Pacific Biosciences of California, Inc.

Ravi Saxena

Annette Claire Grot

Stephen Wilson Turner

Nathaniel McCaffrey

Paul M Lundquist

Scott Edward Helgesen

Takashi Whitney Orimoto

Hou-Pu Chou

Mathieu Foquet

Michael Tzu Ru

Pezhman Monadgemi

Denis Zaccarin

Cheng Frank Zhong

Aaron J Rulison

Peiqian Zhao

Yanqiao Huang

William Robert Hanson

John Dixon

Simone Severi

Nicolaas Tack

Paul M Newby

Bidhan P Chaudhuri

Elizabeth Logan

Frank Zhong

Bert Du Bois

Nathaniel Joseph Mccaffrey

Pilar Gonzalez

Arrays of integrated analytical devices and their methods for production are provided. The arrays 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 integrated devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The arrays and methods of the invention make use of silicon chip fabrication and manufacturing techniques developed for the electronics industry and highly suited for miniaturization and high throughput.

Arrays of integrated analytical devices and methods for production

Arrays of integrated analytical devices and their methods for production are provided. The arrays 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 allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices include an integrated diffractive beam shaping element that provides for the spatial separation of light emitted from the optical reactions.

Arrays of integrated analytical devices

An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed.

Integrated analytical system and method

Arrays of integrated optical devices and their methods for production are provided. The devices include an integrated bandpass filter layer that comprises at least two multi-cavity filter elements with different central bandpass wavelengths. The device arrays 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 device arrays are well suited for miniaturization and high throughput.

Arrays of optical devices comprising integrated bandpass filters and methods of production

Disclosed are packaging methods for the fabrication of analytical device packages and fabricated analytical device packages. The methods include providing a sensor wafer and mounting individual plates or a plate wafer on the sensor wafer. The sensor wafer includes sensor chips with aperture regions and is treated with selective depositions, either prior to or during the fabrication of the analytical device packages, to produce different surface characteristics at different portions of the aperture regions. Before dicing the sensor wafer, openings of the individual plates or the plate wafer are covered by a protective layer to protect surface characteristics at different portions of the aperture regions. A fabricated analytical device package includes a sensor chip with different surface characteristics, a plate, a packaging substrate and an optional cover.

Packaging methods for fabrication of analytical device packages and analytical device packages made thereof

Processes for making high multiplex arrays for use in analyzing discrete reactions at ultra high multiplex with reduced optical noise, and increased system flexibility. The high multiplex arrays include substrates having integrated optical components that increase multiplex capability by one or more of increasing density of reaction regions, improving transmission of light to or collection of light from discrete reactions regions. Integrated optical components include reflective optical elements which re-direct illumination light and light emitted from the discrete regions to more efficiently collect emitted light. Particularly preferred applications include single molecule reaction analysis, such as polymerase mediated template dependent nucleic acid synthesis and sequence determination.

Process for making high multiplex arrays

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San Francisco, CA, United States of America

Ravi Saxena