Cidra Corporation

Illumina Corporation

Weatherford/lamb, Inc.

Cyvek, Inc.

Cyvera Corporation

Other

USA As Represented by Secretary of the Navy

Electronics and Telecommunications Research Institute

Weatherford Technology Holdings, LLC

Robert N. Brucato

Alan D. Kersey

James S. Sirkis

Mark R. Fernald

Martin A. Putnam

Martin A Putnam

Alan D Kersey

John A Moon

Timothy J Bailey

Mark R Fernald

Robert N Brucato

Paul Eric Sanders

James M Sullivan

Michael A Davis

Matthew B Miller

Tuo Li

Jeffrey T Branciforte

Charles O Stanwood

Trevor Wayne MacDougall

Christopher J Wright

James R Dunphy

James S Sirkis

Paul S Szczepanek

David Fournier

Richard Todd Jones

Joseph Francis Pinto

Edward Michael Dowd

Thomas Wolfgang Engel

Joseph Traynor

Jay Walter Dawson

Anthony Rauseo

John Harris Leamon

Andrew S Kuczma

David G Bellemore

Christopher T Chipman

Brian J Pike

Rebecca S Bryant

Jerin J Russell

Michael Arcand

John R Troll

Joseph J Baraglia

Jane M Tu

John J Grunbeck

Robert J Maron

Jin Ung Kang

Guy A Daigle

Irl N Duling, Iii

Michael L Dennis

Richard L Lemoine

Peter C Ogle

Charles G Askins

F Kevin Didden

Walter A Helm

E Joseph Friebele

Jon T Kringlebotn

Trevor W Macdougall

A method of making at least a portion of at least one microfluidic actuator having a flexible diaphragm portion and an opposite surface portion, the diaphragm and opposite surface each having opposed faces, at least one of the faces comprising surface-activated PDMS, and the opposed faces being arranged such that when the opposed faces contact each other, they form a fluidic seal, including performing repeated make-and-break-contact protocol on the contacting opposed faces until the tendency for permanent bonds to form between the contacting faces has been neutralized, thereby enabling the diaphragm portion to perform actuated movements to engage and disengage with the opposite surface portion, without the diaphragm sticking to the opposite surface portion.

Microfluidic assay assemblies and methods of manufacture

A method and system for heating and/or inspecting a portable microfluidic assay cartridge for performing an assay includes receiving the assay cartridge on a receiving region of a translatable table under automated control, heating the cartridge, during performance of the assay, with a planar radiant heater plate, the heater plate having an aperture through which an inspection axis extends, and/or inspecting the cartridge using an optical system constructed to inspect the cartridge along the inspection axis by reading a fluorescent light signal which passes through the aperture in the heater plate. In addition, the cartridge moves with movement of the translation table, and the heater plate and optical system may be stationary, and the inspection axis may be fixed.

Methods and systems for epi-fluorescent monitoring and scanning for microfluidic assays

Microfluidic devices are provided for conducting fluid assays, for example biological assays, that have the ability to move fluids through multiple channels and pathways in a compact, efficient, and low cost manner. Discrete flow detection elements, preferably extremely short hollow flow elements, with length preferably less than 700 micron, preferably less than 500 micron, and internal diameter preferably of between about 50+/&#x2212;25 micron, are provided with capture agent, and are inserted into microfluidic channels by tweezer or vacuum pick-and-place motions at fixed positions in which they are efficiently exposed to fluids for conducting assays. Close-field electrostatic attraction is employed to define the position of the elements and enable ready withdrawal of the placing instruments. The microfluidic devices feature flow elements, channels, valves, and on-board pumps that are low cost to fabricate accurately, are minimally invasive to the fluid path and when implemented for the purpose, can produce multiplex assays on a single portable assay cartridge (chip) that have low coefficients of variation. Novel methods of construction, assembly and use of these features are presented, including co-valent bonding of selected regions of faces of surface-activatable bondable materials, such as PDMS to PDMS and PDMS to glass, while contiguous portions of one flexible sheet completes and seals flow channels, fixes the position of inserted analyte-detection elements in the channels, especially short hollow flow elements through which sample and reagent flow, and other portions form flexible valve membranes and diaphragms of pumps. A repeated make-and-break-contact manufacturing protocol prevents such bonding to interfere with moving the integral valve diaphragm portions from their valve seats defined by the opposed sheet member, which the flexible sheet material engages. Preparation of two subassemblies, each having a backing of relatively rigid material, followed by their assembly face-to-face in a permanent bond is shown. Hollow detection flow elements are shown fixed in channels, that provide by-pass flow paths of at least 50% of the flow capacity through the elements; in preferred implementations, as much as 100% or more. Metallized polyester film is shown to have numerous configurations and advantages in non-permanently bonded constructions. A method of preparing detection elements for an assay comprises batch coating detection elements, or hollow flow elements by mixing and picking and placing the elements in flow channels of a microfluidic device, capturing the flow elements by bonding two opposed layers while sealing the flow channels.

Microfluidic devices and methods of manufacture and use

A method for preparing a plurality of micro-length tubular flow elements for use in a fluid assay, each element having interior and exterior surfaces and having at least one axially-extending flow passage through its interior, includes aggressively agitating the flow elements in a solution of assay capture agent to impart disrupting shear forces on the exterior surface of the elements, the shear forces causing the axially-extending external surfaces of the flow elements to be free of assay capture agent, while at least a portion of the interior surface of the flow elements not experiencing such disruptive shear forces and carrying deposits of the assay capture agent.

Micro-tube particles for microfluidic assays and methods of manufacture

A method for performing a combined protein and nucleic acid assay on a target captured by a capture agent, includes providing a microfluidic device having a microfluidic channel network having at least one microfluidic channel, the channel arranged to receive fluid, the device having at least two micro-particles disposed in fixed position in the channel, the micro-particles being functionalized with a capture agent for the assay, one of the micro-particles in the channel being functionalized with an antibody or antigen capture agent and another of the micro-particles being functionalized with a nucleic acid capture agent. In some embodiments, the network may have at least two microfluidic channels, each channel of the two channels arranged to receive portions of the same fluid and to be fluidicly isolatable from each other, the device having at least two micro-particles disposed in fixed position in the network channels, the micro-particles being functionalized with a capture agent, one of the micro-particles in one of the channels being functionalized with an antibody or antigen capture agent and another of the micro-particles in another of the channels being functionalized with a nucleic acid capture agent. The method may also include detecting both protein and nucleic acid present in an input sample using the respectively functionalized micro particles. In some embodiments, the micro particles may be micro-length tubes or glass nano reactors.

PDMS membrane-confined nucleic acid and antibody/antigen-functionalized microlength tube capture elements, and systems employing them, and methods of their use

A method of flowing a fluid with a tracer in a microfluidic channel of an assay device and detecting the tracer for determining the channel location or condition of the channel.

Methods and systems for manufacture of microarray assay systems, conducting microfluidic assays, and monitoring and scanning to obtain microfluidic assay results

In assembling a portion of a microfluidic device by conducting bonding action by contacting faces of opposed bondable materials, one comprising a flexible sheet, the method, while maintaining continual contact of the faces in a region R2 until bonding is completed, of employing repeated make-and-break-contact manufacturing protocol on a region R1 of the contacted faces of the bondable materials, thereby over time neutralizing the tendency for permanent bonds to form in the region R1, thus to enable making and breaking actuated movements of the region R1 of the flexible sheet relative to the portion of the other material that it opposes.

A method of making an assay device comprising providing micro-elements in the form of micro-particles or micro-length tube detection elements and thereafter with an automated tool, picking and placing the micro-elements into open-sided microfluidic channels in a body.

Microfluidic assay systems employing micro-particles and methods of manufacture

A method of forming a pneumatically controlled microfluidic device containing a micro-fluidic network that includes micro-elements in the form of micro-particles or micro-length hollow flow elements, and a pneumatic network that includes pneumatic micro-channels and micro-valve features enabling membrane valves to operate to control fluid conditions in the microfluidic network, including the steps (a) forming two portions, denominated fluidic layer, in which microfluidic channels are formed, and pneumatic layer, in which pneumatic micro-channels and micro-valve features are formed, each having a backing that is rigid in the plane of extent of the layers, (b) providing an intervening elastic membrane, and (c) permanently bonding both layers to opposite sides of the membrane, the permanent bonding of the membrane to the fluidic layer being effective to permanently enclose a set of inserted micro-elements in the fluidic network and relate the two layers to enable pneumatic control of fluid conditions in the microfluidic network.

Portable microfluidic assay devices and methods of manufacture and use

A microfluidic device comprising a microfluidic channel network sealed on one side by a membrane sheet, the sheet having PDMS defining at least the surface sealing the channel, the membrane sheet on its opposite side sealing one side of a pneumatic channel, the pneumatic channel arranged to enable pneumatic deflection of a deflectable portion of the membrane sheet into contact with an opposed surface to control flow in a channel of the network, the membrane sheet confining in a channel of the network at least one micro-particle, micro-length tube or glass nano reactor, functionalized with a capture agent, that has been inserted into that channel. A microfluidic device having a microfluidic channel containing at least two micro-particles, micro-length tubes or glass nano reactors, one functionalized with nucleic acid and another with antibody or antigen. A microfluidic device having a microfluidic channel containing at least one micro-length tube or glass nano reactor functionalized to capture nucleic acid, the device constructed to enable recovery of the nucleic acid captured by the device.

An operating and reading instrument for performing an assay employing a portable microfluidic assay cartridge, the instrument comprising a translatable table under automated control, the translatable table carrying a receiving region for the portable cartridge and carrying a port system connectable to the cartridge that includes at least one remotely automated valve carried by the translatable table, the valve arranged to apply pressurized flowable substance at selected times to the cartridge while the cartridge is on the translatable table.

A pneumatically driven portable assay cartridge having analyte capture regions associated with microfluidic channels within its interior, the portable cartridge having pneumatic ports clampable against pneumatic ports of an operating instrument for controlled application of positive pressure and vacuum to pneumatic operating channels within the cartridge, the cartridge having a well for receiving sample from a user and microfluidic channels that include pneumatically operated pistons and valves controllable by the pneumatic operating channels to cause all flows of the assay from the reservoirs through reaction regions within the cartridge to on-board waste reservoir during conduct of the assay.

Microfluidic assay operating system and methods of use

Growing community of inventors

Cheshire, CT, United States of America

Martin A Putnam