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    • 3. 发明授权
    • Multiwell incubation apparatus and method of analysis using the same
    • 多孔培养装置及其分析方法
    • US08080412B2
    • 2011-12-20
    • US12297011
    • 2007-04-13
    • Nobuo Shimamoto
    • Nobuo Shimamoto
    • C12M1/00C12M3/00F28F3/12
    • C12M27/16B01F11/0017B01L3/50853B01L7/54B01L2300/0654B01L2300/0829B01L2300/185B01L2300/1883C12M23/12C12M37/00C12M41/14
    • A continuous temperature-gradient incubation apparatus designed to solve the problem of moving of liquid vapor generated on the high-temperature side toward the low-temperature side to thereby cause condensation.There is provided a multiwell incubation apparatus having a well-housing vessel made of a heat conducting material and, detachably housed therein, liquid-storing wells, the wells being arranged in transverse rows and longitudinal rows, the multiwell incubation apparatus being also provided with a liquid or gas flow channel or bath for supply of a gas saturated with vapor of the liquid, the multiwell incubation apparatus being capable of maintaining incubation temperatures differing between individual transverse rows of wells with a predetermined temperature difference, so as to realize a temperature series which forms a predetermined temperature difference profile along the longitudinal rows, characterized in that the multiwell incubation apparatus includes a heat source for realizing a temperature which is the lowest in the given temperature series, the heat source being disposed outside the well rows and along the transversely lined up wells close to a first side of the housing vessel; another heat source for realizing a temperature which is the highest in the given temperature series, the heat source being disposed outside the well rows and along a side opposite to the first side; and a separator provided for each transverse row of a certain temperature.
    • 一种连续的温度梯度培养装置,其设计用于解决在高温侧产生的液体蒸气向低温侧移动从而导致冷凝的问题。 提供了一种多孔培养装置,其具有由导热材料制成的井口容器,并且可拆卸地容纳在其中的液体储存井,井被布置成横排和纵向排,多孔培养装置还设置有 用于供应饱和液体蒸气的气体的液体或气体流动通道或浴,所述多孔培养装置能够保持具有预定温度差异的各个横列排之间的孵育温度,从而实现温度系列 沿纵排形成预定的温度差异分布,其特征在于,多孔培养装置包括用于实现在给定温度系列中最低温度的热源,热源设置在井排外部并沿着横向排列 靠近壳体第一侧的井 l; 用于实现在给定温度系列中最高的温度的另一个热源,热源设置在井排外部并且沿着与第一侧相对的一侧; 以及为一定温度的每个横排设置的隔板。
    • 4. 发明申请
    • Methods for detecting biopolymers; biochips; methods for immobilizing antibodies; and substrates to which antibodies are immobilized
    • 检测生物聚合物的方法; 生物芯片 抗体固定方法; 和固定有抗体的底物
    • US20050191644A1
    • 2005-09-01
    • US10960849
    • 2004-10-06
    • Nobuo ShimamotoMotoki SusaKazuhisa Fukushima
    • Nobuo ShimamotoMotoki SusaKazuhisa Fukushima
    • G01N33/543C12Q1/68C12M1/34G01N33/53H01L21/00
    • G01N33/54393G01N33/5432G01N33/5436
    • The present invention relates to biopolymer detection methods based on antigen-antibody interactions, wherein the methods show improved S/N ratios, improved detection sensitivities, and reduced detection times. The present invention also relates to application of these methods to biochips. The invention further relates to antibody fixation methods wherein antibody molecules are immobilized to amide group-containing gels, or amide group-containing gels on insoluble substances. Using such gels prevents the nonspecific adsorption of antibody-binding molecules. By embedding these antibody-binding molecules in such gels, their antibody-binding activity is prevented from deteriorating. The methods for detecting biopolymers by trapping target biopolymers to the substrate side, comprise the steps of: 1) placing target biopolymers, with probe biopolymers and beads that are identified by antibodies or address probe peptides or biopolymer address linkers attached to their surface, in a solution; 2) hybridizing the target biopolymers with the probe biopolymers; and 3) identifying the address linkers bound to a substrate by the address probe peptide or biopolymers or polyclonal antibody molecules through antigen-antibody interactions. The methods for immobilizing antibodies comprise the steps of: 1) applying an amide group-containing gel embedded with antibody-binding molecules on a substrate of an insoluble substance in two or three dimensions; and 2) attaching the base of the antibody molecules to antibody-binding molecules.
    • 本发明涉及基于抗原 - 抗体相互作用的生物聚合物检测方法,其中所述方法显示改善的S / N比,改进的检测灵敏度和减少的检测时间。 本发明还涉及将这些方法应用于生物芯片。 本发明还涉及抗体固定方法,其中将抗体分子固定在含酰胺基的凝胶或含不溶性物质的含酰胺基的凝胶上。 使用这种凝胶防止抗体结合分子的非特异性吸附。 通过将这些抗体结合分子嵌入这样的凝胶中,可以防止其抗体结合活性恶化。 通过将目标生物聚合物捕获到底物侧来检测生物聚合物的方法包括以下步骤:1)将目标生物聚合物与探针生物聚合物和由抗体或寻址探针肽或生物聚合物地址接头附着在其表面上的珠子放置在 解; 2)将目标生物聚合物与探针生物聚合物杂交; 和3)通过地址探针肽或生物聚合物或多克隆抗体分子通过抗原 - 抗体相互作用鉴定与底物结合的地址接头。 用于固定抗体的方法包括以下步骤:1)将包含抗体结合分子的含酰胺基团的凝胶在两维或三维的不溶性物质的底物上施用; 和2)将抗体分子的碱基附着于抗体结合分子。
    • 5. 发明申请
    • MULTIWELL INCUBATION APPARATUS AND METHOD OF ANALYSIS USING THE SAME
    • MULTIWELL INCUBATION装置及其分析方法
    • US20090170714A1
    • 2009-07-02
    • US12297011
    • 2007-04-13
    • Nobuo Shimamoto
    • Nobuo Shimamoto
    • C40B30/00C40B60/00C40B99/00
    • C12M27/16B01F11/0017B01L3/50853B01L7/54B01L2300/0654B01L2300/0829B01L2300/185B01L2300/1883C12M23/12C12M37/00C12M41/14
    • A continuous temperature-gradient incubation apparatus designed to solve the problem of moving of liquid vapor generated on the high-temperature side toward the low-temperature side to thereby cause condensation.There is provided a multiwell incubation apparatus having a well-housing vessel made of a heat conducting material and, detachably housed therein, liquid-storing wells, the wells being arranged in transverse rows and longitudinal rows, the multiwell incubation apparatus being also provided with a liquid or gas flow channel or bath for supply of a gas saturated with vapor of the liquid, the multiwell incubation apparatus being capable of maintaining incubation temperatures differing between individual transverse rows of wells with a predetermined temperature difference, so as to realize a temperature series which forms a predetermined temperature difference profile along the longitudinal rows, characterized in that the multiwell incubation apparatus includes a heat source for realizing a temperature which is the lowest in the given temperature series, the heat source being disposed outside the well rows and along the transversely lined up wells close to a first side of the housing vessel; another heat source for realizing a temperature which is the highest in the given temperature series, the heat source being disposed outside the well rows and along a side opposite to the first side; and a separator provided for each transverse row of a certain temperature.
    • 一种连续的温度梯度培养装置,其设计用于解决在高温侧产生的液体蒸气向低温侧移动从而导致冷凝的问题。 提供了一种多孔培养装置,其具有由导热材料制成的井口容纳容器,并且可拆卸地容纳在其中的储液孔,井排列成横排和纵排,多孔培养装置还设置有 用于供应饱和液体蒸气的气体的液体或气体流动通道或浴,所述多孔培养装置能够保持具有预定温度差异的各个横列排之间的孵育温度,从而实现温度系列 沿纵排形成预定的温度差异分布,其特征在于,多孔培养装置包括用于实现在给定温度系列中最低温度的热源,热源设置在井排之外并沿着横向排列 靠近壳体第一侧的井 l; 用于实现在给定温度系列中最高的温度的另一个热源,热源设置在井排外部并且沿着与第一侧相对的一侧; 以及为一定温度的每个横排提供的隔板。
    • 6. 发明申请
    • Biopolymer detecting method and biochip
    • 生物聚合物检测方法和生物芯片
    • US20060105383A1
    • 2006-05-18
    • US11322362
    • 2006-01-03
    • Kazubisa FukushimaNobuo Shimamoto
    • Kazubisa FukushimaNobuo Shimamoto
    • C12Q1/68C12M1/34
    • C12Q1/6804C12Q1/6816C12Q1/6837C12Q2563/149C12Q2565/501
    • The present invention relates to biopolymer detection utilizing antigen-antibody reaction, intended to improve the S/N ratio, to increase the detection sensitivity, and to shorten the detection time. According to the present invention, target biopolymers labeled with a fluorescent material and beads, onto the surface of which probe biopolymers and beads-ID recognizing address linkers are fixed, are put in a solution to hybridize the target biopolymers and the probe biopolymers, then the above address linkers are captured by antigen-antibody reaction using the addressing probe protein which is in such relation to the said address linkers as either one of the addressing probe protein and the address linkers is an antigen and the other is the corresponding antibody.
    • 本发明涉及利用抗原 - 抗体反应的生物聚合物检测,旨在提高S / N比,提高检测灵敏度,缩短检测时间。 根据本发明,将用荧光材料标记的目标生物聚合物和珠粒固定在其上的探针生物聚合物和珠ID识别地址接头的表面上,以将目标生物聚合物和探针生物聚合物杂交, 使用寻址探针蛋白通过抗原 - 抗体反应捕获上述地址连接子,寻址探针蛋白与寻址探针蛋白和地址接头之一是抗原而另一个是相应的抗体,所述寻址探针蛋白与所述地址接头具有这种关系。
    • 7. 发明授权
    • Method for recovering soluble protein
    • 回收可溶性蛋白质的方法
    • US06861505B1
    • 2005-03-01
    • US09701005
    • 1999-05-17
    • Nobuo Shimamoto
    • Nobuo Shimamoto
    • C12N15/09C07K1/113C07K1/14C07K1/34C07K14/245C07K14/415C07K14/435C12P21/00C07K1/30
    • C07K1/34C07K1/145
    • The present invention relates in providing a process for recovering a soluble protein having a higher recovery rate by suppressing the aggregation of the protein when a denaturing agent is removed from the solubilization treatment solution containing a solubilized protein; and providing a process for removing a denaturing agent from the above solubilization treatment solution in which the aggregation of the protein is suppressed. In a process for recovering a soluble protein comprising the steps of removing a denaturing agent from a solubilization treatment solution prepared by solubilizing insoluble protein aggregates using the denaturing agent, the process of the present invention is characterized by subjecting the solubilization treatment solution to a treatment of removing the denaturing agent in the presence of a dihydric to tetrahydric, polyhydric alcohol at a concentration of 60 to 99% by volume, and thereafter diluting with a diluent solution the treatment solution obtained after the removal treatment. In a process for removing a denaturing agent from a solubilization treatment solution prepared by solubilizing insoluble protein aggregates using the denaturing agent, the process of the present invention is characterized by subjecting the solubilization treatment solution to a treatment of removing the denaturing agent in the presence of a dihydric to tetrahydric, polyhydric alcohol.
    • 本发明涉及提供当从含有溶解性蛋白质的增溶处理液中除去变性剂时,通过抑制蛋白质的聚集来回收具有较高回收率的可溶性蛋白质的方法; 提供从抑制蛋白质聚集的上述增溶处理液中除去变性剂的方法。 在回收可溶性蛋白质的方法中,包括以下步骤:从通过使用变性剂溶解不溶性蛋白质聚集体制备的增溶处理溶液中除去变性剂的步骤,其特征在于使溶解处理溶液经受 在二元至四元多元醇的存在下,以60〜99体积%的浓度除去变性剂,然后用稀释溶液稀释除去处理后得到的处理液。 在通过使用变性剂溶解不溶性蛋白质聚集体制备的增溶处理溶液中除去变性剂的方法中,本发明的方法的特征在于,使溶解处理溶液在存在下除去变性剂的处理 二元至四元多元醇。