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    • 3. 发明授权
    • Mechanically resonant nanostructures
    • 机械共振纳米结构
    • US06515751B1
    • 2003-02-04
    • US09520984
    • 2000-03-08
    • Harold G. CraigheadDustin W. CarrLidija Sekaric
    • Harold G. CraigheadDustin W. CarrLidija Sekaric
    • G01B902
    • H03H9/02259H03H3/0077H03H9/2405H03H2009/2442
    • Electron beam lithography is used to make very small mechanical structures in single-crystal silicon. The structure may be a mesh having beam widths of less than 30 nm and suspended in a wafer, above a substrate. An rf drive voltage applied between the suspended structure and the underlying substrate produces vibration at or near the resonant frequency of the structure, and optical interference techniques are used to detect and measure the motion of the structure. The small dimensions of the structure provides a resonant frequency above 40 MHz. In one embodiment, the structure is a mesh formed of interconnected, very narrow, high aspect ratio parallel beams spaced about 315 nm apart. This results in a nanostructure having a low mass and a large relative surface area. The mesh is illuminated by laser light having a wavelength greater than the spacing between adjacent beams in the mesh so that small amplitude oscillations can be measured, with the detected change in optical reflection being proportional to the drive amplitude. The suboptical-wavelength features of the mesh provide a high measurement sensitivity, so that small changes in the mechanical properties of the mesh, resulting in corresponding small changes in the amplitude of the vibration, can be detected. A variable DC bias voltage applied to the vibrating structure allows adjustment of the motion of the structure and tuning of its vibration.
    • 电子束光刻用于在单晶硅中制造非常小的机械结构。 该结构可以是具有小于30nm的波束宽度并悬浮在晶片上的基板上的网格。 施加在悬挂结构和下面的衬底之间的射频驱动电压在结构的谐振频率处或附近产生振动,并且使用光学干涉技术来检测和测量结构的运动。 该结构的小尺寸提供高于40MHz的谐振频率。 在一个实施例中,该结构是由相互间隔约315nm的互连的,非常窄的高纵横比的平行光束形成的网格。 这导致具有低质量和大的相对表面积的纳米结构。 网格由波长大于网格中相邻光束之间的间距的激光照射,从而可以测量小振幅振荡,其中检测到的光反射变化与驱动振幅成比例。 网格的次光波长特征提供了高的测量灵敏度,从而可以检测到网格的机械性能的微小变化,从而导致相应的振动幅度的微小变化。 施加到振动结构的可变直流偏置电压允许调整结构的运动并调节其振动。
    • 8. 发明申请
    • STRESS-BASED SENSOR, METHOD, AND APPLICATIONS
    • 基于应力的传感器,方法和应用
    • US20130118228A1
    • 2013-05-16
    • US13637861
    • 2011-03-31
    • Jeevak M. ParpiaHarold G. CraigheadDarren R. SouthworthLeon M. Bellan
    • Jeevak M. ParpiaHarold G. CraigheadDarren R. SouthworthLeon M. Bellan
    • G01N33/497
    • G01N33/497G01N29/022
    • A composite, analyte sensor includes a substrate; a micro- or nano-electro-mechanical (MEMS; NEMS) resonator that is coupled to the substrate at least two edge locations (i.e., it is at least doubly-clamped) of the resonator, wherein the resonator is in a statically-buckled state near a buckling transition point of the resonator; and a chemically-responsive substance covering at least a portion of the surface of the resonator that will undergo a conformational change upon exposure to a given analyte. The resonator may be a double-clamped, statically-buckled beam (or bridge), a multiply-clamped, statically-buckled dome (or crater), or other resonator geometry. The sensor may include two or more at least double-clamped, statically-buckled, composite MEMS or NEMS resonators each operating near a buckling transition point of the respective resonator, and each characterized by a different resonant frequency. A method for sensing an analyte in ambient air.
    • 复合分析物传感器包括基底; 谐振器的至少两个边缘位置(即,它至少被双钳位)耦合到衬底的微机械或纳米机电(MEMS; NEMS)谐振器,其中所述谐振器处于静态弯曲 在谐振器的屈曲转变点附近; 以及覆盖谐振器表面的至少一部分的化学响应物质,其在暴露于给定的分析物时将经历构象变化。 谐振器可以是双夹紧,静态弯曲梁(或桥),多夹紧,静态弯曲的圆顶(或火山口)或其他谐振器几何形状。 传感器可以包括两个或更多个至少双夹紧,静态弯曲的复合MEMS或NEMS谐振器,每个谐振器在相应谐振器的屈曲转变点附近操作,并且每个谐振器的特征在于不同的谐振频率。 用于感测环境空气中的分析物的方法。
    • 9. 发明授权
    • Active micromixer using surface acoustic wave streaming
    • 使用表面声波流动的有源微混合器
    • US07942568B1
    • 2011-05-17
    • US11155108
    • 2005-06-17
    • Darren W. BranchGrant D. MeyerHarold G. Craighead
    • Darren W. BranchGrant D. MeyerHarold G. Craighead
    • B01F11/02
    • B01F11/0266B01F13/0059Y10S366/04
    • An active micromixer uses a surface acoustic wave, preferably a Rayleigh wave, propagating on a piezoelectric substrate to induce acoustic streaming in a fluid in a microfluidic channel. The surface acoustic wave can be generated by applying an RF excitation signal to at least one interdigital transducer on the piezoelectric substrate. The active micromixer can rapidly mix quiescent fluids or laminar streams in low Reynolds number flows. The active micromixer has no moving parts (other than the SAW transducer) and is, therefore, more reliable, less damaging to sensitive fluids, and less susceptible to fouling and channel clogging than other types of active and passive micromixers. The active micromixer is adaptable to a wide range of geometries, can be easily fabricated, and can be integrated in a microfluidic system, reducing dead volume. Finally, the active micromixer has on-demand on/off mixing capability and can be operated at low power.
    • 有源微混合器使用在压电衬底上传播的表面声波,优选瑞利波,以在微流体通道中的流体中引起声流。 可以通过将RF激励信号施加到压电基板上的至少一个叉指式换能器来产生表面声波。 活性微混合器可以在低雷诺数流中快速混合静态流体或层流。 活性微混合器没有移动部件(SAW传感器除外),因此比其他类型的有源和无源微混合器更可靠,对敏感流体的损害较小,并且不易受到结垢和通道堵塞的影响。 活性微混合器适用于宽范围的几何形状,可以容易地制造,并且可以集成在微流体系统中,从而减少死体积。 最后,有源微混频器具有按需开/关混合能力,可以低功耗运行。
    • 10. 发明申请
    • METHOD FOR SEQUENCING NUCLEIC ACID MOLECULES
    • 用于测序核酸分子的方法
    • US20110111401A1
    • 2011-05-12
    • US12841819
    • 2010-07-22
    • Jonas KORLACHWatt W. WebbMichael LeveneStephen TurnerHarold G. CraigheadMathieu Foquet
    • Jonas KORLACHWatt W. WebbMichael LeveneStephen TurnerHarold G. CraigheadMathieu Foquet
    • C12Q1/68
    • C12Q1/6874C12Q1/6869Y10S436/80Y10S436/805Y10T436/143333C12Q2565/537C12Q2537/149C12Q2561/113C12Q2521/543C12Q2565/518C12Q2561/12
    • 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.
    • 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。