Abbott Laboratories Corporation

Ibis Biosciences, Inc.

Other

Katholieke Universiteit Leuven

Abbott Molecular Inc.

Katholieke Universiteit Leuven, K.u. Leuven Research & Development

Mark A Hayden

Jeffrey B Huff

Stephen D Stroupe

John C Russell

Tracey L Colpitts

Maurice Cohen

Paula N Friedman

Michael R Klass

Patricia A Billing-Medel

Graham Davis

Julian D Gordon

Edward N Granados

Steven C Hodges

Jon D Kratochvil

Lisa A Roberts-Rapp

Mark W Eshoo

Andrew G Fischer

Sergey Gershtein

Sophie Laurenson

Shelley R Holets-McCormack

John D Robinson

John Picuri

Jeroen Lammertyn

Peter J Karabatsos

Karen Leirs

Elena Pérez-Ruiz

David J Ecker

Gordon Bruce Collier

Anthony Scott Muerhoff

John M Clemens

Thomas P Leary

Qiaoqiao Ruan

Sergey Y Tetin

Mark R Pope

Dan Wang

Nicholas John Collier

Pathik H Soni

Lyle Yarnell

Dustin House

Edna Prieto-Ballengee

M Felicia Bogdan

Lei Qiao

Richard Haack

Robert Van Renesse

Stefan Hershberger

M Shawn Murphy

Wlodek Mandecki

Karen Xin Zhou Yu

Andrew S Schapals

Andrew T Fischer

Edna M Prieto-Ballengee

Felicia Bogdan

John Robinson

Elena PÉREZ-Ruiz

Thomas Leary

Digital microfluidic and analyte detection device includes a first substrate and a second substrate aligned generally parallel to each other with a gap defined therebetween in side view. At least one of the first and second substrates has an electrode array configured to generate electrical actuation forces to urge at least one droplet within the gap along the at least one of the first substrate and the second substrate. The electrode array has a plurality of electrodes defining an electrode array area in plan view. At least one of the first substrate and the second substrate has a well array defining a well array area in plan view. The well array area is bounded within the electrode array area and overlapping a portion of each of the plurality of electrodes. The well array area overlaps less than 75% of the electrode array area in plan view.

Devices and methods for sample analysis

Methods for detecting target analytes utilizing an array of wells are advantageous for detection of low concentrations of target analytes. Use of an array of wells requires sealing of the wells. The methods provided herein utilize digital microfluidics to seal wells of an array with a fluid that is immiscible with the aqueous liquid present in the wells to prevent evaporation and contamination of the aqueous fluid during analysis of signals from the wells. The disclosed method include generating a biphasic droplet composed of the immiscible fluid and an aqueous fluid. The immiscible fluid present in the biphasic droplet is moved over the array of wells to seal the wells by electrically actuating the aqueous fluid present in the biphasic droplet which in turn pulls the immiscible fluid.

Methods and devices for sample analysis

Integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample. The beads/particles/labels may be detected by moving the droplet to the detection component of the device, which detection component includes an array of wells.

Integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample. The beads/particles/labels may be detected by moving the droplet to the detection component of the device, which detection component includes an array of wells. The detection modules disclosed here can be used for detecting analytes of interest which analytes may have been enriched by amplification, isolation, or other techniques.

Integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample. The beads/particles/labels may be detected by moving the droplet to the detection component of the device, which detection component includes an array of wells. Additional analyte detection devices configured to operate an analyte detection chip to prepare a test sample and to detect an analyte related signal from the prepared test sample in the analyte detection chip are disclosed. The analyte detection chip may include a digital microfluidics (DMF) region and an analyte detection region which may overlap or may be spatially separated. The analyte detection device may be configured for detection of analyte by an optical or electrochemical means operably connected with an analyte detection chip inserted into the device.

Integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample. The beads/particles/labels may be detected by moving the droplet to the detection component of the device, which detection component includes an array of wells. Additonal analyte detection devices configured to operate an analyte detection chip to prepare a test sample and to detect an analyte related signal from the prepared test sample in the analyte detection chip are disclosed. The analyte detection chip may include a digital microfluidics (DMF) region and an analyte detection region which may overlap or may be spatially separated. The analyte detection device may be configured for detection of analyte by an optical or electrochemical means operably connected with an analyte detection chip inserted into the device.

Methods, devices, and systems for analyte analysis using a nanopore are disclosed. The methods, devices, and systems utilize a first and a second binding member that each specifically bind to an analyte in a biological sample. The method further includes detecting and/or counting a cleavable tag attached to the second binding member and correlating the presence and/or the number of tags to presence and/or concentration of the analyte. Certain aspects of the methods do not involve a tag, rather the second binding member may be directly detected/quantitated. The detecting and/or counting may be performed by translocating the tag/second binding member through a nanopore. Devices and systems that are programmed to carry out the disclosed methods are also provided.

Methods, devices, and systems for analyte analysis using a nanopore are disclosed. The methods, devices, and systems utilize a first and a second binding member that each specifically bind to an analyte in a biological sample. The method further includes detecting and/or counting a cleavable tag attached to the second binding member and correlating the presence and/or the number of tags to presence and/or concentration of the analyte. Certain aspects of the methods do not involve a tag, rather the second binding member may be directly detected/quantitated. The detecting and/or counting may be performed by translocating the tag/second binding member through a nanopore. Devices and systems that are programmed to carry out the disclosed methods are also provided. Also provided herein are instruments that are programmed to operate a cartridge that includes an array of electrodes for actuating a droplet and further includes an electrochemical species sensing region. The instrument may be used to analyse a sample in a cartridge that includes an array of electrodes for actuating a droplet and further includes a nanopore layer for detecting translocation of a tag/second binding member through nanopore. An instrument configured to operate a first cartridge that includes an array of electrodes for actuating a droplet and further includes an electrochemical species sensing region and a second cartridge that includes an array of electrodes for actuating a droplet and further includes a nanopore layer for detecting translocation of a tag/second binding member through nanopore is disclosed. An instrument configured to operate a cartridge that includes an array of electrodes for actuating a droplet, an electrochemical species sensing region, and a nanopore layer for detecting translocation of a tag/second binding member through nanopore is disclosed.

Provided herein is technology relating to sequencing nucleic acids, but not exclusively, to compositions, methods, systems, and kits related to nucleotides comprising an electrochemically detectable moiety and one or more photolabile synthesis-inhibiting moieties.

Nucleotide analogs for sequencing

Provided herein are systems and methods for nucleic acid sequencing by synthesis in a plurality of wells using detectably labeled chain terminating nucleotides with photolabile blocking groups and pulses of photocleaving light. In certain embodiments, the systems and methods provides a plurality of deblock-scan cycles comprising an initial deblock time period followed by a scanning light period, wherein at least one of the following occurs in each deblock-scan cycle: 1) the deblock time period is shorter than the scan time period; 2) the deblock time period is only long enough to deblock the photolabile groups that are part of a primer in less than all of the plurality of wells; or 3) the deblock time period is between 25 and 150 mSec and the scan time is at least 200 mSec. Such shorter deblock time periods help prevent the addition of more than one nucleotide to the primer prior to scanning (e.g., accuracy is enhanced).

Sequencing by synthesis using pulse read optics

Provided herein is technology relating to depositing and/or placing a macromolecule at a desired site for an assay and particularly, but not exclusively, to methods and systems for placing or guiding a macromolecule such as a protein, a nucleic acid, or a protein: nucleic acid complex to an assay site, such as near a nanopore, a nanowell, or a zero mode waveguide.

Macromolecule positioning by electrical potential

The present invention provides systems, methods, and compositions for performing molecular tests. In particular, the present invention provides methods, compositions and systems for generating target sequence-linked solid supports (e.g., beads) using a solid support linked to a plurality of capture sequences and capture primers composed of a 3' target-specific portion and a 5&#x2032; capture sequence portion. In certain embodiments, the target sequence linked solid support is used in sequencing methods (e.g., pyrosequencing, zero-mode waveguide type sequencing, nanopore sequencing, etc.) to determine the sequence of the target sequence (e.g., in order to detect the identity of a target nucleic acid in sample).

Capture primers and capture sequence linked solid supports for molecular diagnostic tests

Provided herein is technology relating to sequencing nucleic acids and particularly, but not exclusively, to devices, methods, and systems for sequencing-by-synthesis using changes in pH to monitor base addition. In some embodiments the electrochemical hydrogen ion sensor is a microfabricated mixed metal oxide electrode and in some embodiments the electrochemical hydrogen ion sensor is a membrane electrode. Moreover, in some embodiments the device further comprises a reference electrode. Performing the sequencing reaction involves moving solutions and other fluids (e.g., samples, nucleotide solutions, wash solutions) into and out of the reaction vessel. Thus, in some embodiments, the device further comprises a tube or other transport mechanism or pathway attached to the reaction vessel.

Nucleic acid sequencing by electrochemical detection

Growing community of inventors

Ingleside, IL, United States of America

Mark A Hayden