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1.发明授权High-throughput, dual probe biological assays based on single molecule detection 失效基于单分子检测的高通量双探针生物测定公开(公告)号：US07076092B2
公开(公告)日：2006-07-11
申请号：US10170876
申请日：2002-06-12
申请人： Christopher W. Hollars , Thomas R. Huser , Stephen M. Lane , Rodney L. Balhorn , Olgica Bakajin , Christopher Darrow , Joe H. Satcher, Jr.
发明人： Christopher W. Hollars , Thomas R. Huser , Stephen M. Lane , Rodney L. Balhorn , Olgica Bakajin , Christopher Darrow , Joe H. Satcher, Jr.
IPC分类号： G06K9/00
CPC分类号： G06K9/00127 , B01L3/5027 , G01N21/6428 , G01N21/6456 , G01N33/54353 , G01N33/582 , G01N2021/058 , G01N2021/6421 , G01N2021/6432 , G01N2021/6441
摘要： A method and apparatus with the sensitivity to detect and identify single target molecules through the localization of dual, fluorescently labeled probe molecules. This can be accomplished through specific attachment of the taget to a surface or in a two-dimensional (2D) flowing fluid sheet having approximate dimensions of 0.5 μm×100 μm×100 μm. A device using these methods would have 103–104 greater throughput than previous one-dimensional (1D) micro-stream devices having 1 μm3 interrogation volumes and would for the first time allow immuno- and DNA assays at ultra-low (femtomolar) concentrations to be performed in short time periods (˜10 minutes). The use of novel labels (such as metal or semiconductor nanoparticles) may be incorporated to further extend the sensitivity possibly into the attomolar range.
摘要翻译： 通过双重荧光标记的探针分子的定位，灵敏度检测和识别单个靶分子的方法和装置。 这可以通过将标签特定附着到具有约0.5mum×100mum×100mum的大小的表面或二维（2D）流动流体片材中来实现。 使用这些方法的装置将具有比具有1mum 3以上的一维（1D）微流装置更高的产量10％以上。 >询问体积，并将首次允许在短时间（〜10分钟）内进行超低（飞摩尔）浓度的免疫和DNA测定。 可以引入新的标记（例如金属或半导体纳米颗粒）的使用以进一步将灵敏度扩展到极限范围内。
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2.发明授权Nanosensors based on functionalized nanoparticles and surface enhanced raman scattering 有权基于官能化纳米粒子和表面增强拉曼散射的纳米传感器公开(公告)号：US07301624B2
公开(公告)日：2007-11-27
申请号：US10935783
申请日：2004-09-07
申请人： Chad E. Talley , Thomas R. Huser , Christopher W. Hollars , Stephen M. Lane , Joe H. Satcher, Jr. , Bradley R. Hart , Ted A. Laurence
发明人： Chad E. Talley , Thomas R. Huser , Christopher W. Hollars , Stephen M. Lane , Joe H. Satcher, Jr. , Bradley R. Hart , Ted A. Laurence
IPC分类号： G01J3/44
CPC分类号： G01N21/658 , G01J3/44
摘要： Surface-Enhanced Raman Spectroscopy (SERS) is a vibrational spectroscopic technique that utilizes metal surfaces to provide enhanced signals of several orders of magnitude. When molecules of interest are attached to designed metal nanoparticles, a SERS signal is attainable with single molecule detection limits. This provides an ultrasensitive means of detecting the presence of molecules. By using selective chemistries, metal nanoparticles can be functionalized to provide a unique signal upon analyte binding. Moreover, by using measurement techniques, such as, ratiometric received SERS spectra, such metal nanoparticles can be used to monitor dynamic processes in addition to static binding events. Accordingly, such nanoparticles can be used as nanosensors for a wide range of chemicals in fluid, gaseous and solid form, environmental sensors for pH, ion concentration, temperature, etc., and biological sensors for proteins, DNA, RNA, etc.
摘要翻译： 表面增强拉曼光谱（SERS）是一种振动光谱技术，利用金属表面提供几个数量级的增强信号。 当感兴趣的分子连接到设计的金属纳米粒子时，可以通过单分子检测限达到SERS信号。 这提供了检测分子存在的超灵敏手段。 通过使用选择性化学成分，金属纳米粒子可以被功能化，以在分析物结合时提供独特的信号。 此外，通过使用诸如比例接收的SERS光谱的测量技术，除了静态结合事件之外，这种金属纳米颗粒可用于监测动态过程。 因此，这种纳米颗粒可用作流体，气体和固体形式的广泛化学品的纳米传感器，用于pH，离子浓度，温度等的环境传感器，以及用于蛋白质，DNA，RNA等的生物传感器。
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公开(公告)号：US20080239307A1
公开(公告)日：2008-10-02
申请号：US11731418
申请日：2007-03-30
IPC分类号： G01J3/44
CPC分类号： G01J3/44 , G01J3/02 , G01J3/0208 , G01J3/0229 , G01J3/0262 , G01N21/658
摘要： A surface-enhanced Raman scattering method and apparatus to sequence polymeric biomolecules such as DNA, RNA, or proteins is introduced. The method uses metallic nanostructures such as, for example, spherical or cylindrical Au or Ag nanoparticles having characteristic lengths of 10-100 nm which when illuminated with light of the appropriate wavelength produce resonant oscillations of the conduction electrons (plasmon resonance). Electric field enhancements of 30-1000 near the particle surface resulting from such oscillations increase Raman scattering cross-sections by about 106-1015 due to the E4 dependence of the Raman scattering, wherein the largest enhancements occur in the gap/junction between novel closely spaced structures as disclosed herein.
摘要翻译： 引入表面增强拉曼散射方法和用于对聚合物生物分子如DNA，RNA或蛋白质进行排序的装置。 该方法使用金属纳米结构，例如具有特征长度为10-100nm的球形或圆柱形Au或Ag纳米颗粒，当用适当波长的光照射时，会导致传导电子（等离子体共振）的共振振荡。 由于这种振荡导致的颗粒表面附近的30-1000的电场增强使由于E 4引起的拉曼散射横截面增加约10 -6 -10 15 拉曼散射的依赖性，其中最大的增强发生在本文公开的新颖的紧密间隔的结构之间的间隙/接合处。
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4.发明授权Detection of biological molecules using boronate-based chemical amplification and optical sensors 有权使用基于硼酸盐的化学放大和光学传感器检测生物分子公开(公告)号：US06750311B1
公开(公告)日：2004-06-15
申请号：US09461627
申请日：1999-12-14
申请人： William Peter Van Antwerp , John Joseph Mastrototaro , Stephen M. Lane , Joe H. Satcher, Jr. , Christopher B. Darrow , Thomas A. Peyser , Jennifer Harder
发明人： William Peter Van Antwerp , John Joseph Mastrototaro , Stephen M. Lane , Joe H. Satcher, Jr. , Christopher B. Darrow , Thomas A. Peyser , Jennifer Harder
IPC分类号： C08G1810
CPC分类号： G01N33/66 , Y10T428/31551
摘要： Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.
摘要翻译： 提供了用于确定多羟基化合物，特别是葡萄糖的生物水平浓度的方法。 该方法利用扩增系统，其是固定在聚合物基质中的分析物传感器，其中系统是可植入的和生物相容的。 在通过光学系统询问时，放大系统产生能够在患者皮肤外部检测的信号。 感兴趣的分析物的定量通过测量发射的信号来实现。
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公开(公告)号：US06480730B2
公开(公告)日：2002-11-12
申请号：US09742775
申请日：2000-12-20
IPC分类号： A61B505
CPC分类号： A61B5/0031 , A61B5/14532 , A61B2562/028
摘要： An implantable chemical sensor system for medical applications is described which permits selective recognition of an analyte using an expandable biocompatible sensor, such as a polymer, that undergoes a dimensional change in the presence of the analyte. The expandable polymer is incorporated into an electronic circuit component that changes its properties (e.g., frequency) when the polymer changes dimension. As the circuit changes its characteristics, an external interrogator transmits a signal transdermally to the transducer, and the concentration of the analyte is determined from the measured changes in the circuit. This invention may be used for minimally invasive monitoring of blood glucose levels in diabetic patients.
摘要翻译： 描述了用于医疗应用的可植入化学传感器系统，其允许使用在分析物存在下经历尺寸变化的可扩展生物相容性传感器（例如聚合物）来选择性识别分析物。 当聚合物改变尺寸时，可膨胀聚合物结合到电子电路组件中，其改变其性质（例如，频率）。 随着电路改变其特性，外部询问器将信号经皮传递至换能器，并根据测量的电路变化确定分析物的浓度。 本发明可用于糖尿病患者血糖水平的微创监测。
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公开(公告)号：US06673625B2
公开(公告)日：2004-01-06
申请号：US09823522
申请日：2001-03-30
IPC分类号： G01N3300
CPC分类号： C09B57/08 , A61B5/14532 , A61B5/1459 , C07F5/025 , C09B19/00 , C09B57/10 , G01N33/52 , G01N33/66 , Y10T436/143333 , Y10T436/144444
摘要： The present invention provides formulae for fluorescent compounds that have a number of properties which make them uniquely suited for use in sensors of analytes such as saccharides. The advantageous fluorescent properties include favorable excitation wavelengths, emission wavelengths, fluorescence lifetimes, and photostability. Additional advantageous properties include enhanced aqueous solubility, as well as temperature and pH sensitivity. The compound comprises an aryl or a substituted phenyl botonic acid that acts as a substrate recognition component, a fluorescence switch component, and a fluorophore. Fluorescent compounds are described that are excited at wavelengths greater than 400 nm and emit at wavelengths greater than 450 nm, which is advantageous for optical transmission through skin. The fluorophore is typically selected from transition metal-ligand complexes and thiazine, oxazine, oxazone, or oxazine-one as well as anthracene compounds. The fluorescent compound can be immobilized in a glucose permeable biocompatible polymer matrix that is implantable below the skin.
摘要翻译： 本发明提供具有多种性质的荧光化合物的配方，使其独特地适用于分析物如糖的传感器。 有利的荧光特性包括有利的激发波长，发射波长，荧光寿命和光稳定性。 其他有利的性质包括提高水溶性，以及温度和pH敏感性。 化合物包括用作底物识别组分的芳基或取代的苯基苯甲酸，荧光开关组分和荧光团。 描述了在波长大于400nm被激发并且以大于450nm的波长发射的荧光化合物，这对于通过皮肤的光学透射是有利的。 荧光团通常选自过渡金属 - 配体络合物和噻嗪，恶嗪，恶唑酮或恶嗪 - 以及蒽化合物。 荧光化合物可以固定在可植入皮肤下面的葡萄糖可渗透的生物相容性聚合物基质中。
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公开(公告)号：US06682938B1
公开(公告)日：2004-01-27
申请号：US09663567
申请日：2000-09-15
IPC分类号： G01N3300
CPC分类号： C09B19/00 , A61B5/14532 , A61B5/1459 , C07F5/025 , C09B57/08 , C09B57/10 , G01N33/52 , G01N33/66
摘要： An analyte sensing fluorescent molecule that employs intramolecular electron transfer is designed to exhibit selected fluorescent properties in the presence of analytes such as saccharides. The selected fluorescent properties include excitation wavelength, emission wavelength, fluorescence lifetime, quantum yield, photostability, solubility, and temperature or pH sensitivity. The compound comprises an aryl or a substituted phenyl boronic acid that acts as a substrate recognition component, a fluorescence switch component, and a fluorophore. The fluorophore and switch component are selected such that the value of the free energy for electron transfer is less than about 3.0 kcal mol−1. Fluorescent compounds are described that are excited at wavelengths greater than 400 nm and emit at wavelengths greater than 450 nm, which is advantageous for optical transmission through skin. The fluorophore is typically selected from transition metal-ligand complexes and thiazine, oxazine, oxazone, or oxazine-one as well as anthracene compounds. The fluorescent compound can be immobilized in a glucose permeable biocompatible polymer matrix that is implantable below the skin.
摘要翻译： 使用分子内电子转移的分析物感测荧光分子被设计为在分析物例如糖的存在下显示选择的荧光性质。 所选择的荧光特性包括激发波长，发射波长，荧光寿命，量子产率，光稳定性，溶解度和温度或pH敏感性。 化合物包括用作底物识别组分的芳基或取代的苯基硼酸，荧光开关组分和荧光团。 选择荧光团和开关组分使得电子转移的自由能的值小于约3.0kcal mol -1。 描述了在波长大于400nm被激发并且以大于450nm的波长发射的荧光化合物，这对于通过皮肤的光学透射是有利的。 荧光团通常选自过渡金属 - 配体络合物和噻嗪，恶嗪，恶唑酮或恶嗪 - 以及蒽化合物。 荧光化合物可以固定在可植入皮肤下面的葡萄糖可渗透的生物相容性聚合物基质中。
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8.发明授权Long wave fluorophore sensor compounds and other fluorescent sensor compounds in polymers 有权长波荧光团传感器化合物等聚合物中的荧光传感器化合物公开(公告)号：US06766183B2
公开(公告)日：2004-07-20
申请号：US10033240
申请日：2001-12-28
申请人： Joseph C. Walsh , Aaron M. Heiss , Glenn Noronha , David J. Vachon , Stephen M. Lane , Joe H. Satcher, Jr. , Thomas A. Peyser , William Peter Van Antwerp , John Joseph Mastrototaro
发明人： Joseph C. Walsh , Aaron M. Heiss , Glenn Noronha , David J. Vachon , Stephen M. Lane , Joe H. Satcher, Jr. , Thomas A. Peyser , William Peter Van Antwerp , John Joseph Mastrototaro
IPC分类号： A61B500
CPC分类号： A61B5/1455 , A61B5/0071 , A61B5/14532 , C12Q1/005 , G01N33/66 , Y10T436/143333 , Y10T436/144444
摘要： Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. Embodiments of these biosensor molecules exhibit fluorescence emission at wavelengths greater than about 650 nm. Typical biosensor molecules include a fluorophore that includes an iminium ion, a linker moiety that includes a group that is an anilinic type of relationship to the fluorophore and a boronate substrate recognition/binding moiety, which binds glucose. The fluorescence molecules modulated by the presence or absence of polyhydroxylated analytes such as glucose. This property of these molecules of the invention, as well as their ability to emit fluorescent light at greater than about 650 nm, renders these biosensor molecules particularly well-suited for detecting and measuring in-vivo glucose concentrations.
摘要翻译： 描述荧光生物传感器分子，荧光生物传感器和系统，以及制造和使用这些生物传感器分子和系统的方法。 这些生物传感器分子的实施例在大于约650nm的波长处表现出荧光发射。 典型的生物传感器分子包括包含亚胺离子的荧光团，连接部分，其包含与荧光团相关的苯胺型的基团和结合葡萄糖的硼酸酯底物识别/结合部分。 通过存在或不存在多羟基化分析物如葡萄糖来调节荧光分子。 本发明的这些分子的这种性质以及它们在大于约650nm发射荧光的能力使得这些生物传感器分子特别适用于检测和测量体内葡萄糖浓度。
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9.发明授权Detection of biological molecules using boronate-based chemical amplification and optical sensors 失效使用基于硼酸盐的化学放大和光学传感器检测生物分子
公开(公告)号：US6002954A
公开(公告)日：1999-12-14
申请号：US749366
申请日：1996-11-21
申请人： William Peter Van Antwerp , John Joseph Mastrototaro , Stephen M. Lane , Joe H. Satcher, Jr. , Christopher B. Darrow , Thomas A. Peyser , Jennifer Harder
发明人： William Peter Van Antwerp , John Joseph Mastrototaro , Stephen M. Lane , Joe H. Satcher, Jr. , Christopher B. Darrow , Thomas A. Peyser , Jennifer Harder
CPC分类号： A61B5/14532 , A61B5/1455 , A61B5/1459 , G01N33/66
摘要： Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.
摘要翻译： 提供了用于确定多羟基化合物，特别是葡萄糖的生物水平浓度的方法。 该方法利用扩增系统，其是固定在聚合物基质中的分析物传感器，其中系统是可植入的和生物相容的。 在通过光学系统询问时，放大系统产生能够在患者皮肤外部检测的信号。 感兴趣的分析物的定量通过测量发射的信号来实现。
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公开(公告)号：US06201980B1
公开(公告)日：2001-03-13
申请号：US09166236
申请日：1998-10-05
IPC分类号： A61B505
CPC分类号： A61B5/0031 , A61B5/14532 , A61B2562/028
摘要： An implantable chemical sensor system for medical applications is described which permits selective recognition of an analyte using an expandable biocompatible sensor, such as a polymer, that undergoes a dimensional change in the presence of the analyte. The expandable polymer is incorporated into an electronic circuit component that changes its properties (e.g., frequency) when the polymer changes dimension. As the circuit changes its characteristics, an external interrogator transmits a signal transdermally to the transducer, and the concentration of the analyte is determined from the measured changes in the circuit. This invention may be used for minimally invasive monitoring of blood glucose levels in diabetic patients.
摘要翻译： 描述了用于医疗应用的可植入化学传感器系统，其允许使用在分析物存在下经历尺寸变化的可扩展生物相容性传感器（例如聚合物）来选择性识别分析物。 当聚合物改变尺寸时，可膨胀聚合物结合到电子电路组件中，其改变其性质（例如，频率）。 随着电路改变其特性，外部询问器将信号经皮传递至换能器，并根据测量的电路变化确定分析物的浓度。 本发明可用于糖尿病患者血糖水平的微创监测。
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