CN102520151A - Method for producing quasi three dimensional biological chip - Google Patents
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Abstract
The invention relates to a method for producing a quasi three dimensional biological chip, comprising the following steps: a, growing an array of one-dimensional materials on a substrate to obtain a plane material containing the array of the one-dimensional materials; and b, respectively fixing different sensing materials in the different areas on the array of the one-dimensional materials of the plane material to obtain the quasi three dimensional biological chip, wherein the one-dimensional materials are materials with the ratio of the length to the diameter being larger than 2. According to the invention, the method firstly combines the growth of the one-dimensional materials on the detection substrate with the spotting sample method and in situ synthesis method of the plane microarray biological chip, that is, the preparation of the quasi three dimensional biological chip is compatible with the preparation of a traditional plane microarray biological chip, thus the prepared biological chip has the characteristics of quasi three dimensions and is easy for batch production.
Description
Technical field
The present invention relates to the preparation method of the three-dimensional biochip of a kind of standard, especially the biochip substrate through the basis of shaft-like, the fibrous or tubular material of growth of one-dimensional on again through or point sample method synthetic at sheet fixedly the sensing responsive material prepare certainly three-dimensional biochip.Because the one-dimensional material sensing capabilities is good and growth is easy to control, so this method has simple to operately, and therefore with low cost and characteristics that can prepared in batches help further developing of planar micro array bio-chip.
Background technology
Along with human civilization advance, various fields such as health care, bioengineering, environmental protection and food security are more and more, more and more urgent to the demand of high flux, low cost, convenient and reliable multifunctional bio senser element.For this reason, in the eighties of last century the nineties, people have developed biochip.The initial conception of biochip technology derives from the once impromptu suggestion in the Affymax company of predecessor of U.S. Affymetrix company; The nucleic acid hybridization theory that Fodor organizes semiconductor expert and molecular biology expert to propose by means of Ed Southern; Be mark nucleic acid molecules can with the making nucleic acid molecular hybridization of the complementary pairing with it that is cured, at first designed the oligonucleotides biochip in 1993 ~ 1994 years.Biochip passes through microphotography; According to intermolecular interactional specifically principle; Discontinuous analytic process in the life science is integrated in the miniature organism chemical analysis system of silicon, glass or polymer surface; With realize pair cell, protein, gene and other biological components accurately, fast, the detection of large information capacity, its detection efficiency is hundreds and thousands of times of traditional detection technological means.Be accompanied by the development of the Human Genome Project (HGP); Fusion by means of electronics, biology, physics, chemistry, computer science; Nearly biochip technology has during the last ten years obtained considerable progress; And be applied in advantages such as its unrivaled high information quantity, high flux, microminiaturization and robotizations and comprise fields such as medical diagnosis on disease and treatment, drug screening, Food Hygiene Surveillance, environment measuring, national defence; Demonstrated huge using value, therefore received attracting attention of countries in the world academia and industry member, generally acknowledged and bring a revolution will for life and the medical scientific of 21 century.
Present biochip mainly comprises planar micro array chip and suspension array chip.Wherein the planar micro array chip have position encoded, can with microelectronic technique compatibility and mature preparation process mutually, be the higher biochip of present commercial applications degree therefore.Yet in application process, the low material of content detects challenge to biochip sensitivity and accuracy of detection and but still remains people and further explore and development.People have developed three dimensional gel DNA chip for this reason.People's research shows that three dimensional gel DNA chip is owing to the higher fixed capacity that three-dimensional structure had makes its detection sensitivity obviously improve.And people's research shows that also the Zinc oxide nano-rod microarray is prepared into senser element and has higher detection sensitivity equally on the other hand.These show that all the material with three-dimensional or accurate three-dimensional character has certain application prospect in senser element.Yet present biochip does not still have other similarly three-dimensional or accurate three-dimensional biochip except three dimensional gel DNA chip, for this reason the application propose first in the world at first point sample or original position synthetic technology that in substrate shaft-like, the fibrous or tubular material array of growth of one-dimensional combines biochip then fixedly the sensing responsive material have the biochip of accurate three-dimensional character with formation.This technology has simple to operate, with low cost and can with the characteristics of existing planar micro array bio-chip technical compatibility.
Summary of the invention
Technical matters:The preparation method who the purpose of this invention is to provide the three-dimensional biochip of a kind of standard; The i.e. at first tubulose of growth of one-dimensional or shaft-like microarray in substrate, then through the point sample method or the sheet synthetic method fixedly the sensing responsive material to obtain biochip with accurate three-dimensional character.
Technical scheme:For solving the problems of the technologies described above, the present invention provides the preparation method of the three-dimensional biochip of a kind of standard, and this method comprises the steps:
A, in substrate the array of growth of one-dimensional material to obtain to contain the planar materials of one-dimensional material array;
B, on the one-dimensional material array of planar materials the fixing respectively different sensing responsive materials of zones of different to obtain accurate three-dimensional biochip.
Preferably, said one-dimensional material is a length-to-diameter greater than 2 material.
Preferably, fixing said sensing responsive material is meant that being fixedly connected material earlier in the one-dimensional material array surface connects the sensing responsive material through connecting material again.
Preferably, described zones of different at one-dimensional material respectively the method for fixing different sensing responsive materials comprise the point sample method and in the sheet synthetic method.
Preferably, described in substrate the growth of one-dimensional material be meant and be employed in the basal surface evenly growth or on the lattice array that makes up in advance in the substrate, growing.
Preferably, this method comprises that the planar materials to the one-dimensional material array of having grown cuts, assembles to make up accurate three-dimensional biochip.
The three-dimensional biochip of said standard is through being used for detecting with sample effect to be checked.
Beneficial effect:The growth that the present invention will detect one-dimensional material array in the substrate first is with the point sample method of planar micro array bio-chip and combine in the sheet synthetic method; The preparation compatibility of the preparation of promptly accurate three-dimensional biochip and traditional planar micro array bio-chip; Therefore prepared biochip not only has accurate three-dimensional characteristic, and is easy to produce in batches.
Description of drawings
Fig. 1 is the accurate three-dimensional biochip synoptic diagram of one-dimensional material growth method preparation.
1 substrate;
2 substrate growns the side view of one-dimensional material array;
Fixed the side view of sensing responsive material a, b and c on the 3 one-dimensional material arrays respectively;
Fixed the vertical view of sensing responsive material a, b and c on the 4 one-dimensional material arrays respectively.
Fig. 2 is the accurate three-dimensional biochip synoptic diagram of growth of one-dimensional material Array Method preparation behind the first subregion.
1 ' base side view;
The base side view of 2 ' the Zone coated one-dimensional material growth catalysis material; ' substrate subregion growth of one-dimensional material array side view; ' the fixing different sensing responsive materials A of the different subregions of growth of one-dimensional material array, B, and the side view of C.
Embodiment
Below in conjunction with embodiment the present invention is further described.
The present invention relates to the preparation of the three-dimensional biochip of a kind of standard; Especially behind growth of one-dimensional material array on the base material, fix different sensing responsive materials in its zones of different again, the planar materials that this method adopts following step preparation: a, the array of growth of one-dimensional material contains the one-dimensional material array with acquisition in substrate; B, on the one-dimensional material array of planar materials the fixing respectively different sensing responsive materials of zones of different to obtain accurate three-dimensional biochip.The growth that this method will detect one-dimensional material array in the substrate first is with the point sample method of planar micro array bio-chip and combine in the sheet synthetic method; The preparation compatibility of the preparation of promptly accurate three-dimensional biochip and traditional planar micro array bio-chip; Therefore prepared biochip not only has accurate three-dimensional characteristic, and is easy to produce in batches.
The present invention provides the preparation method of the three-dimensional biochip of a kind of standard, and this method comprises the steps:
A, in substrate the array of growth of one-dimensional material to obtain to contain the planar materials of one-dimensional material array;
B, on the one-dimensional material array of planar materials the fixing respectively different sensing responsive materials of zones of different to obtain accurate three-dimensional biochip.
Said one-dimensional material is a length-to-diameter greater than 2 material.
Fixing said sensing responsive material is meant that being fixedly connected material earlier in the one-dimensional material array surface connects the sensing responsive material through connecting material again.
The method that described zones of different at one-dimensional material is fixed different sensing responsive materials respectively comprises that the point sample method reaches in the sheet synthetic method.
Described in substrate the growth of one-dimensional material be meant and be employed in the basal surface evenly growth or on the lattice array that makes up in advance in the substrate, growing.
This method comprises that the planar materials to the one-dimensional material array of having grown cuts, assembles to make up accurate three-dimensional biochip.
The three-dimensional biochip of said standard is through being used for detecting with sample effect to be checked.
Embodiment one:
At first prepare 4 inches mask plate, on the length of side is arranged is that 100 microns and spacing are 100 microns box-shaped array.On silicon chip, preparing the length of side through microelectronic technique in view of the above then is 100 microns, highly is about 20 microns, is spaced apart 100 microns micro-pit array.
To press 10: 1 mixings of mass ratio by PDMS precursor and hardening agent, and remove to water behind the bubble and cast from the above-mentioned silicon chip mould with micro-pit array, and place baking oven for heating to solidify.Obtaining spacing after the demoulding is 100 microns, highly is about the PDMS template that 20 microns length of sides are about 100 microns convex square array.Then its immersion is contained in the ethanolic solution that contains 1% diethanolamine of zinc acetate of 100mM, take out, treat after the protuberate drying it to be pressed on the clean microslide, then the PDMS template is removed.Microslide was handled 30 minutes in 80 degrees centigrade of following ethanol saturated vapour environment.Handle after 30 minutes under being placed on 600 degrees centigrade then and be cooled to room temperature with 10 degrees celsius/minute.Obtain being coated with the microslide of zinc oxide seed.This microslide is placed 100 milliliters of xylene solutions of the acetic anhydride zinc that contains 30mmol sodium dodecylsulphonate and 3mmol; The pH value to 11.3 of the hydrazine hydrate regulator solution through containing 20% ethanol subsequently; Using washed with de-ionized water and at room temperature dry to obtain in spacing after 5 hours in 90 degrees centigrade of reactions is that 100 microns length of sides are that growth has diameter to be about 80 to 100 nanometers on 100 microns the box-shaped array, and length is about the microslide of 3 microns Zinc oxide nano-rod microarray film.This microslide is handled ethanol cleaning after 10 minutes, drying with the dichloromethane solution of 5% 3-aminopropyl trimethoxysilane successively through the point sample method.Using PH subsequently is that the PBS damping fluid room temperature of 7.4 5% glutaraldehyde was handled 2 hours; With handling 2 hours with the ethanolic solution of 5 % monoethanolamines again after the PBS buffer solution for cleaning, handle 15 minutes so that hydroxyl is contained on the Zinc oxide nano-rod surface with the sodium borohydride aqueous solution of 3M subsequently.Through the ink-jet original position synthetic technology cleaning fluid acetonitrile that the oligonucleotides original position is synthetic, coupling liquid is the acetonitrile solution of 0.1M oligonucleotides monomer and 0.5M tetrazolium subsequently; Confining liquid is acetic anhydride pyridine solution and methylimidazole tetrahydrofuran solution; Oxidation liquid be the acetic acid/acetic anhydride/pyridine/tetrahydrofuran solution of 0.1M iodine and take off DMT liquid promptly 3% trichloroacetic acid dichloromethane solution according to coupling, sealing, oxidation and the repeating step that takes off DMT on the zinc-oxide nano bar array of hydroxyl in sheet synthetic oligonucleotide probe sequence.Designed probe is that a situation arises for methylated in the quantitative examination tumour, and hybridize to understand the methylation status of important GIF IGFBP7 gene in 6 groups of oligonucleotide probes and the tumor sample extracting DNA library promptly formed through exhaustive methylation DNA and two complementary probes of complete non-methylate DNA.Designed probe is respectively 5 '-ACG CTC GTA CCC ACC TT-3 '; 5 '-AAC ACT CAT ACC CAC CTT ACT-3 '; 5 '-CTA AAC CGA ACG ACG CA-3 '; 5 '-CTA AAC CAA ACA ACA CAA AAT-3 '; 5 '-CGT CGA ATA TAC CCT TCG-3 '; 5 '-CCC ATC AAA TAT ACC CTT CA-3 '; 5 '-AAA CCG CCG CGA ACG-3 '; 5 '-AAC AAA ACC ACC ACA AAC AC-3 '; 5 '-ATA AAC AAC GCG AAA CG-3 '; 5 '-AAT AAA CAA CAC AAA ACA AAA C-3 '; 5 '-ACC CGC GAA AAA ATC G-3 '; 5 '-AAA ATA CCC ACA AAA AAA TCA-3 '.
Carrying out the detection of testing sample in addition prepares.At first interrupt the dna fragmentation that the gene that extracted obtains 400bp to 500bp, promptly obtain the testing sample that can be used for hybridizing through methylate DNA co-immunoprecipitation, dna fragmentation linear amplification and fluorescence labeling then through ultrasonic.Testing sample and the above-mentioned genetic chip for preparing that above-mentioned fluorescence labeling is crossed were hybridized 3 hours at 42 degrees centigrade, be carried out to picture with scanner immediately after drying up with the thorough cleaning of TE damping fluid of 10mM Tris and 1mM EDTA composition and with nitrogen subsequently.The strong and weak methylation status that can judge IGFBP7 gene in institute's test sample that has that it's too late according to micro-pillar array different probe zone fluorescence.
Embodiment two:
At first preparing the box-shaped length of side is 200 microns about 10 microns high PDMS seals that are spaced apart 200 microns; Dry up gently at the polylysine WS of PDMS seal surface coated 0.1%w/v and with nitrogen then; Then it is stamped in 30 seconds of clean silicon chip surface; Handle 30 minutes again with the 40 Nano Silver glue solutions of 1%w/v subsequently, and dry up gently with nitrogen.This silicon chip is placed on the tubular furnace middle distance is positioned at graphite and the oxide powder and zinc potpourri downstream about 6 inch places of stove center with 2 to 1 mixing; Feed argon gas with the speed of 100 cubic millimeters of per minutes then, and obtained on silicon chip in 200 microns interval regions the evenly silicon chip of capping oxidation zinc nano rod array in 1 hour 900 degrees centigrade of reactions.With the dichloromethane solution of this silicon chip through 5% 3-aminopropyl trimethoxysilane soaked 5 minutes and use ether, acetone and ethanol to clean the back to use the PH of 5% glutaraldehyde be 7.4 PBS damping fluid room temperature reaction after 2 hours, use the PBS buffer solution for cleaning subsequently three times.The antibody of 50 kinds of common malignant bacteria microorganisms that will contain the PBS damping fluid of 1 mg/ml through the point sample method then dripped different Zinc oxide nano-rod array regions on silicon chip, 4 degrees centigrade of reactions 12 hours.After thoroughly cleaning with the PBS damping fluid, unreacted glutaraldehyde reacts with the PBS buffer solution of 1% BSA and blocked in 2 hours.Thoroughly clean with the PBS damping fluid subsequently, hatched 2 hours with 180rpm speed in oscillator with testing sample, clean three times with PBST buffer solution then at 37 degrees centigrade.Adding is by the mixing PBS buffer solution of the CY3 mark malignant bacteria microorganism antibody of 50 kind of 4 mcg/ml; Hatched 1 hour 37 degrees centigrade of speed with 60RPM; Clean three times and observation under fluorescent microscope having that it's too late power can judge whether contain 50 kinds of common malignant bacteria microorganisms in institute's working sample subsequently according to different Zinc oxide nano-rod array region fluorescence with PBS.
Embodiment three:
The ethanolic solution that contains 1% diethanolamine of the zinc acetate of preparation 2mM immerses wherein also taking-up with microslide and handled 5 minutes at 80 degrees centigrade.Handled 30 minutes at 600 degrees centigrade after repeating 6 times.The said process triplicate is gone up zinc oxide seed to guarantee that microslide all and equably covers.The pH value to 10.6 that in 50 milliliters of xylene, adds the acetic anhydride zinc of 15mmol sodium dodecylsulphonate and 1.5mmol and the hydrazine hydrate regulator solution through containing 20% ethanol in addition; Then the above-mentioned microslide that has covered zinc oxide seed is placed in one; Have diameter to be about 60 nanometers with washed with de-ionized water and at room temperature drying obtains in 90 degrees centigrade of reactions after 5 hours, and length is about 2 microns zinc-oxide nano bar array.With this microslide successively the dichloromethane solution through 5% 3-aminopropyl trimethoxysilane to soak 5 minutes, the PH of 5% glutaraldehyde be that 7.4 PBS damping fluid room temperature reaction is after 2 hours, subsequently with PBS damping fluid cleaning in 10 minutes three times.Carry out point sample and 4 degree centigrade reactions 12 hour through point sample instrument in the zones of different of microslide Zinc oxide nano-rod microarray with the PBS buffer solution of hepatitis A antibody, hbv antibody and the c-hepatitis antibody of 0.2mg/ml respectively then.After thoroughly cleaning with the PBS damping fluid, unreacted glutaraldehyde reacts with the PBS buffer solution of 1% BSA and blocked in 2 hours.After the PBS buffer solution for cleaning itself and testing sample mixed being incorporated in 37 degrees centigrade and in oscillator, hatching 2 hours, then with PBST buffer solution cleaning three times with 180rpm speed.The CY3 mark hepatitis A antibody, hbv antibody and the c-hepatitis antibody PBS buffer solution that add 4 mcg/ml; Hatched 1 hour 37 degrees centigrade of speed, clean three times and under fluorescent microscope, observe the fluorescence of the zones of different of zinc-oxide nano bar array on the microslide subsequently with PBS and can judge having or not of hepatitis A virus in the testing sample, hepatitis B and hepatitis C virus with 60RPM.
Embodiment four:
The length of side that at first prepares box-shaped is 50 microns; Spacing is about 20 microns high PDMS seal of 50 microns; Dry up gently at the polylysine WS of PDMS seal surface coated 0.1%w/v and with nitrogen then, then it is stamped in 30 seconds of silicon chip surface of 2.5 centimetres of 7.5 clean cm x.Handle silicon chip 10 minutes that polylysine handled with the 50 nano colloid gold WS of 1%w/v subsequently and dry up lightly with nitrogen.This silicon chip is put into CVD reactor.The air pressure of CVD reactor is controlled at less than 1mTorr and at argon gas is heated to 550 degrees centigrade under with the speed of 20 cubic millimeters of per minutes and the atmosphere of hydrogen, and be incubated 1 hour with the speed of 60 cubic millimeters of per minutes.Control air pressure then and introduce the SiH that contains 10% argon gas to 70Torr and with the speed of 3 cubic millimeters of per minutes
4Reacted 20 minutes, and obtained the silicon chip of silicon nano rod array.It is that the plasma generator of 40W is gone up hydroxyl with oxygen plasma treatment 2 minutes so that the microtrabeculae that exposes surface connects for 800ml/min power that the silicon chip of silicon nano rod array of will having grown subsequently places oxygen gas flow rate.The dichloromethane solution of this silicon chip through 5% 3-aminopropyl trimethoxysilane soaked 5 minutes thereafter and use ether, acetone and ethanol to clean the back to use the PH of 5% glutaraldehyde be 7.4 PBS damping fluid room temperature reaction after 2 hours, use the PBS buffer solution for cleaning subsequently three times.The sodium borohydride aqueous solution that is placed on reaction 2 hours in the ethanolic solution of 5% monoethanolamine subsequently and cleans after three times with 3M with ethanol again reduced 15 minutes; Washed with de-ionized water subsequently obtains being used in the silicon chip of the synthetic hydroxyl modified silicon nano rod array of sheet oligonucleotides.
Subsequently according to people's gene according to the principle design length of each gene design 3-5 probe be 50mer can be used for detecting 160000 probes that the full genomic expression of people is composed.Thereby on above-mentioned hydroxyl modified silicon nano rod array silicon chip, carry out obtaining the full genomic expression spectrum of people genetic chip according to coupling, sealing, oxidation, the step of taking off DMT through Agilent ink-jet original position synthetic technology subsequently at synthetic 160000 probes of sheet.
Extract 10 in addition
7Individual at the epontic endothelial cell that extracts from human body placenta of Ultimum Ti, then through RNA extract, aRNA is synthetic with fluorescence labeling and fragmentation step after acquisition can with the fluorescence labeling probe of gene chip hybridization.Subsequently with the full genomic expression spectrum gene chip hybridization of fluorescence labeling probe and above-mentioned people and carry out fluoroscopic image scanning through gene chip scanning instrument and can obtain expression conditions at the epontic endothelial cell of Ultimum Ti.Bioinformatic analysis subsequently can help people obtain to probe into the Ultimum Ti surface to the HEC in the influence aspect the gene expression, thereby provide with reference to using for reference foundation for the development of related cardiovascular device.
Embodiment five:
The length of side that at first prepares box-shaped is 50 microns; Spacing is about 20 microns high PDMS seal of 50 microns; Dry up gently at the polylysine WS of PDMS seal surface coated 0.1%w/v and with nitrogen then, then it is stamped in 30 seconds of silicon chip surface of 2.5 centimetres of 7.5 clean cm x.Handle silicon chip 10 minutes that polylysine handled with the 50 nano colloid gold WS of 1%w/v subsequently and dry up lightly with nitrogen.This silicon chip is put into CVD reactor.This silicon chip is placed on the quartzy stove middle distance of level is positioned at graphite and putty powder potpourri downstream about 5 centimeters of stove center placement with 1 to 2 mixing; Speed with 200 cubic millimeters of per minutes feeds argon gas then; And be 50 microns in the length of side that 900 degrees centigrade of reactions obtained on silicon chip, containing the box-shaped of catalyzer collaurum in 1 hour, spacing is the tin oxide nano bar array film of 50 microns interval regions.The dichloromethane solution of this silicon chip through 5% 3-aminopropyl trimethoxysilane soaked 5 minutes thereafter and use ether, acetone and ethanol to clean the back to use the PH of 5% glutaraldehyde be 7.4 PBS damping fluid room temperature reaction after 2 hours, use the PBS buffer solution for cleaning subsequently three times.Then through the point sample method will be relevant with type i diabetes antigen antibody with the zones of different of PBS buffer solution tin oxide nano bar microarray on silicon chip of the concentration of 0.2mg/ml carry out point sample and 4 degrees centigrade the reaction 12 hours.
The antigen that type i diabetes is relevant comprises mumps virus antigen, CB 4 antigens, rubella virus antigen, enteric cytopathogenic human orphan virus antigen, thyroglobulin antigen, thyroid peroxidase antigen, pth receptor antigen, first shape ball microsome antigen; ICAs, IAAs, GADAs, IA one 2As antigen; Islet cells surface antigen, insulin receptor antigen, carboxypeptidase one H, IA one Zp, ' GBM Antibody antigen.
After thoroughly cleaning with the PBS damping fluid, unreacted glutaraldehyde reacts with the PBS buffer solution of 1% BSA and blocked in 2 hours.After the PBS buffer solution for cleaning itself and testing sample mixed being incorporated in 37 degrees centigrade and in oscillator, hatching 2 hours, then with PBST buffer solution cleaning three times with 180rpm speed.The relevant two anti-PBS buffer solution that add the CY3 mark of 4 mcg/ml; Hatched 1 hour 37 degrees centigrade of speed, can judge with PBS cleaning three times and at the fluorescence of observing the zones of different of tin oxide nano bar array on the silicon chip under the fluorescent microscope whether the patient of testing sample suffers from type i diabetes subsequently with 60RPM.
Claims (6)
1. the preparation method of the three-dimensional biochip of standard is characterized in that, this method comprises the steps:
A, in substrate the array of growth of one-dimensional material to obtain to contain the planar materials of one-dimensional material array;
B, on the one-dimensional material array of planar materials the fixing respectively different sensing responsive materials of zones of different to obtain accurate three-dimensional biochip.
2. the preparation method of the three-dimensional biochip of standard according to claim 1 is characterized in that, said one-dimensional material is a length-to-diameter greater than 2 material.
3. the preparation method of the three-dimensional biochip of standard according to claim 1 is characterized in that, fixing said sensing responsive material is meant that being fixedly connected material earlier in the one-dimensional material array surface connects the sensing responsive material through connecting material again.
4. the preparation method of the three-dimensional biochip of standard according to claim 1 is characterized in that, the method that described zones of different at one-dimensional material is fixed different sensing responsive materials respectively comprises that the point sample method reaches in the sheet synthetic method.
5. the preparation method of the three-dimensional biochip of standard according to claim 1 is characterized in that, described in substrate the growth of one-dimensional material be meant and be employed in the basal surface evenly growth or on the lattice array that makes up in advance in the substrate, growing.
6. the preparation method of the three-dimensional biochip of standard according to claim 1 is characterized in that, this method comprises that the planar materials to the one-dimensional material array of having grown cuts, assembles to make up accurate three-dimensional biochip.
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| CN105170209B (en) * | 2015-10-15 | 2017-05-10 | 华中科技大学 | Surface patterning-modified substrate and preparation method therefor |
| CN114182235A (en) * | 2020-09-14 | 2022-03-15 | 北京环境特性研究所 | Method for establishing gas balance flow field in growth chamber |
| CN114182235B (en) * | 2020-09-14 | 2023-09-29 | 北京环境特性研究所 | Method for establishing gas balance flow field in growth chamber |
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