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    • 1. 发明授权
    • Methods and devices for micro-isolation, extraction, and/or analysis of microscale components
    • 微量元件的微分离,提取和/或分析的方法和装置
    • US08889416B2
    • 2014-11-18
    • US13010761
    • 2011-01-20
    • Emil P. KartalovDarryl ShibataClive TaylorLawrence A. Wade
    • Emil P. KartalovDarryl ShibataClive TaylorLawrence A. Wade
    • C12N5/02C12N5/00C12M1/34C12N13/00G01N33/543
    • C12M23/16C12M23/12C12M23/22C12M25/04C12M25/14C12M35/02C12M37/04C12M47/04C12N13/00G01N33/54366
    • Provided herein are devices and methods for the micro-isolation of biological cellular material. A micro-isolation apparatus described can comprise a photomask that protects regions of interest against DNA-destroying illumination. The micro-isolation apparatus can further comprise photosensitive material defining access wells following illumination and subsequent developing of the photosensitive material. The micro-isolation apparatus can further comprise a chambered microfluidic device comprising channels providing access to wells defined in photosensitive material. The micro-isolation apparatus can comprise a chambered microfluidic device without access wells defined in photosensitive material where valves control the flow of gases or liquids through the channels of the microfluidic device. Also included are methods for selectively isolating cellular material using the apparatuses described herein, as are methods for biochemical analysis of individual regions of interest of cellular material using the devices described herein. Further included are methods of making masking arrays useful for the methods described herein.
    • 本文提供用于微生物细胞材料的微分离的装置和方法。 所描述的微分离装置可以包括保护感兴趣区域以防止DNA破坏照明的光掩模。 微型隔离装置还可以包括感光材料,该感光材料在照射之后界定存取孔,随后显影感光材料。 微隔离装置还可以包括腔室微流体装置,其包括通道,其提供对感光材料中限定的孔的通路。 微型隔离装置可以包括腔室微流体装置,其无感光材料中限定的通路孔,阀门通过微流体装置的通道控制气体或液体的流动。 还包括使用本文所述装置选择性分离细胞材料的方法,以及使用本文所述装置的细胞材料的各个感兴趣区域的生物化学分析的方法。 还包括制备用于本文所述方法的掩蔽阵列的方法。
    • 2. 发明申请
    • METHODS AND DEVICES FOR MICRO-ISOLATION, EXTRACTION, AND/OR ANALYSIS OF MICROSCALE COMPONENTS
    • MICROSCALE组件的微分离,提取和/或分析的方法和设备
    • US20110177518A1
    • 2011-07-21
    • US13010761
    • 2011-01-20
    • Emil P. KartalovDarryl ShibataClive TaylorLawrence A. Wade
    • Emil P. KartalovDarryl ShibataClive TaylorLawrence A. Wade
    • C12Q1/68C12M1/00C12N13/00C12Q1/02G01N33/53G03F7/20
    • C12M23/16C12M23/12C12M23/22C12M25/04C12M25/14C12M35/02C12M37/04C12M47/04C12N13/00G01N33/54366
    • Provided herein are devices and methods for the micro-isolation of biological cellular material. A micro-isolation apparatus described can comprise a photomask that protects regions of interest against DNA-destroying illumination. The micro-isolation apparatus can further comprise photosensitive material defining access wells following illumination and subsequent developing of the photosensitive material. The micro-isolation apparatus can further comprise a chambered microfluidic device comprising channels providing access to wells defined in photosensitive material. The micro-isolation apparatus can comprise a chambered microfluidic device without access wells defined in photosensitive material where valves control the flow of gases or liquids through the channels of the microfluidic device. Also included are methods for selectively isolating cellular material using the apparatuses described herein, as are methods for biochemical analysis of individual regions of interest of cellular material using the devices described herein. Further included are methods of making masking arrays useful for the methods described herein.
    • 本文提供用于微生物细胞材料的微分离的装置和方法。 所描述的微分离装置可以包括保护感兴趣区域以防止DNA破坏照明的光掩模。 微型隔离装置还可以包括感光材料,该感光材料在照射之后界定存取孔,随后显影感光材料。 微隔离装置还可以包括腔室微流体装置,其包括通道,其提供对感光材料中限定的孔的通路。 微型隔离装置可以包括腔室微流体装置,其无感光材料中限定的通路孔,阀门通过微流体装置的通道控制气体或液体的流动。 还包括使用本文所述的装置选择性分离细胞材料的方法,以及使用本文所述的装置的细胞材料的各个感兴趣区域的生物化学分析的方法。 还包括制备用于本文所述方法的掩蔽阵列的方法。
    • 3. 发明授权
    • Selective functionalization of carbon nanotube tips allowing fabrication of new classes of nanoscale sensing and manipulation tools
    • 碳纳米管尖端的选择性功能化,允许制造新类型的纳米级感测和操作工具
    • US07514214B2
    • 2009-04-07
    • US10783713
    • 2004-02-20
    • Lawrence A. WadeIan R. ShapiroCharles Patrick CollierMaria J. EsplandiuVern Garrett Bittner, Jr.Konstantinos P. Giapis
    • Lawrence A. WadeIan R. ShapiroCharles Patrick CollierMaria J. EsplandiuVern Garrett Bittner, Jr.Konstantinos P. Giapis
    • C12Q1/68
    • G01Q70/12
    • Embodiments in accordance with the present invention relate to techniques for the growth and attachment of single wall carbon nanotubes (SWNT), facilitating their use as robust and well-characterized tools for AFM imaging and other applications. In accordance with one embodiment, SWNTs attached to an AFM tip can function as a structural scaffold for nanoscale device fabrication on a scanning probe. Such a probe can trigger, with nanometer precision, specific biochemical reactions or conformational changes in biological systems. The consequences of such triggering can be observed in real time by single-molecule fluorescence, electrical, and/or AFM sensing. Specific embodiments in accordance with the present invention utilize sensing and manipulation of individual molecules with carbon nanotubes, coupled with single-molecule fluorescence imaging, to allow observation of spectroscopic signals in response to mechanically induced molecular changes. Biological macromolecules such as proteins or DNA can be attached to nanotubes to create highly specific single-molecule probes for investigations of intermolecular dynamics, for assembling hybrid biological and nanoscale materials, or for developing molecular electronics. In one example, electrical wiring of single redox enzymes to carbon nanotube scanning probes allows observation and electrochemical control over single enzymatic reactions by monitoring fluorescence from a redox-active cofactor or the formation of fluorescent products. Enzymes “nanowired” to the tips of carbon nanotubes in accordance with embodiments of the present invention, may enable extremely sensitive probing of biological stimulus-response with high spatial resolution, including product-induced signal transduction.
    • 根据本发明的实施方案涉及用于生长和附着单壁碳纳米管(SWNT)的技术,便于将其用作用于AFM成像和其它应用的鲁棒且良好表征的工具。 根据一个实施例,附接到AFM尖端的SWNT可以用作扫描探针上的纳米级器件制造的结构支架。 这样的探针可以以纳米精度触发生物系统中的特定生化反应或构象变化。 这种触发的后果可以通过单分子荧光,电学和/或AFM感测实时观察。 根据本发明的具体实施方案利用与单分子荧光成像耦合的碳纳米管的单个分子的感测和操纵,以便响应于机械诱导的分子变化观察光谱信号。 生物大分子如蛋白质或DNA可以连接到纳米管上,以产生用于分子间动力学研究的高度特异性单分子探针,用于组装混合生物和纳米级材料,或用于开发分子电子学。 在一个实例中,单个氧化还原酶与碳纳米管扫描探针的电气配线允许通过监测来自氧化还原活性辅助因子的荧光或荧光产物的形成来观察和电化学控制单个酶反应。 根据本发明的实施方案,“纳米线”纳米线对碳纳米管的尖端可以实现具有高空间分辨率(包括产物诱导的信号转导)的生物刺激反应的极度敏感的探测。
    • 4. 发明授权
    • Biomarker sensors and method for multi-color imaging and processing of single-molecule life signatures
    • 生物标记传感器和多色成像和处理单分子生命特征的方法
    • US08492160B1
    • 2013-07-23
    • US12720103
    • 2010-03-09
    • Lawrence A. WadeCharles Patrick Collier
    • Lawrence A. WadeCharles Patrick Collier
    • G01N1/28C12N13/00
    • G01Q60/42G01Q80/00
    • The invention is a device including array of aciive regions for use in reacting one or more species in at least two of the active regions in a sequential process, e.g., sequential reactions. The device has a transparent substrate member, which has a surface region and a silane material overlying the surface region. A first active region overlies a first portion of the silane material. The first region has a first dimension of less than 1 micron in size and has first molecules capable of binding to the first portion of the silane material. A second active region overlies a second portion of the silane material. The second region has a second dimension of less than 1 micron in size, second molecules capable of binding to the second portion of the active region, and a spatial distance separates the first active region and the second active region.
    • 本发明是一种装置,其包括用于在顺序过程(例如顺序反应)中使至少两个活性区域中的一种或多种物质反应的活性区域的阵列。 该装置具有透明基板部件,该基板部件具有覆盖在表面区域上的表面区域和硅烷材料。 第一活性区域覆盖硅烷材料的第一部分。 第一区域具有尺寸小于1微米的第一尺寸,并且具有能够结合硅烷材料的第一部分的第一分子。 第二活性区域覆盖硅烷材料的第二部分。 第二区域具有尺寸小于1微米的第二尺寸,能够结合有源区域的第二部分的第二分子,以及空间距离分离第一有源区域和第二有源区域。
    • 5. 发明授权
    • Method for nanoscale spatial registration of scanning probes with substrates and surfaces
    • 扫描探针与衬底和表面的纳米级空间配准方法
    • US07808628B1
    • 2010-10-05
    • US11472596
    • 2006-06-21
    • Lawrence A. Wade
    • Lawrence A. Wade
    • G01B11/26
    • G01Q40/00G01Q80/00G03F7/0002
    • Embodiments in accordance with the present invention relate to methods and apparatuses for aligning a scanning probe used to pattern a substrate, by comparing the position of the probe to a reference location or spot on the substrate. A first light beam is focused on a surface of the substrate as a spatial reference point. A second light beam then illuminates the scanning probe being used for patterning. An optical microscope images both the focused light beam, and a diffraction pattern, shadow, or light backscattered by the illuminated scanning probe tip of a scanning probe microscope (SPM), which is typically the tip of the scanning probe on an atomic force microscope (AFM). Alignment of the scanning probe tip relative to the mark is then determined by visual observation of the microscope image. This alignment process may be repeated to allow for modification or changing of the scanning probe microscope tip.
    • 根据本发明的实施例涉及通过将探针的位置与衬底上的参考位置或点对比来对准用于图案化衬底的扫描探针的方法和装置。 第一光束作为空间参考点聚焦在基板的表面上。 然后第二光束照射用于图案化的扫描探针。 光学显微镜对聚焦光束以及由扫描探针显微镜(SPM)的照射扫描探针尖端反向散射的衍射图案,阴影或光进行成像,扫描探针显微镜(SPM)通常是原子力显微镜上的扫描探针的尖端( AFM)。 然后通过目视观察显微镜图像来确定扫描探针尖端相对于标记的对准。 可以重复该对准过程以允许修改或改变扫描探针显微镜尖端。