Illumina Corporation

Qualcomm Incorporated

Ali Agah

Arvin Emadi

Tarun Kumar Khurana

Craig M Ciesla

Aathavan Karunakaran

Stanley S Hong

Merek C Siu

Dietrich A Dehlinger

Arnaud Rival

Tracy Helen Fung

Emrah Kostem

Xiuyu Cai

M Shane Bowen

Poorya Sabounchi

Tara Bozorg-Grayeli

Amirali Kia

Xi-Jun Chen

Fabien Abeille

Craig Lee Hetherington

Steven Mark Barnard

Shahram Abdollahi-Alibeik

Lalitkumar Nathawad

Ke Gong

Alireza Kheirkhahi

Jon Aday

Craig Ciesla

Murali Venkatesan

Pargol Gheissari

Jennifer Wang

Helen Tracy Fung

In one embodiment, a sample surface of a biosensor includes pixel areas and holds a plurality of clusters during a sequence of sampling events such that the clusters are distributed unevenly over the pixel areas. In another embodiment, a biosensor has a sample surface that includes pixel areas and an array of wells overlying the pixel areas, the biosensor including two wells and two clusters per pixel area. The two wells per pixel area include a dominant well and a subordinate well. The dominant well has a larger cross section over the pixel area than the subordinate well. In yet another embodiment, an illumination system is coupled to a biosensor that illuminates the pixel areas with different angles of illumination during a sequence of sampling events, including, for a sampling event, illuminating each of the wells with off-axis illumination to produce asymmetrically illuminated well regions in each of the wells.

Systems and devices for high-throughput sequencing with semiconductor-based detection

Disclosed in one example is an apparatus including a substrate, a sensor over the substrate including an active surface and a sensor bond pad, a molding layer over the substrate and covering sides of the sensor, the molding layer having a molding height relative to a top surface of the substrate that is greater than a height of the active surface of the sensor relative to the top surface of the substrate, and a lidding layer over the molding layer and over the active surface. The lidding layer and the molding layer form a space over the active surface of the sensor that defines a flow channel.

Sensors having an active surface

Devices, systems, and methods for non-volatile storage include a well activation device operable to modify one or more wells from a plurality of wells of a flow cell to provide a set of readable wells. Readable wells are configured to allow exposure of a well to substances from nucleotide sequencing fluids, and prevent exposure to other substances and fluids, such as nucleotide synthesizing fluids. The well activation device may also modify wells to provide a set of writeable wells. This set of wells is configured to allow exposure to the nucleotide synthesizing fluids and substances; and prevent exposure to the nucleotide sequencing fluids and substances. There may also be provisions made for risk mitigation for data errors such as generating commands to write specified data to a nucleotide sequence associated with a particular location in a storage device, reading the nucleotide sequence and performing a comparison.

System and method for storage

A method for reducing sequencing by synthesis cycle time using a microfluidic device is provided. The microfluidic device comprises a flow cell having an inlet port, an outlet port, and a flow channel extending between the inlet port and the outlet port, wherein the flow channel receives an analyte of interest and one or more reagents for analyzing and detecting molecules. To aid in the acceleration of the reactions, the microfluidic device comprises a mixing device to increase the rates of diffusion of the reagents from the fluid bulk to an active surface of the flow cell. The mixing device comprises at least one of an electrothermal mixing device, an active mechanical mixing device, and a vibrational mixing device.

Methods and devices for mixing in a microfluidic system

Provided herein include various examples of an apparatus, a sensor system and examples of a method for manufacturing aspects of an apparatus, a sensor system. The apparatus may include a die. The apparatus may also include a substrate comprising a cavity. The die may be oriented in a portion of the cavity in the substrate, where the orientation defines a first space in the cavity adjacent to a first edge of the upper surface of the die and a second space in the cavity adjacent to the second edge of the upper surface of the die. The apparatus may further include fluidics fan-out regions comprising a first cured material deposited in the first space and the second space, a surface of the fluidics fan-out regions being contiguous with the upper surface of the die.

Fluidic flow channel over active surface of a die

Provided herein include various examples of an apparatus, flow cells that include these examples of the apparatus, and methods of making these examples of the apparatus. The apparatus can include a molding layer over a substrate and covering sides of a light detection device. The molding layer comprises a first region and a second region, which, with the active surface of the light detection device, form a contiguous surface. A waveguide integration layer is between the contiguous surface and a waveguide. The waveguide integration layer comprises optical coupling structures over the first and second regions, to optically couple light waves from a light source to the waveguide. The waveguide utilizes the light waves to excite light sensitive materials in nanowells. A nanostructure layer over the waveguide comprises the nanowells. Each nanowell shares a vertical axis with a location on the active surface of the light detection device.

Waveguide integration with optical coupling structures on light detection device

An image sensor structure including an image stack disposed over a device stack. The image stack includes a plurality of light detectors. A first optical filter stack is disposed over the image stack. The first optical filter stack includes a light guide layer. Light pipe cavities are disposed in the light guide layer. Each light pipe cavity is associated with a light detector. Each light pipe cavity has an aspect ratio that is greater than about 2.5 to about 1. A nanowell layer is disposed over the first optical filter stack. Nanowells are disposed in the nanowell layer. Each nanowell is associated with a light detector.

Image sensor structure with a light guide layer and a nanowell layer

An example image sensor structure includes an image layer. The image layer includes an array of light detectors disposed therein. A device stack is disposed over the image layer. An array of light guides is disposed in the device stack. Each light guide is associated with at least one light detector of the array of light detectors. A passivation stack is disposed over the device stack. The passivation stack includes a bottom surface in direct contact with a top surface of the light guides. An array of nanowells is disposed in a top layer of the passivation stack. Each nanowell is associated with a light guide of the array of light guides. A crosstalk blocking metal structure is disposed in the passivation stack. The crosstalk blocking metal structure reduces crosstalk within the passivation stack.

Image sensor structure

A system writes input data to a storage device as machine-written polynucleotides; and reads machine written polynucleotides from the storage device as output data. The storage device includes a flow cell including a plurality of storage wells in which machine written polynucleotides may be stored. The storage device may include a set of electrodes corresponding to the storage wells that allow for selective interactions with wells across the surface of a flow cell. Operation of the storage device may include receiving a read request associated with a particular location in the storage device, creating a copy of a nucleotide sequence located at the particular location in the storage device, transferring the copy of the nucleotide sequence to a read location, and reading the copy of the nucleotide sequence at the read location.

Storage device, system, and method

Provided herein include various examples of a method for manufacturing aspects of an apparatus, a sensor system. The method may include obtaining a first carrier bonded to an upper surface of the silicon wafer. This wafer includes through silicon vias (TSVs) extended through openings in a passivation stack, with electrical contacts coupled to portions of the TSVs exposed through these openings. The method may include de-bonding the first carrier from the upper surface of the silicon wafer. The method may include dicing the silicon wafer into subsections comprising dies.

Fabricating wafers with electrical contacts on a surface parallel to an active surface

A device for base calling is provided. The device includes a receptacle configured to hold a biosensor having a sample surface holding a plurality of clusters during a sequence of sampling events, an array of sensors sensing information from clusters disposed in corresponding pixel areas of the sample surface during the sampling events and generate sequences of pixel signals and a communication port configured to output the sequences of pixel signals. The device also includes a signal processor coupled to the communication port and configured to receive and process at least one pixel signal in the sequences of pixel signals that mixes light gathered from at least two clusters in a corresponding pixel area, and to base call each of the at least two clusters using the at least one pixel signal.

Semiconductor-based biosensors for base calling

An apparatus includes a flow cell body, a plurality of electrodes, an imaging assembly, and one or more barrier features. The flow cell body defines one or more flow channels and a plurality of wells defined as recesses in the floor of each flow channel. Each well is fluidically coupled with the corresponding flow channel. The flow cell body further defines interstitial surfaces between adjacent wells. Each well defines a corresponding depth. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are to effect writing of polynucleotides in the wells. The imaging assembly is to capture images of polynucleotides written in the wells. The one or more barrier features are positioned in the wells, between the wells, or above the wells. The one or more barrier features contain reactions in each well, reduce diffusion between the wells, or reduce optical cross-talk between the wells.

Flow cell with one or more barrier features

Methods are used for obtaining, cataloguing, and/or storing data derived from a biological source using a flow cell body, electrodes, and an imaging assembly. The data may include DNA and/or RNA obtained from a biological source, such as from the cells of an organism. The methods may be used to obtain, catalog, and/or store data such as DNA or RNA sequence from a pathogen such as a virus and/or a bacteria, human health data over time, and immune system information from an individual. The data obtained using the disclosed methods may be used for a variety of different purposes, including the manufacture of vaccine compositions, and for restoring the immune system of an individual who has undergone an immune system depleting event. The methods may be used for storage of biological cells, which may be used for the screening of compounds, such as small molecules with potential for therapeutic indications.

Growing community of inventors

Menlo Park, CA, United States of America

Ali Agah