公开(公告)号：US07283221B2

公开(公告)日：2007-10-16

申请号：US10723548

申请日：2003-11-25

Applicant: Michael I. Larkin

Inventor： Michael I. Larkin

IPC: G01N21/41

CPC classification number: G01N21/4133

Abstract: An improved cell for a walk-off refractometer is disclosed that permits measurement of the differential refractive index, DRI, between a sample fluid and a reference fluid. In addition, the new cell design permits the measurement of the refractive index, RI, of a fluid relative to the refractive index of the material comprising or surrounding the flow cell. Thus a single instrument may be used to measure separately the RI of a sample fluid and the DRI between a sample fluid and a reference fluid. The new flow cell contains two chambers, typical of a DRI instrument, but an asymmetric internal angle in either the sample or the reference chamber. By the provision of this unique structure, it is an objective of this invention to be able to measure the refractive index of a fluid relative to the refractive index of the material comprising the flow cell or relative to the medium surrounding the flow cell, either of which may be considered a measurement of the RI of the fluid. With the addition of mirror means, it is the further objective of this invention to improve its sensitivity. A further objective of the invention is to measure the asymmetric internal angle of the flow cell using well-characterized reference fluids.

Abstract translation: 公开了用于离散折射计的改进的电池，其允许测量样品流体和参考流体之间的差示折射率DRI。 此外，新的电池设计允许测量流体相对于包含或围绕流动池的材料的折射率的折射率RI。 因此，可以使用单个仪器来单独测量样品流体的RI和样品流体和参考流体之间的DRI。 新的流通池包含典型的DRI仪器的两个腔室，或样品或参考室中的不对称内角。 通过提供这种独特的结构，本发明的目的是能够相对于包含流动池的材料的折射率或相对于流动池周围的介质的折射率来测量流体的折射率， 这可以被认为是流体的RI的测量。 通过添加镜面装置，本发明的另一个目的是提高其灵敏度。 本发明的另一个目的是使用良好表征的参考流体来测量流动池的不对称内角。

公开(公告)号：US09347869B2

公开(公告)日：2016-05-24

申请号：US14553867

申请日：2014-11-25

Applicant: Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

Inventor： Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

IPC: G01N21/00 ,  G01N21/01 ,  G01N21/51 ,  G01N21/03 ,  G01N21/25

CPC classification number: G01N21/01 ,  G01N21/0303 ,  G01N21/253 ,  G01N21/51 ,  G01N2201/06113

Abstract: A lid for a multiwell plates which allows improved light scattering measurement of liquid samples within the wells of a multiwell plate, and which at the same time mitigates evaporation from said samples is disclosed. A surface element protrudes from the bottom of the lid into the fluid in a well. The protruding element may be hollow or solid, and the beam of light, directed into the element may act to capture or direct the beam while preventing backscatter from reaching the light scattering detector or detectors. The protruding element may thus direct the beam from the well without the beam having to pass through a fluid/air interface. The angle and shape of the lid surfaces may be optimized to minimize or eliminate back-reflection. Light absorbing and/or light blocking colorization may also be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

公开(公告)号：US20150077739A1

公开(公告)日：2015-03-19

申请号：US14553867

申请日：2014-11-25

Applicant: Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

Inventor： Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

IPC: G01N21/01 ,  G01N21/51

CPC classification number: G01N21/01 ,  G01N21/0303 ,  G01N21/253 ,  G01N21/51 ,  G01N2201/06113

Abstract: A lid for a multiwell plates which allows improved light scattering measurement of liquid samples within the wells of a multiwell plate, and which at the same time mitigates evaporation from said samples is disclosed. A surface element protrudes from the bottom of the lid into the fluid in a well. The protruding element may be hollow or solid, and the beam of light, directed into the element may act to capture or direct the beam while preventing backscatter from reaching the light scattering detector or detectors. The protruding element may thus direct the beam from the well without the beam having to pass through a fluid/air interface. The angle and shape of the lid surfaces may be optimized to minimize or eliminate back-reflection. Light absorbing and/or light blocking colorization may also be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

Abstract translation: 用于多孔板的盖子，其允许在多孔板的孔内的液体样品的改进的光散射测量，并且同时减轻所述样品的蒸发。 表面元件从盖的底部突出到井中的流体中。 突出元件可以是中空的或固体的，并且引导到元件中的光束可以用于捕获或引导光束，同时防止反向散射到达光散射检测器或检测器。 因此，突出元件可以将梁从井引导，而梁不必通过流体/空气界面。 可以优化盖表面的角度和形状以最小化或消除背反射。 还可以采用光吸收和/或遮光着色来最小化或消除背反射。 蒸发是通过用盖子将油井物理地盖上来控制的，或者密封在井的顶部或者井的内表面。

公开(公告)号：US20230073288A1

公开(公告)日：2023-03-09

申请号：US17800271

申请日：2021-02-24

Applicant: Jennifer C. P. WANG ,  Kelsey A. RICHARDS ,  Jayesh DESAI ,  Bhumit A. PATEL ,  Michael A. WINTERS ,  Patrick M. MCHUGH ,  Philip R. KUHL ,  John P. HIGGINS ,  Michael I. LARKIN ,  Michelle H. CHEN ,  Merck Sharp & Dohme LLC

Inventor： Jennifer C. P. Wang ,  Kelsey A. Richards ,  Jayesh Desai ,  Bhumit A. Patel ,  Michael A. Winters ,  Patrick M. McHugh ,  Philip R. Kuhl ,  John P. Higgins ,  Michael I. Larkin ,  Michelle H. Chen

IPC: A61K39/09 ,  C08B37/00

Abstract: The present invention relates to Polysaccharide Size-Reduction Monitoring Methods useful for the non-invasive, and accurate monitoring of the progress of a polysaccharide size-reduction process.

公开(公告)号：US08976353B2

公开(公告)日：2015-03-10

申请号：US13492527

申请日：2012-06-08

Applicant: Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

Inventor： Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

IPC: G01N21/00 ,  G01N21/01 ,  G01N21/51 ,  G01N21/03 ,  G01N21/25

CPC classification number: G01N21/01 ,  G01N21/0303 ,  G01N21/253 ,  G01N21/51 ,  G01N2201/06113

Abstract: A lid for multiwell plates, allowing improved optical measurement of liquid samples within its wells, while mitigating evaporation from said samples, is disclosed. A surface element protrudes from the bottom of the lid into the fluid within a well. The protruding element may be hollow or solid such that light directed into the element may act to capture or direct the beam while preventing backscatter from reaching one or more detectors. The protruding element may direct the beam from the well without requiring the beam to pass through a fluid/air interface. The angle and shape of the lid surfaces and/or light absorbing/blocking colorization may be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

Abstract translation: 公开了一种用于多孔板的盖，其允许改进其孔内的液体样品的光学测量，同时减轻所述样品的蒸发。 表面元件从盖的底部突出到井内的流体中。 突出元件可以是中空的或固体的，使得被引导到元件中的光可以用于捕获或引导光束，同时防止反向散射到达一个或多个检测器。 突出元件可以将梁从井中引导，而不需要光束通过流体/空气界面。 可以使用盖表面的角度和形状和/或光吸收/阻挡着色来最小化或消除背反射。 蒸发是通过用盖子将油井物理地盖上来控制的，或者密封在井的顶部或者井的内表面。

公开(公告)号：US09658156B2

公开(公告)日：2017-05-23

申请号：US13578593

申请日：2011-02-25

Applicant: Michael I. Larkin

Inventor： Amy D. Hanlon ,  Michael I. Larkin

IPC: G01N21/00 ,  G01N21/49 ,  G01N21/47 ,  G01N15/14 ,  G01N15/02 ,  G01N15/00

CPC classification number: G01N21/49 ,  G01N15/0211 ,  G01N15/1429 ,  G01N15/1434 ,  G01N21/4738 ,  G01N2015/0038 ,  G01N2015/0092 ,  G01N2015/0216 ,  G01N2015/0222 ,  G01N2201/06113 ,  G01N2201/12

Abstract: This invention enables high throughput detection of small molecule effectors of particle association, as well as quantification of association constants, stoichiometry, and conformation. Given a set of particle solutions having different concentrations, dynamic light scattering measurements are used to determine the average hydrodynamic radius, as a function of concentration. The series of average hydrodynamic radii as a function of concentration are fitted with stoichiometric association models containing the parameters of molar mass, modeled concentrations, and modeled hydrodynamic radii of the associated complexes. In addition to the average hydrodynamic radii value analysis, the experimental data may be fit/analyzed in alternate ways. This method may be applied to a single species that is self-associating or to multiple species that are hetero-associating. This method may also be used to characterize and quantify the association between a modulator and the associating species.

公开(公告)号：US07027138B2

公开(公告)日：2006-04-11

申请号：US10961633

申请日：2004-10-07

Applicant: Michael I. Larkin ,  Steven P. Trainoff

Inventor： Michael I. Larkin ,  Steven P. Trainoff

IPC: G01N21/41

CPC classification number: G01N21/4133

Abstract: An improved differential refractometer incorporating a photodetector array is disclosed. Using a multi-element photo array provides the basis for measurement of differential refractive index values with a heretofore unattainable combination of sensitivity of measurement and concurrent range of measurement. Within the large dynamic range attainable, the detector structure provides equal sensitivity irrespective of deflection within the range. The transmitted light beam is tailored to provide a spatial variation of the light intensity at the array improving thereby the precision of measurement of its displacement. This in turn results in improved precision in the reported differential refractive index and in the calculation of the differential refractive index increment dn/dc. Integrating the detector array into the flow cell structure of the parent case results in a detector of exceptional sensitivity and range for sample quantities far smaller than required by conventional differential refractometers.

Abstract translation: 公开了一种结合光电检测器阵列的改进的差示折射计。 使用多元素照片阵列提供了测量差异折射率值的基础，具有迄今无法测量的灵敏度和同时测量范围的组合。 在可获得的大动态范围内，检测器结构提供相等的灵敏度，而与范围内的偏转无关。 传输光束被调整以提供阵列处的光强度的空间变化，从而提高其位移的测量精度。 这反过来导致报告的折射率和在差分折射率增量dn / dc的计算中的精度提高。 将检测器阵列集成到母机壳体的流动池结构中，可以得到远远小于常规差示折射计所需的样品量的特殊灵敏度和范围的检测器。

公开(公告)号：US20130215424A1

公开(公告)日：2013-08-22

申请号：US13578593

申请日：2011-02-25

Applicant: Amy D. Hanlon ,  Michael I. Larkin

Inventor： Amy D. Hanlon ,  Michael I. Larkin

IPC: G01N21/47

CPC classification number: G01N21/49 ,  G01N15/0211 ,  G01N15/1429 ,  G01N15/1434 ,  G01N21/4738 ,  G01N2015/0038 ,  G01N2015/0092 ,  G01N2015/0216 ,  G01N2015/0222 ,  G01N2201/06113 ,  G01N2201/12

Abstract: This invention enables high throughput detection of small molecule effectors of particle association, as well as quantification of association constants, stoichiometry, and conformation. Given a set of particle solutions having different concentrations, dynamic light scattering measurements are used to determine the average hydrodynamic radius, as a function of concentration. The series of average hydrodynamic radii as a function of concentration are fitted with stoichiometric association models containing the parameters of molar mass, modeled concentrations, and modeled hydrodynamic radii of the associated complexes. In addition to the average hydrodynamic radii value analysis, the experimental data may be fit/analyzed in alternate ways. This method may be applied to a single species that is self-associating or to multiple species that are hetero-associating. This method may also be used to characterize and quantify the association between a modulator and the associating species.

Abstract translation: 本发明能够实现小分子效应器的高通量检测，以及关联常数，化学计量学和构象的定量。 给定一组具有不同浓度的颗粒溶液，使用动态光散射测量来确定作为浓度的函数的平均流体动力学半径。 作为浓度函数的一系列平均流体动力学半径拟合含有摩尔质量参数，模拟浓度和相关络合物的模拟流体动力学半径的化学计量关联模型。 除了平均流体动力学半径值分析之外，实验数据可以以替代方式进行拟合/分析。 该方法可以应用于自缔合的单个物种或与异缔合的多种物质。 该方法还可用于表征和量化调节剂与缔合物种之间的关联。

公开(公告)号：US20130176556A1

公开(公告)日：2013-07-11

申请号：US13492527

申请日：2012-06-08

Applicant: Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

Inventor： Michael I. Larkin ,  Amy D. Hanlon ,  Daniel I. Some ,  Richard J. Sleiman ,  David N. Villalpando

IPC: G01N21/01 ,  G01N21/51

CPC classification number: G01N21/01 ,  G01N21/0303 ,  G01N21/253 ,  G01N21/51 ,  G01N2201/06113

Abstract: A lid for multiwell plates, allowing improved optical measurement of liquid samples within its wells, while mitigating evaporation from said samples, is disclosed. A surface element protrudes from the bottom of the lid into the fluid within a well. The protruding element may be hollow or solid such that light directed into the element may act to capture or direct the beam while preventing backscatter from reaching one or more detectors. The protruding element may direct the beam from the well without requiring the beam to pass through a fluid/air interface. The angle and shape of the lid surfaces and/or light absorbing/blocking colorization may be employed to minimize or eliminate back reflection. Evaporation is controlled by physically capping the well with the lid, either sealing against the face at the top of the well or the inside surface of the well.

公开(公告)号：US06975392B2

公开(公告)日：2005-12-13

申请号：US10768600

申请日：2004-01-29

Applicant: Michael I. Larkin

Inventor： Michael I. Larkin

IPC: G01N21/15 ,  G01N21/41 ,  G01N1/10

CPC classification number: G01N21/4133

Abstract: A sensitivity-enhanced flow cell to be used in the determination of the differential refractive index increment of a sample fluid relative to a reference fluid is disclosed. The invention permits the use of smaller sample amounts without sacrificing overall sensitivity. Equally important, said improved flow cell produces measurements of increased precision without requirement for increased sample amount. This is achieved by means of two chambers within said cell whose volumes are different. The sample fluid chamber is the smaller of the two with the reference fluid chamber constructed so that the incident illumination beam, upon passage through said sample chamber and displacement by the partition element located therebetween said sample and reference chambers, passes through said reference chamber without grazing any of the confining walls or striking corners of said sensitivity-enhanced flow cell. As the amount of deflection of said transmitted beam depends upon the refractive indices of the fluids relative to the transparent matter of which the containing cell is comprised, as well as the RI difference between said fluids themselves, the reference chamber is designed to transmit said incident light beam without grazing degradation thereof for all practical ranges of expected fluid and cell refractive indices.

Abstract translation: 公开了用于确定样品流体相对于参考流体的差示折射率增量的灵敏度增强的流动池。 本发明允许使用更小的样品量而不牺牲总体灵敏度。 同样重要的是，所述改进的流动池产生增加的精度的测量，而不需要增加的样品量。 这通过其体积不同的所述电池内的两个室来实现。 样品流体室是两个中较小的一个，其中参考流体室被构造成使得入射照明光束在通过所述样品室并且位于所述样品和参考室之间的分隔元件的位移时通过所述参考室而不放牧 所述灵敏度增强型流动池的任何限制壁或撞击角。 由于所述透射光束的偏转量取决于流体相对于包含容纳细胞的透明物质的折射率以及所述流体本身之间的RI差异，所以参考室被设计成透射所述事件 光束在预期流体和电池折射率的所有实际范围内不会放射降解。