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WO2010056026A2 - Supports et puces à adn pour la génération in situ de puces à protéines, puces à protéines qui en résultent, et procédés de fabrication et d'utilisation associés - Google Patents

Supports et puces à adn pour la génération in situ de puces à protéines, puces à protéines qui en résultent, et procédés de fabrication et d'utilisation associés Download PDF

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Publication number
WO2010056026A2
WO2010056026A2 PCT/KR2009/006587 KR2009006587W WO2010056026A2 WO 2010056026 A2 WO2010056026 A2 WO 2010056026A2 KR 2009006587 W KR2009006587 W KR 2009006587W WO 2010056026 A2 WO2010056026 A2 WO 2010056026A2
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Prior art keywords
protein
array
hydrogel
gene
situ generation
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Ceased
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WO2010056026A3 (fr
Inventor
Dong-Myung Kim
Kyeong-Ohn Kim
Mee Jee Lee
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Industry and Academy Cooperation In Chungnam National University
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Industry and Academy Cooperation In Chungnam National University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00351Means for dispensing and evacuation of reagents
    • B01J2219/00387Applications using probes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277Apparatus
    • B01J2219/00497Features relating to the solid phase supports
    • B01J2219/00527Sheets
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00596Solid-phase processes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00612Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00623Immobilisation or binding
    • B01J2219/0063Other, e.g. van der Waals forces, hydrogen bonding
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00605Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00632Introduction of reactive groups to the surface
    • B01J2219/00637Introduction of reactive groups to the surface by coating it with another layer
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00639Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium
    • B01J2219/00641Making arrays on substantially continuous surfaces the compounds being trapped in or bound to a porous medium the porous medium being continuous, e.g. porous oxide substrates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00659Two-dimensional arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718Type of compounds synthesised
    • B01J2219/0072Organic compounds
    • B01J2219/00722Nucleotides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718Type of compounds synthesised
    • B01J2219/0072Organic compounds
    • B01J2219/00727Glycopeptides

Definitions

  • the present invention relates to a protein array, more particularly to a support and a gene array for in situ generation of a protein array, a protein array obtained therefrom, a method for manufacture thereof, and a method for detection and analysis of proteins using the same.
  • the protein microarray is drawing attention as the most promising technology for large-scale analysis of protein functions.
  • the protein array technology is advantageous over other methods in that a large quantity of sample can be accurately analyzed at the same time and the consumption of materials can be significantly reduced.
  • the protein microarray has the problem that, unlike the gene microarray, it is difficult to stably maintain the activity of the proteins immobilized on the array. It is because the proteins have to be hydrated to maintain a perfect 3-dimensional structure to be active.
  • the complicated processes of gene preparation, cell cultivation and protein purification needed to attain the proteins to be immobilized on the array surface are an obstacle to the full-scale utilization of the protein array technology.
  • this method provides a simplified in situ protein microarray process, the protein structure may not be maintained stably because the proteins directly contact with the glass surface. Further, the reaction solution is easily evaporated and affects the structure or function of the synthesized proteins. In addition, this method may have a problem in detection sensitivity because the quantity of proteins that can be immobilized is limited.
  • the inventors of the present invention have performed researches consistently to develop an in situ protein array which can be manufactured simply and enables a more effective detection and analysis by stably maintaining the activities and structures of proteins.
  • they have succeeded in in situ synthesis of proteins by immobilizing a protein biosynthesis machinery in hydrogel of an array, instead of immobilizing DNAs on the array, and adding individual genes thereto, and have confirmed that the synthesized proteins maintain their activities and structures owing to the humid and buffered condition provided by the hydrogel, thereby enabling quick and easy detection and analysis of expressions of the proteins from the added genes and activities thereof.
  • a first object of the present invention is to provide a support for in situ generation of a protein array having a hydrogel including a protein biosynthesis machinery coated thereon.
  • a second object of the present invention is to provide a gene array for in situ generation of a protein array including the support.
  • a third object of the present invention is to provide a protein array obtained from the gene array.
  • a fourth object of the present invention is to provide a method for manufacture of the support for in situ generation of a protein array.
  • a fifth object of the present invention is to provide a method for manufacture of the gene array for in situ generation of a protein array.
  • a sixth object of the present invention is to provide a method for in situ generation of a protein array using the gene array.
  • a seventh object of the present invention is to provide a method for detection or analysis of a protein using the protein array.
  • the present invention provides a support for in situ generation of a protein array, comprising:
  • the present invention provides a gene array for in situ generation of a protein array, comprising:
  • the present invention provides a protein array generated by placing the gene array under a condition where protein synthesis is allowable, so that protein synthesis occurs from a gene on the array.
  • the present invention provides a method for manufacture of a support for in situ generation of a protein array, comprising:
  • the present invention provides a method for manufacture of a gene array for in situ generation of a protein array, comprising:
  • the present invention provides a method for in situ generation of a protein array, comprising placing thus manufactured gene array under a condition to allow protein synthesis.
  • the present invention provides a method for detection or analysis of a protein, comprising detecting or analyzing the protein synthesized on the protein array.
  • a protein biosynthesis machinery is immobilized on a solid surface and a gene is spotted thereon so that it may be directly translated into a protein.
  • a variety of DNAs or mRNAs cloned or synthesized by polymerase chain reaction (PCR) can be quickly converted into activated proteins in array form. Therefore, the present invention provides an important tool for functional network analysis of various intracellular proteins.
  • the expressed protein molecules can be immobilized within a 3-dimensional porous hydrogel structure, not in the 2-dimensional solid surface, the quantity of proteins that can be immobilized per unit area is increased and, as a result, the sensitivity of analysis using the protein array may be remarkably improved.
  • Fig. 1 schematically shows a process of in situ generation of a protein array according to the present invention.
  • Fig. 2 is a photograph showing a cell-free protein synthesis result within a hydrogel in which a protein biosynthesis machinery is immobilized.
  • Fig. 3 is a photograph showing in situ generation of a protein from a gene spotted on a hydrogel in which a protein biosynthesis machinery is immobilized.
  • Fig. 4 is a photograph showing in situ generation of a protein from a gene spotted on a hydrogel including a film-coated protein biosynthesis machinery by spin coating.
  • the cell-free protein synthesis technology has the advantage that protein synthesis can be performed under various reaction conditions and environments like other biochemical reactions, not just in the limited space inside cells.
  • the inventors of the present invention have recently found out that protein synthesis may be accomplished on a matrix having such an affinity as to allow real-time isolation of polypeptides [Kim, T.W., Oh, I.S., Ahn, J.H., Choi, C.Y., Kim, D.M.(2006) Cell-free synthesis and in situ isolation of recombinant protein. Protein Expr. Purif.
  • Fig. 1 schematically shows a process of in situ generation of a protein array according to the present invention.
  • the inventors of the present invention have investigated whether the cell-free protein synthesis usually performed in a solution inside a test tube or a reactor may occur within the hydrogel structure. As a result, they have confirmed that the protein biosynthesis machineries extracted from the cells operate normally within the hydrogel structure as in solutions. Based on the result, after spotting genes on a hydrogel matrix including protein transcription/translation factors, they have investigated whether the corresponding proteins are expressed and synthesized at the areas where the genes were added. As a result, they have confirmed that the gene array may be effectively converted into the protein array using the protein biosynthesis machinery immobilized within the hydrogel structure.
  • the term "hydrogel” refers to a hydrophilic network polymer which is glassy in dehydrated state but swells and forms a gel in the presence of water.
  • the hydrogel is not specially limited as long as it is miscible with the protein biosynthesis machinery and may be coated on a solid support to exhibit the protein synthesis activity. It includes, for example, agarose gel, polyacrylamide gel, alginate gel, starch gel, polyvinyl alcohol gel and silicone hydrogel, but the scope of the present invention is not limited thereto.
  • the hydrogel is coated on a solid support.
  • the solid support may be any one commonly used for the manufacture of gene or protein chips. It includes, for example, those made of glass, quartz, silicon, plastic, polypropylene, polycarbonate or activated acrylamide, but the scope of the present invention is not limited thereto.
  • the protein biosynthesis machinery may be included in a reaction mixture for cell-free protein synthesis excluding a gene template (which is spotted on the gel after the formation of the hydrogel).
  • the reaction mixture for cell-free protein synthesis may include, for example, a cell lysate including cell organelles necessary for the synthesis of the target protein, an amino acid mixture, an energy source for protein synthesis, a gene template and a buffer solution.
  • Cells to obtain the cell lysate may be selected from E. coli cells, Bacillus subtilis cells, wheat germ, rice germ, barley germ, CHO cells, hybridoma cells or reticulocytes.
  • the cell lysate may be an S30 extract prepared according to the method described in Pratt, J.M.
  • the amino acid mixture may be a mixture of l-amino acids selected from glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tyrosine, tryptophan, cysteine, methionine, serine, threonine, lysine, arginine, histidine, aspartate, glutamate, asparagine and glutamine.
  • the energy source for protein synthesis may be one or more selected from ATP, CTP, GTP, TTP and UTP.
  • the gene template may be a DNA or an mRNA coding for the target protein.
  • the cell-free protein synthesis within the hydrogel structure in accordance with the present invention may be accomplished at 27-37 °C, especially in a 37 °C incubator, for 1-5 hours.
  • the hydrogel used in the present invention may be in wet state.
  • the hydrogel in wet state is considered to be problematic for example in storage with regard to commercial-scale mass production of protein arrays
  • the inventors have spin coated a hydrogel solution including a protein biosynthesis machinery on a support surface in film form. Then, they have investigated whether the protein biosynthesis machinery immobilized in the hydrogel shows activity again when a gene solution is spotted thereon and so the hydrogel is rehydrated. As a result, they have confirmed that proteins are successfully expressed at the areas where the gene was printed.
  • the hydrogel used in the present invention may be in dried state. For example, it may be in film form by spin coating and the protein biosynthesis machinery included therein may be activated by rehydration.
  • Fig. 2 fluorescence activity of proteins was observed from agarose gel spots, which demonstrates that EGFP proteins having fluorescence activity were expressed through transcription and translation from the template DNAs immobilized together with the protein biosynthesis machinery immobilized in the agarose gel. It means that the protein biosynthesis machineries extracted from cells may normally operate within the hydrogel structure to result in transcription, translation and folding of genes. In addition, it was confirmed that proteins may be effectively synthesized from circular plasmid genes amplified through PCR on the agarose matrix.
  • Example 2 In situ generation of protein from genes spotted on agarose gel in which protein biosynthesis machinery is immobilized
  • coli tRNA mixture 90 mM potassium glutamate, 80 mM ammonium acetate, 12 mM magnesium acetate, 34 ⁇ g/mL l-5-formyl-5,6,7,8-tetrahydrofolic acid, 20 amino acids (each 1.5 mM), 2% PEG 8000, 67 mM creatine phosphate (CP), 3.2 ⁇ g/mL creatine kinase (CK), 6.7 ⁇ g/mL DNA, 30% (v/v) S30 extract [Pratt, J.M. (1984) Coupled transcription - translation in prokaryotic cell-free system. In: Hames, B.D., Higgins, S.J.
  • Fig. 3 As seen from Fig. 3, proteins were successfully expressed by the cell-free protein synthesis system at the spots where the genes coding for EGFP were printed. When the fluorescence measurement was repeated after spotting the same quantity of genes repeatedly, it was demonstrated that the protein expression occurs reproducibly.
  • Example 3 Expression of proteins on agarose gel spin coated in film form
  • Example 2 confirms that a gene array can be converted into a protein array using a protein biosynthesis machinery immobilized in the agarose gel structure.
  • An agarose gel including a reaction solution for cell-free protein synthesis was spin coated on a glass plate surface in film form. Then, it was investigated whether the protein biosynthesis machinery immobilized in the agarose gel shows activity again when the agarose gel is rehydrated after spotting a pIVEX2.3d-EGFP gene solution thereon.
  • Fig. 4 As seen from Fig. 4, when the gene solution was printed on the agarose gel including the reaction solution for cell-free protein synthesis spin coated on the glass slide surface in film form using a gene arrayer and reaction was carried out under a saturated humidity condition, the proteins having fluorescence activity were successfully expressed at the areas where the genes were printed.
  • an activated protein array may be manufactured from a commonly used microarrayer by expressing proteins directly from template DNAs/mRNAs, without the complicated procedures of cloning, expression and purification involved with the existing protein array manufacture process.
  • the expressed protein molecules can be immobilized within a 3-dimensional porous hydrogel structure, not in the 2-dimensional solid surface, the quantity of proteins that can be immobilized per unit area is increased and, as a result, the sensitivity of analysis using the protein array may be remarkably improved.

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  • Physics & Mathematics (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne un support permettant la génération in situ d'une puce à protéines, ledit support comprenant un hydrogel sur lequel est déposé un mécanisme de biosynthèse de protéines. L'invention concerne également une puce à ADN comprenant le support, une puce à protéines qui en résulte, et des procédés de fabrication et d'utilisation associés.
PCT/KR2009/006587 2008-11-11 2009-11-10 Supports et puces à adn pour la génération in situ de puces à protéines, puces à protéines qui en résultent, et procédés de fabrication et d'utilisation associés Ceased WO2010056026A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2008-0111667 2008-11-11
KR1020080111667A KR101071069B1 (ko) 2008-11-11 2008-11-11 단백질 어레이의 동소 생성을 위한 지지체 및 유전자 어레이, 이로부터 얻어지는 단백질 어레이, 및 이의 제조 및 사용 방법

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WO2010056026A2 true WO2010056026A2 (fr) 2010-05-20
WO2010056026A3 WO2010056026A3 (fr) 2010-09-23

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015518958A (ja) * 2012-05-23 2015-07-06 アルベルト−ルートヴィヒ−ウニベルシタット フライブルク 分子の集積をリアルタイムに検出する及び/又は分子マイクロアレイの作製プロセスをモニタリングする装置及び方法
CN108660426A (zh) * 2018-04-12 2018-10-16 中国科学院生物物理研究所 一种镍钛非晶合金微阵列支持膜的制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101506596B1 (ko) * 2013-01-31 2015-03-27 충남대학교산학협력단 유전자가 접합된 마이크로비드 및 겔 매트릭스를 이용한 무세포 단백질 발현 및 동소 고정화 방법

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Publication number Priority date Publication date Assignee Title
US20010041349A1 (en) * 2000-04-17 2001-11-15 Andrew Patron Protein expression system arrays and use in biological screening
FR2887261B1 (fr) * 2005-06-20 2007-09-14 Commissariat Energie Atomique Procede d'immobilisation de l'adn superenroule et utilisation pour analyser la reparation de l'adn
US8486621B2 (en) * 2005-08-11 2013-07-16 Cornell Research Foundation, Inc. Nucleic acid-based matrixes

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015518958A (ja) * 2012-05-23 2015-07-06 アルベルト−ルートヴィヒ−ウニベルシタット フライブルク 分子の集積をリアルタイムに検出する及び/又は分子マイクロアレイの作製プロセスをモニタリングする装置及び方法
US9675954B2 (en) 2012-05-23 2017-06-13 Albert-Ludwigs-Universitaet Freiburg Device and method for real-time detection of molecular accumulations and/or monitoring the production process of a molecular microarray
CN108660426A (zh) * 2018-04-12 2018-10-16 中国科学院生物物理研究所 一种镍钛非晶合金微阵列支持膜的制备方法
CN108660426B (zh) * 2018-04-12 2019-08-23 中国科学院生物物理研究所 一种镍钛非晶合金微阵列支持膜的制备方法

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