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1. 发明授权

US06998228B2 Method and apparatus for solid state molecular analysis 失效
公开(公告)号：US06998228B2
公开(公告)日：2006-02-14
申请号：US10179102
申请日：2002-06-25
申请人： Eric Henderson , Curtis Mosher , Michael P. Lynch
发明人： Eric Henderson , Curtis Mosher , Michael P. Lynch
IPC分类号： C12Q1/68
CPC分类号： G01N33/543 , C12Q1/6834 , C12Q1/6837 , Y10S977/853 , Y10S977/858 , C12Q2565/601 , C12Q2565/501
摘要： The invention is a method for the formation and analysis of novel miniature deposition domains. These deposition domains are placed on a surface to form a molecular array. The molecular array is scanned with an AFM to analyze molecular recognition events and the effect of introduced agents on defined molecular interactions. This approach can be carried out in a high throughput format, allowing rapid screening of thousands of molecular species in a solid state array. The procedures described here have the added benefit of allowing the measurement of changes in molecular binding events resulting from changes in the analysis environment or introduction of additional effector molecules to the assay system. The processes described herein are extremely useful in the search for compounds such as new drugs for treatment of undesirable physiological conditions. The method and apparatus of the present invention does not require the labeling of the deposition material or the target sample and may also be used to deposit large size molecules without harming the same.

2. 发明授权

US06897015B2 Device and method of use for detection and characterization of pathogens and biological materials 失效
标题翻译：用于检测和表征病原体和生物材料的装置和方法
公开(公告)号：US06897015B2
公开(公告)日：2005-05-24
申请号：US10160372
申请日：2002-05-30
申请人： Eric R. Henderson , Saju R. Nettikadan , Curtis L. Mosher
发明人： Eric R. Henderson , Saju R. Nettikadan , Curtis L. Mosher
IPC分类号： B05D3/00 , C12Q1/02 , C12Q1/68 , C12Q1/70 , G01N33/552 , G01N33/553 , G01N33/554 , G01N33/569 , G01Q10/00 , G01Q30/20 , G01Q60/34 , G02B26/10
CPC分类号： G01N33/553 , G01N33/56983 , G01N2333/07 , Y10S977/853
摘要： The present invention includes a method and apparatus for the detection of a target material. The method and apparatus includes providing a substrate with a surface and forming a domains of deposited materials thereon. The deposited material can be placed on the surface and bound directly and non-specifically to the surface, or it may be specifically or non-specifically bound to the surface. The deposited material has an affinity for a specific target material. The domains thus created are termed affinity domains or deposition domains. Multiple affinity domains of deposited materials can be deposited on a single surface, creating a plurality of specific binding affinity domains for a plurality of target materials. Target materials may include, for example, pathogens or pathogenic markers such as viruses, bacteria, bacterial spores, parasites, prions, fungi, mold or pollen spores. The device thus created is incubated with a test solution, gas or other supporting environment suspected of containing one or more of the target materials. Specific binding interactions between the target materials and a particular affinity domain occurs and is detected by various methods.
摘要翻译：本发明包括用于检测目标材料的方法和装置。该方法和装置包括提供具有表面的基底并在其上形成沉积材料的区域。沉积的材料可以放置在表面上并且非特异性地结合到表面上，或者可以特异性地或非特异性地结合到表面上。沉积材料对特定靶材料具有亲和力。由此产生的结构域称为亲和结构域或沉积域。沉积材料的多个亲和性结构域可以沉积在单个表面上，为多个目标材料产生多个特异性结合亲和结构域。靶物质可包括例如病原体或致病性标志物，例如病毒，细菌，细菌孢子，寄生虫，朊病毒，真菌，霉菌或花粉孢子。将如此产生的装置与怀疑含有一种或多种目标材料的测试溶液，气体或其它支持环境一起温育。目标材料与特定亲和力域之间的特异性结合相互作用发生并通过各种方法检测。

3. 发明授权

US06800913B2 Hybrid Hall vector magnetometer 失效
标题翻译：混合霍尔矢量磁强计
公开(公告)号：US06800913B2
公开(公告)日：2004-10-05
申请号：US10287876
申请日：2002-11-04
申请人： Mark B. Johnson , Michael Miller , Brian Bennett
发明人： Mark B. Johnson , Michael Miller , Brian Bennett
IPC分类号： H01L2982
CPC分类号： G01R33/07 , Y10S977/853 , Y10S977/865
摘要： A modified hybrid Hall effect device is provided which is the combination of a conventional Hall effect device and a second Hall effect device having a Hall plate coupled to a ferromagnetic layer. The hybrid Hall effect device can be used to determine the independent magnetic field vector components comprising a vector magnetic field, such as for determining the {circumflex over (x)} and the {circumflex over (z)} components of a magnetic field, or for measuring the total magnitude of a vector magnetic field of any orientation. The modified Hall Effect device can be adapted for use as a magnetic field sensor for the detection of macroscopic objects that have associated magnetic fields, or for microscopic objects that have been tagged by microscopic magnetic particles. In one specific form, a plurality of hybrid Hall devices are electrically connected together to form an array in which a plurality of rows of hybrid Hall devices are electrically coupled to each other along a current axis, and the array is used for the detection of microscopic objects.
摘要翻译：提供了一种改进的混合霍尔效应装置，它是常规霍尔效应装置和具有耦合到铁磁层的霍尔板的第二霍尔效应装置的组合。可以使用混合霍尔效应装置来确定包括矢量磁场的独立磁场矢量分量，例如用于确定磁场的x和z分量，或用于测量任意的矢量磁场的总大小方向。修改的霍尔效应装置可以适用于用于检测具有相关磁场的宏观物体的磁场传感器，或用于由微观磁性颗粒标记的微观物体。在一个具体形式中，多个混合霍尔器件电连接在一起以形成阵列，其中多行混合霍尔器件沿着电流轴彼此电耦合，并且该阵列用于微观检测对象

4. 发明申请

US20030013111A1 Method and apparatus for solid state molecular analysis 失效
公开(公告)号：US20030013111A1
公开(公告)日：2003-01-16
申请号：US10179102
申请日：2002-06-25
发明人： Eric Henderson , Curtis Mosher , Michael P. Lynch
IPC分类号： C12Q001/68 , C12M001/34 , B05D003/00
CPC分类号： G01N33/543 , C12Q1/6834 , C12Q1/6837 , Y10S977/853 , Y10S977/858 , C12Q2565/601 , C12Q2565/501
摘要： The invention is a method for the formation and analysis of novel miniature deposition domains. These deposition domains are placed on a surface to form a molecular array. The molecular array is scanned with an AFM to analyze molecular recognition events and the effect of introduced agents on defined molecular interactions. This approach can be carried out in a high throughput format, allowing rapid screening of thousands of molecular species in a solid state array. The procedures described here have the added benefit of allowing the measurement of changes in molecular binding events resulting from changes in the analysis environment or introduction of additional effector molecules to the assay system. The processes described herein are extremely useful in the search for compounds such as new drugs for treatment of undesirable physiological conditions. The method and apparatus of the present invention does not require the labeling of the deposition material or the target sample and may also be used to deposit large size molecules without harming the same.

5. 发明申请

US20020172943A1 Device and method of use for detection and characterization of pathogens and biological materials 失效
标题翻译：用于检测和表征病原体和生物材料的装置和方法
公开(公告)号：US20020172943A1
公开(公告)日：2002-11-21
申请号：US10160372
申请日：2002-05-30
发明人： Eric R. Henderson , Saju R. Nettikadan , Curtis L. Mosher
IPC分类号： C12Q001/70 , G01N033/554 , G01N033/569 , B05D003/00
CPC分类号： G01N33/553 , G01N33/56983 , G01N2333/07 , Y10S977/853
摘要： The present invention includes a method and apparatus for the detection of a target material. The method and apparatus includes providing a substrate with a surface and forming a domains of deposited materials thereon. The deposited material can be placed on the surface and bound directly and non-specifically to the surface, or it may be specifically or non-specifically bound to the surface. The deposited material has an affinity for a specific target material. The domains thus created are termed affinity domains or deposition domains. Multiple affinity domains of deposited materials can be deposited on a single surface, creating a plurality of specific binding affinity domains for a plurality of target materials. Target materials may include, for example, pathogens or pathogenic markers such as viruses, bacteria, bacterial spores, parasites, prions, fungi, mold or pollen spores. The device thus created is incubated with a test solution, gas or other supporting environment suspected of containing one or more of the target materials. Specific binding interactions between the target materials and a particular affinity domain occurs and is detected by various methods.
摘要翻译：本发明包括用于检测目标材料的方法和装置。该方法和装置包括提供具有表面的基底并在其上形成沉积材料的区域。沉积的材料可以放置在表面上并且非特异性地结合到表面上，或者可以特异性地或非特异性地结合到表面上。沉积材料对特定靶材料具有亲和力。由此产生的结构域称为亲和结构域或沉积域。沉积材料的多个亲和性结构域可以沉积在单个表面上，为多个目标材料产生多个特异性结合亲和结构域。靶物质可包括例如病原体或致病性标志物，例如病毒，细菌，细菌孢子，寄生虫，朊病毒，真菌，霉菌或花粉孢子。将如此产生的装置与怀疑含有一种或多种目标材料的测试溶液，气体或其它支持环境一起温育。目标材料与特定亲和力域之间的特异性结合相互作用发生并通过各种方法检测。

6. 发明申请

US20020034757A1 Single-molecule selection methods and compositions therefrom 失效
标题翻译：单分子选择方法及其组合物
公开(公告)号：US20020034757A1
公开(公告)日：2002-03-21
申请号：US09907385
申请日：2001-07-17
发明人： Roger S. Cubicciotti
IPC分类号： C12Q001/68 , C07H019/00 , C07H021/00 , C07H021/02 , C07H021/04 , C12P019/34
CPC分类号： C07H21/00 , Y10S977/853
摘要： Single-molecule selection methods are provided for identifying target-binding molecules from diverse sequence and shape libraries. Complexes and imprints of selected target-binding molecules are also provided. The subject selection methods are used to identify oligonucleotide and nonnucleotide molecules with desirable properties for use in pharmaceuticals, drug discovery, drug delivery, diagnostics, medical devices, cosmetics, agriculture, environmental remediation, smart materials, packaging, microelectronics and nanofabrication. Single oligonucleotide molecules with desirable binding properties are selected from diverse sequence libraries and identified by amplification and sequencing. Alternatively, selected oligonucleotide molecules are identified by sequencing without amplification. Nonnucleotide molecules with desirable properties are identified by single-molecule selection from libraries of conjugated molecules or nucleotide-encoded nonnucleotide molecules. Alternatively, target-specific nonnucleotide molecules are prepared by imprinting selected oligonucleotide molecules into nonnucleotide molecular media. Complexes and imprints of molecules identified by single-molecule selection are shown to have broad utility as drugs, prodrugs, drug delivery systems, willfully reversible cosmetics, diagnostic reagents, sensors, transducers, actuators, adhesives, adherents and novel multimolecular devices.
摘要翻译：提供单分子选择方法用于鉴定来自不同序列和形状文库的靶结合分子。还提供了选择的靶结合分子的复合物和印迹。主题选择方法用于鉴定具有期望性质的寡核苷酸和非核苷酸分子，用于药物，药物发现，药物递送，诊断，医疗器械，化妆品，农业，环境修复，智能材料，包装，微电子学和纳米制造。具有所需结合特性的单寡核苷酸分子选自不同的序列文库，并通过扩增和测序鉴定。或者，选择的寡核苷酸分子通过无扩增的测序鉴定。具有所需性质的非核苷酸分子通过共轭分子文库或核苷酸编码的非核苷酸分子的单分子选择来鉴定。或者，通过将所选择的寡核苷酸分子印记到非核苷酸分子介质中来制备靶特异性非核苷酸分子。通过单分子选择鉴定的分子的复合物和印迹显示出作为药物，前药，药物递送系统，故意可逆化妆品，诊断试剂，传感器，换能器，致动器，粘合剂，附着物和新型多分子装置具有广泛的用途。

7. 发明授权

US5874726A Probe-type near-field confocal having feedback for adjusting probe distance 失效
标题翻译：探头型近场共聚焦显微镜具有调整探头距离的反馈
公开(公告)号：US5874726A
公开(公告)日：1999-02-23
申请号：US731093
申请日：1996-10-09
申请人： Philip G. Haydon
发明人： Philip G. Haydon
IPC分类号： G01Q60/18 , G02B21/00 , G01J1/20 , G01N21/64
CPC分类号： G01Q60/22 , B82Y20/00 , B82Y35/00 , G01Q10/065 , G02B21/0072 , G02B21/0076 , Y10S977/853 , Y10S977/862
摘要： A method and apparatus for achieving optical microscopic images and monitoring metabolic processes of living biological specimens such as cells at a resolution superior to the diffraction limit is disclosed. A primary difficulty in performing near-field scanning optical microscopy of living cells, e.g., determining the separation between the cell surface and the illuminating probe tip, is overcome by using a photon-density feedback method in which a fluorescent dye signal strength is monitored in the cell as the tip is brought to the cell surface, and registering a maximum value, at which point the tip begins to dimple the cell surface and can get no closer to the dye. Thereafter the tip is either maintained in contact with the membrane for point measurements of metabolic processes or is withdrawn a selected distance from the surface as measured against a corresponding decrease in the fluorescent dye signal strength The signal strength serves as a photon-density feedback for maintaining the probe tip at a constant elevation above the cell surface as scanning is performed or time-series measurements of metabolism are recorded. Advantageously, the apparatus also combines confocal means in the form of a pin-hole or the like for high-fidelity light detection in three dimensions from the cell surface in the near-field of the probe tip.
摘要翻译：公开了一种用于实现光学显微镜图像和监测活体生物样品例如细胞的分辨率高于衍射极限的分辨率的方法和装置。通过使用其中监测荧光染料信号强度的光子密度反馈方法克服了执行活细胞的近场扫描光学显微镜（例如，确定细胞表面和照射探针尖端之间的分离）的主要困难，将细胞作为尖端被带到细胞表面，并记录最大值，此时尖端开始使细胞表面凹陷并且不会更接近染料。此后，尖端保持与膜接触，用于代谢过程的点测量，或者相对于荧光染料信号强度的相应降低测量，从表面取出选定距离。信号强度用作维持光子密度反馈在进行扫描时进行细胞表面上方恒定高度的探针尖端或代谢的时间序列测量。有利地，该装置还结合了针孔等形式的共焦装置，用于从探针尖端的近场中的细胞表面三维地进行高保真光检测。

8. 发明授权

US5763768A Analytical method using modified scanning probes 失效
标题翻译：使用修改扫描探针的分析方法
公开(公告)号：US5763768A
公开(公告)日：1998-06-09
申请号：US819667
申请日：1997-03-17
申请人： Eric R. Henderson , Curtis L. Mosher , Vivian Wynne Jones , John-Bruce D. Green , Marc D. Porter
发明人： Eric R. Henderson , Curtis L. Mosher , Vivian Wynne Jones , John-Bruce D. Green , Marc D. Porter
IPC分类号： G01B21/30 , G01N33/543 , G01Q60/42 , G01B5/28 , G01N33/50
CPC分类号： G01Q60/42 , B82Y35/00 , G01N33/54373 , Y10S977/853
摘要： The present invention provides a method of analyzing for a specific material in a sample using a sensor including a resonating member having resonating properties. The resonating member has a probe and a known material is disposed on or forms the probe. The method includes the steps of positioning the sensor proximate to the sample, detecting a force dependent change in the resonance properties of the sensor, and confirming the presence of the specific material based on the identity of the known material and the detection of a resonance change.
摘要翻译：本发明提供一种使用包括具有谐振特性的谐振构件的传感器来分析样品中的特定材料的方法。谐振构件具有探针，已知材料设置在探针上或形成探针。该方法包括以下步骤：将传感器定位在样品附近，检测传感器的共振性质中的力相关变化，以及基于已知材料的身份和谐振变化的检测来确认特定材料的存在。

9. 发明授权

US5660990A Surface immobilization of magnetically collected materials 失效
标题翻译：磁性收集材料的表面固定
公开(公告)号：US5660990A
公开(公告)日：1997-08-26
申请号：US516694
申请日：1995-08-18
申请人： Galla Chandra Rao , Paul A. Liberti
发明人： Galla Chandra Rao , Paul A. Liberti
IPC分类号： C12Q1/68 , G01N33/543 , C12Q1/70 , G01N33/53
CPC分类号： C12Q1/6813 , C12Q1/6834 , G01N33/54313 , Y10S436/807 , Y10S436/824 , Y10S977/838 , Y10S977/853 , Y10S977/918 , Y10S977/958 , Y10S977/96
摘要： A method for determining the presence and/or concentration of a target substance e.g. protein, nucleic acid, bioparticle etc. in a fluid sample is provided. The method disclosed combines elements of immunoassays, coated cup assays and magnetic particle separation to effect the quantitation and recovery of an analyte in solution. Also the method ensures the non-reorientation of magnetically collected material by linking the magnetic particles to a collection surface via a specific binding pair. This linkage immobilizes the magnetic-analyte-containing material and thus allows for vigorous washing and reagent addition without significant redistribution or displacement. Thus the assay of this invention offers the speed of diffusion controlled kinetics as in a ferrofluid assay, the speed of collection of labeled target substance as in a magnetic assay as well as the ability to magnetically monolayer the ferrofluid, all of which is combined with the ease of washing and signal detection found in a coated cup assay.
摘要翻译：用于确定靶物质的存在和/或浓度的方法，例如，提供了流体样品中的蛋白质，核酸，生物颗粒等。所公开的方法组合了免疫测定，涂覆杯测定和磁性颗粒分离的元件，以实现溶液中分析物的定量和回收。此外，该方法通过经由特异性结合对将磁性颗粒连接到收集表面来确保磁性收集材料的非重新取向。该连接固定了含有磁性分析物的材料，从而允许剧烈的洗涤和试剂添加，而不会有显着的再分配或位移。因此，本发明的测定提供了如铁磁流体测定中的扩散控制动力学速度，如在磁性测定中收集标记的靶物质的速度以及磁性单层铁磁流体的能力，所有这些都与在涂层杯测定中发现易洗涤和信号检测。

10. 发明授权

US5609744A Assembly suitable for identifying a code sequence of a biomolecule in a gel embodiment 失效
标题翻译：适合于在凝胶实施例中识别生物分子的代码序列的装配
公开(公告)号：US5609744A
公开(公告)日：1997-03-11
申请号：US405481
申请日：1995-03-16
申请人： Frederic Zenharusern , Hemantha K. Wickramasinghe
发明人： Frederic Zenharusern , Hemantha K. Wickramasinghe
IPC分类号： G01N27/447 , G01Q60/18 , B01D61/42 , C12M3/00
CPC分类号： G01Q60/22 , B82Y20/00 , B82Y35/00 , Y10S977/853
摘要： An assembly suitable for identifying a code sequence of at least a portion of a biomolecule in a gel embodiment. The assembly comprises first means for migrating and separating a portion of a biomolecule in a gel; second means comprising a near-field probe for generating a super-resolution chemical analysis of a portion of a biomolecule; and, third means for correlating the super-resolution chemical analysis of the portion of the biomolecule with a broad spectral content of a referent biomolecule, for generating a code sequencing of the portion of the biomolecule.
摘要翻译：一种适于识别凝胶实施方案中生物分子的至少一部分的编码序列的组合体。组件包括用于迁移和分离凝胶中生物分子的一部分的第一装置; 第二装置包括用于产生生物分子的一部分的超分辨率化学分析的近场探针; 以及用于将生物分子部分的超分辨率化学分析与参照生物分子的宽光谱含量相关联的第三装置，用于产生该部分生物分子的编码测序。

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