Ciphergen Biosystems, Inc.

Gennext Technologies, Inc.

Hewlett-packard Company

Spectra-physics Gmbh

Molecular Sensing, Inc.

Vanderbilt University

Linear Instruments

Spectra-physics Analytical, Inc.

Scot Randy Weinberger

Robert W Egan

Ernst Gassmann

Joshua Shane Sharp

Louis Hlousek

Jeffrey Jonathan Persoff

Ronald Carl Orlando

Thomas W Hoppe

E Rocco Tarantino

Bruce J Richardson

Martin M Schar

Klaus O Bornsen

Edward P Donlon

Raymond G Bryan

Darryl J Bornhop

Michael G Youngquist

Jody E Beecher

Edward J Gavin

Kamen Voivodov

James L Mills

Yevgeny Kaplun

Liang Li

Larry Russon

Pete Tornatore

Emily Elizabeth Chea

Tan Huu Bui

Sandeep Misra

Darryl L Bornhop

William Landgraf

Tor C Anderson

Randy Whittal

Frank Scheufele

Stephen Dotson

Kirk C Odencrantz

Jeffrey Johnathan Persoff

David Allan Holman

Nathan Harris

Elia R Tarantino

Thomas W Hoppe, Deceased

Michelle Jones

Robert Wallace Egan

Systems and methods of in vivo and in vitro radical protein foot-printing using an opto-fluidic array are presented. These teachings may be used to, for example, study three-dimensional protein structure or bio-kinetics. Radical dosimetry including an optional intrinsic standard is used. Real-time feedback based on an internal standard provides comparability between different experiments and in vivo and in vitro analysis results in data that is representative of actual biological conditions.

Opto-fluidic array for radical protein foot-printing

Systems and methods of in vivo hydroxyl radical protein foot-printing are presented. These teachings may be used to, for example, study three-dimensional protein structure or bio-kinetics. Radical Dosimetry including an optional intrinsic standard is used on isolated intact cells. Real-time feedback based on an internal standard provides comparability between different experiments and in vivo analysis results in data that is representative of actual biological conditions.

In vivo radical dosimetry and in vivo hydroxyl radical protein foot-printing

Flash Photo-Oxidation Device and Higher Order Structural Analysis is employed for higher order structural analysis of biomolecules. Biomolecular higher order structure (HOS) results from the confounded superimposition of a biomolecule's secondary, tertiary, and quaternary structure and defines the manner in which a biomolecule presents itself and interacts with other biomolecules in living systems. A rapidly growing class of therapeutic drugs, known as biotherapeutics, comprises a variety of proteins, whose therapeutic properties are inherently linked and dependent upon their HOS. As such, HOS analysis of biotherapeutics is an important analytical requirement in the biopharmaceutical industry. The present invention provides new means and methods for the determination of biopharmaceutical HOS and associated conformation using improved devices and methodologies for flash photo-oxidation of proteins to determine their higher order biomolecular structure, and such is responsive to the increased demand for new and improved HOS analytical means in the biopharmaceutical industry.

Radical dosimetry methods for in vivo hydroxyl radical protein foot-printing

The three-dimensional structural analysis of pharmaceutical and/or biological molecules is performed by the reaction of OH radicals on the surfaces of the molecules of interest. Quantitation and/or completeness of the OH radicals are optionally measured using buffers intrinsic to the sample solutions as internal standards. Measurements of the reactions of these buffers with OH radicals provide an internal standard while avoiding the use of prior art internal standards that can have unwanted effects on the three-dimensional structures of interest.

Radical dosimetry for analysis of biopharmaceuticals and biological molecules

Flash photo-oxidation device and higher order structural analysis

A microfluidic system includes a chip with a microfluidic channel opening onto a chip inlet and a chip outlet. The channel has a sensing area and fluid delivery area. A fluidic adaptor channel opening onto an adaptor inlet and an adaptor outlet can receive a pipette tip through the adaptor inlet wherein receipt of the pipette tip into the adaptor channel creates a direct fluid path between the pipette tip and the channel and wherein the microfluidic system is configured for sensing in the sensing area by interferometry.

Microfluidic systems

Devices and methods for detecting interaction between components associated with lipid membranes and analytes are described herein. In certain methods, a surface of a compartment of a device is coated with a material that attaches to lipid membrane from a sample. An analyte is introduced and interaction is detected, for example, by back scattering interferometry. In another method, a surface is passivated with a material that does not bind a lipid membrane. A sample is introduced that contains a membrane comprising a component for testing and an analyte. Interaction is detected. In a third method, a channel is filled with a first liquid that does not comprise a lipid membrane. A bolus of a second liquid that comprises a membrane comprising a component for testing and an analyte is introduced under laminar flow conditions so that a leading edge of the second liquid does not completely displace the first liquid in a sensing area that is interrogated by optical methods, for example, a laser. Interaction between the analyte and the component is detected.

Method for detecting binding interactions between membrane proteins and analytes in a homogenous assay

This invention provides an interferometric detection device configured to maintain a temperature of a sensing area to within 20 m&#xb0; C. of a first target temperature and to maintain a temperature of the medium within 500 m&#xb0; C. of a second target temperature The device can do so under conditions in which ambient temperature changes from 0.1&#xb0; C. to 5&#xb0; C. over 5 minutes.

Temperature-stable interferometer

A method and a device for detecting an analyte, including a substrate having a chemically selective surface; and a fluidic system disposed on the substrate, the manifold having at least one fluid path in communication with at least a discrete region of the surface, wherein the one fluid path and the discrete region together define a contained sample region on the surface. The fluidic system has a removable portion, wherein the removal of the removable portion of the fluidic system renders the discrete region directly interrogatable by a surface-based analytical tool.

Apparatus for microfluidic processing and reading of biochip arrays

Methods for producing a preponderance of gas phase ions having higher order charge states during laser desorption ionization of an analyte are presented, the methods comprising irradiating the analyte in the presence of energy absorbing molecules at a mid-IR wavelength that is offset from an IR absorption maximum of the energy absorbing molecules.

Off-resonance mid-IR laser desorption ionization

Laser desorption/ionization tandem mass spectrometer instruments that include immediate post source collisional cooling are presented, as are analytical methods that employ such instruments to achieve increased sensitivity and ion yield. Also presented are laser desorption/ionization mass spectrometry methods that improve sensitivity and relative ion yield by combining affinity capture probes with matrices having low melting point energy absorbing molecules combined with alkali metal scavengers.

Methods and apparatus for improved laser desorption ionization tandem mass spectrometry

A laser optical bench for use with a laser desorption/ionization mass spectrometer. The laser optical bench includes a laser for producing light, a focusing structure that receives light from the laser and focuses predominantly in a single plane, an attenuator that receives light from the focusing structure, beam steering structure for directing light from the attenuator from the target; and a final focusing element for focusing light from the beam steering structure on the target. Further focusing elements may be included for further focusing and dispersing the light beam in different planes. Additionally, photodetectors or photodiodes may be included for energy measurement and sensing a lasing event.

Laser optical bench for laser desorption ion sources and method of use thereof

A method for calibrating a time-of-flight mass spectrometer is disclosed. The method includes determining the time-of-flight values, or values derived from the time-of-flight values for a calibration substance at each of a plurality of different addressable locations on a sample substrate. Then, one of the addressable locations on the substrate is identified as a reference addressable location. A plurality correction factors are then calculated for the respective addressable locations on the substrate using the time-of-flight value, or a value derived from the time-of-flight value.

Method for calibrating a mass spectrometer

This invention provides a mass spectrometry probe including a substrate having a surface and a film that coats the surface. The film includes openings that define features for the presentation of an analyte. The film also has a lower surface tension that the surface tension of the substrate surface, and has a water contact angle between 120&deg; and 180&deg;.

Probes with hydrophobic coatings for gas phase ion spectrometers

Growing community of inventors

Montara, CA, United States of America

Scot Randy Weinberger