Illumina Corporation

Advanced Liquid Logic, Inc.

Duke University

Philip Y Paik

Michael G Pollack

Vamsee K Pamula

Jay Taylor

James Michael Osmus

Vijay Srinivasan

Erik Allegoren

Jack Godfrey Wood

Carlos Dominguez

James Christopher Blake

Jack Godfrey-Wood

Ryan A Sturmer

Richard B Fair

Tsukasa Takahashi

Hong Ren

Brandon Westerberg

Tarun Kumar Khurana

Allen E Eckhardt

Poorya Sabounchi

Bradley Kent Drews

Max Warren Pollock

Yan-You Lin

Behnam Javanmardi

Gregory F Smith

Paul Crivelli

Arjun Sudarsan

Cyril Delattre

Prasanna Krishnan Thwar

Keith R Brafford

Darren Segale

Matthew William Hage

Alexander Shenderov

Zhishan Hua

Wesley A Cox-Muranami

Jennifer Olivia Foley

Minsoung Rhee

Dwayne J Allen

Yan-you Lin

Jeffrey Liu

Alex Moroz-smietana

David Hertzog

Xiaoxiao Ma

Richard M West

An instrument includes a reagent management system. The reagent management system includes a plurality of reagent wells, each reagent well operable to contain a reagent of a plurality of reagents positioned therein. The reagent management system is operable to select a flow of reagent from one of the plurality of reagents. A flexible connection includes a laminate stack and includes a first flexible channel in fluid communication with the reagent management system. The first flexible channel is operable to route the flow of reagent therethrough. A flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is operable to route the flow of reagent over analytes positioned in the flow channel. The flexible connection enables the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.

Flow cell with flexible connection

Flow cell cartridge

Flow cell device

Cartridge cover

Sequencing cartridge assembly

Reagent cartridge

A stack of fluidics layers of a microfluidic cartridge for sequencing nucleic acid molecules includes a sequencing chamber layer having a sequencing chamber area configured for carrying out clustering and sequencing reactions, and a sequencing chamber bottom layer disposed under the sequencing chamber layer. The sequencing chamber bottom layer has an opening configured to hold an image sensor with the image sensor having an active area disposed under the sequencing chamber area. The sequencing chamber area spans substantially all of the active area of the image sensor. The stack of fluidics layers includes a flexible printed circuit board (PCB) layer under the sequencing chamber bottom layer, and a fluidics channels layer disposed under the flexible PCB layer. The fluidics channels layer includes fluidics channels that are configured to deliver reactants to the sequencing chamber area. The fluidics channels do not substantially overlap with the active area of the image sensor.

Disposable, integrated microfluidic cartridge and methods of making and using same

The disclosed embodiments concern microfluidic cartridges for detecting biological reactions. In some embodiments, the microfluidic cartridges are configured to perform sequencing operations on a nucleic acid sample. In one aspect, a microfluidic cartridge includes a stack of fluidics layers defining channels and valves for processing the nucleic acid sample to be sequenced, and a solid state CMOS biosensor integrated in the stack. The biosensor has an active area configured to detect signals of biological reactions, wherein substantially all of the active area is available for reagent delivery and illumination during operation. In another aspect, a microfluidic cartridge includes: (a) a flow cell including a reaction site area encompassing one or more reaction sites; (b) fluidics channels for delivering reactants to and/or removing reactants from the reaction site area; (c) a biosensor having an active area configured to detect signals of biological reactions in the reaction site area. The reaction site area is proximal to the active area of the biosensor and the reaction site area spans substantially all of the active area of the biosensor. In some embodiments, the fluidics channels do not substantially overlap with the active area of the biosensor. Methods for manufacturing and operating the microfluidic cartridges are also disclosed.

Growing community of inventors

Durham, NC, United States of America

Philip Y Paik