WO2018131731A1 - Device for partitioning liquid sample on nano unit - Google Patents

Device for partitioning liquid sample on nano unit Download PDF

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Publication number
WO2018131731A1
WO2018131731A1 PCT/KR2017/000423 KR2017000423W WO2018131731A1 WO 2018131731 A1 WO2018131731 A1 WO 2018131731A1 KR 2017000423 W KR2017000423 W KR 2017000423W WO 2018131731 A1 WO2018131731 A1 WO 2018131731A1
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substrate
micro
hydrophilic
container
dispensing mechanism
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PCT/KR2017/000423
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French (fr)
Korean (ko)
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신상모
김동민
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한밭대학교 산학협력단
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Priority to PCT/KR2017/000423 priority Critical patent/WO2018131731A1/en
Publication of WO2018131731A1 publication Critical patent/WO2018131731A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices

Definitions

  • the present invention relates to a mechanism for dispensing a liquid sample in nano units, and more particularly, to a technique for evenly dispersing an aqueous solution of biomolecules having a small volume or diameter at a desired position on a substrate.
  • Microphysical or chemical sensor technology has been applied to the biotechnology field with the development of ultra-high density semiconductor technology.
  • MEMS microelectromechanical systems
  • semiconductor manufacturing technology for the analysis of gene sequencing, proteomics, biometabolism detection and trace amount of reactants in life science, genetic engineering, medical diagnosis, new drug development, etc. Actively researched.
  • unlike classical methods it is possible to analyze single cells, very small amounts of genetic material, proteins, and complex and unpurified complex samples without using many samples for bioanalysis.
  • PCR polymerase chain reaction
  • Korean Patent No. 10-0723427 (apparatus and method for printing biomolecule droplets on a substrate)
  • Korean Patent Publication No. 2005-0072540 (apparatus for printing biomolecules on a substrate using electrohydraulic phenomena and a printing method thereof)
  • an object of the present invention is to provide a sample dispensing mechanism capable of dispersing and containing as many biomolecules as desired.
  • the present invention which is derived to achieve the object as described above, is a mechanism for distributing a liquid sample in nano units, and includes a substrate, and a micro container formed on the substrate with opposite characteristics of the hydrophilicity and hydrophobicity of the substrate. It features.
  • the microcontainers are stacked at a height of 500-800 nm or etched to a depth of 500-800 nm relative to the substrate.
  • the plurality of micro-containers are provided on the substrate, the plurality of micro-containers gradually increase or decrease in size in a specific direction.
  • the apparatus further includes a temperature adjusting unit configured to adjust the temperature of the substrate by heating or cooling the substrate.
  • the apparatus further includes a nozzle unit for providing a liquid sample, and an XY drive unit for adjusting the position of the nozzle unit to a position of a specific microcontainer on the substrate.
  • the substrate is hydrophobic and the microvessel is hydrophilic.
  • the substrate is a silicon wafer or mica.
  • the micro container is formed of a hydrophilic oxide.
  • the micro container is formed by laminating a hydrophilic material on the substrate.
  • the bottom surface of the microcontainer has a hydrophilic slope so as to become more hydrophilic toward the edge.
  • the micro container is formed by etching the substrate and laminating a hydrophilic material at the etched position.
  • the bottom surface of the microchamber has a hydrophilic slope so that the hydrophilicity is weaker toward the edge.
  • micro-containers can be manufactured and mounted on micro analysis equipment or mounted on molecular analysis equipment, thereby enabling efficient molecular analysis.
  • use of a mask allows for the mass production of sample dispensing devices, thereby reducing the cost of biotechnology research and medical analysis.
  • the present invention to overcome the phenomenon that the droplets on the micro-container and the droplets of the neighboring micro-container to maintain the droplets of the nano-volume on the micro-vessel can do.
  • the temperature of the micro-container through the present invention it is possible to freeze or dry the droplets, and to induce the droplets to cause a chemical reaction at a specific temperature.
  • FIG. 1 is a view showing a sample dispensing mechanism in which nano-sized micro containers are integrated on a substrate by an embodiment of the present invention.
  • FIG. 2 is a plan view of a sample dispensing mechanism in which the size of the microcontainers is gradually changed according to another embodiment of the present invention.
  • FIG 3 is a view for explaining a method for producing a nano-sized micro-container according to an embodiment of the present invention.
  • FIG. 4 is a view for explaining that biomolecules are dispersed in a microcontainer according to the present invention.
  • FIG. 5 is a view for explaining a sample dispensing mechanism according to still another embodiment of the present invention.
  • FIG. 1 is a diagram illustrating a sample dispensing mechanism 100 in which a nano-sized microcontainer 104 is integrated on a substrate 102 according to an embodiment of the present invention.
  • the micro-container 104 is formed by laminating or etching a nano-sized pattern on the substrate 104, and may contain a very small amount of biomolecule aqueous solution.
  • Biomolecules include probe DNA, RNA, peptide nucleic acid (PNA), nucleic acid such as LNA, proteins such as antigens and antibodies, oligopeptides, human cells, animal cells, plants Cells such as cells, microorganisms such as viruses, bacteria, and the like, but other biomolecules may also be included.
  • PNA peptide nucleic acid
  • LNA peptide nucleic acid
  • proteins such as antigens and antibodies
  • oligopeptides human cells, animal cells, plants
  • Cells such as cells, microorganisms such as viruses, bacteria, and the like, but other biomolecules may also be included.
  • the substrate 102 is composed of a silicon wafer, mica, or the like having a hydrophobic component.
  • Substrate 102 may also be composed of other hydrophobic solids.
  • Substrate 102 may be hydrophobic to prevent biomolecules from contacting.
  • a plasma treatment using a gas, a deposition treatment, a wet treatment, or the like can be used.
  • plasma treatment using a gas such as NH 3 , NF 3 , F 2 , or the like, Si 3 N 4 , SiF 4 , or the like is deposited on the substrate 102, electrolytic plating, electroless plating, or the like. Wet treatment can be performed.
  • a microcontainer 104 capable of containing an extremely small amount of aqueous solution is manufactured.
  • the pattern may be SiO 2 , polyvinylidene fluoride, alkoxy oxide, or the like.
  • the trace amount refers to the size of the micro-container 104, that is, the stack height or the trench depth of 500-800 nm, the bottom surface of a 50 nm diameter circle, the length of one side 50 nm square, etc. Corresponds to the volume in the form.
  • the size of the micro container 104 may be determined by designing a pattern of a mask used for etching, and may be variously determined according to the size of the biomolecule.
  • the stack height or trench depth of the microcontainer 104 is preferably 500-800 nm in which the contrast between the microcontainer 104 which is a hydrophilic oxide and the hydrophobic silicon substrate 102 can be maximized.
  • the object of the present invention can be achieved even outside the stack height or trench depth.
  • the bottom surface of the micro container 104 may be formed in various forms such as a circular shape having a diameter of 50 nm and a square having a length of 50 nm on one side thereof.
  • the area of the bottom surface of the micro-container 104 may be varied according to the type within a large classification such as the size of the molecule, the average size of the protein, and the average size of the cells, which are most used for gene sequencing.
  • the microcontainer 104 may contain and distribute as many biomolecules as desired according to the following description so as to enable efficient molecular analysis.
  • FIG. 2 is a plan view of a sample dispensing mechanism 200 in which the size of the microcontainer 204 is gradually changed in a particular direction of the substrate 202 according to another embodiment of the present invention.
  • the microcontainer 204 gradually increases or decreases in size in the horizontal direction on the substrate 202.
  • the microcontainer 204 is formed of a stacked hydrophilic pattern or an etched hydrophilic pattern on the substrate 202.
  • the hydrophilic pattern introduces a discontinuous hydrophilic slope to prevent the dispersion of biomolecules in the process of preparing a microvolume of the sample.
  • Discontinuous hydrophilic gradients can be created by patterning hydrophilic materials using a series of masks in which the size of the hydrophilic pattern is adjusted sequentially.
  • FIG 3 is a view for explaining a method for producing a nano-sized micro-container according to an embodiment of the present invention.
  • FIG. 3A illustrates a method of manufacturing the microcontainer 306 formed by stacking the hydrophilic pattern 304 on the substrate 302.
  • the degree of evaporation and sublimation can be maintained by giving a hydrophilic gradient to the bottom surface of the stacked microcontainer 306 toward the edge thereof so as to maintain hydrophilicity.
  • FIG. 3B illustrates a method of manufacturing the micro container 316 prepared by etching the hydrophilic pattern 314 on the substrate 312.
  • the etched microcontainer 316 is made less hydrophilic toward the edge of the bottom surface and the wall so that the surface tension with water molecules is weak.
  • the micro containers of the same area may be integrated on one substrate, or the micro containers may be integrated such that various areas are sequentially mixed.
  • 3A and 3B illustrate a case where the micro containers are integrated such that various areas are sequentially mixed.
  • FIG. 4 is a view for explaining that the biomolecules 48 are dispersed in the microchamber 404 formed on the substrate 402 according to the present invention.
  • the area of the microcontainer 404 to be used is determined according to the size of the biomolecule 408 to be analyzed, and the liquid 406 containing the biomolecule 408 prepared by diluting the concentration of the sample is prepared in a micro liquid transport apparatus or atmosphere. Sprinkle with a atomizer to contain as many biomolecules 408 as desired in each microcontainer 404.
  • aqueous solution 406 in which the biomolecule 408 is dissolved can be uniformly contained in each microcontainer 404 by using hydrophilicity and hydrophobic selectivity, the same number of molecules are confined by confining any number of molecules in a drop of any size. Cheap samples can be made cheaply and simply.
  • the ID and location information of the microvessel 404 may be etched using a mask near the edge of the microvessel 404 to store the information of the microvessel 404.
  • the sample dispensing mechanism 600 includes a substrate 602, microcontainers 604a and 604b, a nozzle unit 606, an XY drive unit 610, solution transfer tubes 612 and 616, and a pump 614. And a solution reservoir 618, a control unit 620, and a temperature adjusting unit 624.
  • the description of the substrate 602 and the microcontainers 604a and 604b is as described above.
  • the nozzle unit 606 drops droplets 608a and 608b containing biomolecules into the microcontainers 604a and 604b.
  • the nozzle unit 606 is mounted to the XY drive unit 610, the XY drive unit 610 adjusts the position of the nozzle unit 606 so that the nozzle unit 606 can drop the droplets in a specific micro-container.
  • the shift of the XY driver 610 is controlled by the controller 620.
  • the control line 628 transmits the shift-related control signal generated by the controller 620 to the XY driver 610.
  • the pump 614 provides the sample solution stored in the solution reservoir 618 to the nozzle unit 606 via the solution transfer pipes 616 and 614.
  • the control unit 620 drives the pump 614 after the position of the nozzle unit 606 is moved to a specific micro container by the XY drive unit 610.
  • the control line 626 transmits a pump related control signal generated by the controller 620 to the pump 614.
  • the edges of the hydrophilic microcontainers 604a and 604b have high hydrophilicity so that the droplets 608a and 608b are retained on the microcontainers 604a and 604b.
  • the droplets 608a and 608b may be frozen or dried by adjusting the temperature of the substrate 602 supporting the microcontainers 604a and 604b through the temperature adjusting unit 624, and the droplets 608a at a specific temperature. 608 may be mounted on an analytical instrument to induce a chemical reaction.
  • the control line 630 transmits a temperature related control signal generated by the controller 620 to the temperature adjuster 624.
  • nano-sized micro-container When manufacturing a device for printing a solution containing a biomolecule on the substrate by such a method, highly efficient molecular analysis is possible when the nano-sized micro-container is manufactured and mounted on a micro analysis device or on a molecular analysis device.
  • nano-sized containers can be mounted on analytical instruments, and mass production can be made using the manufactured masks, thereby reducing the cost of biotechnology research and medical analysis and increasing the efficiency of analysis.
  • sample dispensing mechanism 100, 200, 300, 310, 400, 600: sample dispensing mechanism
  • control unit 620 control unit

Abstract

The present invention relates to a technique in which an aqueous solution of biomolecules having a small volume or diameter is uniformly dispersed at desired positions on a substrate. A sample partitioning device of the present invention comprises: a substrate; and a micro-container formed on the substrate, wherein the substrate and the micro-container are opposed to each other in view of hydrophilicity-hydrophobicity characteristics.

Description

액상 시료를 나노 단위로 분배하는 기구Instrument for dispensing liquid samples in nano units
본 발명은 액상 시료를 나노 단위로 분배하는 기구에 관한 것으로서, 보다 상세하게는 기판상의 원하는 위치에 작은 부피 또는 직경을 갖는 생체분자 수용액을 고르게 분산하는 기술에 관한 것이다.The present invention relates to a mechanism for dispensing a liquid sample in nano units, and more particularly, to a technique for evenly dispersing an aqueous solution of biomolecules having a small volume or diameter at a desired position on a substrate.
초소형의 물리 센서 또는 화학 센서 기술은 초고집적 반도체 기술의 발전에 따라 그 응용이 생명공학 분야에까지 넓혀지게 되었다. 최근에는 생명과학, 유전공학, 의료진단, 신약개발 등의 분야에서 유전자 염기서열 분석, 단백질체 분석, 생체대사 물질 검출, 반응물질의 극미량 측정을 위해 반도체 제조 기술을 응용한 MEMS(microelectromechanical systems) 기술이 활발히 연구되고 있다. 그 결과, 고전적인 방법과 달리 바이오 분석을 위하여 많은 시료를 사용하지 않고, 단일 세포, 극소량의 유전물질, 단백질, 분리 및 정제되지 않은 복합 시료의 분석이 가능하게 되었다.Microphysical or chemical sensor technology has been applied to the biotechnology field with the development of ultra-high density semiconductor technology. Recently, MEMS (microelectromechanical systems) technology using semiconductor manufacturing technology for the analysis of gene sequencing, proteomics, biometabolism detection and trace amount of reactants in life science, genetic engineering, medical diagnosis, new drug development, etc. Actively researched. As a result, unlike classical methods, it is possible to analyze single cells, very small amounts of genetic material, proteins, and complex and unpurified complex samples without using many samples for bioanalysis.
이와 관련하여 극소량의 바이오 시료를 일정하게 담는 기술이 요구된다. 종래에도 친수성-소수성 차이를 이용한 여러 마이크로 단위의 어레이 및 용기에 대한 기술들은 존재하지만, 나노 단위(nanoscale)의 극소량에 이용하기에는 어려움이 있다. 극소량의 시료를 사용한 분석법인 이유로 몇 가지 장애가 존재하는데, 그 중 하나는 미세분석 장치의 각각의 미세용기 안에 의도한 양으로 바이오 시료를 분산하여 담는 것이 매우 어렵다는 것이다. In this regard, there is a need for a technique of constantly containing very small amounts of biosamples. Conventional techniques exist for arrays and vessels of several micro units using hydrophilic-hydrophobic differences, but are difficult to use for very small nanoscale quantities. There are several obstacles for analysis with very small amounts of samples, one of which is that it is very difficult to disperse a biosample in the intended amount in each microvessel of the microanalysis apparatus.
예를 들어, 초소형 PCR(polymerase chain reaction) 증폭장치의 경우, 하나의 미세용기에 DNA의 한 분자가 담기도록 하기 위해 시료를 희석하므로, 시료가 담기지 않은 빈 용기들이 높은 빈도로 발생되어 분석 효율이 떨어지고, 분석 비용이 증가하는 문제가 있다. 또한, 현재까지 개발된 마이크로 단위의 우물(well) 형태의 용기에는 나노 단위의 액적(droplet)을 담을 수 없다.For example, in a small polymerase chain reaction (PCR) amplification apparatus, a sample is diluted to contain one molecule of DNA in one microcontainer. There is a problem that falls, the analysis cost increases. In addition, micro-well well-developed containers up to now cannot contain nano-scale droplets.
[선행기술문헌][Preceding technical literature]
[특허문헌][Patent Documents]
1. 한국등록특허 제10-0723427호 (기판상에 생체분자 액적을 프린팅하는 장치 및 방법)1. Korean Patent No. 10-0723427 (apparatus and method for printing biomolecule droplets on a substrate)
2. 한국공개특허 제2005-0072540호 (전기수력학적 현상을 이용하여 기판상에 생체분자를 프린팅하는 장치 및 그 프린팅 방법)2. Korean Patent Publication No. 2005-0072540 (apparatus for printing biomolecules on a substrate using electrohydraulic phenomena and a printing method thereof)
따라서 본 발명은 원하는 수만큼의 생체분자를 분산하여 담을 수 있는 시료 분배 기구를 제공하는 것을 일 목적으로 한다.Accordingly, an object of the present invention is to provide a sample dispensing mechanism capable of dispersing and containing as many biomolecules as desired.
또한, 본 발명은 분자 분석 장비에 장착하여 효율성 높은 분자 분석을 가능하게 하는 시료 분배 기구를 제공하는 것을 다른 목적으로 한다. It is another object of the present invention to provide a sample dispensing mechanism which is mounted on molecular analysis equipment to enable efficient molecular analysis.
또한, 본 발명은 생명공학 연구 및 의료 분석의 비용을 절감할 수 있는 시료 분배 기구를 제공하는 것을 또 다른 목적으로 한다. It is another object of the present invention to provide a sample dispensing apparatus that can reduce the cost of biotechnology research and medical analysis.
전술한 바와 같은 목적을 달성하기 위해 도출된 본 발명은 액상 시료를 나노 단위로 분배하는 기구로서, 기판과, 상기 기판과 친수성-소수성의 특성이 반대되며 상기 기판 위에 형성되는 미세용기를 포함하는 것을 특징으로 한다. The present invention, which is derived to achieve the object as described above, is a mechanism for distributing a liquid sample in nano units, and includes a substrate, and a micro container formed on the substrate with opposite characteristics of the hydrophilicity and hydrophobicity of the substrate. It features.
바람직하게는, 상기 미세용기는 상기 기판에 비해 500-800㎚의 높이로 적층되거나 500-800㎚의 깊이로 식각된다. 또한, 상기 미세용기는 상기 기판 위에 복수개가 구비되며, 상기 복수개의 미세용기는 특정 방향으로 크기가 점차 커지거나 작아진다. Preferably, the microcontainers are stacked at a height of 500-800 nm or etched to a depth of 500-800 nm relative to the substrate. In addition, the plurality of micro-containers are provided on the substrate, the plurality of micro-containers gradually increase or decrease in size in a specific direction.
바람직하게는, 상기 기판을 가열하거나 냉각하여 상기 기판의 온도를 조정하는 온도 조정부를 더 구비한다. 또한, 액상 시료를 제공하는 노즐부와, 상기 노즐부의 위치를 상기 기판 위의 특정 미세용기의 위치로 조정하는 XY 구동부를 더 포함한다. Preferably, the apparatus further includes a temperature adjusting unit configured to adjust the temperature of the substrate by heating or cooling the substrate. The apparatus further includes a nozzle unit for providing a liquid sample, and an XY drive unit for adjusting the position of the nozzle unit to a position of a specific microcontainer on the substrate.
바람직하게는, 상기 기판은 소수성이고, 상기 미세용기는 친수성이다. 상기 기판은 실리콘 웨이퍼 또는 운모(mica)이다. 상기 미세용기는 친수성 산화물로 형성된다. Preferably, the substrate is hydrophobic and the microvessel is hydrophilic. The substrate is a silicon wafer or mica. The micro container is formed of a hydrophilic oxide.
바람직하게는, 상기 미세용기는 상기 기판에 친수성 물질을 적층하여 형성된다. 상기 미세용기의 바닥면은 가장자리 쪽으로 갈수록 친수성이 강하도록 친수성 기울기를 갖는다. Preferably, the micro container is formed by laminating a hydrophilic material on the substrate. The bottom surface of the microcontainer has a hydrophilic slope so as to become more hydrophilic toward the edge.
바람직하게는, 상기 미세용기는 상기 기판을 식각하고, 상기 식각된 위치에 친수성 물질을 적층하여 형성된다. 상기 미세용기의 바닥면은 가장자리 쪽으로 갈수록 친수성이 약하도록 친수성 기울기를 갖는다. Preferably, the micro container is formed by etching the substrate and laminating a hydrophilic material at the etched position. The bottom surface of the microchamber has a hydrophilic slope so that the hydrophilicity is weaker toward the edge.
전술한 구성을 갖는 본 발명을 통해 각 미세용기에 원하는 수만큼의 생체분자를 골고루 분산하여 담을 수 있다. 또한, 나노 크기의 미세용기를 제작하여 초소형 분석 장비에 장착하거나 분자 분석 장비에 장착할 경우 효율성 높은 분자 분석이 가능하다. 또한, 마스크(mask)를 사용하여 시료 분배 기구의 대량 제조가 가능하여 생명공학 연구 및 의료 분석 비용을 절감할 수 있다. Through the present invention having the above-described configuration, it is possible to evenly disperse as many biomolecules as desired in each microcontainer. In addition, nano-sized micro-containers can be manufactured and mounted on micro analysis equipment or mounted on molecular analysis equipment, thereby enabling efficient molecular analysis. In addition, the use of a mask allows for the mass production of sample dispensing devices, thereby reducing the cost of biotechnology research and medical analysis.
또한, 본 발명을 통해 미세용기의 패턴이 나노 크기로 촘촘하게 기판상에 배치되더라도 미세용기 상의 액적이 이웃한 미세용기의 액적과 합쳐지는 현상을 극복하여 상기 미세용기 상에 나노 부피의 액적이 유지되도록 할 수 있다. In addition, even if the pattern of the micro-container is densely arranged on the substrate in a nano-size through the present invention to overcome the phenomenon that the droplets on the micro-container and the droplets of the neighboring micro-container to maintain the droplets of the nano-volume on the micro-vessel can do.
또한, 본 발명을 통해 미세용기의 온도를 조절함으로써 액적을 동결 또는 건조시킬 수 있으며, 특정 온도에서 액적이 화학 반응을 일으킬 수 있도록 유도할 수 있다.In addition, by controlling the temperature of the micro-container through the present invention it is possible to freeze or dry the droplets, and to induce the droplets to cause a chemical reaction at a specific temperature.
도 1은 본 발명의 일 실시예에 의해 기판 위에 나노 크기의 미세용기가 집적된 시료 분배 기구를 나타내는 도면이다.1 is a view showing a sample dispensing mechanism in which nano-sized micro containers are integrated on a substrate by an embodiment of the present invention.
도 2는 본 발명의 다른 실시예에 의해 미세용기의 크기가 점차 변하는 시료 분배 기구의 평면도이다. 2 is a plan view of a sample dispensing mechanism in which the size of the microcontainers is gradually changed according to another embodiment of the present invention.
도 3은 본 발명의 실시예에 따라 나노 크기의 미세용기를 제작하는 방법을 설명하기 위한 도면이다. 3 is a view for explaining a method for producing a nano-sized micro-container according to an embodiment of the present invention.
도 4는 본 발명에 의해 미세용기에 생체분자가 분산되어 있는 것을 설명하는 도면이다. 4 is a view for explaining that biomolecules are dispersed in a microcontainer according to the present invention.
도 5는 본 발명의 또 다른 실시예에 의한 시료 분배 기구를 설명하는 도면이다.5 is a view for explaining a sample dispensing mechanism according to still another embodiment of the present invention.
이하, 첨부된 도면을 참조하여 본 발명에 따른 실시 예를 상세하게 설명한다. 본 발명의 구성 및 그에 따른 작용 효과는 이하의 상세한 설명을 통해 명확하게 이해될 것이다.Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. The construction of the present invention and the effects thereof will be clearly understood through the following detailed description.
본 발명의 상세한 설명에 앞서, 동일한 구성요소에 대해서는 다른 도면상에 표시되더라도 가능한 동일한 부호로 표시하며, 공지된 구성에 대해서는 본 발명의 요지를 흐릴 수 있다고 판단되는 경우 구체적인 설명은 생략하기로 함에 유의한다.Prior to the detailed description of the present invention, the same components are denoted by the same reference numerals as much as possible even if displayed on different drawings, and the known components will be omitted if it is determined that the gist of the present invention may obscure the gist of the present invention. do.
도 1은 본 발명의 일 실시예에 의해 기판(102) 위에 나노 크기의 미세용기(104)가 집적된 시료 분배 기구(100)를 나타내는 도면이다. 도시된 바와 같이, 미세용기(104)는 기판(104) 상에 나노 크기의 패턴이 적층되거나 식각되어 형성되며, 극미량의 생체분자 수용액을 담을 수 있다.1 is a diagram illustrating a sample dispensing mechanism 100 in which a nano-sized microcontainer 104 is integrated on a substrate 102 according to an embodiment of the present invention. As shown, the micro-container 104 is formed by laminating or etching a nano-sized pattern on the substrate 104, and may contain a very small amount of biomolecule aqueous solution.
생체분자는 탐침(probe) DNA, RNA, PNA(Peptide nucleic acid), LNA 등의 핵산(nucleic acid)류, 항원, 항체 등의 단백질(Protein)류, 올리고 펩티드류, 인간 세포, 동물 세포, 식물 세포 등의 세포류, 바이러스, 박테리아 등의 미생물류를 포함하나, 그 외의 다른 생체분자도 포함될 수 있다. Biomolecules include probe DNA, RNA, peptide nucleic acid (PNA), nucleic acid such as LNA, proteins such as antigens and antibodies, oligopeptides, human cells, animal cells, plants Cells such as cells, microorganisms such as viruses, bacteria, and the like, but other biomolecules may also be included.
기판(102)은 소수성 성분을 띄는 실리콘 웨이퍼, 운모(mica) 등으로 구성된다. 기판(102)은 다른 소수성 고체로도 구성될 수 있다. 기판(102)은 생체분자가 접촉되지 않도록 소수성 처리될 수 있다. 이와 같은 소수성 처리로는 기체를 이용한 플라즈마 처리, 증착 처리, 습식 처리 등을 이용할 수 있다. 예컨대, 소수성 처리를 위해, NH3, NF3, F2 등의 기체를 이용한 플라즈마 처리를 하거나, Si3N4, SiF4 등을 기판(102) 위에 증착시키거나, 전해 도금, 무전해 도금 등을 이용한 습식 처리를 수행할 수 있다.The substrate 102 is composed of a silicon wafer, mica, or the like having a hydrophobic component. Substrate 102 may also be composed of other hydrophobic solids. Substrate 102 may be hydrophobic to prevent biomolecules from contacting. As such hydrophobic treatment, a plasma treatment using a gas, a deposition treatment, a wet treatment, or the like can be used. For example, for hydrophobic treatment, plasma treatment using a gas such as NH 3 , NF 3 , F 2 , or the like, Si 3 N 4 , SiF 4 , or the like is deposited on the substrate 102, electrolytic plating, electroless plating, or the like. Wet treatment can be performed.
기판(102) 위에 나노 크기의 친수성인 산화물 패턴을 적층하거나 식각하여 극미량의 수용액을 담을 수 있는 미세용기(104)를 제작한다. 상기 패턴은 SiO2, 폴리염화비닐리덴(polyvinylidene fluoride), 알콕시(alkoxy)계 산화물 등을 사용할 수 있다. 여기에서 극미량이라 함은 미세용기(104)의 크기 즉, 적층 높이 또는 트렌치(trench) 깊이가 500-800㎚이고, 바닥면은 지름 50㎚의 원형, 한 변의 길이가 50㎚인 사각형 등의 여러 형태인 경우의 체적에 해당한다. By stacking or etching a nano-sized hydrophilic oxide pattern on the substrate 102, a microcontainer 104 capable of containing an extremely small amount of aqueous solution is manufactured. The pattern may be SiO 2 , polyvinylidene fluoride, alkoxy oxide, or the like. Here, the trace amount refers to the size of the micro-container 104, that is, the stack height or the trench depth of 500-800 nm, the bottom surface of a 50 nm diameter circle, the length of one side 50 nm square, etc. Corresponds to the volume in the form.
미세용기(104)의 크기는 식각에 사용하는 마스크(mask)의 패턴을 디자인하여 결정할 수 있고, 생체분자의 크기에 따라 다양하게 결정할 수 있다. 미세용기(104)의 적층 높이　또는 트렌치 깊이는 친수성 산화물인 미세용기(104)와 주변의 소수성인 실리콘 기판(102) 사이의 대비가 최대가 될 수 있는 500-800㎚로 하는 것이 바람직하나, 상기 적층 높이 또는 트렌치 깊이를 벗어나더라도 본 발명의 목적을 달성할 수 있다.The size of the micro container 104 may be determined by designing a pattern of a mask used for etching, and may be variously determined according to the size of the biomolecule. The stack height or trench depth of the microcontainer 104 is preferably 500-800 nm in which the contrast between the microcontainer 104 which is a hydrophilic oxide and the hydrophobic silicon substrate 102 can be maximized. The object of the present invention can be achieved even outside the stack height or trench depth.
미세용기(104)의 바닥면은 지름 50㎚의 원형, 한 변의 길이가 50㎚인 사각형 등의 여러 가지 형태로 형성될 수 있다. 유전자 염기서열 분석에 가장 많이 쓰는 분자의 크기, 단백질의 평균 크기, 세포의 평균 크기 등의 큰 분류 안에서 종류에 따라 미세용기(104)의 바닥면의 면적을 다르게 할 수 있다.The bottom surface of the micro container 104 may be formed in various forms such as a circular shape having a diameter of 50 nm and a square having a length of 50 nm on one side thereof. The area of the bottom surface of the micro-container 104 may be varied according to the type within a large classification such as the size of the molecule, the average size of the protein, and the average size of the cells, which are most used for gene sequencing.
미세용기(104)는 효율성 높은 분자 분석이 가능하도록 이하의 설명에 따라 원하는 수만큼의 생체분자를 골고루 분산하여 담을 수 있다. The microcontainer 104 may contain and distribute as many biomolecules as desired according to the following description so as to enable efficient molecular analysis.
도 2는 본 발명의 다른 실시예에 의해 미세용기(204)의 크기가 기판(202)의 특정 방향으로 점차 변하는 시료 분배 기구(200)의 평면도이다. 도 2에서 미세용기(204)는 기판(202) 상에서 수평 방향으로 크기가 점차적으로 커지거나 작아진다. 미세용기(204)는 기판(202) 상의 적층된 친수성 패턴 또는 식각된 친수성 패턴으로 형성된다. 친수성 패턴은 불연속적인 친수성 기울기를 도입하여 미세 부피의 시료가 준비되는 과정에서 생체분자의 분산도가 흐트러지지 않게 하다. 불연속적인 친수성 기울기는 친수성 패턴의 크기를 순차적으로 조절한 마스크 여러 장을 순차적으로 사용하여 친수성 물질을 패터닝함으로써 만들 수 있다. 2 is a plan view of a sample dispensing mechanism 200 in which the size of the microcontainer 204 is gradually changed in a particular direction of the substrate 202 according to another embodiment of the present invention. In FIG. 2, the microcontainer 204 gradually increases or decreases in size in the horizontal direction on the substrate 202. The microcontainer 204 is formed of a stacked hydrophilic pattern or an etched hydrophilic pattern on the substrate 202. The hydrophilic pattern introduces a discontinuous hydrophilic slope to prevent the dispersion of biomolecules in the process of preparing a microvolume of the sample. Discontinuous hydrophilic gradients can be created by patterning hydrophilic materials using a series of masks in which the size of the hydrophilic pattern is adjusted sequentially.
도 3은 본 발명의 실시예에 따라 나노 크기의 미세용기를 제작하는 방법을 설명하기 위한 도면이다. 3 is a view for explaining a method for producing a nano-sized micro-container according to an embodiment of the present invention.
도 3의 (A)는 기판(302) 위에 친수성 패턴(304)을 적층하여 제작한 미세용기(306)를 제작하는 방법을 도시하고 있다. 적층식 미세용기(306)의 바닥면에 가장자리 쪽으로 갈수록 친수성이 강하도록 친수성 기울기를 주어 증발 및 승화의 정도를 조절함으로써 생체분자의 분산도를 유지할 수 있다.FIG. 3A illustrates a method of manufacturing the microcontainer 306 formed by stacking the hydrophilic pattern 304 on the substrate 302. The degree of evaporation and sublimation can be maintained by giving a hydrophilic gradient to the bottom surface of the stacked microcontainer 306 toward the edge thereof so as to maintain hydrophilicity.
도 3의 (B)는 기판(312) 위에 친수성 패턴(314)을 식각하여 제작한 미세용기(316)를 제작하는 방법을 도시하고 있다. 식각식 미세용기(316)는 물 분자와의 표면장력이 약하도록 바닥면의 가장자리와 벽면으로 갈수록 친수성이 약하게 제작된다.FIG. 3B illustrates a method of manufacturing the micro container 316 prepared by etching the hydrophilic pattern 314 on the substrate 312. The etched microcontainer 316 is made less hydrophilic toward the edge of the bottom surface and the wall so that the surface tension with water molecules is weak.
미세용기의 집적체는 하나의 기판에 동일 면적의 미세용기가 집적되거나 다양한 면적이 순차적으로 혼재되도록 미세용기가 집적될 수 있다. 도 3의 (A)와 (B)는 다양한 면적이 순차적으로 혼재되도록 미세용기가 집적되는 경우를 도시하고 있다. In the integrated body of the micro container, the micro containers of the same area may be integrated on one substrate, or the micro containers may be integrated such that various areas are sequentially mixed. 3A and 3B illustrate a case where the micro containers are integrated such that various areas are sequentially mixed.
도 4는 본 발명에 의해 기판(402)에 형성된 미세용기(404)에 생체분자(48)가 분산되어 있는 것을 설명하는 도면이다. 분석하고자 하는 생체분자(408)의 크기에 따라 사용할 미세용기(404)의 면적을 결정하고, 시료의 농도를 희석하여 준비한 생체분자(408)를 함유하는 액체(406)를 미량 액체 이송 장치나 애토마이저(atomizer)로 뿌려서 각 미세용기(404)에 원하는 수만큼의 생체분자(408)를 담는다.4 is a view for explaining that the biomolecules 48 are dispersed in the microchamber 404 formed on the substrate 402 according to the present invention. The area of the microcontainer 404 to be used is determined according to the size of the biomolecule 408 to be analyzed, and the liquid 406 containing the biomolecule 408 prepared by diluting the concentration of the sample is prepared in a micro liquid transport apparatus or atmosphere. Sprinkle with a atomizer to contain as many biomolecules 408 as desired in each microcontainer 404.
친수성, 소수성의 선택성을 이용하여 생체분자(408)를 용해한 수용액(406)을 각 미세용기(404)에 골고루 빠짐없이 담을 수 있으면, 임의 개수의 분자를 임의 크기의 물방울 속에 가두어 동일한 개수의 분자를 가진 시료를 싸고 간단히 만들어낼 수 있다.If the aqueous solution 406 in which the biomolecule 408 is dissolved can be uniformly contained in each microcontainer 404 by using hydrophilicity and hydrophobic selectivity, the same number of molecules are confined by confining any number of molecules in a drop of any size. Cheap samples can be made cheaply and simply.
한편, 미세용기(404)의 가장자리 근처에 미세용기(404)의 ID와 위치정보를 마스크를 이용하여 식각함으로써 미세용기(404)의 정보를 저장할 수 있다. Meanwhile, the ID and location information of the microvessel 404 may be etched using a mask near the edge of the microvessel 404 to store the information of the microvessel 404.
도 5는 본 발명의 또 다른 실시예에 의한 시료 분배 기구(600)를 설명하는 도면이다. 도시된 바와 같이, 시료 분배 기구(600)는 기판(602), 미세용기(604a, 604b), 노즐부(606), XY 구동부(610), 용액 이송관(612, 616), 펌프(614), 용액 저장통(618), 제어부(620), 온도 조정부(624)를 구비한다. 5 is a view for explaining a sample dispensing mechanism 600 according to another embodiment of the present invention. As shown, the sample dispensing mechanism 600 includes a substrate 602, microcontainers 604a and 604b, a nozzle unit 606, an XY drive unit 610, solution transfer tubes 612 and 616, and a pump 614. And a solution reservoir 618, a control unit 620, and a temperature adjusting unit 624.
기판(602)과 미세용기(604a, 604b)에 대한 설명은 전술한 바와 같다. 노즐부(606)는 미세용기(604a, 604b)에 생체분자를 함유하는 액적(608a, 608b)를 떨어 뜨린다. 노즐부(606)는 XY 구동부(610)에 장착되며, XY 구동부(610)는 노즐부(606)가 특정 미세용기에 액적을 떨어뜨릴 수 있도록 노즐부(606)의 위치를 조절한다. XY 구동부(610)의 변이는 제어부(620)에 의해 제어된다. 제어선(628)은 제어부(620)에서 생성된 변이 관련 제어신호를 XY 구동부(610)로 전송한다. 펌프(614)는 용액 저장통(618)에 저장되어 있는 시료 용액을 용액 이송관(616, 614)을 경유하여 노즐부(606)에 제공한다. 제어부(620)는 XY 구동부(610)에 의해 노즐부(606)의 위치가 특정 미세용기로 이동된 후에 펌프(614)를 구동한다. 제어선(626)은 제어부(620)에서 생성된 펌프 관련 제어신호를 펌프(614)로 전송한다. The description of the substrate 602 and the microcontainers 604a and 604b is as described above. The nozzle unit 606 drops droplets 608a and 608b containing biomolecules into the microcontainers 604a and 604b. The nozzle unit 606 is mounted to the XY drive unit 610, the XY drive unit 610 adjusts the position of the nozzle unit 606 so that the nozzle unit 606 can drop the droplets in a specific micro-container. The shift of the XY driver 610 is controlled by the controller 620. The control line 628 transmits the shift-related control signal generated by the controller 620 to the XY driver 610. The pump 614 provides the sample solution stored in the solution reservoir 618 to the nozzle unit 606 via the solution transfer pipes 616 and 614. The control unit 620 drives the pump 614 after the position of the nozzle unit 606 is moved to a specific micro container by the XY drive unit 610. The control line 626 transmits a pump related control signal generated by the controller 620 to the pump 614.
미세용기의 패턴이 나노 크기로 촘촘하게 기판(602) 상에 배치될 경우, 미세용기(604a) 상의 액적(608a)이 이웃한 미세용기(604b)의 액적(608b)과 합쳐지는 현상이 나타날 수 있다. 본 실시예에서는 이를 억제하기 위하여 친수성 미세용기(604a, 604b)의 가장자리가 높은 친수성을 갖도록 함으로써 미세용기(604a, 604b) 상에 액적(608a, 608b)이 유지되도록 한다. When the pattern of the microcontainers is disposed on the substrate 602 densely in nano size, a phenomenon in which the droplets 608a on the microcontainers 604a merge with the droplets 608b of the neighboring microcontainers 604b may occur. . In this embodiment, the edges of the hydrophilic microcontainers 604a and 604b have high hydrophilicity so that the droplets 608a and 608b are retained on the microcontainers 604a and 604b.
SiO2를 이용하여 미세용기 패턴을 제작한 후, 접촉각 측정을 통해 친수성을 계산한 결과 평균 -31.2 mN/m의 수화 에너지(wettable energy)를 갖음을 확인하였다. After preparing the micro-container pattern using SiO 2 , it was confirmed that the hydrophilicity was calculated by the contact angle measurement to have a wettable energy of average -31.2 mN / m.
본 실시예에서는 온도 조정부(624)를 통해 미세용기(604a, 604b)를 지지하는 기판(602)의 온도를 조절함으로써 액적(608a, 608b)을 동결 또는 건조시킬 수 있으며, 특정 온도에서 액적(608a, 608)이 화학 반응을 하도록 유도하여 분석 기기에 장착할 수 있다. 제어선(630)은 제어부(620)에서 생성된 온도 관련 제어신호를 온도 조정부(624)로 전송한다. In the present embodiment, the droplets 608a and 608b may be frozen or dried by adjusting the temperature of the substrate 602 supporting the microcontainers 604a and 604b through the temperature adjusting unit 624, and the droplets 608a at a specific temperature. 608 may be mounted on an analytical instrument to induce a chemical reaction. The control line 630 transmits a temperature related control signal generated by the controller 620 to the temperature adjuster 624.
이와 같은 방법에 의해 기판상에 생체분자를 포함하는 용액을 프린팅하는 장치를 제조하는 경우, 나노 크기의 미세용기를 제작하여 초소형 분석 장비에 장착하거나 분자 분석 장비에 장착할 경우 효율성 높은 분자 분석을 가능하게 하고, 나노 크기의 미세용기를 분석 기기에 장착할 수 있으며, 제작한 mask를 사용하여 대량 제조가 가능하여 생명공학 연구 및 의료 분석 비용을 절감하고 분석의 효율성을 높일 수 있다. When manufacturing a device for printing a solution containing a biomolecule on the substrate by such a method, highly efficient molecular analysis is possible when the nano-sized micro-container is manufactured and mounted on a micro analysis device or on a molecular analysis device In addition, nano-sized containers can be mounted on analytical instruments, and mass production can be made using the manufactured masks, thereby reducing the cost of biotechnology research and medical analysis and increasing the efficiency of analysis.
본 발명은 전술한 실시예 및 첨부된 도면에 의해 한정되는 것이 아니다. 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자에게 있어, 본 발명의 기술적 사상을 벗어나지 않는 범위 내에서 본 발명에 따른 구성요소를 치환, 변형 및 변경할 수 있다는 것이 명백할 것이다.The present invention is not limited by the above-described embodiment and the accompanying drawings. It will be apparent to those skilled in the art that the present invention may be substituted, modified, and changed in accordance with the present invention without departing from the spirit of the present invention.
따라서 본 발명의 명세서에 개시된 실시 예들은 본 발명을 한정하는 것이 아니다. 본 발명의 범위는 아래의 특허청구범위에 의해 해석되어야 하며, 그와 균등한 범위 내에 있는 모든 기술도 본 발명의 범위에 포함되는 것으로 해석해야 할 것이다.Therefore, the embodiments disclosed in the specification of the present invention are not intended to limit the present invention. The scope of the present invention should be construed by the claims below, and all techniques within the scope equivalent thereto will be construed as being included in the scope of the present invention.
[부호의 설명][Description of the code]
100, 200, 300, 310, 400, 600 : 시료 분배 기구100, 200, 300, 310, 400, 600: sample dispensing mechanism
102, 202, 302, 312, 402, 602 : 기판102, 202, 302, 312, 402, 602: substrate
104, 204, 304, 314, 404, 604a, 604b : 미세용기104, 204, 304, 314, 404, 604a, 604b: Micro containers
606 : 노즐부606: nozzle unit
610 : XY 구동부610: XY drive unit
612, 616 : 용액 이송관612, 616: solution transfer pipe
614 : 펌프614: Pump
618 : 용액 저장통618: solution reservoir
620 : 제어부620: control unit
624 : 온도 조정부624: temperature control unit

Claims (12)

  1. 액상 시료를 나노 단위로 분배하는 기구에 있어서,In the apparatus for dispensing a liquid sample in nano units,
    기판과,Substrate,
    상기 기판과 친수성-소수성의 특성이 반대되며 상기 기판 위에 형성되는 미세용기를The micro-vessel formed on the substrate is opposite the hydrophilicity-hydrophobicity of the substrate
    포함하는 것을 특징으로 하는 시료 분배 기구. A sample dispensing mechanism comprising a.
  2. 제1항에 있어서,The method of claim 1,
    상기 기판은 소수성이고, 상기 미세용기는 친수성인 것을 특징으로 시료 분배 기구. And said substrate is hydrophobic and said microcontainer is hydrophilic.
  3. 제2항에 있어서,The method of claim 2,
    상기 기판은 실리콘 웨이퍼 또는 운모(mica)인 것을 특징으로 하는 시료 분배 기구. And the substrate is a silicon wafer or mica.
  4. 제2항에 있어서,The method of claim 2,
    상기 미세용기는 친수성 산화물로 형성된 것을 특징으로 하는 시료 분배 기구. Sample dispensing mechanism, characterized in that the micro-container is formed of a hydrophilic oxide.
  5. 제2항에 있어서,The method of claim 2,
    상기 미세용기는 상기 기판에 친수성 물질을 적층하여 형성된 것을 특징으로 하는 시료 분배 기구.The fine container is a sample distribution mechanism, characterized in that formed by laminating a hydrophilic material on the substrate.
  6. 제5항에 있어서,The method of claim 5,
    상기 미세용기의 바닥면은 가장자리 쪽으로 갈수록 친수성이 강하도록 친수성 기울기를 갖는 것을 특징으로 하는 시료 분배 기구.Sample dispensing mechanism, characterized in that the bottom surface of the micro-vessel has a hydrophilic slope so as to become more hydrophilic toward the edge.
  7. 제2항에 있어서,The method of claim 2,
    상기 미세용기는 상기 기판을 식각하고, 상기 식각된 위치에 친수성 물질을 적층하여 형성된 것을 특징으로 하는 시료 분배 기구.And the micro container is formed by etching the substrate and laminating a hydrophilic material at the etched position.
  8. 제7항에 있어서,The method of claim 7, wherein
    상기 미세용기의 바닥면은 가장자리 쪽으로 갈수록 친수성이 약하도록 친수성 기울기를 갖는 것을 특징으로 하는 시료 분배 기구.Sample dispensing mechanism, characterized in that the bottom surface of the micro-vessel having a hydrophilic slope so that the hydrophilicity is weaker toward the edge.
  9. 제1항에 있어서,The method of claim 1,
    상기 미세용기는 상기 기판에 비해 500-800㎚의 높이로 적층되거나 500-800㎚의 깊이로 식각되어 있는 것을 특징으로 하는 시료 분배 기구.And the microcontainer is stacked at a height of 500-800 nm or etched to a depth of 500-800 nm relative to the substrate.
  10. 제1항에 있어서,The method of claim 1,
    상기 미세용기는 상기 기판 위에 복수개가 구비되며,The plurality of micro containers are provided on the substrate,
    상기 복수개의 미세용기는 특정 방향으로 크기가 점차 커지거나 작아지는 것을 특징으로 하는 시료 분배 기구. Sample dispensing mechanism, characterized in that the plurality of micro-container is gradually increased or reduced in size in a specific direction.
  11. 제1항에 있어서,The method of claim 1,
    상기 기판을 가열하거나 냉각하여 상기 기판의 온도를 조정하는 온도 조정부를 더 구비하는 것을 특징으로 하는 시료 분배 기구.And a temperature adjusting unit for heating or cooling the substrate to adjust the temperature of the substrate.
  12. 제1항에 있어서,The method of claim 1,
    액상 시료를 제공하는 노즐부와,A nozzle unit for providing a liquid sample,
    상기 노즐부의 위치를 상기 기판 위의 특정 미세용기의 위치로 조정하는 XY 구동부를XY drive unit for adjusting the position of the nozzle portion to the position of the specific micro-container on the substrate
    더 포함하는 것을 특징으로 하는 시료 분배 기구.Sample dispensing mechanism further comprising.
PCT/KR2017/000423 2017-01-12 2017-01-12 Device for partitioning liquid sample on nano unit WO2018131731A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115064618A (en) * 2022-08-17 2022-09-16 苏州晶台光电有限公司 COB module packaging method

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1164213A (en) * 1997-06-09 1999-03-05 Fuji Photo Film Co Ltd Sample plate
US20030080143A1 (en) * 2001-04-04 2003-05-01 Arradial, Inc. System and method for dispensing liquids
KR20030088782A (en) * 2002-05-15 2003-11-20 삼성전자주식회사 A process for producing array plate for a biomolecule comprising a hydrophilic region and a hydrophobic region
US20100028985A1 (en) * 2005-03-29 2010-02-04 Shimadzu Corporation Reaction Vessel, Reaction Vessel Processing Apparatus and Diagnostic Apparatus
KR20100114238A (en) * 2009-04-15 2010-10-25 임현우 The highly sensitive pre-patterned micro array chip for bio-molecules detection with hydrophobic and hydrophilic surface and fabrication method thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1164213A (en) * 1997-06-09 1999-03-05 Fuji Photo Film Co Ltd Sample plate
US20030080143A1 (en) * 2001-04-04 2003-05-01 Arradial, Inc. System and method for dispensing liquids
KR20030088782A (en) * 2002-05-15 2003-11-20 삼성전자주식회사 A process for producing array plate for a biomolecule comprising a hydrophilic region and a hydrophobic region
US20100028985A1 (en) * 2005-03-29 2010-02-04 Shimadzu Corporation Reaction Vessel, Reaction Vessel Processing Apparatus and Diagnostic Apparatus
KR20100114238A (en) * 2009-04-15 2010-10-25 임현우 The highly sensitive pre-patterned micro array chip for bio-molecules detection with hydrophobic and hydrophilic surface and fabrication method thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115064618A (en) * 2022-08-17 2022-09-16 苏州晶台光电有限公司 COB module packaging method
CN115064618B (en) * 2022-08-17 2022-11-29 苏州晶台光电有限公司 COB module packaging method

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