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1. 发明申请

US20070134716A1 Zero-mode metal clad waveguides for performing spectroscopy with confined effective observation volumes 有权
标题翻译：零模式金属包层波导用于执行限制有效观察体积的光谱
公开(公告)号：US20070134716A1
公开(公告)日：2007-06-14
申请号：US11670906
申请日：2007-02-02
申请人： Michael Levene , Jonas Korlach , Stephen Turner , Harold Craighead , Watt Webb
发明人： Michael Levene , Jonas Korlach , Stephen Turner , Harold Craighead , Watt Webb
IPC分类号： C12Q1/68 , G01N33/53 , C12M3/00
CPC分类号： C12Q1/25 , C12Q1/6825 , G01N21/47 , G01N21/6408 , G01N21/6428 , G01N21/645 , G01N21/6452 , G01N21/65 , G01N33/54373 , G01N2333/9015 , G01Q60/22 , G02B6/10 , G02B6/241
摘要： The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode wave guide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.
摘要翻译：本发明涉及用于分析分析物的方法和装置。该方法包括提供零模式波导，该零模式波导包括围绕芯的包层，其中覆层被配置为阻止频率小于截止频率的电磁能量沿纵向穿过零模式波导的芯的传播。分析物位于零模式波导的核心中，然后在零模式波导的核心中经受有效允许分析的条件下激活小于截止频率的频率的电磁辐射分析物在有效观察体积中比如果在没有零模式波导的情况下进行分析时更紧凑。

2. 发明申请

US20070020779A1 Quantum dot conjugates in a sub-micrometer fluidic channel 有权
标题翻译：量子点共轭在亚微米流体通道
公开(公告)号：US20070020779A1
公开(公告)日：2007-01-25
申请号：US11280941
申请日：2005-11-16
申请人： Samuel Stavis , Joshua Edel , Kevan Samiee , Harold Craighead
发明人： Samuel Stavis , Joshua Edel , Kevan Samiee , Harold Craighead
IPC分类号： H01L21/66
CPC分类号： A61K49/0067 , A61K49/0056 , B82Y5/00 , B82Y10/00 , B82Y15/00 , B82Y20/00 , B82Y30/00 , G01N33/588 , Y10S438/962 , Y10S977/70 , Y10S977/774
摘要： A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.
摘要翻译：使用在约500nm正方形横截面的熔融二氧化硅中制造的纳米流体通道来分离，检测和识别各种量子点缀合物。该通道可以快速检测溶液中的每个荧光实体。使用选定波长的激光来激发多种量子点和有机分子，并且发射光谱被解析而没有显着的信号抑制。然后将量子点与有机分子缀合并检测以证明有效的多色检测。 PCH用于分析重合检测并表征结合程度。使用小的流体通道检测量子点作为荧光标记被证明是多重单分子研究的有效技术。单分子结合事件的检测具有多种应用，包括高通量免疫测定。

3. 发明申请

US20060238239A1 Thermal-mechanical signal processing 有权
标题翻译：热机械信号处理
公开(公告)号：US20060238239A1
公开(公告)日：2006-10-26
申请号：US11358917
申请日：2006-02-20
申请人： Maxim Zalalutdinov , Robert Reichenbach , Keith Aubin , Brian Houston , Jeevak Parpia , Harold Craighead
发明人： Maxim Zalalutdinov , Robert Reichenbach , Keith Aubin , Brian Houston , Jeevak Parpia , Harold Craighead
IPC分类号： H03D3/00
CPC分类号： H03D1/00 , G02B26/0858 , H03B5/30 , H03C1/46 , H03D1/02 , H03D3/34 , H03H3/0072 , H03H9/02259 , H03H9/2405 , H03H9/2436 , H03H2009/02488 , H03H2009/02511
摘要： A source signal is converted into a time-variant temperature field with transduction into mechanical motion. In one embodiment, the conversion of a source signal into the time-variant temperature field is provided by utilizing a micro-fabricated fast response, bolometer-type radio frequency power meter. A resonant-type micromechanical thermal actuator may be utilized for temperature read-out and demodulation.
摘要翻译：源信号被转换成具有转换为机械运动的时变温度场。在一个实施例中，通过利用微制造的快速响应，测辐射热表型射频功率计，提供源信号到时变温度场的转换。谐振型微机械热致动器可用于温度读出和解调。

4. 发明申请

US20060176122A1 MEMS OSCILLATOR DRIVE 有权
标题翻译： MEMS振荡器驱动器
公开(公告)号：US20060176122A1
公开(公告)日：2006-08-10
申请号：US11275653
申请日：2006-01-20
申请人： Keith Aubin , Bojan Ilic , Maxim Zalalutdinov , Robert Reichenbach , Jeevak Parpia , Harold Craighead
发明人： Keith Aubin , Bojan Ilic , Maxim Zalalutdinov , Robert Reichenbach , Jeevak Parpia , Harold Craighead
IPC分类号： H03L1/00
CPC分类号： H03B5/30 , B81B3/0029 , B81B2203/0118 , H03H9/02259 , H03H9/2457 , H03H2009/02511
摘要： The temperature of a remote portion of device having a microelectromechanical oscillator is modulated to create oscillation of the oscillators. In one embodiment, a localized heat source is placed on a device layer of a multilayered stack, consisting of device, sacrificial and substrate layers. The localized heat source may be a laser beam in one embodiment. The oscillator is supported by the device layer and may be formed in the device layer in various embodiments. The oscillator may be spaced apart from the localized heat source.
摘要翻译：具有微机电振荡器的器件的远端部分的温度被调制以产生振荡器的振荡。在一个实施例中，将局部热源放置在由器件，牺牲层和衬底层组成的多层叠层的器件层上。在一个实施例中，局部热源可以是激光束。振荡器由器件层支撑，并且可以在各种实施例中形成在器件层中。振荡器可以与局部热源间隔开。

5. 发明申请

US20060166218A1 Protective coating for array material deposition 有权
标题翻译：用于阵列材料沉积的保护涂层
公开(公告)号：US20060166218A1
公开(公告)日：2006-07-27
申请号：US10939121
申请日：2004-09-10
申请人： Reid Orth , David Lin , Theodore Clark , Yung-Fu Chang , Harold Craighead , Jose Moran-Mirabal
发明人： Reid Orth , David Lin , Theodore Clark , Yung-Fu Chang , Harold Craighead , Jose Moran-Mirabal
IPC分类号： C12Q1/68 , C12M1/34 , H01L21/00 , B05D3/02
CPC分类号： B01J19/0046 , B01J2219/00432 , B01J2219/00527 , B01J2219/00585 , B01J2219/00596 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00619 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659
摘要： An array is formed with a protective cover on a substrate. The protective cover is patterned to produce an array of openings to the substrate. Desired material is deposited on the substrate through the openings. The protective cover may then be removed. In one embodiment, the protective cover is a conformal polymer, such as di-para-xylylene. It may be removed by mechanical peeling. The material may be biological material such as DNA. The protective cover may be used to prevent non-specific hybridization in inter-spot regions by performing hybridization with the cover still in place. Hybridization that occurs in such regions between the spots may be removed with removal of the protective cover.
摘要翻译：在衬底上形成有保护罩的阵列。将保护盖图案化以产生到基板的开口阵列。期望的材料通过开口沉积在基底上。然后可以移除保护盖。在一个实施方案中，保护性覆盖物是保形聚合物，例如二对二甲苯。可以通过机械剥离除去。该材料可以是诸如DNA的生物材料。保护罩可以用于通过与盖仍然在位的杂交来防止斑间区域中的非特异性杂交。在斑点之间的这些区域中发生的杂交可以通过去除保护盖而被去除。

6. 发明申请

US20050202466A1 Method for sequencing nucleic acid molecules 有权
标题翻译：核酸分子测序方法
公开(公告)号：US20050202466A1
公开(公告)日：2005-09-15
申请号：US11015138
申请日：2004-12-16
申请人： Jonas Korlach , Watt Webb , Michael Levene , Stephen Turner , Harold Craighead , Mathieu Foquet
发明人： Jonas Korlach , Watt Webb , Michael Levene , Stephen Turner , Harold Craighead , Mathieu Foquet
IPC分类号： G01N33/50 , C12M1/00 , C12N15/09 , C12Q1/68 , G01N33/58 , C12P19/34
CPC分类号： C12Q1/6874 , C12Q1/6869 , Y10S436/80 , Y10S436/805 , Y10T436/143333 , C12Q2565/537 , C12Q2537/149 , C12Q2561/113 , C12Q2521/543 , C12Q2565/518 , C12Q2561/12
摘要： The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.
摘要翻译：本发明涉及对具有多个碱基的靶核酸分子进行测序的方法。在其原理中，聚合反应中碱添加的时间顺序是在核酸分子上测量的，即核酸聚合酶在待测序的模板核酸分子上的活性被实时跟踪。通过在碱添加序列的每个步骤中通过核酸聚合酶的催化活性鉴定哪个碱基被掺入靶核酸的生长互补链中来推断该序列。在靶核酸分子复合物上提供聚合酶，其适于沿着靶核酸分子移动并在活性位点延伸寡核苷酸引物。多个标记类型的核苷酸类似物在活性位点附近提供，每种可区分类型的核苷酸类似物与靶核酸序列中的不同核苷酸互补。生长的核酸链通过使用聚合酶延伸到活性位点处的核酸链的核苷酸类似物，其中加入的核苷酸类似物与活性位点上的靶核酸的核苷酸互补。鉴定作为聚合步骤的结果添加到寡核苷酸引物中的核苷酸类似物。重复提供标记的核苷酸类似物，聚合生长的核酸链和鉴定添加的核苷酸类似物的步骤，使得核酸链进一步延长并确定靶核酸的序列。

7. 发明申请

US20050178960A1 Electrospray emitter for microfluidic channel 有权
标题翻译：微流体通道的电喷发射体
公开(公告)号：US20050178960A1
公开(公告)日：2005-08-18
申请号：US11082329
申请日：2005-03-17
申请人： Jun Kameoka , Harold Craighead
发明人： Jun Kameoka , Harold Craighead
IPC分类号： G01N30/72 , H01J49/04 , H01J49/16 , B01D59/44
CPC分类号： H01J49/165 , G01N30/7266 , H01J49/0018 , G01N30/6095
摘要： An electrospray ionization device incorporates a shaped thin film with a microfluidic channel. The device may be interfaced to a time-of-flight mass spectrometer (TFOMS). In one embodiment, the shaped thin film has a polygonal-shaped or triangle-shaped thin polymer tip formed by lithography and etching. The microfluidic channel is approximately 20 micrometer wide and 10 micrometers deep, and embossed in a substrate using a silicon master. The shaped thin film is aligned with the channel and bonded between the channel substrate and a flat plate to create a microfluidic channel with a wicking tip protruding from the end of the channel. Application of a high voltage at one end of the channel creates an electrospray from the tip, which is provided to the TFOMS.
摘要翻译：电喷雾离子化装置结合了具有微流体通道的成形薄膜。该装置可以连接到飞行时间质谱仪（TFOMS）。在一个实施例中，成形薄膜具有通过光刻和蚀刻形成的多边形或三角形的薄聚合物尖端。微流体通道约20微米宽和10微米深，并使用硅母版在基底上压花。成形的薄膜与通道对准并且结合在通道基板和平板之间以产生具有从通道的端部突出的吸液尖端的微流体通道。在通道的一端施加高电压从尖端产生电喷雾，其提供给TFOMS。

8. 发明申请

US20050164255A1 Method for sequencing nucleic acid molecules 有权
公开(公告)号：US20050164255A1
公开(公告)日：2005-07-28
申请号：US11013578
申请日：2004-12-15
申请人： Jonas Korlach , Watt Webb , Michael Levene , Stephen Turner , Harold Craighead , Mathieu Foquet
发明人： Jonas Korlach , Watt Webb , Michael Levene , Stephen Turner , Harold Craighead , Mathieu Foquet
IPC分类号： G01N33/50 , C12M1/00 , C12N15/09 , C12Q1/68 , G01N33/58 , C12P19/34
CPC分类号： C12Q1/6874 , C12Q1/6869 , Y10S436/80 , Y10S436/805 , Y10T436/143333 , C12Q2565/537 , C12Q2537/149 , C12Q2561/113 , C12Q2521/543 , C12Q2565/518 , C12Q2561/12
摘要： The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

9. 发明申请

US20070200648A1 MEMS controlled oscillator 有权
标题翻译： MEMS控制振荡器
公开(公告)号：US20070200648A1
公开(公告)日：2007-08-30
申请号：US11598097
申请日：2006-11-09
申请人： Robert Reichenbach , Keith Aubin , Maxim Zalalutdinov , Jeevak Parpia , Harold Craighead
发明人： Robert Reichenbach , Keith Aubin , Maxim Zalalutdinov , Jeevak Parpia , Harold Craighead
IPC分类号： H03H9/70
CPC分类号： H03H9/02401 , G01S7/032 , H01Q3/26 , H03H3/0072 , H03H9/2436
摘要： An array of micromechanical oscillators have different resonant frequencies based on their geometries. In one embodiment, a micromechanical oscillator has a resonant frequency defined by an effective spring constant that is modified by application of heat. In one embodiment, the oscillator is disc of material supported by a pillar of much smaller diameter than the disc. The periphery of the disc is heated to modify the resonant frequency (or equivalently the spring constant or stiffness) of the disc. Continuous control of the output phase and frequency may be achieved when the oscillator becomes synchronized with an imposed sinusoidal force of close frequency. The oscillator frequency can be detuned to produce an easily controlled phase differential between the injected signal and the oscillator feedback. A phased array radar may be produced using independent phase controllable oscillators.
摘要翻译：微机械振荡器阵列根据其几何形状具有不同的谐振频率。在一个实施例中，微机械振荡器具有由通过施加热来修改的有效弹簧常数限定的谐振频率。在一个实施例中，振荡器是由比该盘小得多的直径支柱支撑的材料盘。加热盘的周边以改变盘的共振频率（或等效地为弹簧常数或刚度）。当振荡器与施加的接近频率的正弦力同步时，可以实现输出相位和频率的连续控制。振荡器频率可以失谐，以在注入的信号和振荡器反馈之间产生容易控制的相位差。可以使用独立的相位可控振荡器来产生相控阵雷达。

10. 发明申请

US20060154288A1 Methods for analyzing nucleic acid sequences 有权
标题翻译：分析核酸序列的方法
公开(公告)号：US20060154288A1
公开(公告)日：2006-07-13
申请号：US11336122
申请日：2006-01-19
申请人： Jonas Korlach , Watt Webb , Michael Levene , Stephen Turner , Harold Craighead , Mathieu Foquet
发明人： Jonas Korlach , Watt Webb , Michael Levene , Stephen Turner , Harold Craighead , Mathieu Foquet
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6874 , C12Q1/6869 , Y10S436/80 , Y10S436/805 , Y10T436/143333 , C12Q2565/537 , C12Q2537/149 , C12Q2561/113 , C12Q2521/543 , C12Q2565/518 , C12Q2561/12
摘要： The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.
摘要翻译：本发明涉及对具有多个碱基的靶核酸分子进行测序的方法。在其原理中，聚合反应中碱添加的时间顺序是在核酸分子上测量的，即核酸聚合酶在待测序的模板核酸分子上的活性被实时跟踪。通过在碱添加序列的每个步骤中通过核酸聚合酶的催化活性鉴定哪个碱基被掺入靶核酸的生长互补链中来推断该序列。在靶核酸分子复合物上提供聚合酶，其适于沿着靶核酸分子移动并在活性位点延伸寡核苷酸引物。多个标记类型的核苷酸类似物在活性位点附近提供，每种可区分类型的核苷酸类似物与靶核酸序列中的不同核苷酸互补。生长的核酸链通过使用聚合酶延伸到活性位点处的核酸链的核苷酸类似物，其中加入的核苷酸类似物与活性位点上的靶核酸的核苷酸互补。鉴定作为聚合步骤的结果添加到寡核苷酸引物中的核苷酸类似物。重复提供标记的核苷酸类似物，聚合生长的核酸链和鉴定添加的核苷酸类似物的步骤，使得核酸链进一步延长并确定靶核酸的序列。

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