Element Biosciences, Inc.

Second Sight Medical Products, Inc.

Illumina Corporation

Doheny Eye Institute

Chunhong Zhou

Michael Previte

Kelly Hobart McClure

Arup Roy

Robert Jay Greenberg

Pishoy Maksy

Minghao Guo

James Singleton Little

Rongqing Dai

Sumit Yadav

John J Reinhold

Kea-Tiong Tang

Steve Xiangling Chen

Molly Min He

Richard Agustin Castro

Matthew William Kellinger

Sinan Arslan

Derek Fuller

Matthew J McMahon

Dao Min Zhou

David Daomin Zhou

Lei Sun

Avraham I Caspi

Junhua Zhao

Ryan Kelly

Mark Salman Humayun

Neha J Parikh

Stanley S Hong

Cheng-Yao Chen

Dustin W Blair

Francisco Jose Garcia

James David Weiland

Simon Prince

Merek C Siu

Hui Zhen Mah

Adeline Huizhen Mah

Haosen Wang

Alan Matthew Horsager

Lorenzo Berti

Danilo Condello

Semyon Kruglyak

Rigo Pantoja

Peter Meilstrup

Leon Zilun Zhang

William Light

Hua Yu

John Bailey

Michael Kim

Ashkan Arianpour

Tsung-Li Liu

Ramreddy Tippana

Richard Augustin Castro

Steven Xiangling Chen

Hui Zhen Ma

Kelly H Mcclure

Xiangling Chen

Kelly Mcclure

Mark S Humayun

Neha Jagdish Parikh

Matthew J Mcmahon

The present disclosure provides compositions and related methods, e.g., for preparing immobilized nucleic acid nanostructures using compaction oligonucleotides. In some embodiments, rolling circle amplification reaction can be conducted with compaction oligonucleotides on-support or in-solution to generate concatemer molecules having multiple copies of a polynucleotide unit arranged in tandem. Each polynucleotide unit comprises a sequence-of-interest and at least one universal adaptor sequence that binds one end of a compaction oligonucleotide. The 5' and 3′ regions of the compaction oligonucleotide can hybridize to the concatemer to pull together distal portions of the concatemer causing compaction of the concatemer to form a nanostructure. Nanostructures having tighter size and shape compared to concatemers generated in the absence of the compaction oligonucleotides. The compact and stable characteristics of the nucleic acid nanostructures improves sequencing accuracy by increasing signal intensity and they retain their shape and size during multiple sequencing cycles.

Compositions and methods for preparing nucleic acid nanostructures using compaction oligonucleotides

Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.

Multipart reagents having increased avidity for polymerase binding

Multivalent binding composition for nucleic acid analysis

Methods and systems for image analysis are provided, and in particular for identifying a set of base-calling locations in a flow cell for DNA sequencing. These include capturing flow cell images after each sequencing step performed on the flow cell, and identifying candidate cluster centers in at least one of the flow cell images. Intensities are determined for each candidate cluster center in a set of flow cell images. Purities are determined for each candidate cluster center based on the intensities. Each candidate cluster center with a purity greater than the purity of the surrounding candidate cluster centers within a distance threshold is added to a template set of base-calling locations.

Single-pass primary analysis

Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the sample plane to capture a series of images (e.g., of different fields-of-view), and improved imaging system duty cycle, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications.

High performance fluorescence imaging module for genomic testing assay

Flow cell devices, cartridges, and systems are described that provide reduced manufacturing complexity, lowered consumable costs, and flexible system throughput for nucleic acid sequencing and other chemical or biological analysis applications. The flow cell device can include a capillary flow cell device or a microfluidic flow cell device.

Flow cell device and use thereof

Imaging systems and methods comprising imaging a first interior surface and a second interior surface of a flow cell are described. In some embodiments, the imaging systems may comprise: a) an objective lens; b) at least one image sensor; and c) at least one tube lens disposed in an optical path between the objective lens and the at least one image sensor; wherein the at least one tube lens is configured to correct imaging performance such that images of the first interior surface of the flow cell and the second interior surface of the flow cell have substantially the same optical resolution.

Tube lens design for improved depth-of-field

Methods and systems for sequencing a nucleic acid molecule are described that comprise imaging a first surface and an axially-displaced second surface using a compensation-free optical system, the system comprising an objective lens and at least one image sensor, wherein said optical system has a numerical aperture (NA) of less than 0.6 and a field-of-view (FOV) of greater than 1.0 mm; and) processing the images of the first surface and the axially-displaced second surface to correct for optical aberration such that the images of the first surface and the axially-displaced second surface have substantially the same optical resolution.

Nucleic acid sequencing systems

A method of distinguishing nucleotide sequences for different nucleic acid molecules including the steps of (a) mixing a plurality of different nucleic acid molecules with polymerase molecules and nucleotide molecules, wherein the different nucleic acid molecules are attached to a surface in the form of an array of nucleic acid features; (b) determining a transient state of the polymerase molecules at the nucleic acid features; and (c) identifying a subset of nucleic acid features that correctly incorporate the nucleotide molecules based on the transient state of the polymerase molecules at the nucleic acid features, thereby distinguishing the nucleotide sequences for the different nucleic acid molecules.

Apparatus and methods for kinetic analysis and determination of nucleic acid sequences

In electrically stimulating neural tissue it is important to prevent over stimulation and unbalanced stimulation, which would cause damage to the neural tissue, the electrode, or both. It is critical that neural tissue is not subjected to any direct current or alternating current above a safe threshold. Further, it is important to identify defective electrodes, as continued use may result in neural damage and further electrode damage. The present invention presents system and stimulator control mechanisms to prevent damage to neural tissue.

Method and apparatus to provide safety checks for neural stimulation

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San Diego, CA, United States of America

Chunhong Zhou