CN101104954A - Method for preparing compound chip by in situ synthesis, prepared carrier and luminous substrate - Google Patents
Method for preparing compound chip by in situ synthesis, prepared carrier and luminous substrate Download PDFInfo
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- CN101104954A CN101104954A CNA2007100210245A CN200710021024A CN101104954A CN 101104954 A CN101104954 A CN 101104954A CN A2007100210245 A CNA2007100210245 A CN A2007100210245A CN 200710021024 A CN200710021024 A CN 200710021024A CN 101104954 A CN101104954 A CN 101104954A
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Abstract
The invention discloses a method for in-situ synthesis of compound chips, which comprises firstly preparing an ultraviolet LED light-emitting array on a substrate, wherein the light-emitting array is distributed coincidently with the preset points of a compound to be synthesized; then performing surface modification of the ultraviolet LED light-emitting array or other chip material to form a coating of active groups and to bond with compound monomers with a photosensitive protective group; sequentially controlling the radiation of ultraviolet LED according to the distribution of homogeneous monomers in the compound to be synthesized, debonding the photosensitive protective group of the correspondent monomers, stopping radiation, allowing the monometer with photosensitive protective group to be bonded to contact with the chip surface and to react with the debonded protective monometer; and repeating the steps to synthesize the compound with desired group length, obtaining the compound chip. The invention has the advantages of no need of photomask plate and operation in ultra-clean room, reduced cost, and suitability for the in-situ reaction in photoetching or photo-acid technique.
Description
Technical field
The present invention relates to a kind of method of preparing compound chip by in situ synthesis, and carrier that is adopted in this method and luminous substrate.
Background technology
In recent years, tremendous development along with combinatorial chemistry, short period of time, synthetic a large amount of compounds became possibility, had also increased the quantity of new target protein with geometricprogression with the stylish genetics research such as the Human Genome Project etc., and the breakneck acceleration to compound has proposed new requirement thus.Adopt common screening method, be difficult to handle at short notice so a large amount of compound molecule, thereby so-called high flux screening technology (HTS, High Throughput Screening) beginning is fast-developing.Difference according to synthetic route, HTS can be divided into liquid phase screening and solid phase screening, wherein utilizing solid phase carrier to synthesize required compound on the different positions of surface is a kind of very promising method, and thus obtained product is called as compound chip.Difference according to the synthetic classes of compounds, compound chip can be divided into: DNA chip (DNA chip), RNA chip, iRNA chip, PNA (peptide nucleic acid(PNA)) chip, LNA (Locked Nucleic Acids) chip, protein chip (protein chip), glycan molecule chip etc., they have development prospect widely in fields such as bioanalysis and drug developments.
Prepare such compound chip, two kinds of methods are arranged usually, a kind of is synthetic respectively earlier good required compound, uses the corresponding position that they is respectively fixed to chip then.This method only is suitable for the situation that flux is low, density requirements is not high.Another kind is an original position synthetic method, and it is that different positions at chip surface directly synthesizes different molecules, by sophisticated photoetching technique (photolithography), can disposablely make high-density, high-throughout compound chip.
Original position synthetic chip, usually by silicon chip, glass, polymeric film etc. as substrate, substrate surface is handled, as amination processing, aldehyde radical processing, poly-lysine handle, the polymer surfaces bag is modified etc., so that realize covalently bound with the synthetic compound.Original position synthetic method comprises that photolithography, point sample method, ink jet method, electricity cause the micro mirror projective technique of technic acid, photic technic acid, no mask plate etc., and wherein, photolithography is a kind of synthetic of original position preferably method that has dropped into practical application.
With photolithography original position synthetic DNA chip is example, is suitable for making oligonucleotide and oligopeptides microarray chip, has that resultant velocity is fast, relative cost is low, be convenient to advantages such as large-scale production.Use photoetching technique to combine in the U.S. Affymetrix company that enjoys high reputation aspect the biochip development and make extensive integrated gene chip with DNA and polypeptide solid state chemistry synthetic technology, this technology can be in the default site of surface of glass slide according to synthetic a large amount of different types of oligonucleotide of predetermined sequence or peptide molecule, and oligonucleotide after original position is synthetic or peptide molecule and slide are covalently bound.It adopts 4 kinds of base monomers that special light deprotection base group modification is arranged, and when synthetic, seeing through photomask blank with UV-light needs the light deprotection group of reactive moieties to slough surface of glass slide, and reaction connects upward required base monomer then; Then connecting the monomeric place of another kind of base at needs sloughs blocking group with UV-light, and reaction connects goes up corresponding monomer; Just can synthesize required individual layer base by 4 circulations like this in the corresponding position of surface of glass slide.According to the DNA length of design, repeat above-mentioned circulation and just can prepare corresponding D NA chip.The shortcoming of this method is that each circulation all needs different mask plates, just need about 100 mask plates for the chip of 25 bases, and every mask plate needs hundreds of dollars, thereby synthetic cost is very high.
Based on the above method; someone guides the used technology photosensitive against corrosion of synthetic technology and semi-conductor industry to combine light; with acid as removing protective material; per step synthetic yield is brought up to 99%; but it is many that the complexity of manufacturing process has increased; and, do not have to solve yet a large amount of use mask plates make the problem that increases considerably of cost.
Summary of the invention
The object of the invention provides a kind of new original position synthetic method, to simplify the preparation technology of compound chip, reduces preparation cost.
For achieving the above object, the technical solution used in the present invention is:
A kind of method of preparing compound chip by in situ synthesis comprises the following steps:
(1) preparation ultraviolet LED light emitting array in substrate, described light emitting array distributes consistent with the position, preset of compound to be synthesized;
(2) the ultraviolet LED light emitting array is carried out finishing, the surface forms one deck active group thereon, and connects the compound monomer that has light deprotection group;
(3) according to monomeric distribution situation of the same race in the compound chip to be synthesized, it is luminous to control corresponding ultraviolet LED, slough corresponding surface and connect monomeric smooth deprotection group, stop luminous, the monomer that has light deprotection group that needs to connect is contacted with chip surface, be connected with the monomer reaction of sloughing protection;
(4) according to the monomeric distribution situation of required connection, repeating step (3) is realized the various monomeric connection of this layer;
(5) according to compound sequence to be synthesized, repeating step (3), (4) synthesize the compound of desired length, obtain compound chip.
In the technique scheme, the finishing in the described step (2) is that ultraviolet LED luminescence chip upper surface is a silicon dioxide layer, adopts the silane and the described silicon dioxde reaction that have active group to make the one deck of surface formation thereon active group; Described smooth deprotection group is selected from 2-nitrophenyl sec.-propyl oxygen base carbonyl (2-(2-nitrophenyl) propyloxycarbonyl; NPPOC), methylene dioxy base hexanitro-phenyl one ethyl chloride formic acid ([R; S]-1-[3; 4-[methylene-dioxy]-6-nitrophenyl] ethyl chloroformate); MeNPoc) or 3; 4 nitro veratryl oxygen base carbonyls (o-nitroveratryloxycarbonyl, NVOC).
Wherein, described synthetic compound is DNA, RNA, iRNA, PNA, LNA, protein or glycan molecule, can prepare DNA, RNA, iRNA, PNA, LNA, protein, polypeptide or glycan molecule chip thus.
When realizing aforesaid method, a kind of carrier that is used for preparing compound chip by in situ synthesis that is adopted, comprise the substrate made from silicon or sapphire, a surface arrangement in described substrate has the ultraviolet LED chip, be provided with light blocking layer around the described ultraviolet LED chip, the light blocking layer end face has light hole, is filled with silicon dioxide layer in the light hole.
With the another kind of method of the same design of aforesaid method be:
A kind of method of preparing compound chip by in situ synthesis comprises the following steps:
(1) preparation ultraviolet LED light emitting array in substrate, described light emitting array distributes and cooperates with the position, preset of compound to be synthesized;
(2) chip material is carried out finishing, the surface forms one deck active group thereon, and connects the compound monomer that has light deprotection group;
(3) substrate and chip material are arranged in parallel the position, a compound to be synthesized preset of the corresponding chip material of irradiation position when making each ultraviolet LED luminous;
(4) according to monomeric distribution situation of the same race in the compound chip to be synthesized, it is luminous to control corresponding ultraviolet LED, the correspondence position of irradiation chip material, slough the light deprotection group on it, stop luminous, the monomer that has light deprotection group that needs to connect is contacted with the chip material surface, be connected with the monomer reaction of sloughing protection;
(5) according to the monomeric distribution situation of required connection, repeating step (4) is realized the various monomeric connection of this layer;
(6) according to compound sequence to be synthesized, repeating step (4), (5) synthesize the compound of desired length, obtain compound chip.
In the technique scheme, described chip material adopts a kind of preparation in glass, quartz, silicon chip or the polymeric film.
Realize a kind of luminous substrate that is used for preparing compound chip by in situ synthesis that aforesaid method adopted, comprise the substrate made from silicon or sapphire, a surface arrangement in described substrate has the ultraviolet LED chip, be provided with light blocking layer around the described ultraviolet LED chip, the light blocking layer end face has light hole, and the distributing position of described ultraviolet LED chip cooperates with position, preset on the compound chip to be synthesized.
During use, utilize between luminous substrate and the chip optical lens with luminous substrate on the light of each point poly-to the corresponding position of compound chip.
Further technical scheme is provided with the condensing lens structure in described light hole.Described condensing lens structure can be convex lens or the set of lenses that is provided with in the light hole, and one side focus is positioned at ultraviolet LED chip place, and the opposite side focus is positioned at the compound chip place that is arranged in parallel when using.
The present invention prepares the light source of highdensity emitting semiconductor (LED) array as the synthetic compound chip by photoetching technique; in the process of synthetic compound chip; control selectively that some unit in the led array is luminous sloughs its respective surfaces or it is projected in the light deprotection group of the compound of chip surface position; also can utilize these luminously to produce acid or alkali is taken off these blocking groups, make its activation.The zone reaction that then required reaction monomers is transported to after chip surface activates with these links, and activated partial is not owing to there is blocking group protection avtive spot just can not respond generation.Repeating so repeatedly just can be at the synthetic different monomer of last layer of the different positions of chip surface.Repeating said process more just can synthesize and contain the monomeric compound chip of multilayer.
Because the technique scheme utilization, the present invention compared with prior art has following advantage:
1. the present invention is provided with the ultraviolet LED light emitting array, passes through the optionally light dealkylation reaction of luminous realization correspondence position in the synthesis chip process, thereby does not need photomask blank, also need not operate in ultra-clean chamber, thereby reduce cost significantly;
2. the present invention utilizes integrated luminescent device to control compound to carry out original position synthetic method and produce compound library on its surface or other substrate surfaces, the reaction in that is suitable for photolithography or photic technic acid can be used for preparing DNA, RNA, iRNA, PNA (peptide nucleic acid(PNA)), LNA (LockedNucleic Acids), protein (protein chip) or glycan molecule chip.
Description of drawings
Accompanying drawing 1 is the reaction process synoptic diagram of the embodiment of the invention one;
Accompanying drawing 2 is the ultraviolet LED structural representation among Fig. 1;
Accompanying drawing 3 is the reaction process synoptic diagram of the embodiment of the invention two;
Accompanying drawing 4 is the reaction process synoptic diagram of the embodiment of the invention three;
Accompanying drawing 5 is the ultraviolet LED structural representation among Fig. 4.
Wherein: 1, substrate; 2, ultraviolet LED chip; 3, light blocking layer; 4, silicon dioxide layer; 5, light deprotection group; 6, chip material; 7, condensing lens structure.
Embodiment
Below in conjunction with drawings and Examples the present invention is further described:
Embodiment one: shown in accompanying drawing 1 and accompanying drawing 2, the synthetic method for preparing the DNA chip of a kind of original position comprises the following steps:
(1) preparation ultraviolet LED light emitting array in substrate 1, described light emitting array distributes consistent with the position, preset of compound to be synthesized, and material preparations such as silicon or sapphire are adopted in substrate;
Thus, obtain a kind of carrier that is used for preparing compound chip by in situ synthesis, comprise the substrate 1 made from silicon or sapphire, a surface arrangement in described substrate has ultraviolet LED chip 2, be provided with light blocking layer 3 around the described ultraviolet LED chip, light blocking layer 3 end faces have light hole, are filled with silicon dioxide layer 4 in the light hole.Each ultraviolet LED chip is electrically connected to a control chip respectively, can be controlled that it is luminous by control chip; Wherein, light blocking layer also can be made of the electrode that is electrically connected.
(2) the ultraviolet LED light emitting array is carried out finishing, the surface forms one deck active group thereon, and connects the compound monomer that has light deprotection group 5;
Described active group can be hydroxyl, amido etc., and described finishing can realize by some silane and silicon dioxde reactions substrate surface that has the different activities group.Can be directly connected to substrate surface by the dna single body that some chemical reactions will be marked with light deprotection group then.This smooth deprotection group can be 2-nitrophenyl sec.-propyl oxygen base carbonyl (2-(2-nitrophenyl) propyloxycarbonyl; NPPOC), methylene dioxy base hexanitro-phenyl one ethyl chloride formic acid ([R; S]-1-[3; 4-[methylene-dioxy]-6-nitrophenyl] ethyl chloroformate); MeNPoc) or 3; 4 nitro veratryl oxygen base carbonyls (o-nitroveratryloxycarbonyl, NVOC) etc.Linkage flag has the technological process of the dna single body of light deprotection group can adopt arbitrary existing techniques in realizing.
(3) after reactant that the first layer has a light deprotection group is connected to substrate surface, it is luminous just can to control the relevant LED that needs to connect a certain monomers (as A), sloughs the light deprotection group of its respective surfaces, exposes active hydroxyl.Then the liquid of the monomer A that light deprotection radical protection is arranged is led to the entire chip surface; through just being connected to the relevant chip surface to the monomer A that light deprotection radical protection is arranged after a series of standard DNA building-up reactions, there is not the generation that then can not respond of the surface of deprotection group.Repeat process just now like this, control needs the relevant LED of connection dna single body G luminous, sloughs the light deprotection group of its respective surfaces, just can connect monomer G on the surface of these LED.By that analogy, can be at the corresponding position on chip LED surface synthetic respectively last layer dna single body A, G, C and T.
(4) repeat that previous step is rapid just can come out in the sequence that chip surface synthesizes different DNA as required.As want the dna sequence dna of 5 base length of Synthetic 2, it is just passable just to repeat 25 steps (3).
Embodiment two: shown in accompanying drawing 3, the synthetic method for preparing protein chip of a kind of original position comprises the following steps:
(1) preparation ultraviolet LED light emitting array in substrate, described light emitting array distributes consistent with the position, preset of compound to be synthesized, and material preparations such as silicon or sapphire are adopted in substrate;
(2) the ultraviolet LED light emitting array is carried out finishing, the surface forms one deck active group thereon, and connects the compound monomer that has light deprotection group;
Described active group can be hydroxyl, amido etc., and this modification can realize by some silane and silicon dioxde reactions substrate surface that has the different activities group.Can be directly connected to substrate surface by the protein monomers that some chemical reactions will be marked with light deprotection group then.This smooth deprotection group can be NPPOC (2-(2-nitrophenyl) propyloxycarbonyl), MeNPoc (5 '-O-(a-methyl-6nitropiperonylox-ycarbonyl)-N-acyl-2 '-deoxynucleosides), NVOC (o-nitroveratryloxycarbonyl) etc.
(3) after reactant that the first layer has a light deprotection group is connected to substrate surface, it is luminous just can to control the relevant LED that needs to connect a certain monomers (as Gly), sloughs the light deprotection group of its respective surfaces, exposes active amido.Then the liquid of the monomer Gly that light deprotection radical protection is arranged is led to the entire chip surface; through just being connected to the relevant chip surface to the monomer A that light deprotection radical protection is arranged after a series of standard protein building-up reactions, there is not the generation that then can not respond of the surface of deprotection group.Repeat process just now like this, control needs the relevant LED of connection protein monomers Ala luminous, sloughs the light deprotection group of its respective surfaces, just can connect monomer A la on the surface of these LED.By that analogy, can be in the synthetic respectively last layer protein monomers in the corresponding position on chip LED surface.
(4) repeating previous step just can synthesize different proteinic sequences as required at chip surface suddenly and come out.As want the protein sequence of 5 element lengths of Synthetic 2, it is just passable just to repeat 25 steps (3).
Embodiment three: shown in accompanying drawing 4 and accompanying drawing 5, the synthetic method for preparing the DNA chip of a kind of original position comprises the following steps:
(1) preparation ultraviolet LED light emitting array in substrate, described light emitting array distributes and cooperates with the position, preset of compound to be synthesized, and associated materials preparations such as silicon or sapphire are adopted in described substrate.
Obtain a kind of luminous substrate that is used for preparing compound chip by in situ synthesis thus, comprise the substrate 1 made from silicon or sapphire, a surface arrangement in described substrate has ultraviolet LED chip 2, be provided with light blocking layer 3 around the described ultraviolet LED chip, the light blocking layer end face has light hole, and the distributing position of described ultraviolet LED chip cooperates with position, preset on the compound chip to be synthesized; In described light hole, be provided with condensing lens structure 7.
Another kind method is not established the condensing lens structure in each light hole, but in use, utilize between luminous substrate and the chip optical lens with luminous substrate on the light of each point poly-to the corresponding position of compound chip.
(2) chip material is carried out finishing, the surface forms one deck active group thereon, and connects the compound monomer that has light deprotection group;
Described active group can be hydroxyl, amido etc., and this modification can realize by some silane and silicon dioxde reactions substrate surface that has the different activities group.This chip can be glass, quartz, silicon chip, polymeric film etc.Can be directly connected to chip surface by the dna single body that some chemical reactions will be marked with light deprotection group then.This smooth deprotection group can be 2-nitrophenyl sec.-propyl oxygen base carbonyl (2-(2-nitrophenyl) propyloxycarbonyl; NPPOC), methylene dioxy base hexanitro-phenyl one ethyl chloride formic acid ([R; S]-1-[3; 4-[methylene-dioxy]-6-nitrophenyl] ethyl chloroformate); MeNPoc) or 3; 4 nitro veratryl oxygen base carbonyls (o-nitroveratryloxycarbonyl, NVOC) etc.
(3) substrate 1 and chip material 6 are arranged in parallel the position, a compound to be synthesized preset of the corresponding chip material of irradiation position when making each ultraviolet LED luminous;
(4) after reactant that the first layer has a light deprotection group is connected to substrate surface, it is luminous just can to control the relevant LED that needs to connect a certain monomers (as A), sloughs the light deprotection group of the chip surface of its projection, exposes active hydroxyl.Then the liquid of the monomer A that light deprotection radical protection is arranged is led to the entire chip surface; through just being connected to the relevant chip surface to the monomer A that light deprotection radical protection is arranged after a series of standard DNA building-up reactions, there is not the generation that then can not respond of the surface of deprotection group.Repeat process just now like this, control needs the relevant LED of connection dna single body G luminous, sloughs the light deprotection group on the respective chip surface of its projection, just can connect monomer G on the surface of these chips.By that analogy, can be at the corresponding position of chip surface synthetic respectively last layer dna single body A, G, C and T.
(5) repeating step (4) just can come out in the sequence that chip surface synthesizes different DNA as required.As want the dna sequence dna of 5 base length of Synthetic 2, it is just passable just to repeat 25 steps (4).
Claims (8)
1. the method for a preparing compound chip by in situ synthesis comprises the following steps:
(1) preparation ultraviolet LED light emitting array in substrate, described light emitting array distributes consistent with the position, preset of compound to be synthesized;
(2) the ultraviolet LED light emitting array is carried out finishing, the surface forms one deck active group thereon, and connects the compound monomer that has light deprotection group;
(3) according to monomeric distribution situation of the same race in the compound chip to be synthesized, it is luminous to control corresponding ultraviolet LED, slough corresponding surface and connect monomeric smooth deprotection group, stop luminous, the monomer that has light deprotection group that needs to connect is contacted with chip surface, be connected with the monomer reaction of sloughing protection;
(4) according to the monomeric distribution situation of required connection, repeating step (3) is realized the various monomeric connection of this layer;
(5) according to compound sequence to be synthesized, repeating step (3), (4) synthesize the compound of desired length, obtain compound chip.
2. the method for preparing compound chip by in situ synthesis according to claim 1, it is characterized in that: the finishing in the described step (2) is, ultraviolet LED luminescence chip upper surface is a silicon dioxide layer, adopts the silane and the described silicon dioxde reaction that have active group to make the one deck of surface formation thereon active group; Described smooth deprotection group is selected from 2-nitrophenyl sec.-propyl oxygen base carbonyl, methylene dioxy base hexanitro-phenyl one ethyl chloride formic acid or 3,4 nitro veratryl oxygen base carbonyls.
3. the method for preparing compound chip by in situ synthesis according to claim 1, it is characterized in that: described synthetic compound is DNA, RNA, iRNA, PNA, LNA, protein, polypeptide or glycan molecule.
4. carrier that is used for preparing compound chip by in situ synthesis, comprise the substrate made from silicon or sapphire, it is characterized in that: a surface arrangement in described substrate has the ultraviolet LED chip, be provided with light blocking layer around the described ultraviolet LED chip, the light blocking layer end face has light hole, is filled with silicon dioxide layer in the light hole.
5. the method for a preparing compound chip by in situ synthesis comprises the following steps:
(1) preparation ultraviolet LED light emitting array in substrate, described light emitting array distributes and cooperates with the position, preset of compound to be synthesized;
(2) chip material is carried out finishing, the surface forms one deck active group thereon, and connects the compound monomer that has light deprotection group;
(3) substrate and chip material are arranged in parallel the position, a compound to be synthesized preset of the corresponding chip material of irradiation position when making each ultraviolet LED luminous;
(4) according to monomeric distribution situation of the same race in the compound to be synthesized, it is luminous to control corresponding ultraviolet LED, the correspondence position of irradiation chip material, slough the light deprotection group on it, stop luminous, the monomer that has light deprotection group that needs to connect is contacted with the chip material surface, be connected with the monomer reaction of sloughing protection;
(5) according to the monomeric distribution situation of required connection, repeating step (4) is realized the various monomeric connection of this layer;
(6) according to compound sequence to be synthesized, repeating step (4), (5) synthesize the compound of desired length, obtain compound chip.
6. the method for preparing compound chip by in situ synthesis according to claim 5 is characterized in that: a kind of preparation in described chip material employing glass, quartz, silicon chip or the polymeric film.
7. luminous substrate that is used for preparing compound chip by in situ synthesis, comprise the substrate made from silicon or sapphire, it is characterized in that: a surface arrangement in described substrate has the ultraviolet LED chip, be provided with light blocking layer around the described ultraviolet LED chip, the light blocking layer end face has light hole, and the distributing position of described ultraviolet LED chip cooperates with position, preset on the compound chip to be synthesized.
8. luminous substrate according to claim 7 is characterized in that: be provided with the condensing lens structure in described light hole.
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| CN102004833A (en) * | 2010-11-25 | 2011-04-06 | 中南大学 | Generating method of virtual mask for genetic chip in-situ synthesis |
| CN103234948A (en) * | 2013-05-09 | 2013-08-07 | 中南大学 | Application of pyrene and derivative as photosensitive perssad deprotection sensibilization reagent in biological chip production |
| US9249175B2 (en) | 2008-09-05 | 2016-02-02 | The Royal Institute For The Advancement Of Learning/Mcgill University | RNA monomers containing O-acetal levulinyl ester groups and their use in RNA microarrays |
| CN108120754A (en) * | 2016-11-28 | 2018-06-05 | 瀚生医电股份有限公司 | Biosensor and the method that probe is formed on the surface of solids of biosensor |
| CN109839805A (en) * | 2017-11-27 | 2019-06-04 | 台湾生捷科技股份有限公司 | Microarray and forming method thereof |
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| EP4107782A4 (en) * | 2020-02-19 | 2024-03-20 | Polymer Forge Inc | Microarrays |
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- 2007-03-20 CN CN200710021024A patent/CN100588759C/en not_active Expired - Fee Related
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| US10287313B2 (en) | 2008-09-05 | 2019-05-14 | The Royal Institution For The Advancement Of Learning/Mcgill University | RNA monomers containing 0-acetal levulinyl ester groups and their use in RNA microarrays |
| US9249175B2 (en) | 2008-09-05 | 2016-02-02 | The Royal Institute For The Advancement Of Learning/Mcgill University | RNA monomers containing O-acetal levulinyl ester groups and their use in RNA microarrays |
| CN102639552B (en) * | 2008-09-05 | 2016-05-25 | 高端学术皇家研究会/麦吉尔大学 | The RNA monomer that contains O-acetal levulic acid ester group (O-acetal levulinyl ester) and the application in RNA microarray thereof |
| CN102004833A (en) * | 2010-11-25 | 2011-04-06 | 中南大学 | Generating method of virtual mask for genetic chip in-situ synthesis |
| CN103234948A (en) * | 2013-05-09 | 2013-08-07 | 中南大学 | Application of pyrene and derivative as photosensitive perssad deprotection sensibilization reagent in biological chip production |
| CN103234948B (en) * | 2013-05-09 | 2015-07-22 | 中南大学 | Application of pyrene and derivative as photosensitive perssad deprotection sensibilization reagent in biological chip production |
| US11435291B2 (en) | 2016-04-07 | 2022-09-06 | Global Analyzer Systems Limited | Photolytic converter |
| CN108120754A (en) * | 2016-11-28 | 2018-06-05 | 瀚生医电股份有限公司 | Biosensor and the method that probe is formed on the surface of solids of biosensor |
| US11820655B2 (en) | 2017-05-11 | 2023-11-21 | Global Analyzer Systems Limited | Method of controlling recombination or back reactions of products and byproducts in a dissociation reaction |
| CN109839805A (en) * | 2017-11-27 | 2019-06-04 | 台湾生捷科技股份有限公司 | Microarray and forming method thereof |
| US10872924B2 (en) | 2017-11-27 | 2020-12-22 | Centrillion Technologies Taiwan Co. LTD. | Microarray and method for forming the same |
| EP4107782A4 (en) * | 2020-02-19 | 2024-03-20 | Polymer Forge Inc | Microarrays |
| WO2022250914A1 (en) * | 2021-05-26 | 2022-12-01 | Microsoft Technology Licensing, Llc | Photon generating substrates for oligonucleotide synthesis |
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