Caliper Technologies Corporation

Caliper Life Sciences, Inc.

Leland Stanford Junior University

Wako Pure Chemical Industries, Inc.

H Garrett Wada

Robert S Dubrow

Marja Liisa Alajoki

J Wallace Parce

Anne R Kopf-Sill

Luc J Bousse

Javier Anibal Farinas

Andrea W Chow

Benjamin N Wang

Matthew B Murphy

Steven A Sundberg

Theo Teofanov Nikiforov

Yutaka Miki

Irina G Kazakova

Toshinari Ohashi

Yevgeny Yurkovetsky

Futoshi Kanke

Katherine S Fok

Howard H Sussman

C Nicholas Hodge

This invention provides methods and compositions, e.g., to reduce interference from non-specific binding sample constituents in a migration shift assay. Interference due to non-specific binding of sample constituents to an affinity substance (e.g., an affinity molecule or a conjugate of an affinity molecule and a charged carrier molecule) is prevented by, e.g., binding the constituents to charged polymers such as heparin sulfate. The present invention also provides methods to concentrate an analyte of interest with high concentration and to detect the analyte with high sensitivity, and further to optimize the reaction conditions for easily concentrating the analyte. Such objects of the present invention are attained, for example, by concentrating a complex of the analyte and a conjugate which is formed by contacting the analyte in a sample with an affinity molecule bound to a charged carrier molecule such as DNA.

Reduction of migration shift assay interference

The present invention provides novel methods for controlling/manipulating materials flowing in a fluidic device. In particular, the methods of the invention create and utilize differences between dispersion rates and/or average velocity of materials in order to manipulate the materials.

Channel cross-section geometry to manipulate dispersion rates

Methods of detecting a component of interest, such as a protein, in a microfluidic system are provided. The methods include the use of a component-binding moiety specific to the component of interest, such as an antibody, to detect the component of interest. Also included are microfluidic devices and integrated systems for performing such assays, including devices utilizing flowable or fixed particle sets.

Microfluidic analytic detection assays, devices, and integrated systems

Apparatus and methods for modulating flow rates in microfluidic devices are provided. The methods involve modulating downstream pressure in the device to change the flow rate of materials in an upstream region of the device. Such methods include electrokinetic injection or withdrawal of materials through a side channel and the use of an absorbent material to induce wicking in the channel system. The apparatus provided includes a prefabricated wick in the device to provide for flow rate control. Additional methods for determining velocity of a particle and cell incubation time are also provided.

Apparatus for continuous liquid flow in microscale channels using wicking

Transmembrane potential measurement methods using cationic dyes, and anionic dyes are provided. Compositions of the cationic and anionic dyes and microfluidic systems which include the dyes and membranes are provided in conjunction with processing elements for transmembrane potential measurements.

Use of Nernstein voltage sensitive dyes in measuring transmembrane voltage

Use of nernstein voltage sensitive dyes in measuring transmembrane voltage

Methods of monitoring transporter activity, gradient induced activity, and binding activity in microscale systems, as well as corresponding microscale devices, systems and kits are provided.

Microscale assays and microfluidic devices for transporter, gradient induced, and binding activities

Methods and systems for particle focusing to increase assay throughput and sensitivity in microscale systems are provided. The invention includes methods for providing substantially uniform flow velocity to flowing particles in microfluidic devices. Methods of sorting members of particle populations, such as cells and various subcellular components are also provided. Integrated systems in which particles are focused and/or sorted are additionally included.

Focusing of microparticles in microfluidic systems

Methods for determining a function of cells, which comprises a suspension of cells flowing along a first fluid channel. The cells have a first detectable property associated therewith, and wherein the cells produce a second detectable property upon activation of the function of the cells, the first and second detectable properties being distinguishable from each other. Levels of the first and second detectable properties are measured. The level of the second detectable property is compared to the level of first detectable property to determine the relative function of the cells.

High throughput methods, systems and apparatus for performing cell based screening assays

Methods and systems for particle focusing to increase assay throughput in microscale systems are provided. The invention includes methods for providing substantially uniform flow velocity to flowing particles in microfluidic devices. Methods of sorting members of particle populations, such as cells and various subcellular components are also provided. Integrated systems in which particles are focused and/or sorted are additionally included.

Method and apparatus for continuous liquid flow in microscale channels using pressure injection, wicking, and electrokinetic injection

Intracellular binding reactions, and particularly DNA/DNA binding protein reactions are detected in situ, using intracellular fluorescence polarization detection. The methods comprise providing a biological cell having at least a first component of a binding reaction disposed therein. The cell is contacted with a second component of the binding reaction whereby the second component is internalized within the biological cell. At least one of the first and second components has a fluorescent label. The amount of binding between the first and second components within the cell is determined by measuring a level of polarized and/or depolarized fluorescence emitted from within the biological cell.

Methods and systems for monitoring intracellular binding reactions

Copper chelates serve as cytotoxic agents in conjunction with a surface membrane protein receptor internalizing agent, particularly TNF, which has independent cytotoxic activity, for use against target cells. By employing concentrations of the two agents, where the agents have substantially reduced adverse side effects, the combination is shown to have effective cytotoxic activity.

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Atherton, CA, United States of America

H Garrett Wada