Christopher B Sims

US Patent:

6335201, Jan 1, 2002

Filed:

Jul 21, 1999

Appl. No.:

09/358504

Inventors:

Nancy L. Allbritton - Irvine CA
Christopher E. Sims - Irvine CA
Michael W. Berns - Coto de Caza CA
Gavin D. Meredith - Cardiff-by-the-Sea CA
Bruce J. Tromberg - Irvine CA

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

G01N 3348

US Classification:

436 63, 436164, 436172, 422 8205, 422 8208, 435 4, 435 29, 435 30, 4352887, 204451, 204400, 204403, 204601

Abstract:

The activity of intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon chemical reaction such as that catalyzed by an enzyme. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific enzymes. Thus the activity of a specific enzyme or class of enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest, typically after exposure of the cell to a stimulus that activates a particular enzymatic pathway. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of a single cell into which reporter substrate molecules have been introduced. The cell contents are then subjected to capillary electrophoresis and enzymatic activity is determined by comparing amounts of substrate molecules to amounts of enzymatically altered substrate molecules which are separated by the electrophoresis and identified by the presence of a fluorescent label.

US Patent:

6740497, May 25, 2004

Filed:

May 17, 2001

Appl. No.:

09/859650

Inventors:

Nancy Allbritton - Irvine CA
Christopher Sims - Irvine CA

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12Q 148

US Classification:

435 15, 435 29

Abstract:

The activity of oncogenic intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon a chemical reaction such as that catalyzed by an enzyme or kinase. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific oncogenic enzymes. Thus the activity of an oncogenic enzyme or class of oncogenic enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of said cell or cells into which reporter substrate molecules have been introduced. The cell contents are then subjected to capillary electrophoresis and oncogenic enzymatic activity is determined by comparing amounts of unaltered substrate molecules to the amounts of altered substrate molecules which are separated by the electrophoresis and identified by the presence of a fluorescent label.

US Patent:

7157223, Jan 2, 2007

Filed:

Aug 30, 2001

Appl. No.:

09/945396

Inventors:

Nancy Allbritton - Irvine CA, US
Christopher Sims - Irvine CA, US
Michael W. Berns - Coto de Caza CA, US
Gavin D. Meredith - Cardiff-By-The-Sea CA, US
Bruce J. Tromberg - Irvine CA, US
Chao L. Lee - Taipei, TW

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12Q 1/00

US Classification:

435 4, 435 29, 435 30, 4352887, 435 74, 435 71, 436 2, 436 63, 436164, 436516, 422 8205, 422 8208

Abstract:

The activity of intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon chemical reaction such as that catalyzed by an enzyme. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific enzymes. Thus the activity of a specific enzyme or class of enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest, typically after exposure of the cell to a stimulus that activates a particular enzymatic pathway. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of a single cell into which reporter substrate molecules have been introduced. The cell contents are then subjected to capillary electrophoresis and enzymatic activity is determined by comparing amounts of substrate molecules to amounts of enzymatically altered substrate molecules which are separated by the electrophoresis and identified by the presence of a fluorescent label.

US Patent:

7236888, Jun 26, 2007

Filed:

Nov 21, 2001

Appl. No.:

09/990413

Inventors:

Nancy Allbritton - Irvine CA, US
Christopher Sims - Irvine CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

G06F 19/00
C12Q 1/25

US Classification:

702 19, 435 4

Abstract:

The activity of multiple proteins in a single living cell, portion of a cell or in a group of cells is simultaneously measured by introducing reporter molecules into the cell(s) or a portion thereof, chemically modifying the reporter(s) by the enzyme of interest, terminating the modification reactions, removing the reporter(s) and modified reporter(s), and determining the amount of enzyme activity present by measuring or comparing the amount of reporter(s) and modified reporter(s) present. By performing a series of experiments at different time points, conditions, and varieties of cell types, a database is developed for molecular cellular mechanisms in health and disease states. By exposing cells to a variety of compounds data for drug development and screening is provided.

US Patent:

7695954, Apr 13, 2010

Filed:

Oct 4, 2005

Appl. No.:

11/243926

Inventors:

Mark Bachman - Irvine CA, US
Nancy Allbritton - Irvine CA, US
Christopher Sims - Irvine CA, US

Assignee:

The Regents of The University of California - Oakland CA

International Classification:

C12M 1/34
C12M 3/00

US Classification:

4352884

Abstract:

A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses.

US Patent:

7759119, Jul 20, 2010

Filed:

Apr 9, 2007

Appl. No.:

11/733053

Inventors:

Nancy Allbritton - Irvine CA, US
Christopher E. Sims - Irvine CA, US
Yuli Wang - Irvine CA, US
Mark Bachman - Irvine CA, US
Eric Stanbridge - Corona Del Mar CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12N 15/00
C12N 5/02
C12N 5/00
C12N 15/01
C12N 1/02

US Classification:

435325, 435440, 4352523, 4351739, 435174

Abstract:

A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses. Use of the plate advantageously enables the selection and sorting of cells based on dynamic phenomena and the rapid establishment of stable tranfectants.

US Patent:

8383378, Feb 26, 2013

Filed:

Oct 9, 2006

Appl. No.:

11/539695

Inventors:

Yuli Wang - Irvine CA, US
Mark Bachman - Irvine CA, US
Christopher E. Sims - Irvine CA, US
Nancy Allbritton - Irvine CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12N 11/02
C12Q 1/68
C12M 1/34

US Classification:

435174, 435177, 435180, 4352872, 4352885, 530812, 530813, 422407, 422552

Abstract:

Systems and methods are provided for patterning biological and non-biological material at specific sites on a plate, as well as growing three dimensional structures. Preferred embodiments comprise a plate with regions that will trap gas, usually in the form of bubbles, when the plate is submerged in liquid. Other embodiment of the present invention include a method for placing materials on the plate at pre-determined locations through the use of trapped gas to prevent materials from collecting at unwanted regions. The plate has great utility for plating cells and tissues at specific sites, such as on an array. The disclosed method can also be used to coat the surface of a plate with coatings at specific locations for patterned coating applications and to build up materials to produce three dimensional structures, including micro-mechanical structures—where the structures may be formed from living or non-living material, tissue or non-tissue, organic or inorganic, and the like.

US Patent:

20040058423, Mar 25, 2004

Filed:

May 2, 2003

Appl. No.:

10/429282

Inventors:

Nancy Albritton - Irvine CA, US
Mark Bachman - Irvine CA, US
Christopher Sims - Irvine CA, US
Futian Han - Ames IA, US

International Classification:

C12M001/42
C12N013/00

US Classification:

435/173700, 435/285200, 435/288400, 435/305200, 435/306100, 204/451000, 204/601000

Abstract:

The invention provides apparatus and methods for subsecond lysis of selected cells in a cell chamber using a voltage pulse of 10 ms to 10 s in duration followed by nearly simultaneous collection of the lysed cellular contents into a capillary electrophoresis tube or other suitable micro-collection device. Cell chambers and capillary electrophoresis tubes configured with electrodes for performing the electrical lysis are described. The influence of variables that govern the rate of cell lysis, such as inter-electrode distance, pulse duration, and pulse strength are also described. The methods are illustrated using fluorophores that are loaded into a cell then collected following electrical lysis, separated by electrophoresis, and then detected by laser-induced fluorescence detection in a capillary electrophoresis system.