California Institute of Technology

Incyte Pharmaceuticals, Inc.

Nexstar Pharmaceuticals, Inc.

Vestar, Inc.

John D. Baldeschwieler

John D Baldeschwieler

Ronald C Gamble

Thomas P Theriault

Raymond P Goodrich, Jr

Stephen D O'Connor

Jesse L Beauchamp

Dmitri A Kossakovski

Marcia R Mauk

Marc Alexander Unger

Tsung-Ying Shen

Mitree M Ponpipom

George W Tin

David Randall Baselt

Marcel Widmer

Ming P Li

Albert M Lin

A scanning probe microscope is combined with a laser induced breakdown spectrometer to provide spatially resolved chemical analysis of the surface correlated with the surface topography. Topographical analysis is achieved by scanning a sharp probe across the sample at constant distance from the surface. Chemical analysis is achieved by the means of laser induced breakdown spectroscopy by delivering pulsed laser radiation to the sample surface through the same sharp probe, and consequent collection and analysis of emission spectra from plasma generated on the sample by the laser radiation. The method comprises performing microtopographical analysis of the sample with a scanning probe, selecting a scanned topological site on the sample, generating a plasma plume at the selected scanned topological site, and measuring a spectrum of optical emission from the plasma at the selected scanned topological site. The apparatus comprises a scanning probe, a pulsed laser optically coupled to the probe, an optical spectrometer, and a controller coupled to the scanner, laser and spectrometer for controlling the operation of the scanner, laser and spectrometer. The probe and scanner are used for topographical profiling the sample. The probe is also used for laser radiation delivery to the sample for generating a plasma plume from the sample. Optical emission from the plasma plume is collected and delivered to the optical spectrometer so that analysis of emission spectrum by the optical spectrometer allows for identification of chemical composition of the sample at user selected sites.

Method and apparatus for chemical and topographical microanalysis

The present invention discloses an improved method and apparatus for analyzing the surface of materials using sub-micron laser desorption gas phase analysis. The method uses a combination of Near-field Optical Microscopy and Time-of Flight Mass Spectroscopy.

Sub-micron chemical imaging with near-field laser desorption

A method and apparatus are provided for preparing a substrate upon which is located microdrop-sized loci at which chemical compounds are synthesized or diagnostic tests are conducted. The loci are formed by applying microdrops from a dispenser from which a microdrop is pulse fed onto the surface of the substrate.

Method and substrate for performing multiple sequential reactions on a

Devices and methods are provided for precise reduction of arrays of microspots. A pulse jetting device is employed having a capillary of micron dimensions, with a portion of the capillary proximal to the jetting orifice circumferentially surrounded by a piezoelectric transducer. By appropriate design of the capillary, orifice and piezoelectric transducer, droplets can be formed on a surface, separated by as little as 80 microns center-to-center, and having at least about a 15 micron spacing at the border. The subject substrate arrays can be used for providing miniaturized arrays of reagents, such as nucleic acids, for detecting the presence of homologous sequences in a sample.

Jet droplet device

An apparatus for the automated synthesis of molecular arrays. A jetting device is employed along with a reaction chamber to dispense reagents used in the synthesis onto the substrate. A positioning system moves the substrate from the jet to the reaction chamber. A controller controls the movement of the substrate and the application of the reagents so that the synthesis is carried out according to a pre-determined procedure. The apparatus will synthesize nucleotides in an array of micron-size spots according to a pattern selected by the operator immediately prior to synthesis.

Apparatus for the chemical synthesis of molecular arrays

Devices and methods are provided for precise production of arrays of microspots. A pulse jetting device is employed having a capillary of micron dimensions, with a portion of the capillary proximal to the jetting orifice circumferentially surrounded by a piezoelectric transducer. By appropriate design of the capillary, orifice and piezoelectric transducer, droplets can be formed on a surface, separated by as little as 80 microns center-to-center, and having at least about a 15 micron spacing at the border. The subject substrate arrays can be used for providing miniaturized arrays of reagents, such as nucleic acids, for detecting the presence of homologous sequences in a sample.

Methods for performing multiple sequential reactions on a matrix

Probes for sensing and manipulating microscopic environments and structures, their method of preparation and methods of use are disclosed.

Method of preparing probes for sensing and manipulating microscopic

Liposomes of a size of less than 200 nanometers target ischemic myocardial tissue and preferentially deliver active agents to infarcted areas.

Liposomal targeting of ischemic tissue

Liposomes of a size of less than 200 nanometers target ischemic myocardial tissue and preferentially deliver active agents to infarcted areas in the absence of antibodies bound to the liposomes to effect the delivery.

Compositions for cryopreservation of phosphoglyceride-containing biological and synthetic membranes are provided in which a lipophilic anchor molecule is modified by the attachment of a preferably carbohydrate moiety placed at a predetermined, variable distance from the hydrophobic portion of the molecule by means of a hydrophilic linker unit. A method for the use of the compositions is also provided.

Cryoprotective reagent

Closed, unilamellar vesicles are spontaneously formed by adding a cholesteryl compound substituted with a hydroxyl terminated polyethylene oxide containing 1 to 4 ethylene oxide groups to a polar liquid. Multilamellar vesicles are formed by sonicating a cholesteryl compound containing polyethylene oxide or polyamine side-chains. The vesicles can be utilized to dispense polar, non-polar or ampholphilic compounds.

Lamellar vesicles formed of cholesterol derivatives

The ability of phosphoglyceride-containing membranes to withstand the disruptive effects of freezing, thawing, or freeze-drying is enhanced when treated with (a) a compound of the formula R-X-R.sub.1, wherein R is a lipid or lipophilic anchor, X is a hydrophilic linker group, and R.sub.1 is a polyalcohol or carbohydrate group, and (b) ascorbic acid.

Cryoprotective reagents in freeze-drying membranes

An immunoassay method for detection of antigen is disclosed. The method employs complement mediated lysis of vesicles loaded with In-111 or other gamma-emitting cation, and quantitative detection of the lysis by gamma-ray perturbed angular correlation (PAC) spectroscopy. The vesicles are labeled with a substance competitive to the antigen to be measured, and the concentration of the antigen in the sample measured by assessing the diminution in lysis due to the presence of the competing antigen. The method may also be used to assess the immunologic competence of a subject by injecting suitably sensitized vesicles and monitoring the in vivo lysis pattern by (PAC).

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Pasadena, CA, United States of America

John D Baldeschwieler