公开(公告)号：US08232095B2

公开(公告)日：2012-07-31

申请号：US11719749

申请日：2005-11-18

申请人： Chih-Ming Ho ,  Pak Kin Wong ,  Ren Sun ,  Fuqu Yu

发明人： Chih-Ming Ho ,  Pak Kin Wong ,  Ren Sun ,  Fuqu Yu

IPC分类号： C12M1/00 ,  G05B19/42

CPC分类号： C12Q1/02 ,  C12M41/48 ,  C12Q3/00 ,  G01N35/0092 ,  G01N2035/0094 ,  Y02A90/26

摘要： The invention provides systems and methods for manipulating, e.g., optimizing and controlling, biological systems, e.g., for eliciting a more desired biological response of biological sample, such as a tissue, organ, and/or a cell. In one aspect, systems and methods of the invention operate by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system, e.g., a bioreactor. In alternative aspects, systems include a device for sustaining cells or tissue samples, one or more actuators for stimulating the samples via biochemical, electromagnetic, thermal, mechanical, and/or optical stimulation, one or more sensors for measuring a biological response signal of the samples resulting from the stimulation of the sample. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The compositions and methods of the invention can be used, e.g., to for systems optimization of any biological manufacturing or experimental system, e.g., bioreactors for proteins, e.g., therapeutic proteins, polypeptides or peptides for vaccines, and the like, small molecules (e.g., antibiotics), polysaccharides, lipids, and the like. Another use of the apparatus and methods includes combination drug therapy, e.g. optimal drug cocktail, directed cell proliferations and differentiations, e.g. in tissue engineering, e.g. neural progenitor cells differentiation, and discovery of key parameters in complex biological systems.

摘要翻译： 本发明提供了用于操纵，例如优化和控制生物系统的系统和方法，例如用于引发生物样品例如组织，器官和/或细胞的更期望的生物反应。 在一个方面，本发明的系统和方法通过有效地搜索刺激和系统参数的大参数空间来操作，控制和优化在系统例如生物反应器中维持的生物样品的响应。 在替代方面，系统包括用于维持细胞或组织样本的装置，用于通过生物化学，电磁，热，机械和/或光刺激刺激样品的一个或多个致动器，用于测量生物反应信号的一个或多个传感器 样品刺激产生的样品。 在一个方面，本发明的系统和方法使用至少一种优化算法，以响应于传感器的响应信号的输出来修改致动器的用于刺激的控制输入。 本发明的组合物和方法可用于例如任何生物制备或实验系统的系统优化，例如用于蛋白质的生物反应器，例如用于疫苗的治疗性蛋白质，多肽或肽等，小分子（例如， ，抗生素），多糖，脂质等。 该装置和方法的另一用途包括组合药物治疗，例如， 最佳药物混合物，定向细胞增殖和分化，例如。 在组织工程中。 神经祖细胞分化，以及复杂生物系统中关键参数的发现。

公开(公告)号：US20070031961A1

公开(公告)日：2007-02-08

申请号：US11501424

申请日：2006-08-09

申请人： Chih-Ming Ho ,  Tza-Huei Wang

发明人： Chih-Ming Ho ,  Tza-Huei Wang

IPC分类号： C12Q1/68 ,  C12M1/34

CPC分类号： B01L3/5027 ,  B01J2219/00317 ,  B01J2219/00511 ,  B01J2219/00576 ,  B01J2219/00605 ,  B01J2219/00653 ,  B01J2219/00666 ,  B01J2219/00702 ,  B01L3/502707 ,  B01L2300/168 ,  C12Q1/6825 ,  C40B60/14 ,  G01N21/0303 ,  G01N21/05 ,  G01N21/6428 ,  G01N21/645 ,  G01N27/4145 ,  G01N27/447 ,  G01N2021/0346 ,  G01N2021/058 ,  G01N2021/6463 ,  G01N2021/6476 ,  G01N2021/6482

摘要： The invention disclosed herein provides biosensors and methods which increase the sensitivity of assays of optically labelled molecules fluorescently tagged polypeptides and polynucleotides while decreasing the sample volume required for detection. By integrating reflective sidewalls into the receptacles used in such assays, the signal-to-noise ratio of the optical signal is increased significantly. Typically the receptacles are microchannels. In addition, the geometry of the receptacles can be controlled to further optimize the signal-to-noise ratio of the optical signal. The invention disclosed herein further provides methods and devices involving integrated electronics, wherein an element such as a diode, a transistor, an integrated circuit etc., is integrated with a bio-reactor/channel in order to facilitate the detection or fabrication of bio-materials.

摘要翻译： 本文公开的本发明提供了生物传感器和方法，其增加光学标记分子荧光标记的多肽和多核苷酸的测定的灵敏度，同时降低检测所需的样品体积。 通过将反射侧壁集成在这种测定中使用的插座中，光信号的信噪比显着增加。 通常，插座是微通道。 此外，可以控制插座的几何形状以进一步优化光信号的信噪比。 本文公开的本发明进一步提供了涉及集成电子器件的方法和装置，其中诸如二极管，晶体管，集成电路等的元件与生物反应器/通道集成，以便于生物反应器/通道的检测或制造， 材料

公开(公告)号：US06902313B2

公开(公告)日：2005-06-07

申请号：US09923477

申请日：2001-08-07

申请人： Chih-Ming Ho ,  Patrick Tabeling ,  Yi-Kuen Lee ,  Joanne Helene Deval

发明人： Chih-Ming Ho ,  Patrick Tabeling ,  Yi-Kuen Lee ,  Joanne Helene Deval

IPC分类号： B01F5/06 ,  B01F13/00 ,  B81B1/00

CPC分类号： B01F13/0076 ,  B01F5/0618 ,  B01F5/0646 ,  B01F5/065 ,  B01F5/0654 ,  B01F5/0655 ,  B01F13/0001 ,  B01F13/0005 ,  B01F13/0006 ,  B01F13/0077 ,  Y10S366/01 ,  Y10S366/02

摘要： A micro mixer for use in a microdevice which utilizes time-varying force fields to induce bulk fluid and/or sample component motion leading to homogenization of sample components. Time-varying force fields employed includes at least one of a physical displacement field, electrical field, pressure field or magnetic field to generate transverse forces which induce the mixing of samples within the micro mixer.

摘要翻译： 用于微型装置的微型混合器，其利用时变力场来诱导体液和/或样品组分运动，导致样品组分的均匀化。 使用的时变力场包括物理位移场，电场，压力场或磁场中的至少一个，以产生诱导微混合器内的样品混合的横向力。

公开(公告)号：US20050089924A1

公开(公告)日：2005-04-28

申请号：US10332606

申请日：2001-08-14

申请人： Chih-Ming Ho ,  Tza-Huei Wang

发明人： Chih-Ming Ho ,  Tza-Huei Wang

IPC分类号： B01L3/00 ,  C12M1/34 ,  C12Q1/68 ,  C12Q1/6825 ,  C40B60/14 ,  G01N21/03 ,  G01N21/05 ,  G01N21/64 ,  G01N33/53

CPC分类号： B01L3/5027 ,  B01J2219/00317 ,  B01J2219/00511 ,  B01J2219/00576 ,  B01J2219/00605 ,  B01J2219/00653 ,  B01J2219/00666 ,  B01J2219/00702 ,  B01L3/502707 ,  B01L2300/168 ,  C12Q1/6825 ,  C40B60/14 ,  G01N21/0303 ,  G01N21/05 ,  G01N21/6428 ,  G01N21/645 ,  G01N27/4145 ,  G01N27/447 ,  G01N2021/0346 ,  G01N2021/058 ,  G01N2021/6463 ,  G01N2021/6476 ,  G01N2021/6482

摘要： The invention disclosed herein provides biosensors and methods which increase the sensitivity of assays of optically labelled molecules fluorescently tagged polypeptides and polynucleotides while decreasing the sample volume required for detection. By integrating reflective sidewalls into the receptacles used in such assays, the signal-to-noise ratio of the optical signal is increased significantly. Typically the receptacles are microchannels. In addition, the geometry of the receptacles can be controlled C to further optimize the signal-to-noise ratio of the optical signal. The invention disclosed herein further provides methods and devices involving integrated electronics, wherein an element such as a diode, a transistor, an integrated circuit etc., is integrated with a bioreactor/channel in order to facilitate the detection or fabrication of bio-materials.

摘要翻译： 本文公开的本发明提供了生物传感器和方法，其增加光学标记分子荧光标记的多肽和多核苷酸的测定的灵敏度，同时降低检测所需的样品体积。 通过将反射侧壁集成在这种测定中使用的插座中，光信号的信噪比显着增加。 通常，插座是微通道。 此外，可以控制插座的几何形状以进一步优化光信号的信噪比。 本文公开的本发明进一步提供涉及集成电子器件的方法和装置，其中诸如二极管，晶体管，集成电路等的元件与生物反应器/通道集成，以便促进生物材料的检测或制造。

公开(公告)号：US4519423A

公开(公告)日：1985-05-28

申请号：US512291

申请日：1983-07-08

申请人： Chih-Ming Ho ,  Ephraim Gutmark

发明人： Chih-Ming Ho ,  Ephraim Gutmark

IPC分类号： B01F5/04 ,  F16K19/00

CPC分类号： B01F5/045 ,  B01F5/0463 ,  Y10T137/87587 ,  Y10T137/87595 ,  Y10T137/87652

摘要： An apparatus for mixing fluids includes at least one noncircular orifice having unequal major and minor axis dimensions, with the major axis dimension being less than approximately 5 times the minor axis dimension. A first fluid is emitted from the orifice as a jet for mixing with another fluid in a region downstream of the orifice. The mixing region extends downstream a distance at least equal to the minor axis dimension, and then either terminates in a wall in the path of the jet or continues downstream to a total distance of at least approximately 3 times the minor axis dimension. The mixing region has a lateral width of at least 2(a+0.4x) in a direction parallel to the major axis and a lateral width of at least 2(b+0.4x) in a direction parallel to the minor axis, where a and b are one-half the major and minor axis dimensions, respectively, and x is the distance downstream of the orifice.

摘要翻译： 用于混合流体的装置包括至少一个具有不等的主轴和短轴尺寸的非圆形孔，其长轴尺寸小于短轴尺寸的大约5倍。 第一流体作为喷嘴从孔口排出，用于与孔口下游区域中的另一流体混合。 混合区域在下游延伸至少等于短轴尺寸的距离，然后终止于喷射路径中的壁，或者在下游延伸到至少约3倍于短轴尺寸的总距离。 混合区域在平行于长轴的方向上具有至少2（a + 0.4x）的横向宽度，并且在平行于短轴的方向上具有至少2（b + 0.4x）的横向宽度，其中a 和b分别是主轴和短轴尺寸的一半，x是孔口下游的距离。

公开(公告)号：US08765459B2

公开(公告)日：2014-07-01

申请号：US13562216

申请日：2012-07-30

申请人： Chih-Ming Ho ,  Pak Kin Wong ,  Ren Sun ,  Fuqu Yu

发明人： Chih-Ming Ho ,  Pak Kin Wong ,  Ren Sun ,  Fuqu Yu

IPC分类号： C12M1/00 ,  G05B19/42

CPC分类号： C12Q1/02 ,  C12M41/48 ,  C12Q3/00 ,  G01N35/0092 ,  G01N2035/0094 ,  Y02A90/26

摘要： The invention provides systems and methods for manipulating biological systems, for example to elicit a more desired biological response from a biological sample, such as a tissue, organ, and/or a cell. In one aspect, the invention operates by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The invention can be used, e.g., to optimize any biological system, e.g., bioreactors for proteins, and the like, small molecules, polysaccharides, lipids, and the like. Another use of the apparatus and methods includes is for the discovery of key parameters in complex biological systems.

摘要翻译： 本发明提供了用于操纵生物系统的系统和方法，例如从生物样品（例如组织，器官和/或细胞）引出更希望的生物反应。 在一个方面，本发明通过有效搜索刺激的大参数空间和系统参数来操作，控制和优化系统中持续的生物样品的响应。 在一个方面，本发明的系统和方法使用至少一种优化算法，以响应于传感器的响应信号的输出来修改致动器的用于刺激的控制输入。 本发明可用于例如优化任何生物系统，例如用于蛋白质的生物反应器等，小分子，多糖，脂质等。 该装置和方法的另一用途包括在复杂生物系统中发现关键参数。

公开(公告)号：US08411344B2

公开(公告)日：2013-04-02

申请号：US12805545

申请日：2010-08-05

申请人： Tsung-Hui Tsai ,  Fu-cheng Wang ,  Chih-Ming Ho ,  Chi-Te Liang

发明人： Tsung-Hui Tsai ,  Fu-cheng Wang ,  Chih-Ming Ho ,  Chi-Te Liang

IPC分类号： G02B26/02

CPC分类号： G02B26/004

摘要： The present invention discloses an electrical control light valve apparatus having liquid gallium. The invention comprises the transparent glass as a substrate, ITO transparent conductive film as the electrodes, the liquid gallium as the valve located on the ITO transparent conductive film, and the partial-transparent glass is located on the top of the electrical control light valve apparatus.

摘要翻译： 本发明公开了一种具有液态镓的电控光阀装置。 本发明包括作为基板的透明玻璃，作为电极的ITO透明导电膜，作为阀的液态镓位于ITO透明导电膜上，部分透明玻璃位于电动控制光阀装置的顶部 。

公开(公告)号：US06273553B1

公开(公告)日：2001-08-14

申请号：US09535903

申请日：2000-03-24

申请人： Chang-Jin Kim ,  Fan-Gang Tseng ,  Chih-Ming Ho

发明人： Chang-Jin Kim ,  Fan-Gang Tseng ,  Chih-Ming Ho

IPC分类号： B41J214

CPC分类号： B41J2/1404 ,  B05B1/14 ,  B05B17/04 ,  B41J2/14056 ,  B41J2/14072 ,  B41J2/14137 ,  B41J2002/1437 ,  B41J2002/14387 ,  B41J2202/05

摘要： An apparatus and method for forming a bubble within a microchannel of a microinjector to function as a valve mechanism between the chamber and manifold, that provides for a high resistance to liquid exiting the chamber through the manifold during fluid ejection through an orifice and that also provides a low resistance to refilling of liquid into the chamber after ejection of fluid and collapse of the bubble. This effectively minimizes cross talk between adjacent chambers and increases injection frequency of the microinjector. The formation of a second bubble within the chamber coalesces with a first formed bubble between the chamber and manifold to abruptly terminate the ejection of fluid, thereby eliminating satellite droplets.

摘要翻译： 一种用于在微型注射器的微通道内形成气泡的装置和方法，用作腔室和歧管之间的阀机构，其在通过孔口的流体喷射期间提供通过歧管离开腔室的液体的高抵抗力，并且还提供 弹出液体后液体进入室内的低阻力和气泡崩溃。 这有效地最小化相邻室之间的串扰，并增加微型注射器的注射频率。 室内的第二个气泡的形成与腔室和歧管之间的第一个形成的气泡结合在一起，从而突然终止流体的喷射，从而消除卫星液滴。

公开(公告)号：US6102530A

公开(公告)日：2000-08-15

申请号：US235663

申请日：1999-01-22

申请人： Chang-Jin Kim ,  Fan-Gang Tseng ,  Chih-Ming Ho

发明人： Chang-Jin Kim ,  Fan-Gang Tseng ,  Chih-Ming Ho

IPC分类号： B41J2/05 ,  B05B1/14 ,  B05B17/04 ,  B41J2/14 ,  F02M53/04

CPC分类号： B41J2/14137 ,  B05B17/04 ,  B41J2/1404 ,  B41J2/14056 ,  B41J2/14072 ,  B05B1/14 ,  B41J2002/1437 ,  B41J2002/14387 ,  B41J2202/05

摘要： An apparatus and method for forming a bubble within a microchannel of a microinjector to function as a valve mechanism between the chamber and manifold, that provides for a high resistance to liquid exiting the chamber through the manifold during fluid ejection through an orifice and that also provides a low resistance to refilling of liquid into the chamber after ejection of fluid and collapse of the bubble. This effectively minimizes cross talk between adjacent chambers and increases injection frequency of the microinjector. The formation of a second bubble within the chamber coalesces with a first formed bubble between the chamber and manifold to abruptly terminate the ejection of fluid, thereby eliminating satellite droplets.

摘要翻译： 一种用于在微型注射器的微通道内形成气泡的装置和方法，用作腔室和歧管之间的阀机构，其在通过孔口的流体喷射期间提供通过歧管离开腔室的液体的高抵抗力，并且还提供 弹出液体后液体进入室内的低阻力和气泡崩溃。 这有效地最小化相邻室之间的串扰，并增加微型注射器的注射频率。 室内的第二个气泡的形成与腔室和歧管之间的第一个形成的气泡结合在一起，从而突然终止流体的喷射，从而消除卫星液滴。

公开(公告)号：US5883310A

公开(公告)日：1999-03-16

申请号：US428334

申请日：1995-04-25

申请人： Chih-Ming Ho ,  Yu-Chong Tai ,  Fukang Jiang ,  Chang Liu ,  Jin-Biao Huang

发明人： Chih-Ming Ho ,  Yu-Chong Tai ,  Fukang Jiang ,  Chang Liu ,  Jin-Biao Huang

IPC分类号： G01F1/684 ,  G01P5/12 ,  G01B7/16

CPC分类号： G01P5/12 ,  G01F1/6845

摘要： A micromachined hot-wire anemometer having fast response times and higher sensitivities than conventional hot-wire anemometers is provided by micromachining doped polysilicon wires carried on silicon supports cantilevered from a substrate including one or more insulating layers disposed between said substrate and supports. The micromachined polysilicon hot-wire anemometer is fabricated using surface micromachining techniques.A shear stress sensor is micromachined to define a thin diaphragm over a cavity defined in a substrate underlying the diaphragm. The cavity is evacuated, sealed, and a thermistor disposed over the diaphragm. The thermistor is thus thermally insulated from the substrate and provides a low profile shear stress sensor for measuring flow rates in boundary layers above a flow surface.

摘要翻译： 具有比常规热线风速计更快的响应时间和更高灵敏度的微加工热线风速计通过微机械加工在从包括设置在所述衬底和支撑件之间的一个或多个绝缘层悬垂的硅衬底上的掺杂多晶硅线提供。 使用表面微加工技术制造微加工多晶硅热丝风速计。 剪切应力传感器被微加工以在限定在隔膜下方的基板中的空腔上限定薄膜。 空腔被抽真空，密封，并且设置在隔膜上方的热敏电阻。 因此，热敏电阻与基板热绝缘，并提供用于测量流动表面上方边界层中的流速的低剖面剪切应力传感器。