University of California

Other

Lawrence Livermore National Security, LLC

The Fix, LLC

The United States of America As Represented by the Department of Energy

Minimed, Inc.

Tahoe Institute for Rural Health, LLC

Sunol Technologies, Inc.

Stephen M Lane

Joe H Satcher, Jr

Christopher B Darrow

Troy W Barbee, Jr

John Joseph Mastrototaro

William P Van Antwerp

Thomas Arnold Peyser

Dennis L Matthews

William D Wilson

Thomas R Huser

Michael P Surh

Abraham Phillip Lee

Marco Wo

Matthew A Coleman

Joe Anh Tran

Michael K Allio

Amy W Wang

Douglas R Cary

Christopher W Hollars

Jennifer Harder

John M Boone

Olgica Bakajin

David J Vachon

Glenn Noronha

Rodney L Balhorn

Zachary Pace Smith

James W Chan

Bradley R Hart

Ted Alfred Laurence

Stanley G Prussin

Clinton M Logan

Ronald Li

Aaron M Heiss

Joseph C Walsh

Chad E Talley

Joanna Albala

Denis Dwyre

Laurence Heifetz

James Hood

John C Rutledge

Keith Tatsukawa

Douglas S Taylor

Rupa S Rao

Deanna Lynn Thompson

Donald E Hoffman

Theodore Zwerdling

Howard Spracklen

Sebastian Wachsmann-Hogiu

Tingjuan Gao

Sebastian Wachmann-Hogiu

Raman spectra of cells, such as normal human T- and B-cells from peripheral blood or human tonsil and the corresponding transformed cells are obtained by optically trapping the cells and obtaining their Raman spectra. The trapped cells can be subjected to one, two, or more different excitation wavelengths, and each wavelength of the corresponding Raman spectra can be stored in a separate channel. In preferred embodiments, two spectra are subtracted from each other to give a difference spectrum and each channel is analyzed independently to characterize the trapped cell. Alternatively, the Raman spectrum can be subjected to Principal Component Analysis (PCA) in order to characterize the trapped cell. The trapped cell thus classified can be sorted, or further manipulated.

Single-cell raman spectroscopy for the non-destructive, non-invasive analysis of cells and cellular components

Described herein are compositions, methods, and devices for relief of a cough, cold, sore throat, or allergy, or a related symptom. Also described herein are compositions, methods, and devices for the prevention, treatment and/or amelioration of a digestive illness or digestive discomfort, or a related symptom of either. Such compositions may be in the form of a liquid composition and include a plurality of pharmaceutical ingredients and a plurality of botanical ingredients.

Compositions and methods for combination ingredient delivery

This disclosure describes the development of a sample preparation, measurement, and analysis method that permits accurate characterization of red blood cells, platelets, and white blood cells, including a 3-part differential of the white blood cells count, to be performed on small volumes of a biological sample. This method is compatible with compact and portable instrumentation that permits the sample collection to be performed in a subject's home and analysis to be performed elsewhere by transmission of the data to a laboratory or doctor's office.

Portable blood count monitor

Described herein are compositions, methods, and devices for relief of a cough, cold, sore throat, or allergy, or a related symptom. Also described herein are compositions, methods, and devices for the prevention, treatment and/or amelioration of a digestive illness or digestive discomfort, or a related symptom of either.

A device and array coupled to capture molecules are provided. Specifically, the device and array can be used for detecting the presence and concentration of biomarkers in a sample from a subject. The device and array can also allow the use of a method for scoring a sample for, e.g., the purpose of diagnosing a disease. The method can also be advantageous to applications where there is a need to accurately determine the disease stage of a subject for the purpose of making therapeutic decisions.

Device, array, and methods for disease detection and analysis

A hand-held portable microarray reader for biodetection includes a microarray reader engineered to be small enough for portable applications. The invention includes a high-powered light-emitting diode that emits excitation light, an excitation filter positioned to receive the excitation light, a slide, a slide holder assembly for positioning the slide to receive the excitation light from the excitation filter, an emission filter positioned to receive the excitation light from the slide, a lens positioned to receive the excitation light from the emission filter, and a CCD camera positioned to receive the excitation light from the lens.

Hand-held portable microarray reader for biodetection

Surface-Enhanced Raman Spectroscopy (SERS) is a vibrational spectroscopic technique that utilizes metal surfaces to provide enhanced signals of several orders of magnitude. When molecules of interest are attached to designed metal nanoparticles, a SERS signal is attainable with single molecule detection limits. This provides an ultrasensitive means of detecting the presence of molecules. By using selective chemistries, metal nanoparticles can be functionalized to provide a unique signal upon analyte binding. Moreover, by using measurement techniques, such as, ratiometric received SERS spectra, such metal nanoparticles can be used to monitor dynamic processes in addition to static binding events. Accordingly, such nanoparticles can be used as nanosensors for a wide range of chemicals in fluid, gaseous and solid form, environmental sensors for pH, ion concentration, temperature, etc., and biological sensors for proteins, DNA, RNA, etc.

Nanosensors based on functionalized nanoparticles and surface enhanced raman scattering

A microfluidic device made from nanolaminate materials that are capable of electrophoretic selection of particles on the basis of their mobility. Nanolaminate materials are generally alternating layers of two materials (one conducting, one insulating) that are made by sputter coating a flat substrate with a large number of layers. Specific subsets of the conducting layers are coupled together to form a single, extended electrode, interleaved with other similar electrodes. Thereby, the subsets of conducting layers may be dynamically charged to create time-dependent potential fields that can trap or transport charge colloidal particles. The addition of time-dependence is applicable to all geometries of nanolaminate electrophoretic and electrochemical designs from sinusoidal to nearly step-like.

Nanolaminate microfluidic device for mobility selection of particles

A method and apparatus with the sensitivity to detect and identify single target molecules through the localization of dual, fluorescently labeled probe molecules. This can be accomplished through specific attachment of the taget to a surface or in a two-dimensional (2D) flowing fluid sheet having approximate dimensions of 0.5 &#x3bc;m&#xd7;100 &#x3bc;m&#xd7;100 &#x3bc;m. A device using these methods would have 10&#x2013;10greater throughput than previous one-dimensional (1D) micro-stream devices having 1 &#x3bc;minterrogation volumes and would for the first time allow immuno- and DNA assays at ultra-low (femtomolar) concentrations to be performed in short time periods (&#x2dc;10 minutes). The use of novel labels (such as metal or semiconductor nanoparticles) may be incorporated to further extend the sensitivity possibly into the attomolar range.

High-throughput, dual probe biological assays based on single molecule detection

Nanochannel electrophoretic and electrochemical devices having selectively-etched nanolaminates located in the fluid transport channel. The normally flat surfaces of the nanolaminate having exposed conductive (metal) stripes are selectively-etched to form trenches and baffles. The modifications of the prior utilized flat exposed surfaces increase the amount of exposed metal to facilitate electrochemical redox reaction or control the exposure of the metal surfaces to analytes of large size. These etched areas variously increase the sensitivity of electrochemical detection devices to low concentrations of analyte, improve the plug flow characteristic of the channel, and allow additional discrimination of the colloidal particles during cyclic voltammetry.

Selectively-etched nanochannel electrophoretic and electrochemical devices

Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. Embodiments of these biosensor molecules exhibit fluorescence emission at wavelengths greater than about 650 nm. Typical biosensor molecules include a fluorophore that includes an iminium ion, a linker moiety that includes a group that is an anilinic type of relationship to the fluorophore and a boronate substrate recognition/binding moiety, which binds glucose. The fluorescence molecules modulated by the presence or absence of polyhydroxylated analytes such as glucose. This property of these molecules of the invention, as well as their ability to emit fluorescent light at greater than about 650 nm, renders these biosensor molecules particularly well-suited for detecting and measuring in-vivo glucose concentrations.

Long wave fluorophore sensor compounds and other fluorescent sensor compounds in polymers

Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

Detection of biological molecules using boronate-based chemical amplification and optical sensors

An analyte sensing fluorescent molecule that employs intramolecular electron transfer is designed to exhibit selected fluorescent properties in the presence of analytes such as saccharides. The selected fluorescent properties include excitation wavelength, emission wavelength, fluorescence lifetime, quantum yield, photostability, solubility, and temperature or pH sensitivity. The compound comprises an aryl or a substituted phenyl boronic acid that acts as a substrate recognition component, a fluorescence switch component, and a fluorophore. The fluorophore and switch component are selected such that the value of the free energy for electron transfer is less than about 3.0 kcal mol . Fluorescent compounds are described that are excited at wavelengths greater than 400 nm and emit at wavelengths greater than 450 nm, which is advantageous for optical transmission through skin. The fluorophore is typically selected from transition metal-ligand complexes and thiazine, oxazine, oxazone, or oxazine-one as well as anthracene compounds. The fluorescent compound can be immobilized in a glucose permeable biocompatible polymer matrix that is implantable below the skin.

Glucose sensing molecules having selected fluorescent properties

The present invention provides formulae for fluorescent compounds that have a number of properties which make them uniquely suited for use in sensors of analytes such as saccharides. The advantageous fluorescent properties include favorable excitation wavelengths, emission wavelengths, fluorescence lifetimes, and photostability. Additional advantageous properties include enhanced aqueous solubility, as well as temperature and pH sensitivity. The compound comprises an aryl or a substituted phenyl botonic acid that acts as a substrate recognition component, a fluorescence switch component, and a fluorophore. Fluorescent compounds are described that are excited at wavelengths greater than 400 nm and emit at wavelengths greater than 450 nm, which is advantageous for optical transmission through skin. The fluorophore is typically selected from transition metal-ligand complexes and thiazine, oxazine, oxazone, or oxazine-one as well as anthracene compounds. The fluorescent compound can be immobilized in a glucose permeable biocompatible polymer matrix that is implantable below the skin.

Saccharide sensing molecules having enhanced fluorescent properties

Growing community of inventors

Davis, CA, United States of America

Stephen M Lane