Carl W Hansen

US Patent:

7052545, May 30, 2006

Filed:

Jun 22, 2001

Appl. No.:

09/887997

Inventors:

Stephen R. Quake - San Marino CA, US
Carl L. Hansen - Pasadena CA, US

Assignee:

California Institute of Technology - Pasadena CA
The Regents of the University of California - Oakland CA

International Classification:

C30B 7/08

US Classification:

117 68, 117 69, 117 70, 117201, 117202

Abstract:

High throughput screening of crystallization of a target material is accomplished by simultaneously introducing a solution of the target material into a plurality of chambers of a microfabricated fluidic device. The microfabricated fluidic device is then manipulated to vary the solution condition in the chambers, thereby simultaneously providing a large number of crystallization environments. Control over changed solution conditions may result from a variety of techniques, including but not limited to metering volumes of crystallizing agent into the chamber by volume exclusion, by entrapment of volumes of crystallizing agent determined by the dimensions of the microfabricated structure, or by cross-channel injection of sample and crystallizing agent into an array of junctions defined by intersecting orthogonal flow channels.

US Patent:

7195670, Mar 27, 2007

Filed:

Apr 5, 2002

Appl. No.:

10/117978

Inventors:

Carl L. Hansen - Pasadena CA, US
Stephen R. Quake - San Marino CA, US
James M. Berger - Kensington CA, US

Assignee:

California Institute of Technology - Pasadena CA
The Regents of the University of California - Oakland CA

International Classification:

C30B 7/14

US Classification:

117 68, 117 69, 117 70, 117201, 117202

Abstract:

High throughput screening of crystallization of a target material is accomplished by simultaneously introducing a solution of the target material into a plurality of chambers of a microfabricated fluidic device. The microfabricated fluidic device is then manipulated to vary the solution condition in the chambers, thereby simultaneously providing a large number of crystallization environments. Control over changed solution conditions may result from a variety of techniques, including but not limited to metering volumes of crystallizing agent into the chamber by volume exclusion, by entrapment of volumes of crystallizing agent determined by the dimensions of the microfabricated structure, or by cross-channel injection of sample and crystallizing agent into an array of junctions defined by intersecting orthogonal flow channels.

US Patent:

7217321, May 15, 2007

Filed:

Mar 26, 2004

Appl. No.:

10/810350

Inventors:

Carl L. Hansen - Pasadena CA, US
Stephen R. Quake - San Marino CA, US
James M. Berger - Kensington CA, US

Assignee:

California Institute of Technology - Pasadena CA

International Classification:

C30B 29/16

US Classification:

117 68, 117 69, 117 70, 4222451

Abstract:

The present invention relates to microfluidic devices and methods facilitating the growth and analysis of crystallized materials such as proteins. In accordance with one embodiment, a crystal growth architecture is separated by a permeable membrane from an adjacent well having a much larger volume. The well may be configured to contain a fluid having an identity and concentration similar to the solvent and crystallizing agent employed in crystal growth, with diffusion across the membrane stabilizing that process. Alternatively, the well may be configured to contain a fluid having an identity calculated to affect the crystallization process. In accordance with the still other embodiment, the well may be configured to contain a material such as a cryo-protectant, which is useful in protecting the crystalline material once formed.

US Patent:

7244402, Jul 17, 2007

Filed:

Aug 7, 2003

Appl. No.:

10/637847

Inventors:

Carl L. Hansen - Pasadena CA, US
Morten Sommer - Copenhagen NV, DK
Stephen R. Quake - San Marino CA, US

Assignee:

California Institute of Technology - Pasadena CA

International Classification:

C30B 29/54

US Classification:

4222451, 117 68, 117 69

Abstract:

The use of microfluidic structures enables high throughput screening of protein crystallization. In one embodiment, an integrated combinatoric mixing chip allows for precise metering of reagents to rapidly create a large number of potential crystallization conditions, with possible crystal formations observed on chip. In an alternative embodiment, the microfluidic structures may be utilized to explore phase space conditions of a particular protein crystallizing agent combination, thereby identifying promising conditions and allowing for subsequent focused attempts to obtain crystal growth.

US Patent:

7306672, Dec 11, 2007

Filed:

Oct 4, 2002

Appl. No.:

10/265473

Inventors:

Carl L. Hansen - Pasadena CA, US
Stephen R. Quake - San Marino CA, US
James M. Berger - Kensington CA, US

Assignee:

California Institute of Technology - Pasadena CA
The Regents of the University of California - Oakland CA

International Classification:

C30B 7/14

US Classification:

117 68, 117 69, 117 70, 4222451

Abstract:

A static fluid and a second fluid are placed into contact along a microfluidic free interface and allowed to mix by diffusion without convective flow across the interface. In accordance with one embodiment of the present invention, the fluids are static and initially positioned on either side of a closed valve structure in a microfluidic channel having a width that is tightly constrained in at least one dimension. The valve is then opened, and no-slip layers at the sides of the microfluidic channel suppress convective mixing between the two fluids along the resulting interface. Applications for microfluidic free interfaces in accordance with embodiments of the present invention include, but are not limited to, protein crystallization studies, protein solubility studies, determination of properties of fluidics systems, and a variety of biological assays such as diffusive immunoassays, substrate turnover assays, and competitive binding assays.

US Patent:

7407799, Aug 5, 2008

Filed:

Dec 14, 2004

Appl. No.:

11/012852

Inventors:

Frederick Balagadde - Pasadena CA, US
Carl L. Hansen - Pasadena CA, US
Emil Kartalov - Pasadena CA, US
Stephen R. Quake - Stanford CA, US

Assignee:

California Institute of Technology - Pasadena CA

International Classification:

C12P 19/04
C12M 1/00

US Classification:

4352891

Abstract:

A chemostat is described that includes a growth chamber having a plurality of compartments. Each of the compartments may be fluidly isolated from the rest of the growth chamber by one or more actuatable valves. The chemostat may also include a nutrient supply-line to supply growth medium to the growth chamber, and an output port to remove fluids from the growth chamber. Also, a method of preventing biofilm formation in a growth chamber of a chemostat is described. The method may include the steps of adding a lysis agent to a isolated portion of the growth chamber, and reuniting the isolated portion with the rest of the growth chamber.

US Patent:

7413712, Aug 19, 2008

Filed:

Apr 30, 2004

Appl. No.:

10/837025

Inventors:

Jian Liu - Pasadena CA, US
Carl L. Hansen - Pasadena CA, US
Stephen R. Quake - San Marino CA, US

Assignee:

California Institute of Technology - Pasadena CA

International Classification:

C12Q 1/68
F16K 11/10
F15C 1/04

US Classification:

422100, 435 6, 4352872, 435 79

Abstract:

A microfluidic device comprises a matrix of rotary flow reactors. The microfluidic matrix device offers a solution to the “world-to-chip” interface problem by accomplishing two important goals simultaneously: an economy of scale in reagent consumption is achieved, while simultaneously minimizing pipetting steps. Nindependent assays can be performed with only 2N+1 pipetting steps, using a single aliquot of enzyme amortized over all reactors. The chip reduces labor relative to conventional fluid handling techniques by using an order of magnitude less pipetting steps, and reduces cost by consuming two to three orders of magnitude less reagents per reaction. A PCR format has immediate applications in medical diagnosis and gene testing. Beyond PCR, the microfluidic matrix chip provides a universal and flexible platform for biological and chemical assays requiring parsimonious use of precious reagents and highly automated processing.

US Patent:

7459022, Dec 2, 2008

Filed:

Dec 6, 2004

Appl. No.:

11/006522

Inventors:

Carl L. Hansen - Pasadena CA, US
Morten Sommer - Copenhagen NV, DK
Stephen R. Quake - Stanford CA, US

Assignee:

California Institute of Technology - Pasadena CA

International Classification:

C30B 7/14

US Classification:

117 68, 117 69, 117 70

Abstract:

The use of microfluidic structures enables high throughput screening of protein crystallization. In one embodiment, an integrated combinatoric mixing chip allows for precise metering of reagents to rapidly create a large number of potential crystallization conditions, with possible crystal formations observed on chip. In an alternative embodiment, the microfluidic structures may be utilized to explore phase space conditions of a particular protein crystallizing agent combination, thereby identifying promising conditions and allowing for subsequent focused attempts to obtain crystal growth.