CN1637405B - 生物芯片基体夹持方法 - Google Patents
生物芯片基体夹持方法 Download PDFInfo
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Abstract
在测量生物芯片时,其中基体夹持在底座上并且样品点样在基体上的一个阵列的位置上,通过将生物芯片基体分别以点样和测量的方式用等价的夹持机构夹持生物芯片基体,本发明提供了一种生物芯片基体夹持方法,其特征在于,生物芯片基体是通过以下方式被夹持的,即:通过使生物芯片基体的相邻两个侧边接触三个支柱,即以三点接触支撑基体,以及通过从相对的角部对基体施加压力,基体的其它两个侧边彼此相交在该角部;或者通过向垂直于两个侧边的每一边的两个方向施加压力,所述方法不产生在将多个样品排列在生物芯片上与将生物芯片安装到生物芯片阅读器上之间的位置定位的偏差,并且不需要定位对齐。本发明还提供使用所述方法的生物芯片阅读器。
Description
发明领域
本发明涉及一种生物芯片基体夹持方法,更具体地,涉及一种生物芯片基体夹持方法,其中生物芯片位点的位置具有很好的可重复性,以及涉及使用所述方法的生物芯片阅读器。
背景技术
传统生物芯片阅读器的设计是通过向每个生物芯片位点上的样品照射激发光,如激光,读出从样品中产生的荧光(例如,参见专利文献1)。
这些传统的生物芯片阅读器包括:扫描的类型(扫描型),使用其中布置有多个显微透镜的显微透镜阵列,并且在通过显微透镜后照射光束是扫描的;或者不使用扫描的非扫描的类型(非扫描型),或者不使用显微透镜阵列的类型。
在所有这些生物芯片阅读器中,用于生物芯片的基体(下面称为生物芯片基体或简单地称为基体),通常使用适于显微镜或类似设备的样品夹持器固定在底座上。图1表示上述样品夹持机构的一个例子。样品夹持器(如图1所示)装有载玻片支撑件2和旋转臂4,旋转臂4的安装,使其可以在底座1上通过连接器3转动,并且利用设置在连接器3中的螺旋弹簧(未图示)的作用力,将矩形载玻片(等价于生物芯片基体)5上彼此相邻两侧的端面5a和5b挤压在载玻片支撑件2上(例如,参见专利文献2)。
[专利文献1]
JP-A2003-028799
[专利文献2]
JP-A-10-39230
但是,传统样品夹持器存在如下缺点:
(1)由于样品夹持器的定位机构在生物芯片安装和拆卸时不充分,因此生物芯片位点的位置在x、y和/或z方向(x和y方向是垂直于光轴的方向,而z方向是光轴自身的方向)上偏离。这就需要在安装之后进行定位。
(2)在非扫描类型的情况下,显微透镜的位置与生物芯片位点偏离,因此需要对齐位置。
(3)即使样品夹持器不是非扫描型,也必须使用图案识别或类似的技术校正位置的偏离。
(4)对于生物芯片基体,由于它们的外形尺寸的精度不是非常高,它们的侧边不是直的,并且相邻两个侧边也不是彼此垂直,因此使用上述样品夹持器的载玻片支撑件2和旋转臂4定位不准确,并且可重复性差,造成不精确的定位。
(5)由于样品点样到生物芯片每个位点时生物芯片固定方案与样品夹持器中使用的生物芯片固定方案不同,在非扫描型的情况下,在位点6与相应的光束照射位置7之间产生偏离(在x、y和θ方向),如图2(a)所示。另外,θ表示生物芯片基体14的表面上形成的角度,与光轴正交。每个位点和相应的光束照射位置必须彼此一致,如图2(b)所示。
发明内容
本发明的目的是解决上述问题,从而提供一种生物芯片基体夹持方法,其中生物芯片基体是通过以下方式被夹持的,即:通过使生物芯片基体的相邻两个侧边接触三个支柱,即以三点接触支撑基体,以及通过从相对的角部对基体施加压力,基体的其它两个侧边彼此相交在该角部;或者通过向垂直于两个侧边的每一边的两个方向施加压力,它不造成测量过程中位点位置的偏离,从而不需要在将多个样品布置在生物芯片上时以及将生物芯片安装到生物芯片阅读器上时,通过使生物芯片基体夹持机构等同来进行位置对齐,并且提供一种使用所述方法的生物芯片阅读器。
附图说明
图1是表示传统样品夹持器的结构图;
图2是表示生物芯片的所处位置与相应光束照射位置之间关系的图;
图3是表示用于实现本发明生物芯片夹持方法的基体夹持机构一个实施例的结构图;
图4是本发明生物基体夹持机构的两个鸟瞰图;
图5是表示本发明生物芯片基体夹持机构的另一个实施例的图;以及
图6是本发明生物芯片基体夹持机构的另一个实施例的图。
具体实施方式
下面将参考附图详细描述本发明。图3是表示用于实现本发明生物芯片夹持方法的基体夹持机构一个实施例的结构图。
在图3中,标号10表示底座,标号11、12和13表示装在底座10上的支柱,标号14表示生物芯片基体(下面简称为“基体”),在其上面多个样品排列成阵列,标号15表示基体14上的位点,标号16表示加压装置。
支柱11到13固定在底座10上,从而装在底座10上的基体14的两个相邻侧边的端面接触这些支柱。这些支柱由圆的柱体或圆柱体(例如,销)形成,并且与基体14的侧面点接触。
当基体14接触这三个支柱时,加压装置16从非接触侧边的两个侧边互相交叉的角部,沿倾斜方向朝接触侧边施加压力。
在这种结构中,如果基体14的两个相邻侧边被压向支柱11到13,基体14总是以良好的可重复性装在底座10的预定位置上,而不会受到侧边的弯曲或者两个侧边之间角度的影响,因为基体14仅接触这三个点。
在这种情况下,如图4所示,无论在点样生物芯片样品(图4(a))还是在用阅读器测量(图4(b))过程中,都使用本质上相同的三点接触结构夹持基体。使用上述结构,消除了测量时在位点位置上产生的偏离。
并且,本发明不限于上述实施例,而是可以在不偏离本发明实质的情况下,以其它的具体形式、变化和变形实施。
例如,也可以通过加压装置16沿垂直于彼此正交的两个侧边的每一侧边的两个方向施加压力,如图5所示,而不是如上述实施例所述的沿倾斜方向加压.
并且,支柱11到13的外形不限于圆形,而可以是多边形,例如,图6所示的三角形。但是,它们的棱边必须以点接触方式接触生物芯片。
另外,DNA、RNA、蛋白质、糖链和生物代谢物(活体中除蛋白质以外的低分子物质)以及类似的物质可以用作样品。
并且,利用本发明的基体夹持机构夹持基体,将样品点样到生物芯片位点上,可以使用点样钉、喷墨、静电吸附以及类似的方法。
而且,作为夹持目标的基体可以是载玻片或药盒。
从上面的描述可以看出,本发明具有如下的效果:
(1)当样品点样在生物芯片基体上时,通过使阅读器的生物芯片基体夹持机构与夹持机构一致,在使用阅读器的测量过程中的位置偏差可以达到最低程度。
(2)不必执行位点位置对齐的调整以及基于传统阅读器中所需的图像而进行的图案匹配。
(3)由于生物芯片是由三个点支撑的,可以容易地得到好的支撑可重复性,而不会受到基体侧边的直线度以及两个侧边的正交性或者类似因素的影响。
(4)载玻片或合成树脂或药盒可以作为生物芯片基体。
Claims (2)
1.一种生物芯片基体夹持方法,其中,
当对通过将生物芯片基体夹持在底座上、并且将样品点样于在所述生物芯片基体上排成阵列的位点上而得到的生物芯片进行测量时,生物芯片基体在所述点样和所述测量中分别被等价的夹持机构夹持,
其特征在于,所述生物芯片基体是通过以下方式被夹持的,即:
通过使所述生物芯片基体的相邻两个侧边接触三个支柱,即以三点接触支撑所述基体,以及
通过从相对的角部对所述基体施加压力,所述基体的其它两个侧边彼此相交在该角部;或者通过向垂直于所述两个侧边的每一边的两个方向施加压力。
2.如权利要求1所述的生物芯片基体夹持方法,其中,
所述点样是通过点样钉、喷墨或静电吸附来实现。
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JP2003424539 | 2003-12-22 | ||
JP2003424539A JP4370900B2 (ja) | 2003-12-22 | 2003-12-22 | バイオチップ基板保持方法およびバイオチップ読取装置 |
JP2003-424539 | 2003-12-22 |
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CN1637405A CN1637405A (zh) | 2005-07-13 |
CN1637405B true CN1637405B (zh) | 2010-05-12 |
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US (2) | US20050136533A1 (zh) |
JP (1) | JP4370900B2 (zh) |
CN (1) | CN1637405B (zh) |
DE (1) | DE102004045133A1 (zh) |
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KR101059565B1 (ko) | 2009-02-11 | 2011-08-26 | 어플라이드 프레시젼, 인코포레이티드 | 밝은 기준점 표지를 갖는 마이크로어레이 및 그로부터 광 데이터를 수집하는 방법 |
CN103878038B (zh) * | 2012-12-19 | 2015-09-09 | 中国科学院大连化学物理研究所 | 一种通用型微流控芯片夹具 |
CN103013823B (zh) * | 2012-12-26 | 2014-05-07 | 中国人民解放军第三军医大学第三附属医院 | 多功能组织细胞体视学定量分析玻片系统 |
CN103278618A (zh) * | 2013-05-09 | 2013-09-04 | 董建国 | 一种生物芯片信息读取装置及信息分析方法 |
JP2014226055A (ja) * | 2013-05-20 | 2014-12-08 | 株式会社ニコン | 検出方法、検出装置、スクリーニング方法、スクリーニング装置、及びバイオチップ |
RU2727554C2 (ru) | 2015-12-23 | 2020-07-22 | Конинклейке Филипс Н.В. | Флуоресцентный калибровочный слайд |
EP3385771B1 (de) | 2017-04-05 | 2023-10-25 | Leica Mikrosysteme GmbH | Haltevorrichtung für probenträger und verfahren zum ein- und ausbringen eines probenträgers |
JP2018049034A (ja) * | 2017-12-18 | 2018-03-29 | 株式会社ニコン | 検出方法、検出装置、スクリーニング方法、スクリーニング装置、及びバイオチップ |
EP3703861B1 (en) | 2018-01-26 | 2024-05-22 | Hewlett-Packard Development Company, L.P. | Dispenser stages |
CN110031961B (zh) * | 2019-04-08 | 2023-08-01 | 上海健康医学院 | 显微镜双向移动载玻片平台 |
KR102242330B1 (ko) * | 2019-12-16 | 2021-04-20 | 재단법인 오송첨단의료산업진흥재단 | 바이오칩을 포함한 측정시스템 |
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- 2003-12-22 JP JP2003424539A patent/JP4370900B2/ja not_active Expired - Lifetime
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2004
- 2004-08-30 US US10/928,184 patent/US20050136533A1/en not_active Abandoned
- 2004-09-17 DE DE102004045133A patent/DE102004045133A1/de not_active Withdrawn
- 2004-11-15 CN CN2004100908291A patent/CN1637405B/zh not_active Expired - Fee Related
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CN2157524Y (zh) * | 1993-05-18 | 1994-02-23 | 何虹彩 | 袖珍显微镜 |
US20030199097A1 (en) * | 1999-04-16 | 2003-10-23 | Tomohiro Suzuki | Substrate measuring method and device |
CN1335504A (zh) * | 2001-03-28 | 2002-02-13 | 上海晶泰生物技术有限公司 | 用于免疫学分析的蛋白质芯片 |
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US20070122834A1 (en) | 2007-05-31 |
JP4370900B2 (ja) | 2009-11-25 |
JP2005181181A (ja) | 2005-07-07 |
DE102004045133A1 (de) | 2005-07-21 |
US20050136533A1 (en) | 2005-06-23 |
CN1637405A (zh) | 2005-07-13 |
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