公开(公告)号：US20060229818A1

公开(公告)日：2006-10-12

申请号：US11101096

申请日：2005-04-07

申请人： Ye Fang ,  Ann Ferrie ,  Norman Fontaine ,  Anthony Frutos ,  Eric Mozdy ,  Chuan-Che Wang ,  Po Yuen

发明人： Ye Fang ,  Ann Ferrie ,  Norman Fontaine ,  Anthony Frutos ,  Eric Mozdy ,  Chuan-Che Wang ,  Po Yuen

IPC分类号： G06F19/00

CPC分类号： G01N21/7743 ,  G01N21/253

摘要： The present invention includes several methods for modifying the current processes of manufacturing optical sensing microplates that use continuous waveguide films to reduce/eliminate crosstalk between the biosensors that are incorporated within wells. The methods include (1) physically deteriorating/removing the waveguide film between individual biosensors; (2) chemically depositing highly absorbing materials within the waveguide film between individual biosensors; (3) patterning disordered (scattering) regions between the diffraction gratings that define individual biosensors; (4) using a specific mask and depositing individual patches of waveguide film, where each patch defines at least one biosensor. Each of these methods and several other methods described herein prevent the propagation of light between individual sensing regions, thereby eliminating optical crosstalk between the biosensors. The present invention also includes the resulting microplate.

摘要翻译： 本发明包括几种用于修改制造光学感测微板的当前工艺的方法，其使用连续波导膜来减少/消除结合在孔内的生物传感器之间的串扰。 所述方法包括（1）在各个生物传感器之间物理劣化/去除波导膜; （2）在各个生物传感器之间在波导膜内化学沉积高吸收材料; （3）在限定单个生物传感器的衍射光栅之间图形化无序（散射）区域; （4）使用特定掩模并沉积波导膜的各个贴片，其中每个贴片限定至少一个生物传感器。 这些方法和本文所描述的其它方法中的每一种都防止光在各个感测区域之间的传播，从而消除了生物传感器之间的光学串扰。 本发明还包括所得到的微孔板。

公开(公告)号：US20070237447A1

公开(公告)日：2007-10-11

申请号：US11236060

申请日：2005-09-26

申请人： Eric Mozdy

发明人： Eric Mozdy

IPC分类号： G02B6/00

CPC分类号： G01N21/7743 ,  G01N21/21 ,  G01N21/253 ,  G01N33/54373

摘要： An optical interrogation system and a GCW sensor are described herein that are used to determine whether a biological substance (e.g., cell, molecule, protein, drug) is located in a sensing region of the GCW sensor. The optical interrogation system includes a light source, a polarization modulator and a detection system. The light source outputs a polarized light beam and the polarization modulator modulates the polarized light beam and outputs a polarization-modulated light beam. The GCW sensor receives and converts the polarization-modulated light beam into an amplitude modulated light beam that is directed towards the detection system. The detection system receives the amplitude modulated light beam and demodulates the received amplitude modulated light beam by responding to signals at a modulation frequency of the polarization-modulated light beam and ignoring noise affecting the signals outside the modulation frequency to detect a resonant condition (e.g., resonant angle, resonant wavelength). The detected resonant condition that has a one-to-one relationship with the refractive index of the superstrate containing the biological substance is analyzed to determine whether or not the biological substance is located in the sensing region of the GCW sensor.

摘要翻译： 本文描述了用于确定生物物质（例如，细胞，分子，蛋白质，药物）是否位于GCW传感器的感测区域中的光学询问系统和GCW传感器。 光学询问系统包括光源，偏振调制器和检测系统。 光源输出偏振光束，偏振光调制器调制偏振光束并输出偏振调制光束。 GCW传感器将偏振调制光束接收并转换成朝向检测系统的幅度调制光束。 检测系统接收幅度调制光束并通过响应于偏振调制光束的调制频率的信号来解调所接收的幅度调制光束，并且忽略影响调制频率外的信号的噪声以检测谐振条件（例如， 谐振角，谐振波长）。 分析与包含生物物质的覆盖物的折射率具有一对一关系的检测到的共振条件，以确定生物物质是否位于GCW传感器的感测区域中。

公开(公告)号：US20050236554A1

公开(公告)日：2005-10-27

申请号：US11100199

申请日：2005-04-05

申请人： Norman Fontaine ,  Eric Mozdy ,  Po Yuen

发明人： Norman Fontaine ,  Eric Mozdy ,  Po Yuen

IPC分类号： H01L27/00

CPC分类号： G01N21/6452 ,  G01N21/253 ,  G01N21/553 ,  G01N21/6456 ,  G01N21/7743

摘要： An optical interrogation system and method are described herein that can interrogate a two-dimensional (2D) array of optical sensors (e.g., grating coupled waveguide sensors) located in a 2D specimen plate (e.g., microplate). In one embodiment, the optical interrogation system has a launch system which directs an array of light beams towards the array of sensors in the two-dimensional specimen plate. The optical interrogation system also has a receive system that includes a Keplerian beam expander (used in reverse as a beam condenser) which receives an array of light beams output from the array of sensors and directs each received light beam to a unique region on the detection plane of a small area detector (e.g., CCD camera). In addition, the optical interrogation system has a processor that analyzes changes in the position or shape of each detected light beam to determine if a binding event (bio-chemical interaction) or a mass transport (cell-based assay) occurred, or to determine the rate of binding (kinetics) that occurred on each sensor.

摘要翻译： 本文描述了可以询问位于2D样本板（例如微板）中的光学传感器（例如，光栅耦合波导传感器）的二维（2D）阵列的光学询问系统和方法。 在一个实施例中，光学询问系统具有发射系统，该发射系统将光束阵列引向二维样本板中的传感器阵列。 光学询问系统还具有接收系统，其包括开普勒光束扩展器（反向用作光束聚光器），其接收从传感器阵列输出的光束阵列，并将每个接收的光束引导到检测上的唯一区域 平面的小区域检测器（例如CCD摄像机）。 此外，光学询问系统具有处理器，其分析每个检测到的光束的位置或形状的变化，以确定是否发生结合事件（生物化学相互作用）或质量传输（基于细胞的测定）或确定 在每个传感器上发生的结合速率（动力学）。

公开(公告)号：US20080063569A1

公开(公告)日：2008-03-13

申请号：US11900263

申请日：2007-09-11

申请人： Norman Fontaine ,  Prantik Mazumder ,  Mark Quesada ,  Eric Mozdy ,  Po Yuen

发明人： Norman Fontaine ,  Prantik Mazumder ,  Mark Quesada ,  Eric Mozdy ,  Po Yuen

IPC分类号： G01N21/01

CPC分类号： G01N21/7743 ,  G01N21/05 ,  G01N21/276 ,  G01N21/553 ,  G01N2021/0346 ,  G01N2021/058 ,  G01N2201/108 ,  G01N2201/1211 ,  G01N2201/1217 ,  G01N2201/127 ,  G01N2201/12723 ,  G01N2201/128 ,  Y10T436/117497 ,  Y10T436/2575

摘要： A system and method are described herein for self-referencing a sensor that is used to detect a biomolecular binding event and/or kinetics which occur in a sample solution flowing along side a reference solution in a micron-sized deep flow channel.

摘要翻译： 本文描述了一种系统和方法，用于自我参考用于检测在微米尺寸深流动通道中沿着参考溶液侧流动的样品溶液中发生的生物分子结合事件和/或动力学的传感器。

公开(公告)号：US20060141486A1

公开(公告)日：2006-06-29

申请号：US11027400

申请日：2004-12-29

申请人： Everett Coonan ,  Ye Fang ,  Ann Ferrie ,  Xiaodong Fu ,  Yulong Hong ,  Thomas Leslie ,  Xinghua Li ,  Beth Monahan ,  Eric Mozdy ,  Dirk Muller ,  Cameron Tanner ,  Patrick Tepesch ,  John Wight ,  Po Yuen

发明人： Everett Coonan ,  Ye Fang ,  Ann Ferrie ,  Xiaodong Fu ,  Yulong Hong ,  Thomas Leslie ,  Xinghua Li ,  Beth Monahan ,  Eric Mozdy ,  Dirk Muller ,  Cameron Tanner ,  Patrick Tepesch ,  John Wight ,  Po Yuen

IPC分类号： C12Q1/68 ,  G01N33/53 ,  C12M1/34 ,  B05D3/02

CPC分类号： B01L3/5085 ,  B01J2219/00315 ,  B01J2219/00317 ,  B01J2219/00423 ,  B01J2219/00639 ,  B01J2219/00644 ,  B01J2219/00722 ,  B01L2300/0819

摘要： The present invention relates to arrays comprising porous substrates for attachment of nucleic acids, polypeptides, membranes, or other biological or organic materials. In many embodiments, the arrays of the present invention have a flow-through configuration such that washing buffers or samples can access to the porous substrates from at least two sides of the arrays. The present invention also features arrays comprising UV-compatible porous substrates, arrays comprising three-dimensional membranes in sol-gels, and arrays comprising silica-based porous substrates prepared using a low-temperature fusion process.

摘要翻译： 本发明涉及包含用于连接核酸，多肽，膜或其它生物或有机材料的多孔底物的阵列。 在许多实施例中，本发明的阵列具有流通构型，使得洗涤缓冲液或样品可以从阵列的至少两侧进入多孔基底。 本发明还具有包含UV兼容的多孔基材，溶胶凝胶中包含三维膜的阵列和包含使用低温熔融法制备的基于二氧化硅的多孔基材的阵列的阵列。

公开(公告)号：US20050099622A1

公开(公告)日：2005-05-12

申请号：US11019439

申请日：2004-12-21

申请人： Stephen Caracci ,  Norman Fontaine ,  Eric Mozdy ,  Po Yuen

发明人： Stephen Caracci ,  Norman Fontaine ,  Eric Mozdy ,  Po Yuen

IPC分类号： G01N21/25 ,  G02B27/10 ,  G01J3/50

CPC分类号： G01N21/253 ,  G01N2201/04 ,  G01N2201/10 ,  G02B27/1086

摘要： Optical interrogation systems and methods are described herein that are capable of measuring the angles (or changes in the angles) at which light reflects, transmits, scatters, or is emitted from an array of sensors or specimens that are distributed over a large area 2-dimensional array. In one embodiment of the present invention, the optical interrogation system has a far-field diffraction measurement configuration so it can simultaneously receive the light from sensors in all or a sub-section of a sensor array at a detector. In another embodiment of the present invention, the optical interrogation system incorporates an anamorphic optical receive system that enables parallel detection of angular responses from the sensors in the 2D array. In yet another embodiment of the present invention, the optical interrogation system incorporates an angular measurement system which measures the change in angular tilt of the sensor plane when the sensor array is moved or removed and then replaced in the measurement system. Several other embodiments of optical interrogation systems and methods are also described herein. A significant advantage of the present invention is that the system has no critical moving or scanning parts, which are frequently the source of measurement sensitivity limitations.

摘要翻译： 本文描述了光学询问系统和方法，其能够测量光从其分布在大面积上的传感器或样本阵列2反射，透射，散射或发射的角度（或角度变化） 维数组。 在本发明的一个实施例中，光学询问系统具有远场衍射测量配置，因此它可以在检测器处同时从传感器阵列的全部或子部分接收来自传感器的光。 在本发明的另一实施例中，光学询问系统包括变形光学接收系统，其能够并行地检测来自2D阵列中的传感器的角度响应。 在本发明的另一个实施例中，光学询问系统包括角度测量系统，该系统测量当传感器阵列移动或移除并随后在测量系统中被更换时传感器平面的角度倾斜度的变化。 本文还描述了光询问系统和方法的其他几个实施例。 本发明的显着优点是该系统没有关键的移动或扫描部件，其经常是测量灵敏度限制的来源。

公开(公告)号：US20050025421A1

公开(公告)日：2005-02-03

申请号：US10632276

申请日：2003-08-01

申请人： Stephen Caracci ,  Mircea Despa ,  Eric Mozdy ,  Mark Salik

发明人： Stephen Caracci ,  Mircea Despa ,  Eric Mozdy ,  Mark Salik

IPC分类号： G01N21/77 ,  G02B6/34

CPC分类号： G01N21/7743

摘要： A grating-coupled waveguide (GCW) and a method are described herein that can be used to detect the presence of a biological substance (e.g., cell, drug, chemical compound) in a sensing region of the GCW. The GCW includes a substrate, a diffraction grating and a waveguide film that has a higher index of refraction than the substrate which has an index of refraction ≦1.5. The relatively low-index substrate effectively increases the sensitivity of the GCW by causing the waveguide mode to shift towards a biological substance located in a sensing region above the waveguide film, thereby increasing the field strength of the mode's evanescent tail in this region. In one embodiment, an array of the GCWs are incorporated within the wells of a microplate.

摘要翻译： 本文描述了可用于检测GCW感测区域中生物物质（例如细胞，药物，化合物）的存在的光栅耦合波导（GCW）和方法。 GCW包括具有比折射率<= 1.5的衬底更高的折射率的衬底，衍射光栅和波导膜。 相对低折射率的衬底通过使波导模式朝向位于波导膜上方的感测区域中的生物物质移动，从而有效地增加了GCW的灵敏度，从而增加了该区域中模式的渐逝尾部的场强。 在一个实施方案中，将GCW的阵列并入微板的孔内。

公开(公告)号：US20060093254A1

公开(公告)日：2006-05-04

申请号：US10977520

申请日：2004-10-28

申请人： Eric Mozdy

发明人： Eric Mozdy

IPC分类号： G02B6/26

CPC分类号： G01N21/253 ,  G02B6/02 ,  G02B6/4246

摘要： An interrogation system and method are described herein which use a single-fiber launch/receive system for interrogating a biosensor (optical sensor) to detect the occurrence of a bio-chemical interaction (e.g., biological binding of ligands with analytes). In one embodiment, the single-fiber launch/receive system utilizes a multimode fiber to help interrogate the biosensor. In another embodiment, the single-fiber launch/receive system utilizes a downjacketed singlemode fiber to help interrogate the biosensor.

摘要翻译： 本文描述了一种询问系统和方法，其使用单纤维发射/接收系统来询问生物传感器（光学传感器）以检测生物化学相互作用的发生（例如，配体与分析物的生物结合）。 在一个实施例中，单纤维发射/接收系统利用多模光纤来帮助询问生物传感器。 在另一个实施例中，单纤维发射/接收系统利用下夹式单模光纤来帮助询问生物传感器。

公开(公告)号：US20050070027A1

公开(公告)日：2005-03-31

申请号：US10676352

申请日：2003-09-30

申请人： Jacques Gollier ,  Eric Mozdy ,  Garrett Piech

发明人： Jacques Gollier ,  Eric Mozdy ,  Garrett Piech

IPC分类号： G01N21/55 ,  G01N33/543

CPC分类号： G01N21/7743 ,  Y10S436/805

摘要： A method for using a double resonance effect within a grating-coupled waveguide (GCW) sensor, as generated from a light beam with a given span of wavelengths or angles, is provided. The method can be used for label-independent detection of biological and chemical agents, to interrogate biological-binding events or chemical reactions within a sensing region at increased sensitivity, and with decreased sensitivity to environmental perturbations. Also described is an optical interrogation system incorporating the method.

摘要翻译： 提供了从具有给定的波长或角度的光束产生的在光栅耦合波导（GCW）传感器内使用双重共振效应的方法。 该方法可用于生物和化学试剂的标签无关检测，以增加的灵敏度询问感测区域内的生物结合事件或化学反应，并且对环境扰动的敏感性降低。 还描述了结合该方法的光学询问系统。

公开(公告)号：US20050018944A1

公开(公告)日：2005-01-27

申请号：US10627438

申请日：2003-07-25

申请人： Eric Mozdy

发明人： Eric Mozdy

IPC分类号： G01N21/21 ,  G01N21/25 ,  G01N21/77 ,  G01N33/543 ,  G02B6/00

CPC分类号： G01N21/7743 ,  G01N21/21 ,  G01N21/253 ,  G01N33/54373

摘要： An optical interrogation system and a GCW sensor are described herein that are used to determine whether a biological substance (e.g., cell, molecule, protein, drug) is located in a sensing region of the GCW sensor. The optical interrogation system includes a light source, a polarization modulator and a detection system. The light source outputs a polarized light beam and the polarization modulator modulates the polarized light beam and outputs a polarization-modulated light beam. The GCW sensor receives and converts the polarization-modulated light beam into an amplitude modulated light beam that is directed towards the detection system. The detection system receives the amplitude modulated light beam and demodulates the received amplitude modulated light beam by responding to signals at a modulation frequency of the polarization-modulated light beam and ignoring noise affecting the signals outside the modulation frequency to detect a resonant condition (e.g., resonant angle, resonant wavelength). The detected resonant condition that has a one-to-one relationship with the refractive index of the superstrate containing the biological substance is analyzed to determine whether or not the biological substance is located in the sensing region of the GCW sensor.

摘要翻译： 本文描述了用于确定生物物质（例如，细胞，分子，蛋白质，药物）是否位于GCW传感器的感测区域中的光学询问系统和GCW传感器。 光学询问系统包括光源，偏振调制器和检测系统。 光源输出偏振光束，偏振光调制器调制偏振光束并输出偏振调制光束。 GCW传感器将偏振调制光束接收并转换成朝向检测系统的幅度调制光束。 检测系统接收幅度调制光束并通过响应于偏振调制光束的调制频率的信号来解调所接收的幅度调制光束，并且忽略影响调制频率外的信号的噪声以检测谐振条件（例如， 谐振角，谐振波长）。 分析与包含生物物质的覆盖物的折射率具有一对一关系的检测到的共振条件，以确定生物物质是否位于GCW传感器的感测区域中。