Illumina Corporation

Mgi Tech Co., Ltd.

Mgi Holdings Co., Limited

Illumina France Sarl

Yan-You Lin

Tarun Kumar Khurana

Yir-Shyuan Wu

Cheng Frank Zhong

Poorya Sabounchi

Shifeng Li

Liang Wang

M Shane Bowen

Mostafa Ronaghi

Steven Mark Barnard

Dietrich A Dehlinger

Jian Gong

Maria Candelaria Rogert Bacigalupo

Dajun Yuan

Cyril Delattre

Filiz Gorpe-Yasar

Fabien Abeille

Erich B Jaeger

Victoria Popic

Frank Zhong

Philip Y Paik

Jeffrey S Fisher

Alex Aravanis

Arnaud Rival

Arash Jamshidi

Bala Murali Venkatesan

Xi-Jun Chen

Behnam Javanmardi

Gordon M Cann

Jennifer Olivia Foley

Hamed Amini

Farnaz Absalan

Yiwen Ouyang

Sz-Chin Lin

Sarah Stuart

Majid Babazadeh

Tarun Khurana

Implementations of a method for seeding sequence libraries on a surface of a sequencing flow cell that allow for spatial segregation of the libraries on the surface are provided. The spatial segregation can be used to index sequence reads from individual sequencing libraries to increase efficiency of subsequent data analysis. In some examples, hydrogel beads containing encapsulated sequencing libraries are captured on a sequencing flow cell and degraded in the presence of a liquid diffusion barrier to allow for the spatial segregation and seeding of the sequencing libraries on the surface of the flow cell. Additionally, examples of systems, methods and compositions are provided relating to flow cell devices configured for nucleic acid library preparation and single cell sequencing. Some examples include flow cell devices having a hydrogel with genetic material disposed therein, and which is retained within the hydrogel during nucleic acid processing.

Spatial indexing of genetic material and library preparation using hydrogel beads and flow cells

A method and device for displacing fluid from a reagent cartridge () into a microfluidic device () and for loading the fluid into the reagent cartridge (). The reagent cartridge () may include a cartridge body and a pipette array with pipette tips () to engage inlets of a microfluidics or other cartridge, wherein the pipette tips () correspond in position to the plurality of inlets () of the microfluidic device (). Fluid may be loaded into or displaced from the microfluidic device () by a system of plungers (). The reagent cartridge may alternatively include blisters () having fluid reservoirs and dispensing tips (), each dispensing tip () including a pathway () that is fluidly coupled to a blister (). The fluid may be displaced from or loaded into the blister () via the dispensing tip (). A deformable seal () may be overlaid on the blisters () to seal the volumes of fluid within the blisters (), and may be deformed to displace the fluid.

Reagent cartridges for in-vitro devices

A microfluidic device includes first and second substrate structures. The first substrate structure has a first substrate surface configured to receive one or more droplets. A plurality of electrodes configured to apply an electric field to the droplets. The second substrate structure has a second substrate surface facing the first substrate surface and spaced apart from the first substrate surface to form a fluid channel. The microfluidic device has a first heating element adjacent to the first substrate structure and disposed on an opposite side of the first substrate surface, and a second heating element adjacent to the second substrate structure and disposed on an opposite side of the second substrate surface. The microfluidic device further includes one or more temperature sensors disposed adjacent to the fluid channel between the first substrate structure and the second substrate structure.

Temperature control on digital microfluidics device

An apparatus for forming a plurality of microdroplets from a droplet includes a substrate, a dielectric layer on the substrate and having a plurality of hydrophilic surface regions spaced apart from each other by a hydrophobic surface, and a plurality of electrodes covered by the dielectric layer. The electrodes are configured to form an electric field across the droplet in response to voltages provided by a control circuit to move the droplet across the dielectric layer in a lateral direction while leaving portions of the droplet on the hydrophilic surface regions to form the plurality of microdroplets on the hydrophilic surface regions.

Method for manufacturing an apparatus for manipulating a droplet

An apparatus () including multiple biological chips () includes a substrate (), a first adhesive layer () disposed on the substrate (), a first biological chip () and a second biological chip () disposed on the first adhesive layer () and attached to the substrate () by the adhesive layer (). The apparatus () further includes a filler () disposed between the first biological chip () and the second biological chip (). The filler () includes a second adhesive layer () extending between a side surface () of the first biological chip () and a side surface () of the second biological chip (), the second adhesive layer () attaching the first biological chip () to the second biological chip (). The filler () also includes a surface layer () disposed over the second adhesive layer (). The surface layer () has a hydrophobic surface that is co-planar with a top surface () of the first biological chip () and a top surface () of the second biological chip ().

System and method for integration of biological chips

A method for forming sequencing flow cells can include providing a semiconductor wafer covered with a dielectric layer and forming a patterned layer on the dielectric layer. The patterned layer has a differential surface that includes alternating first surface regions and second surface regions. The method can also include attaching a cover wafer to the semiconductor wafer to form a composite wafer structure including a plurality of flow cells. The composite wafer structure can then be singulated to form a plurality of dies. Each die forms a sequencing flow cell. The sequencing flow cell can include a flow channel between a portion of the patterned layer and a portion of the cover wafer, an inlet, and an outlet. Further, the method can include functionalizing the sequencing flow cell to create differential surfaces.

Wafer level sequencing flow cell fabrication

Multilayer electrical connection for digital microfluidics on substrates

Embodiments provided herewith are directed to self-assembled methods of preparing a patterned surface for sequencing applications including, for example, a patterned flow cell or a patterned surface for digital fluidic devices. The methods utilize photolithography to create a patterned surface with a plurality of microscale or nanoscale contours, separated by hydrophobic interstitial regions, without the need of oxygen plasma treatment during the photolithography process. In addition, the methods avoid the use of any chemical or mechanical polishing steps after the deposition of a gel material to the contours.

Self assembled patterning using patterned hydrophobic surfaces

A method for forming sequencing flow cells can include providing a semiconductor wafer covered with a dielectric layer, and forming a patterned layer on the dielectric layer. The patterned layer has a differential surface that includes alternating first surface regions and second surface regions. The method can also include attaching a cover wafer to the semiconductor wafer to form a composite wafer structure including a plurality of flow cells. The composite wafer structure can then be singulated to form a plurality of dies. Each die forms a sequencing flow cell. The sequencing flow cell can include a flow channel between a portion of the patterned layer and a portion of the cover wafer, an inlet, and an outlet. Further, the method can include functionalizing the sequencing flow cell to create differential surfaces.

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

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Fremont, CA, United States of America

Yan-You Lin