Pacific Biosciences of California, Inc.

Caliper Life Sciences, Inc.

Canon U.S. Life Sciences, Inc.

Space Systems/loral, LLC

Canon U.s.a., Inc.

Aaron J Rulison

Mark E McDonald

Paul M Lundquist

Shang Wang

Michael Slater

Michael R Knapp

Steven A Sundberg

Edward P Donlon

Wesley Bryan Dong

Ivor T Knight

Deborah John Boles

Robert John Moti

Andrew Fabans

Allen R Boronkay

Mathieu Foquet

Ariel Herrmann

Alexey Kuritsyn

Russell Berman

Stephen Wilson Turner

Annette Claire Grot

Pezhman Monadgemi

Cheng Frank Zhong

Ravi Saxena

Denis Zaccarin

Peiqian Zhao

Yanqiao Huang

Deborah Pao-Tung Kwo

Tsuei-Lian Wang

Michael Greenstein

Jeffrey A Wolk

Morten Juel Jensen

Persefoni E Kechagia

Wael Kamel

Bruce Brogden

Ed Donlon

Richard W Schiek

Ernest Cw Lee

Masayoshi Hayashi

Mark Mcdonald

Frank Zhong

Ernest C W Lee

Ernest CW Lee

Deborah J Boles

Edward Dolon

Allen Borankay

Integrated target waveguide devices and optical analytical systems comprising such devices are provided. The target devices include an optical coupler that is optically coupled to an integrated waveguide and that is configured to receive optical input from an optical source through free space, particularly through a low numerical aperture interface. The devices and systems are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices provide for the efficient and reliable coupling of optical excitation energy from an optical source to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination. The devices and systems are well suited for miniaturization and high throughput.

Integrated target waveguide devices and systems for optical coupling

Provided herein are systems, devices, and methods for improved optical waveguide transmission and alignment in an analytical system. Waveguides in optical analytical systems can exhibit variable and increasing back reflection of single-wavelength illumination over time, thus limiting their effectiveness and reliability. The systems are also subject to optical interference under conditions that have been used to overcome the back reflection. Novel systems and approaches using broadband illumination light with multiple longitudinal modes have been developed to improve optical transmission and analysis in these systems. Novel systems and approaches for the alignment of a target waveguide device and an optical source are also disclosed.

Systems, devices, and methods for improved optical waveguide transmission and alignment

We describe methods of producing gratings such as Bragg gratings with optical waveguides. Described are the writing and erasing of gratings within SiON waveguides by forming standing waves. Methods, systems, instruments, and devices are described that provide improved transmission of light through such waveguides.

Producing bragg gratings in optical waveguides

The present invention provides novel methods and devices that employ microfluidic technology to generate molecular melt curves. In particular, the devices and methods in accordance with the invention are useful in providing for the analysis of PCR amplification products.

Method and apparatus for generating thermal melting curves in a microfluidic device

Optical delivery devices and integrated analytical systems comprising the optical delivery devices are provided. The optical delivery devices include optical inputs, optical outputs, and integrated optical waveguides that are configured for coupling of optical energy to a target waveguide device through free space. The integrated analytical systems include the optical delivery devices in combination with the target waveguide device. The devices and systems are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices provide for the efficient coupling of optical excitation energy from an optical source to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination. The devices and systems are well suited for miniaturization and high throughput.

Integrated devices and systems for free-space optical coupling

We have seen that some waveguides exhibit variable and increasing back reflection of single wavelength illumination over time, limiting their effectiveness and reliability. We have developed approaches to improve the transmission of these waveguides. We have found that by modulating the illumination wavelength over a small wavelength range we can reduce or eliminate this back reflection from the waveguide. In addition, we describe the writing and erasing of gratings within SiON waveguides by forming standing waves. Methods, systems, instruments, and devices are described that provide improved transmission of light through such waveguides.

Waveguide transmission

Apparatus, systems and methods for use in analyzing discrete reactions are provided. The analytical devices of the invention use an array of nanoscale regions (a chip) that has discrete patches, for example, patches of nanoscale regions. In some embodiments an analytical system is provided that has an analysis chip with an array of patches, each of the patches comprising nanoscale regions that emit fluorescent light when illuminated. The system has a two-dimensional (x, y) array of dichroic prisms, each prism comprising a dichroic element that diverts illumination light up in the z dimension of the array to a patch on the analysis chip above it. Each dichroic element transmits fluorescent light emitted by the patch that it illuminates, whereby the emitted light from each patch passes down through each dichroic prism. The analytical system also has a detector below the array of dichroic prisms that detects the transmitted fluorescent light. Such systems are useful for monitoring many analytical reactions at one time including single molecule sequencing reactions.

Analytical devices having dichroic prism arrays

Apparatus, systems and methods for use in analyzing discrete reactions are provided. The analytical devices of the invention use an array of nanoscale regions (a chip) that has discrete patches of nanoscale regions. The chip mates with a collection device comprising an array of compact lens trains (CLTs) where each of the CLTs corresponds to a single patch of nanoscale regions. Each CLT collects the emitted light from a patch on the chip, collimates the light, performs color separation on the collimated emitted light, and focuses the separated light onto a portion of pixels on the detector below the CLT. Such systems are useful for monitoring many analytical reactions at one time including single molecule sequencing reactions.

Analytical devices having compact lens train arrays

Growing community of inventors

Mountain View, CA, United States of America

Aaron J Rulison