University of Southern California

California Institute of Technology

The United States of America as Represented by the Department of Health

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Genetic Therapy, Inc.

Other

The United States of America as Represented by the Secretary Deptartment

W French Anderson

Frederick L Hall

Erlinda Maria Gordon

Yi Zhao

Tingchao Chen

Stephen R Quake

Vincent Studer

Noriyuki Kasahara

Christopher R Logg

Jong Wook Hong

Jared Leadbetter

Martin Eglitis

Vaughn A Starnes

Axel Scherer

Steven A Rosenberg

Emil Paskalev Kartalov

R Michael Blaese

Yawen L Chiang

James M Mason

Jeanne R McLachlin

Michael Blaese

Leon F Baltrucki

Christopher I Walker

David R Hinton

Sebastian J Maerkl

Stephen J Ryan

J Anthony Thompson

Bonnie Weimin Wu

Erlina M Gordon

Nucleic acid from cells and viruses sampled from a variety of environments may purified and expressed utilizing microfluidic techniques. Individual or small groups of cells or viruses may be isolated in microfluidic chambers by dilution, sorting, and/or segmentation. The isolated cells or viruses may be lysed directly in the microfluidic chamber, and the resulting nucleic acid purified by exposure to affinity beads. Subsequent elution of the purified nucleic acid may be followed by ligation and cell transformation, all within the same microfluidic chip. Cell isolation, lysis, and nucleic acid purification may be performed utilizing a highly parallelized microfluidic architecture to construct gDNA and cDNA libraries.

Microfluidic nucleic acid analysis

Nucleic acid from cells and viruses sampled from a variety of environments may purified and expressed utilizing microfluidic techniques. In accordance with one embodiment of the present invention, individual or small groups of cells or viruses may be isolated in microfluidic chambers by dilution, sorting, and/or segmentation. The isolated cells or viruses may be lysed directly in the microfluidic chamber, and the resulting nucleic acid purified by exposure to affinity beads. Subsequent elution of the purified nucleic acid may be followed by ligation and cell transformation, all within the same microfluidic chip. In one specific application, cell isolation, lysis, and nucleic acid purification may be performed utilizing a highly parallelized microfluidic architecture to construct gDNA and cDNA libraries.

Apparatus for preparing cDNA libraries from single cells

Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of Il-12 for bone marrow preservation or recovery.

Uses of IL-12 in hematopoiesis

Methods for enhancing or stimulating hematopoiesis including the step of administering Interleukin-12 (IL-12) to yield hematopoietic recovery in a mammal in need. Preferred methods include the step of administering IL-12 as an adjuvant therapy to alleviate the hematopoietic toxicities associated with one or more treatment regimens used to combat a disease state. Other methods include administering IL-12 to ameliorate various hematopoietic deficiencies. Still other methods are directed to uses of IL-12 for in-vivo proliferation of hematopoietic repopulating cells, hematopoietic progenitor cells and hematopoietic stem cells. Other disclosed methods are directed to uses of IL-12 for bone marrow preservation or recovery.

Method for bone marrow preservation or recovery

Method for treating deficiency in hematopoiesis

A recombinant replication competent retrovirus for gene deliver and gene therapy is provided. The recombinant retrovirus has a heterologous nucleic acid sequence, a sequence encoding a cell- or tissue-specific ligand or a sequence for transcriptional targeting, or a combination of both a cell- or tissue-specific ligand and a cell- or tissue-specific transcriptional targeting sequence.

Gene delivery system and methods of use

Gene delivery system and method of use

Using basic physical arguments, a design and method for the fabrication of microfluidic valves using multilayer soft lithography is presented. Embodiments of valves in accordance with the present invention feature elastomer membrane portions of substantially constant thickness, allowing the membranes to experience similar resistance to an applied pressure across their entire width. Such on-off valves fabricated with upwardly- or downwardly-deflectable membranes can have extremely low actuation pressures, and can be used to implement active functions such as pumps and mixers in integrated microfluidic chips. Valve performance was characterized by measuring both the actuation pressure and flow resistance over a wide range of design parameters, and comparing them to both finite element simulations and alternative valve geometries.

Microfluidic large scale integration

By use of the vias a microfluidic autoregulator is fabricated comprising an origin of a fluid, a sink for the fluid, a main flow channel coupling the origin and the sink, a valve communicated to the main flow channel to selectively control flow of fluid therethrough, and means dependent on flow through the main flow channel for creating a pressure differential across the valve to at least partially activate the valve to control flow of fluid through the main flow channel. The means for dependent on flow for creating a pressure differential comprises either a dead-end detour channel from the flow channel to the valve, or a loop channel fed back to the control chamber of the valve.

Microfluidic autoregulator devices and arrays for operation with newtonian fluids

Component microfluidic devices which are integrated with polydimethylsiloxane (PDMS) microfluidic chips, include designs for an electrical and optical pressure gauge, valve, electrostatic and magnetic pumps, alternating or mixing pumps, a solenoid, a magnetometer, a magnetically actuated reversible filter and valve, and a hydrolysis valve. These devices enhance and miniaturize microfluidic control, thereby expanding the available capabilities and allowing complete system miniaturization for handheld diagnostic apparatuses.

PMDS microfluidic components and methods of operation of the same

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San Marino, CA, United States of America

W French Anderson