公开(公告)号：US06569672B1

公开(公告)日：2003-05-27

申请号：US09489586

申请日：2000-01-21

Applicant: James A. Laugharn, Jr. ,  Gustav H. Dreier ,  Edwin A. Rudd ,  David J. Green

Inventor： James A. Laugharn, Jr. ,  Gustav H. Dreier ,  Edwin A. Rudd ,  David J. Green

IPC: C12M136

CPC classification number: C12N9/00 ,  B01J3/00 ,  B01J19/185 ,  B01J2219/00162 ,  B01J2219/002 ,  B01J2219/00211 ,  B01J2219/00229 ,  Y10T436/143333

Abstract: Methods and apparatus in which pressure provides precise control over the timing and preferably synchronization of chemical reactions, particularly enzymatic reactions.

Abstract translation: 压力提供对时间的精确控制的方法和装置，优选化学反应特别是酶反应的同步。

公开(公告)号：US06258534B1

公开(公告)日：2001-07-10

申请号：US09035652

申请日：1998-03-05

Applicant: James A. Laugharn, Jr. ,  David J. Green ,  Robert A. Hess

Inventor： James A. Laugharn, Jr. ,  David J. Green ,  Robert A. Hess

IPC: C12Q168

CPC classification number: C12Q1/6813 ,  C12Q2527/113

Abstract: A method of hybridizing a first nucleic acid to a second nucleic acid at least partially complementary to the first nucleic acid by (1) providing a sample vessel and pressure controller for the vessel; and (2) contacting the first and second nucleic acids within the vessel at a pressure above ambient pressure that is effective to enhance hybridization of the first and second nucleic acids.

Abstract translation: （1）提供用于血管的样品容器和压力控制器的将第一核酸与至少部分与第一核酸互补的第二核酸杂交的方法; 和（2）在高于环境压力的压力下使容器内的第一和第二核酸接触，其有效增强第一和第二核酸的杂交。

公开(公告)号：US09267867B2

公开(公告)日：2016-02-23

申请号：US12489693

申请日：2009-06-23

Applicant: James A. Laugharn, Jr.

Inventor： James A. Laugharn, Jr.

IPC: C12M1/33 ,  C12M3/06 ,  G01N1/28 ,  B01F11/02 ,  G01N35/00

CPC classification number: G01N1/286 ,  B01F11/0283 ,  B01J2219/00308 ,  B01J2219/00344 ,  B01J2219/00486 ,  B01J2219/00722 ,  B01J2219/0074 ,  G01N2035/00554

Abstract: Method and apparatus for controlling acoustic treatment of a sample including a liquid. A processing volume in which the sample is acoustically treated may be controlled, e.g., by positioning a suitable element so as to reduce and/or eliminate a headspace at a sample/gas interface. An interaction between the acoustic energy and the sample may be controlled, e.g., by using an energy director positioned at least partially in the sample that helps to reduce splashing or other sample ejection that would otherwise occur.

Abstract translation: 用于控制包括液体的样品的声学处理的方法和装置。 可以例如通过定位合适的元件以减少和/或消除样品/气体界面处的顶部空间来控制其中声学处理样品的处理体积。 可以例如通过使用至少部分地定位在样品中的能量导向器来控制声能和样品之间的相互作用，这有助于减少否则将发生的飞溅或其它样品喷射。

公开(公告)号：US08709359B2

公开(公告)日：2014-04-29

申请号：US12984919

申请日：2011-01-05

Applicant: James A. Laugharn, Jr.

Inventor： James A. Laugharn, Jr.

IPC: G01N1/28 ,  G02B21/34 ,  B01L3/00

CPC classification number: G01N1/286 ,  G01N2001/2866

Abstract: Method and apparatus for holding and/or treating a sample material. A sample material may be positioned in a vessel between top and bottom flexible films where the flexible films are connected together by a substantially rigid support structure that surrounds the sample material. A crushing force may be applied to the sample material via the top and bottom flexible films, e.g., to pulverize the sample at cryogenic temperatures. A sample holder may have two vessels, one arranged for applying a crushing force to a first sample and another for holding a sample for other processing, such as a histology analysis.

Abstract translation: 用于保持和/或处理样品材料的方法和设备。 样品材料可以位于顶部和底部柔性膜之间的容器中，其中柔性膜通过围绕样品材料的基本刚性的支撑结构连接在一起。 可以通过顶部和底部柔性膜将样品材料施加破碎力，例如在低温下粉碎样品。 样品架可以具有两个容器，一个被布置用于对第一个样品施加破碎力，另一个容纳用于其他处理的样品，例如组织学分析。

公开(公告)号：US06274726B1

公开(公告)日：2001-08-14

申请号：US09016062

申请日：1998-01-30

Applicant: James A. Laugharn, Jr. ,  Robert A. Hess ,  Feng Tao

Inventor： James A. Laugharn, Jr. ,  Robert A. Hess ,  Feng Tao

IPC: C07H2100

CPC classification number: G01N30/00 ,  B01L3/5027 ,  B01L3/50273 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/14 ,  B01L2400/0406 ,  B01L2400/0418 ,  B01L2400/0421 ,  B01L2400/0487 ,  B01L2400/0688 ,  C12N1/06 ,  C12N15/101 ,  G01N27/44704 ,  G01N30/02 ,  G01N30/14 ,  G01N30/52 ,  G01N30/6047 ,  G01N2030/009 ,  G01N2030/285 ,  G01N2030/522 ,  G01N2030/8813 ,  B01D15/365 ,  B01D15/32

Abstract: The invention is based on the discovery that hyperbaric, hydrostatic pressure reversibly alters the partitioning of biomolecules between certain adsorbed and solvated phases relative to partitioning at ambient pressure. The new methods and devices disclosed herein make use of this discovery for highly selective and efficient, low salt isolation and purification of nucleic acids from a broad range of sample types, including forensic samples, blood and other body fluids, and cultured cells. In one embodiment, the invention features a pressure-modulation apparatus. The apparatus includes an electrode array system having at least two (i.e., two, three, four, or more) electrodes; and a conduit interconnecting the electrodes. The conduit contains an electrically conductive fluid in contact with a phase positioned in a pressure chamber. The phase can be, for example, a binding medium or stationary phase.

Abstract translation: 本发明基于以下发现：高压静水压力相对于在环境压力下的分配可逆地改变某些吸附和溶剂化相之间生物分子的分配。 本文公开的新方法和装置利用这一发现，从广泛范围的样品类型（包括法医样品，血液和其他体液以及培养的细胞）中高度选择性和有效的低盐分离和纯化核酸。在一个 本发明的特征在于压力调制装置。 该装置包括具有至少两个（即，两个，三个，四个或更多个）电极的电极阵列系统; 和连接电极的导管。 导管包含与定位在压力室中的相位接触的导电流体。 该相可以是例如结合介质或固定相。

公开(公告)号：US06245506B1

公开(公告)日：2001-06-12

申请号：US08903615

申请日：1997-07-30

Applicant: James A. Laugharn, Jr. ,  Robert A. Hess

Inventor： James A. Laugharn, Jr. ,  Robert A. Hess

IPC: C12Q168

CPC classification number: C12Q1/37 ,  C12Q1/6874 ,  G01N33/6818 ,  G01N33/6848 ,  C12Q2527/109 ,  C12Q2537/149

Abstract: The invention is based on the discovery that the sequence of monomers in a polymeric biomolecule can be determined in a self-contained, high pressure reaction and detection apparatus, without the need for fluid flow into or out from the apparatus. The pressure is used to control the activity of enzymes that digest the polymeric biomolecule to yield the individual monomers in the sequence in which they existed in the polymer. High pressures modulate enzyme kinetics by reversibly inhibiting those enzymatic processes which result in a higher average activation volume, when compared to the ground state, and reversibly accelerating those processes which have lower activation volumes than the ground state. Modulating the pressure allows the experimenter to precisely control the activity of the enzyme. Conditions can be found, for example, where the enzyme removes only one monomer (e.g., a nucleotide or amino acid) from the biomolecule before the pressure is again raised to a prohibitive level. The identity of the single released nucleotide or amino acid can be determined using a detector that is in communication with a probe in the detection zone within the reaction vessel.

Abstract translation: 本发明基于以下发现：聚合物生物分子中的单体序列可以在独立的高压反应和检测装置中测定，而不需要流体流入或流出装置。 压力用于控制消化聚合物生物分子的酶的活性，以产生它们存在于聚合物中的序列中的各个单体。 高压通过可逆地抑制这些酶过程来调节酶动力学，其导致与基态相比更高的平均活化体积，并且可逆地加速具有比基态更低的活化体积的那些过程。 调节压力允许实验者精确控制酶的活性。 可以发现条件，例如，在再次将压力升至高水平之前酶仅从生物分子中除去一种单体（例如，核苷酸或氨基酸）的情况。 可以使用与反应容器内的检测区域中的探针连通的检测器来确定单个释放的核苷酸或氨基酸的身份。

公开(公告)号：US6127534A

公开(公告)日：2000-10-03

申请号：US10892

申请日：1998-01-22

Applicant: Robert A. Hess ,  James A. Laugharn, Jr.

Inventor： Robert A. Hess ,  James A. Laugharn, Jr.

IPC: C12N15/10 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04

CPC classification number: C12N15/1006

Abstract: The invention is based on the discovery that pressure-induced changes in the free ion activity of a solution can be used to reversibly modulate the rate or the equilibrium position of chemical reactions, including catalytic reactions and associating/dissociating reactions. Pressure-induced changes in free-ion activity can also be used to improve separation processes.

Abstract translation: 本发明基于以下发现：溶液的自由离子活性的压力诱导变化可用于可逆地调节化学反应的速率或平衡位置，包括催化反应和缔合/解离反应。 压力诱导的游离离子活性变化也可用于改善分离过程。

公开(公告)号：US6111096A

公开(公告)日：2000-08-29

申请号：US962280

申请日：1997-10-31

Applicant: James A. Laugharn, Jr. ,  Robert A. Hess ,  Feng Tao

Inventor： James A. Laugharn, Jr. ,  Robert A. Hess ,  Feng Tao

IPC: B01L3/00 ,  C12M1/33 ,  C12N1/06 ,  C12N15/10 ,  G01N27/447 ,  G01N30/00 ,  G01N30/02 ,  G01N30/14 ,  G01N30/28 ,  G01N30/52 ,  G01N30/60 ,  G01N30/88 ,  C07H21/00

CPC classification number: G01N30/00 ,  B01L3/5027 ,  B01L3/50273 ,  C12N1/06 ,  C12N15/101 ,  G01N27/44704 ,  G01N30/52 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/14 ,  B01L2400/0406 ,  B01L2400/0418 ,  B01L2400/0421 ,  B01L2400/0487 ,  B01L2400/0688 ,  G01N2030/009 ,  G01N2030/285 ,  G01N2030/522 ,  G01N2030/8813 ,  G01N30/02 ,  G01N30/14 ,  G01N30/6047

Abstract: The invention is based on the discovery that hyperbaric, hydrostatic pressure reversibly alters the partitioning of nucleic acids between certain adsorbed and solvated phases relative to partitioning at ambient pressure. The new methods and devices disclosed herein make use of this discovery for highly selective and efficient, low salt isolation and purification of nucleic acids from a broad range of sample types, including forensic samples, blood and other body fluids, and cultured cells.

Abstract translation: 本发明基于以下发现：高压静水压力相对于在环境压力下的分配可逆地改变在某些吸附和溶剂化相之间的核酸分配。 本文公开的新方法和装置利用这一发现，用于从范围广泛的样品类型（包括法医样品，血液和其他体液以及培养细胞）中高度选择性和有效的低盐分离和纯化核酸。

公开(公告)号：US09108194B2

公开(公告)日：2015-08-18

申请号：US13242665

申请日：2011-09-23

Applicant: Guillaume Durin ,  James A. Laugharn, Jr.

Inventor： Guillaume Durin ,  James A. Laugharn, Jr.

IPC: G01N1/28 ,  B01L3/00 ,  C12N15/10 ,  C12Q1/68

CPC classification number: B01L3/50215 ,  B01L3/5021 ,  B01L3/50255 ,  B01L2200/0631 ,  B01L2200/0663 ,  B01L2200/141 ,  B01L2300/042 ,  B01L2300/0681 ,  B01L2300/0838 ,  B01L2300/0841 ,  B01L2300/0854 ,  B01L2400/0409 ,  B01L2400/0463 ,  B01L2400/086 ,  C12N15/10 ,  C12Q1/6806 ,  G01N1/28 ,  Y10T436/25

Abstract: Systems and methods include processing devices used to fragment nucleic acids to average nucleic acid sizes ranging from between about 5 kbp and about 20 kbp. A processing device may include an inlet portion and a channel upstream from a shearing region arranged so that a relatively constant pressure is established and maintained (e.g., a pressure that changes by less than about 40%) at an entrance of the shearing region during a majority of sample flow through the shearing region. In some embodiments, after forcing the sample through the shearing region once, the processing device may be taken out of the centrifuge, inverted and placed back into the centrifuge so that the sample is forced through the shearing region again.

Abstract translation: 系统和方法包括用于分解核酸以平均约5kbp至约20kbp的核酸大小的加工装置。 处理装置可以包括入口部分和从剪切区域上游的通道，其布置成使得在剪切区域的入口处建立和维持相对恒定的压力（例如，变化小于约40％的压力） 大部分样品流过剪切区域。 在一些实施方案中，在将样品强制通过剪切区域一次之后，处理装置可以从离心机中取出，倒置并放回到离心机中，使得样品再次被迫穿过剪切区域。

公开(公告)号：US08459121B2

公开(公告)日：2013-06-11

申请号：US12914370

申请日：2010-10-28

Applicant: James A. Laugharn, Jr. ,  Carl Beckett

Inventor： James A. Laugharn, Jr. ,  Carl Beckett

IPC: G01N29/28

CPC classification number: B01J19/10 ,  A61L2/025 ,  B01F3/08 ,  B01F3/12 ,  B01F11/02 ,  B01F11/0283 ,  B01F2215/0037 ,  B01J19/006 ,  B01J19/008 ,  B01J19/245 ,  B01J2219/00094 ,  C12N13/00

Abstract: Methods and systems for acoustically treating material using a continuous process in which material may be caused to flow in a continuous or intermittent fashion into/out of an acoustic treatment chamber where the material is exposed to focused acoustic energy. The methods and systems may be arranged to permit continuous processing for extended periods while an acoustic energy source operates at a relatively high power output. Treatment chambers may include features such as an acoustic window, a heat exchanger, inlet/outlet flow arrangements, an inspection window, insert elements that define a treatment volume size or shape, etc. Treatment system configurations relating to arrangements of a treatment chamber relative to an acoustic source and coupling medium, material flow paths, and others are provided.