University of Washington

Mark R Holl

Bernhard Hans Weigl

Gerald L Klein

Floyd Edwards

Robert J Morff

Paul Yager

Margaret A Kenny

Caicai Wu

Paul Charles Galambos

James P Brody

Fred K Forster

Diane M Zebert

Andrew Kamholz

Gregory Hixson

David Schutte

Catherine R Cabrera

M Diane Zebert

Roya R Sabeti

Katerina Macounova

The present invention provides an apparatus and method for storing a particle-containing liquid. The storage apparatus comprises a microfluidic convoluted flow channel having a plurality of particle capture regions. The storage channel is preferably an isotropic spatially periodic channel. Sedimented particles can be resuspended following storage. This invention further provides a microfluidic analysis cartridge having a convoluted storage channel therein. The sample analysis can use optical, electrical, pressure sensitive, or flow sensitive detection. A plurality of analysis channels can be included in a single cartridge. The analysis channels can be joined to reagent inlets for diluents, indicators or lysing agents. A mixing channel can be positioned between the reagent inlet and the analysis region to allow mixing and reaction of the reagent. The cartridge can include additional valves and pumps for flow management. The analysis cartridge can be a self-contained disposable cartridge having an integral waste storage container. This invention further provides a sheath flow assembly. The sheath flow assembly includes a sample channel and first and second sheath fluid channels positioned on either side of and converging with the sample channel. The assembly also includes upper and lower sheath fluid chambers positioned above and below and converging with the sample channel. The flow cartridges of this invention can be formed by molding, machining or etching. In a preferred embodiment they are laminated. This invention further provides a method of fabricating a laminated microfluidic flow device. In the method, flow elements are formed in rigid sheets and abutting surfaces of the sheets are bonded together.

Liquid analysis cartridge

The present invention provides an apparatus and method for storing a particle-containing liquid. The storage apparatus comprises a microfluidic convoluted flow channel having a plurality of article capture regions. The storage channel is preferably an isotropic spatially periodic channel. Sedimented particles can be resuspended following storage. This invention further provides a microfluidic analysis cartridge having a convoluted storage channel therein. The sample analysis can use optical, electrical, pressure sensitive, or flow sensitive detection. A plurality of analysis channels can be included in a single cartridge. The analysis channels can be joined to reagent inlets for diluents, indicators or lysing agents. A mixing channel can be positioned between the reagent inlet and the analysis region to allow mixing and reaction of the reagent. The cartridge can include additional valves and pumps for flow management. The analysis cartridge can be a self-contained disposable cartridge having an integral waste storage container. This invention further provides a sheath flow assembly. The sheath flow assembly includes a sample channel and first and second sheath fluid channels positioned on either side of and converging with the sample channel. The assembly also includes upper and lower sheath fluid chambers positioned above and below and converging with the sample channel. The flow cartridges of this invention can be formed by molding, machining or etching. In a preferred embodiment they are laminated. This invention further provides a method of fabricating a laminated microfluidic flow device. In the method, flow elements are formed in rigid sheets and abutting surfaces of the sheets are bonded together.

Sample analysis instrument

Method of making a liquid analysis cartridge

A reference T-sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlets in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of analyte particles by a detectable change in property when contacted with the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or an internal standard stream; c) wherein the laminar flow channel has a depth and/or width sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to form a detection area; and (d) an outlet for conducting the streams out of the laminar flow channel preferably to form a single mixed stream.

Simultaneous analyte determination and reference balancing in reference T-sensor devices

Sheath flow assembly

Disposable hematology cartridge

An electro&ouml;smotic mixing device and a method for mixing one or more fluids for use in meso- or microfluidic device applications. The mixing device provides batch or continuous mixing of one or more fluids in meso- or microfluidic channels. An electric field is generated in the channel in substantial contact with chargeable surfaces therein. No alterations of the geometry of existing flow paths need be made, and the degree of mixing in the device can be controlled by the length of the electrodes, the flow rate past the electrodes, and the voltage applied to those electrodes. The degree of mixing is affected by choice of materials for the chargeable surface (in some cases by the selection of materials or coatings for channel walls) and the ionic strength of the fluids and the type and concentration of ions in the fluids. The ionic strength of fluids to be mixed is sufficiently low to allow electroosmotic flow. The method and device of this invention is preferably applied to fluids to having low ionic strength less than or equal to about 1 mM.

Meso- and microfluidic continuous flow and stopped flow electro&ouml;smotic mixer

This invention provides microfabricated systems for extraction of desired particles from a sample stream containing desired and undesired particles. The sample stream is placed in laminar flow contact with an extraction stream under conditions in which inertial effects are negligible. The contact between the two streams is maintained for a sufficient period of time to allow differential transport of the desired particles from the sample stream into the extraction stream. In a preferred embodiment the differential transport mechanism is diffusion. The extraction system of this invention coupled to a microfabricated diffusion-based mixing device and/or sensing means allows picoliter quantities of fluid to be processed or analyzed on devices no larger than silicon wafers. Such diffusion-based mixing or sensing devices are preferably channel cell systems for detecting the presence and/or measuring the quantity of analyte particles in a sample stream.

Microfabricated devices and methods

A reference sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlet means in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or internal standard stream; and, c) wherein the laminar flow channel has a depth and/or width sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to form a detection area. Branching channels may be provided as outlet means for conducting the streams out of the laminar flow channel. Also provided are methods of using the device to improve accuracy and increase convenience of measuring the concentration of analytes in a sample. Monitoring reference stream(s) in laminar flow with sample stream(s) allows for calibration or for monitoring or correcting for the effects of experimental conditions which might otherwise degrade accuracy. A reference stream which serves as both a control stream and an internal standard stream is convenient and economical. The device of this invention also needs less frequent calibration than previously-known fluid analysis devices because the devices and methods of this invention provide for continuous and simultaneous quality control and internal standardization.

A method and apparatus including programmed computers are provided for determining the viscosity of a first stream in a laminar flow and a second stream in a laminar flow, the flow rates, the centerline of the flow channel, and the position of the interface between the streams with respect to the centerline, and for calculating viscosity ratio of the first stream to the second.

Method for determining concentration of a laminar sample stream

Methods and apparatuses including programmed computers are provided for determining the initial concentration of diffusible particles in a sample stream introduced into a system wherein the sample stream which contains the diffusible particles flows in adjacent laminar flow with an indicator stream containing an indicator substance capable of exhibiting an observable change at a known concentration of the diffusible particles.

A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising: a) a laminar flow channel; b) two inlets in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of the analyte particles by a detectable change in property when contacted with the analyte particles, and (2) the sample stream; c) wherein the laminar flow channel has a depth sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to the substantial exclusion of the larger particles in the sample stream to form a detection area; and d) an outlet for conducting the streams out of the laminar flow channel to form a single mixed stream.

Microfabricated diffusion-based chemical sensor

A reference T-sensor system is provided for detecting the presence and/or measuring the concentration of analyte particles in a sample stream. The system includes: a) a laminar flow channel; b) three or more inlet means in fluid connection with the laminar flow channel for respectively conducting into the laminar flow channel (1) an indicator stream which may include an indicator substance which indicates the presence of the analyte particles, (2) the sample stream, and (3) a reference stream, which can be a control stream and/or internal standard stream; c) wherein the laminar flow channel has a depth and/or width sufficiently small to allow laminar flow of the streams and a length sufficient to allow particles of the analyte to diffuse into the indicator stream to form a detection area; and d) outlet means for conducting the streams out of the laminar flow channel preferably to form a single mixed stream. Also provided are methods of using the device to improve accuracy and increase convenience of measuring the concentration of analytes in a sample. Monitoring reference stream(s) in laminar flow with sample stream(s) allows for calibration or for monitoring or correcting for the effects of experimental conditions which might otherwise degrade accuracy. A reference stream which serves as both a control stream and an internal standard stream is convenient and economical. The device of this invention also needs less frequent calibration than previously-known fluid analysis devices because the devices and methods of this invention provide for continuous and simultaneous quality control and internal standardization.

Growing community of inventors

Seattle, WA, United States of America

Mark R Holl