Illumina Corporation

Illumina Cambridge Limited

Lightspeed Genomics, Inc.

Optical Biosystems, Inc.

Stanley S Hong

Merek C Siu

Tarun Kumar Khurana

Craig M Ciesla

Ali Agah

Aathavan Karunakaran

Geraint Wyn Evans

Arvin Emadi

Simon Prince

Danilo Condello

Gary Mark Skinner

John A Moon

Peter Clarke Newman

Dale Buermann

Mark Wang

Bryan Crane

Jason Harris

Wenyi Feng

Matthew William Hage

Mark J Nibbe

Frederick G Erie

M Shane Bowen

Michael J Carney

Mark R Pratt

Robert Ezra Langlois

Hongji Ren

Dietrich A Dehlinger

Dustin W Blair

Amirali Kia

Alex Nemiroski

Jonathan Mark Boutell

Mark T Reed

Steven J Boege

Chunhong Zhou

Joseph Francis Pinto

Erik Lewis Williamson

Drew R Verkade

Jason Bryant

Jason Richard Betley

Patrick Leung

Anindita Dutta

Michael S Graige

Marco A Krumbuegel

Yinghua Sun

Andrew James Carson

Dakota Watson

Aaron Liu

Jong Buhm Park

Shaoping Lu

Jekwan Ryu

Kevin Wayne Bartig

Rico Otto

Olga Andreevna Souverneva

John Bailey

Frank DeWitt, Iv

Ashkan Arianpour

Anthony Lam

Bojan Obradovic

Chunhong (Allen) Zhou

Xiangling (Steve) Chen

William McGuigan

Alexander Kindwall

Vincent Hsieh

Jeffrey Gau

Yina Wang

Shane Bowen

Alexander P Kindwall

Matthew Hage

Changqin Ding

Eric Williamson

Frederick Erie

Chunhong (allen) Zhou

Xiangling (steve) Chen

Marco Krumbuegel

Frank Dewitt Iv

Xiangling Chen

A method for extending a depth of field of a nucleic acid sequencer may comprise optimization steps which are repeated one or more times, in which a result of passing light through an objective lens and a mask is compared with an ideal result, and any discrepancy is used to update the mask. Such a mask may be incorporated into a nucleic acid sequencer which adds fluorescent tags to nucleic acid sites and then detect light emitted from the fluorescent tags, thereby extending the sequencer's depth of field.

Apparatus and method for extended depth of field

A method is used to generate an analysis image of a moving sample based on one or more exposures. An illumination source illuminates a field of view of a camera for one or more pulses while the sample moves through the field of view. The distance moved by the sample during each of these one or more pulses may be less than the size of one pixel in an image captured by the camera.

Apparatus and method of obtaining an image of a sample in motion

Apparatus and methods for controlling heating of an objective in a linescanning sequencing system to improve resolution are disclosed. In accordance with a first implementation, an apparatus includes or comprises a beam source for providing input radiation and a beam shaping group including or comprising one or more optical elements positioned to receive the input radiation from the beam source, and to perform beam shaping on the input radiation to form a shaped beam. The apparatus further including or comprising an objective positioned to receive the shaped beam and to transform the shaped beam into a probe beam and configured to provide the probe beam to a focal plane of the objective for optically probing a sample. The beam shaping group is configured to adjust one or more properties of the shaped beam over time to generally uniformly heat the objective over a region of incidence for the shaped beam.

Apparatus and methods for controlling heating of an objective in a linescanning sequencing system to improve resolution

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

An imaging system includes: a sample container including a flowcell that includes a plurality of attachment elements at a plurality of sample locations, wherein a single DNA template molecule is attached to each of the attachment elements, and further wherein an average distance between adjacent attachment elements is less than Abbe's limit; and an imager positioned to image photo-switching occurring at the plurality of attachment elements by capturing on and off events in a plurality of color channels at the same time as the on and off events are occurring for the attached molecules when a stochastic photo-switching chemistry is applied to all of the attached molecules at the same time causing the attached molecules to fluoresce in the on and off events in up to four different colors.

Generalized stochastic super-resolution sequencing

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

For example, a flowcell includes: a nanowell layer having a first set of nanowells and a second set of nanowells to receive a sample; a first linear waveguide associated with the first set of nanowells, and a second linear waveguide associated with the second set of nanowells; and a first grating for the first linear waveguide, and a second grating for the second linear waveguide, the first and second gratings providing differential coupling of first light and second light.

Flowcells with linear waveguides

A system includes: an objective lens; a first light source to feed first illuminating light through the objective lens and into a flowcell (e.g., with a relatively thin film waveguide) to be installed in the system, the first illuminating light to be fed using a first grating on the flowcell; and a first image sensor to capture imaging light using the objective lens, wherein the first grating is positioned outside a field of view of the first image sensor. Dual-surface imaging can be performed. Flowcells with multiple swaths bounded by gratings can be used. An auto-alignment process can be performed.

Illumination for fluorescence imaging using objective lens

A system includes a plurality of modular subassemblies and a plate; wherein each modular subassembly comprises an enclosure and a plurality of optical components aligned to the enclosure, and each enclosure comprises a plurality of mounting structures; and wherein each modular subassembly is mechanically coupled to the plate by attachment of a mounting structure of the modular subassembly directly to a corresponding mounting structure located on the plate, such that by mechanically coupling each modular subassembly to the plate using the mounting structure of the modular subassembly and the corresponding mounting structure on the plate, adjacent modular subassemblies are aligned to each other upon such attachment, and wherein two of the modular subassemblies mechanically coupled to the plate are also attached to each other by mechanically coupling an alignment structure on one of the two modular subassemblies to a respective alignment structure on the other of the two modular subassemblies.

Modular optical analytic systems and methods

An imaging system may include a sample stage comprising a surface to support a sample container, the sample container including a sample having a plurality of sample locations; an optical stage to image the sample at the plurality of sample locations; one or more actuators physically coupled to at least one of the sample stage and the optical stage to move the sample stage relative to the optical stage to focus the optical stage onto a current sample location of the plurality of sample locations; a first light source to illuminate the current sample location; a second light source to project a pair of spots on a next sample location of the plurality of sample locations; and a controller to determine, based on an image of the pair of spots projected on the next sample location, a focus setting for the next sample location.

Predictive focus tracking apparatus and methods

Techniques are described for reducing the number of angles needed in structured illumination imaging of biological samples through the use of patterned flowcells, where nanowells of the patterned flowcells are arranged in, e.g., a square array, or an asymmetrical array. Accordingly, the number of images needed to resolve details of the biological samples is reduced. Techniques are also described for combining structured illumination imaging with line scanning using the patterned flowcells.

Reduced dimensionality structured illumination microscopy with patterned arrays of nanowells

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

An apparatus includes a flow cell body, a plurality of electrodes, an integrated circuit, and an imaging assembly. The flow cell body defines one or more flow channels and a plurality of wells. Each flow channel is configured to receive a flow of fluid. Each well is fluidically coupled with the corresponding flow channel. Each well is configured to contain at least one polynucleotide. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are operable to effect writing of polynucleotides in the corresponding wells. The integrated circuit is operable to drive selective deposition or activation of selected nucleotides to attach to polynucleotides in the wells to thereby generate polynucleotides representing machine-written data in the wells. The imaging assembly is operable to capture images indicative of one or more nucleotides in a polynucleotide.

Flow cell with selective deposition or activation of nucleotides

The disclosure provides for structured illumination microscopy (SIM) imaging systems. In one set of implementations, a SIM imaging system may be implemented as a multi-arm SIM imaging system, whereby each arm of the system includes a light emitter and a beam splitter (e.g., a transmissive diffraction grating) having a specific, fixed orientation with respect to the system's optical axis. In a second set of implementations, a SIM imaging system may be implemented as a multiple beam splitter slide SIM imaging system, where one linear motion stage is mounted with multiple beam splitters having a corresponding, fixed orientation with respect to the system's optical axis. In a third set of implementations, a SIM imaging system may be implemented as a pattern angle spatial selection SIM imaging system, whereby a fixed two-dimensional diffraction grating is used in combination with a spatial filter wheel to project one-dimensional fringe patterns on a sample.

Multi-arm structured illumination imaging

Growing community of inventors

Palo Alto, CA, United States of America

Stanley S Hong