University of Washington

Diane M Zebert

Bernhard Hans Weigl

Margaret A Kenny

Mark R Holl

Caicai Wu

Paul Yager

Paul Charles Galambos

James P Brody

Andrew Kamholz

Fred K Forster

Gregory Hixson

David Schutte

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

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 device and method for introducing a second laminar fluid layer to, or removing a second laminar fluid layer from, a first laminar fluid layer are provided. Each laminar fluid layer can contain two or more side by side laminar streams. The device includes a main flow channel, and at least one tributary channel in fluid connection with a bridge channel which is in fluid connection with main flow channel. The device can be formed in a single piece of material, which can be optically transparent. Optionally, the channels can be formed in a first plate, the first and optionally the second surfaces of which are sealed to a second and optionally a third plate. The second and third plates can be optically transparent to allow for optical detection and analysis. A first laminar fluid layer is introduced into the main flow channel. If a second laminar fluid layer is to be added to the first laminar fluid layer, then the former is introduced into the tributary channel, from whence it flows into the bridge channel and then into the main flow channel, where it flows below the first laminar fluid layer and diffusionally mixes with it. Preferably, the width of the main flow channel is relatively small, so that particles in an added second laminar fluid layer diffusionally mix into the first laminar fluid layer rapidly. If a second laminar fluid layer is to be removed from a first laminar fluid layer, then the latter is split into two portions: one portion continues flowing down the main flow channel and one portion flows into the bridge channel from whence it flows into the tributary channel.

Device for rapidly joining and splitting fluid layers

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

Diane M Zebert