different carrier of sheet glass, tinsel and silicon chip.Its shortcoming is exactly with respect to laser printer, and the time of response is long, print speed is slower.
About marking ink, along with being showing improvement or progress day by day of nanotechnology, some has reached nano level state of the art aspect the colorant in the ink-jet printing ink ranks.Have nano level colorant and make ink have a lot of special nature, as disclosed among Chinese patent CN 1687258A and the CN 1982383A.But the stable dispersion colloid of the containing metal nano particle of the aqueous solution is used for the application patent of the biological aspect of spray ink Printing also not to be occurred now.Meanwhile, the metal nanoparticle technology of preparing becomes more consummate day by day.
Summary of the invention
The purpose of this invention is to provide a kind of gold nano grain template with the growth of promotion cell and preparation method thereof.
Gold nano grain template provided by the present invention is to prepare according to the method that comprises the steps: the inkjet water-soluble ink that will contain gold nano grain prints micro-nano golden array pattern by ink-jet printer in substrate; After the spontaneous curing substrate with described array pattern is calcined or laser ablation, remove the macromolecule dispersant on gold nano grain surface, obtain described gold nano grain template.
The used inkjet water-soluble ink that contains gold nano grain is that application reference number is disclosed ink in 200810101214.2 the patent application among the present invention.
Described substrate is to can be used in the anti-calcining of formation substrate or the solid material of laser ablation, comprises having can covalently or non-covalently being attached to the character on the particulate or can being derivatized to any solid material with this character.As the material of substrate including, but not limited to: glass, silica, silicon chip, silicon-dioxide, metal, pottery (porcelain) etc. when removing macromolecule dispersant, the solid material that substrate can stable existence.This substrate also comprises the substrate of being made up of different material layer.
Calcining to substrate with described array pattern can be carried out in retort furnace, and calcining temperature is more than 250 ℃, and the time is more than 5 hours, specifically can pass through TGA assessment as a result.But according to energy-conservation principle, generally be selected between 400-1200 ℃ and calcined 6-12 hour.Laser ablation is carried out in substrate with described array pattern, can at room temperature directly carry out.
The size and dimension of described array pattern can be set at size and the shape of any requirement as required.Big or small as 1cm * 1cm or bigger, 100 μ m * 100 μ m; Shape is as annular, oval, square, rectangle or can comprise irregularly shaped.
After gold nano grain template provided by the invention and cell are cultivated mutually, cell occurred and printed visibly different selective adsorption on the array, fixing and growing state with gold nano grain in the substrate.This gold nano grain template can be used for directly preparing cell biological chip.
Described cell comprises neuronal cell, cervical cancer cell HeLa, the plain cell ESF of people's embryo fibroblast, human breast cancer cell MCF7[MCF-7], the former leukemia cell K-562 of the chronic marrow of people, mouse embryo cell NIH/3T3, cells such as hamster ovary cell CHO.
The present invention is directed to the existing problem that cell chip template preparation cost is higher, technology is loaded down with trivial details, a kind of preparation method who need not complex operations condition and the uniform cell chip template of dot matrix is provided.This method utilizes commercially available ink-jet printer and the inkjet water-soluble ink that contains gold nano grain to print the template of required various cell biological device chip models in multiple substrate; through methods such as calcining or laser ablations; after removing the outer macromolecule dispersant of nano particle, make and print the part that nano particle is arranged in the template chip and become a kind of gold nano grain " naked gold " district that can promote the cell growth.The classification cell biological chip quality better, tolerance range height, the good reproducibility that utilize this template to prepare.
The employed inkjet water-soluble ink that contains gold nano grain prepares according to following method among the present invention: gold nano grain, water-soluble cosolvent, macromolecule dispersing agent, interfacial agent and redistilled water are mixed, through pre-dispersed, concentrate or lyophilize, obtain containing the inkjet water-soluble ink of gold nano grain;
Wherein, the described inkjet water-soluble ink that contains gold nano grain is made up of the material of following quality percentage composition: 1%～25% gold nano grain, 10%～50% water-soluble cosolvent, 0%～20% macromolecule dispersing agent, 0%～20% interfacial agent, 25%～75% redistilled water;
Described gold nano grain is the water-soluble gold nano particle;
Described water-soluble cosolvent is hexanaphthene, methyl alcohol, ethanol, 2-propyl alcohol, two-1,2-propylene glycol, Diethylene Glycol, triethylene glycol, ethylene glycol, propylene glycol, butyleneglycol, pentanediol, hexylene glycol and contain a kind of in the polyvalent alcohol of at least three hydroxyls or greater than more than one mixture; Preferred alcohol.
The preparation method is as follows more specifically: elder generation's adding water soluble cosolvent in macromolecule dispersing agent, and the consumption of described water-soluble cosolvent is 10%～50% of described macromolecule dispersing agent quality, and macromolecule dispersing agent is dissolved fully; Add gold nano grain, redistilled water and interfacial agent then, in the ultrasonic cleaning instrument, heat ultrasonic carry out pre-dispersed and concentrated or lyophilize, obtain the described inkjet water-soluble ink that contains gold nano grain.
Described in the ultrasonic cleaning instrument heating ultrasonic to carry out pre-dispersed and concentrated temperature be 10～70 ℃, the time is 0.5～24 hour.
The median size of gold nano grain is less than 300nm in the described inkjet water-soluble ink that contains gold nano grain; Preferred median size is 1～100nm.
Described interfacial agent can be 2-Pyrrolidone, N-N-methyl-2-2-pyrrolidone N-, 2,4,7,9-tetramethyl--5-n-heptylacetylene-4,7-glycol, 1,1, a kind of in 1-TriMethylolPropane(TMP), polyoxyethylene glycol, polypropylene glycol, polyvinylpyrrolidone and the polyvinyl pyridine or greater than more than one mixture.
Described macromolecule dispersing agent can be copolymerization resin, poly-butyl resin, acroleic acid resin or a kind of polymkeric substance that contains wetting ability functional group and lipophilicity functional group simultaneously etc. of oxyalkylene addition compound, derivatived cellulose, vinylbenzene and the propylene of oxyethane and epoxypropane copolymerization thing, butylene oxide ring and oxyethane co-polymer, gelatin and glutaraldehyde cross-linking mixture, maleic and cinnamic co-polymer, dioctyl sulfenyl amber esterification sodium, ethylene glycol.
In the present invention, before utilizing gold nano grain template and co-culture of cells, need template, biological reagent (as PBS buffer reagent, EDTA, substratum DMEM, serum etc.) and the equipment sterilising treatment that carries out disinfection, the method that adopts can be the most conventional simple uv irradiating sterilization and autoclaving, also can be ozone sterilization, desiccating method, γShe Xianmiejun method and other sterilising method.
Characteristics of the present invention are:
1, the micro-nano array that prints has better biocompatibility after removing macromolecule dispersant, have undissolved function in water, in biological buffered soln and the nutrient solution.
2, biological substance such as cell has different absorption, fixing, the ability that promotes cell growth or apoptosis in array and substrate.
3, array is being that character by the micro-nano golden mould material itself after the calcining is determined aspect the ability that promotes the cell growth.
4, the method by simple calcining or laser ablation realizes a kind of preparation that can promote the gold nano grain template of cell growth, and to make cell finish quick cell chip preparation at chip be outstanding characteristic of the present invention.
The present invention has satisfied the cell chip template should have specific stability, selectivity and detectability.Cell chip method for preparing template of the present invention is than employed method for preparing template is more simple and convenient traditionally at present, controllability is strong, and its repeatability and operability provide new experimental basis, thinking and direction for possible large-scale production after it.And cell chip template of the present invention substrate can be selected multiple material for use, the material of or laser ablation high temperature resistant as sheet glass, aluminium foil and silicon chip etc., have good repeatability, the stability of well being combined with material and stability and with the characteristics of biology and solution reaction thereof.Cell biological chip template of the present invention is having incomparable advantage aspect the preparation of biochip, bio-reactor and the micro-fluidic preparation, for its later application provides vast potential for future development.
Description of drawings
Fig. 1 is the gold nano grain aggregate along with the prolongation of the time inverted microscope photo to impact cell.
Fig. 2 is for the silicon chip being the cell biological chip photo of the gold nano grain template preparation of substrate.
Fig. 3 is for being in the cell chip array pattern on the gold nano grain template of substrate with the silicon chip, local magnified sweep electron microscope picture (SEM figure).
Fig. 4 can successfully prepare the possible principle schematic of cell chip fast for the cell chip template.
Embodiment
Below by specific embodiment method of the present invention is described, but the present invention is not limited thereto.
Experimental technique described in the following embodiment if no special instructions, is ordinary method; Described reagent and biomaterial if no special instructions, all can obtain from commercial channels.
The inkjet water-soluble ink that contains gold nano grain used among the following embodiment is the 200810101214.2 method preparations of announcing with reference to application number.When preparation contained the inkjet water-soluble ink of gold nano grain, used gold nano grain was to prepare according to the method among the Chinese patent CN200510108023.5.
The preparation of embodiment 1, HeLa cell chip template
Preparation contains the inkjet water-soluble ink of particle diameter 2nm gold nano grain, and concrete preparation method is as follows:
1) at first prepare the stable particle diameter 2nm gold nano grain dispersion of polymer protection, after unnecessary macromolecule dispersant is removed in dialysis, lyophilize, being mixed with mass concentration with the redistilled water behind the autoclaving is 10% gold nano grain solution.Before adding macromolecule dispersing agent, under the room temperature, obtain the cotton-shaped polymkeric substance of black among Fig. 1 after cultivating more than the 52h with the DMEM that contains 10% serum altogether with gold nano grain.Cotton-shaped polymkeric substance and the co-culture of cells of gold nano grain the results are shown in shown in Figure 1.As shown in Figure 1, along with the increase of incubation time altogether, cytoactive per-cent raises, and proves that the gold nano grain aggregate has promoter action to the energy for growth of HeLa cell.
2) in 0.80g oxyethane and epoxypropane copolymerization thing solid (macromolecule dispersing agent), add 2ml ethanol (cosolvent) earlier, after the dissolving fully, the mass concentration that adds above-mentioned preparation is 10% gold nano grain solution 4ml, N-N-methyl-2-2-pyrrolidone N-(interfacial agent) 0.40g, 25 ℃ of ultra-sonic dispersion 30 minutes are namely prepared as printing the needed ink of cellular array template.
Use ink-jet printer IP4500 to print the various templates that need in substrate, after the spontaneous curing, after 6 hours, prepare the gold nano grain template that can promote the cell growth through 500 ℃ of calcinings.
The gold nano grain template of preparation is put into culture plate in sterilization under the ultraviolet lamp after 4 hours, add the HeLa cell and in CO2gas incubator, cultivate altogether more than 24 hours, just prepared needed cell chip.According to the length of incubation time, can allocate the amount of cell on the classification cell chip arbitrarily.
HeLa cell chip of the present invention (template) can be printed on sheet glass, tinsel and the silicon chip, and wherein, the HeLa cell chip on silicon chip pattern is as a result seen Fig. 2 and 3.Wherein, Fig. 2 illustrates in the substrate of silicon chip or sheet glass, cell quantity seldom, but the gold nano grain array region after printing calcining, the quantity of cell is a lot, the substrate naked eyes can be seen one deck white cell; Fig. 3 amplifies the picture of being behind the SEM to Fig. 2, and obviously see and print the dense growth of cell on the gold nano grain array of removing macromolecule dispersant, and considerably less at substrate position cell quantity.Schematic diagram is seen Fig. 4; after nano particle protective material outside changes or after removing; gold nano grain becomes the big aggregate that forms, and can not enter the HeLa cell and impel apoptosis, and the aggregate that gold nano grain is big is adsorbed on the growth of the surface promotion cell of HeLa cell on the contrary.
The preparation of embodiment 2, K-562 cell chip template
Preparation contains the inkjet water-soluble ink of particle diameter 10nm gold nano grain, and concrete preparation method is as follows:
1) at first prepare the gold nano grain dispersion of the stable particle diameter 10nm of polymer protection, after unnecessary macromolecule dispersant is removed in dialysis, lyophilize, being mixed with mass concentration with the redistilled water behind the autoclaving is 18% gold nano grain solution.Before adding macromolecule dispersing agent, under the room temperature, obtain the cotton-shaped polymkeric substance of black among Fig. 1 after cultivating more than the 52h with the DMEM that contains 10% serum altogether with gold nano grain, cotton-shaped polymkeric substance and the co-culture of cells of getting gold nano grain the results are shown in shown in Figure 1.Along with the increase of incubation time altogether, cytoactive per-cent raises, and proves that the gold nano grain aggregate has promoter action to the energy for growth of K562 cell.
2) in 0.80g maleic and cinnamic co-polymer (macromolecule dispersing agent), add the 2mL hexylene glycol earlier as cosolvent, after the dissolving fully, the mass concentration that adds above-mentioned preparation is 18% gold nano grain solution 4ml and N-N-methyl-2-2-pyrrolidone N-(interfacial agent) 0.40g, 40 ℃ were heated ultra-sonic dispersion 60 minutes, namely prepared as the needed ink of template of printing cellular array.
Use the various templates that ink-jet printer IP4500 prints to be needed, after the spontaneous curing, laser ablation is removed the macromolecule dispersant on gold nano grain surface, prepares the gold nano template that can promote the cell growth.
The gold nano grain template of preparation is put into culture plate in sterilization under the ultraviolet lamp after 4 hours, add the K-562 cell and in CO2gas incubator, cultivate altogether more than 24 hours, just prepared needed cell chip.According to the length of incubation time, can allocate the amount of cell on the cell chip arbitrarily.
K-562 cell chip of the present invention (template) can be printed on the high temperature resistant composites such as sheet glass, tinsel and silicon chip.Wherein, Fig. 2 illustrates in the substrate of silicon chip or sheet glass, cell quantity seldom, but the gold nano grain array region after printing calcining, the quantity of cell is a lot, the substrate naked eyes can be seen one deck white cell; Fig. 3 is the figure after Fig. 2 is SEM and amplifies, obviously sees and prints the dense growth of cell on the gold nano grain array of removing macromolecule dispersant, and considerably less at substrate position cell quantity.Schematic diagram is seen Fig. 4; after nano particle protective material outside changes or after removing; the big back of the change of gold nano grain forms aggregate, can not enter the K562 cell and impel apoptosis, and the aggregate that gold nano grain is big is adsorbed on the growth of the surface promotion K562 cell of cell on the contrary.
The preparation of embodiment 3, ESF cell chip template
Preparation contains the inkjet water-soluble ink of particle diameter 25nm gold nano grain, and concrete preparation method is as follows:
1) at first prepare the stable particle diameter 25nm gold nano grain dispersion of polymer protection, after unnecessary macromolecule dispersant is removed in dialysis, lyophilize, being mixed with mass concentration with the redistilled water behind the autoclaving is 8% gold nano grain solution.Before adding macromolecule dispersing agent, under the room temperature, obtain the cotton-shaped polymkeric substance of black among Fig. 1 after cultivating more than the 52h with the DMEM that contains 10% serum altogether with gold nano grain, cotton-shaped polymkeric substance and the co-culture of cells of getting gold nano grain the results are shown in shown in Figure 1.Along with the increase of incubation time altogether, cytoactive per-cent raises, and proves that the gold nano grain aggregate has promoter action to the energy for growth of ESF cell as can be seen from Figure 1.
2) in 0.80g gelatin and glutaraldehyde cross-linking mixture (macromolecule dispersing agent), add the 2mL glycerol earlier, after the dissolving fully, add mass concentration in the solution of above-mentioned preparation and be 8% gold nano grain solution 4.0ml and 1,1,1-TriMethylolPropane(TMP) (interfacial agent) 0.40g, 37 ℃ were heated ultra-sonic dispersion 60 minutes, namely prepared as the needed ink of template of printing cellular array.
Use the various chip templates that ink-jet printer IP4500 prints to be needed, after the spontaneous curing, prepared the gold nano template that can promote the cell growth in 8 hours 600 ℃ of calcinings.
The gold nano grain template of preparation is put into culture plate in sterilization under the ultraviolet lamp after 4 hours, add the ESF cell and in CO2gas incubator, cultivate altogether more than 48 hours, just prepared needed cell chip.According to the length of incubation time, can allocate the amount of cell on the cell chip arbitrarily.
ESF cell chip of the present invention (template) can be printed on sheet glass, tinsel and the silicon chip.
The preparation of embodiment 4, Chinese hamster ovary celI chip template
1) at first prepare the stable particle diameter 2nm gold nano grain dispersion of polymer protection, after unnecessary macromolecule dispersant is removed in dialysis, lyophilize, being mixed with mass concentration with the redistilled water behind the autoclaving is 15% gold nano grain solution.Before adding macromolecule dispersing agent, under the room temperature, obtain the cotton-shaped polymkeric substance of black among Fig. 1 after cultivating more than the 52h with the DMEM that contains 10% serum altogether with gold nano grain, cotton-shaped polymkeric substance and the co-culture of cells of getting gold nano grain the results are shown in shown in Figure 1.Along with the increase of incubation time altogether, the active per-cent of Chinese hamster ovary celI raises, and proves that the gold nano grain aggregate has promoter action to the energy for growth of Chinese hamster ovary celI as shown in Figure 1.
2) in 0.80g acrylic resin (macromolecule dispersing agent), add 2mL ethylene glycol earlier, after the dissolving fully, the mass concentration that adds above-mentioned preparation is 15% gold nano grain solution 4ml and N-N-methyl-2-2-pyrrolidone N-(interfacial agent) 0.40g, 60 ℃ were heated ultra-sonic dispersion 60 minutes, namely prepared as the needed ink of template of printing cellular array.
Use the various chip templates that ink-jet printer IP4500 prints to be needed, after the spontaneous curing, after 6 hours, prepare the gold nano grain template that can promote the cell growth 700 ℃ of calcinings.
The gold nano grain template autoclaving of preparation was put into culture plate after 20 minutes, and the adding Chinese hamster ovary celI is cultivated altogether in CO2gas incubator and has just been prepared needed cell chip more than 24 hours.According to the length of incubation time, can allocate the amount of cell on the cell chip arbitrarily.
It is first-class that Chinese hamster ovary celI chip of the present invention (template) can be printed on sheet glass, tinsel and silicon chip.
Claims (10)
1. a method for preparing the gold nano grain template comprises the steps: that the inkjet water-soluble ink that will contain gold nano grain prints micro-nano golden array pattern by ink-jet printer in substrate; After the spontaneous curing substrate with described array pattern is calcined or laser ablation, obtain described gold nano grain template;
The described inkjet water-soluble ink that contains gold nano grain prepares according to following method: gold nano grain, water-soluble cosolvent, macromolecule dispersing agent, interfacial agent and redistilled water are mixed, through pre-dispersed, concentrate, obtain containing the inkjet water-soluble ink of gold nano grain;
Wherein, the described inkjet water-soluble ink that contains gold nano grain is made up of the material of following quality percentage composition: 1%～25% gold nano grain, 10%～50% water-soluble cosolvent, 0%～20% macromolecule dispersing agent, 0%～20% interfacial agent, 25%～75% redistilled water;
Described gold nano grain is the water-soluble gold nano particle;
Described water-soluble cosolvent is hexanaphthene, methyl alcohol, ethanol, 2-propyl alcohol, two-1,2-propylene glycol, Diethylene Glycol, triethylene glycol, ethylene glycol, propylene glycol, butyleneglycol, pentanediol, hexylene glycol and contain the polyvalent alcohol of at least three hydroxyls;
Described substrate is made of the solid phase material of anti-calcining or laser ablation.
2. method according to claim 1, its feature in: the temperature of described calcining is more than 250 ℃, and the time of calcining is more than 5 hours.
3. method according to claim 2, its feature in: described calcining temperature is 400-1200 ℃, and the time is 6-12 hour.
4. according to the arbitrary described method of claim 1-3, it is characterized in that: the described inkjet water-soluble ink that contains gold nano grain prepares according to following method: elder generation's adding water soluble cosolvent in macromolecule dispersing agent dissolves macromolecule dispersing agent fully; Add gold nano grain, redistilled water and interfacial agent then, in the ultrasonic cleaning instrument heating ultrasonic carry out pre-dispersed, concentrate, obtain the described inkjet water-soluble ink that contains gold nano grain.
5. method according to claim 4, its feature is being: described in the ultrasonic cleaning instrument heating ultrasonic to carry out pre-dispersed and concentrated temperature be 10～70 ℃, the time is 0.5～24 hour.
6. according to arbitrary described method among the claim 1-3, it is characterized in that: the median size of gold nano grain is less than 300nm in the described inkjet water-soluble ink that contains gold nano grain.
7. according to arbitrary described method among the claim 1-3, it is characterized in that: described interfacial agent is 2-Pyrrolidone, N-N-methyl-2-2-pyrrolidone N-, 2,4,7,9-tetramethyl--5-n-heptylacetylene-4,7-glycol, 1,1, the mixture of one or more in 1-TriMethylolPropane(TMP), polyoxyethylene glycol, polypropylene glycol, polyvinylpyrrolidone and the polyvinyl pyridine;
Described macromolecule dispersing agent is the copolymerization resin of oxyalkylene addition compound, derivatived cellulose, vinylbenzene and the propylene of oxyethane and epoxypropane copolymerization thing, butylene oxide ring and oxyethane co-polymer, gelatin and glutaraldehyde cross-linking mixture, maleic and cinnamic co-polymer, dioctyl sulfenyl amber esterification sodium, ethylene glycol, poly-butyl resin or acroleic acid resin.
8. the gold nano grain template for preparing according to arbitrary described method among the claim 1-7.
9. the application of the described gold nano grain template of claim 8 in the preparation cell chip.
10. application according to claim 9 is characterized in that: described cell is neuronal cell, cervical cancer cell HeLa, the plain cell ESF of people's embryo fibroblast, human breast cancer cell MCF7, the former leukemia cell K-562 of the chronic marrow of people, mouse embryo cell NIH/3T3 or hamster ovary cell CHO.
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| CN1308131A (en) * | 2000-12-22 | 2001-08-15 | 郭占军 | Low density biochip and its making process |
| CN101519552A (en) * | 2008-02-29 | 2009-09-02 | 中国科学院化学研究所 | Method for preparing inkjet water-soluble ink containing noble metal nano particles |
| CN101892285A (en) * | 2010-06-23 | 2010-11-24 | 西安交通大学 | Method for preparing three-dimensional cell chip |
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| CN1308131A (en) * | 2000-12-22 | 2001-08-15 | 郭占军 | Low density biochip and its making process |
| CN101519552A (en) * | 2008-02-29 | 2009-09-02 | 中国科学院化学研究所 | Method for preparing inkjet water-soluble ink containing noble metal nano particles |
| CN101892285A (en) * | 2010-06-23 | 2010-11-24 | 西安交通大学 | Method for preparing three-dimensional cell chip |
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