Patents by Inventor Stephen R. Quake

Stephen R. Quake has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20120046639
    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.
    Type: Application
    Filed: August 19, 2011
    Publication date: February 23, 2012
    Applicants: The Regents of the University of California, California Institute of Technology
    Inventors: Carl L. Hansen, Stephen R. Quake, James M. Berger
  • Patent number: 8104515
    Abstract: A method of fabricating an elastomeric structure, comprising: forming a first elastomeric layer on top of a first micromachined mold, the first micromachined mold having a first raised protrusion which forms a first recess extending along a bottom surface of the first elastomeric layer; forming a second elastomeric layer on top of a second micromachined mold, the second micromachined mold having a second raised protrusion which forms a second recess extending along a bottom surface of the second elastomeric layer; bonding the bottom surface of the second elastomeric layer onto a top surface of the first elastomeric layer such that a control channel forms in the second recess between the first and second elastomeric layers; and positioning the first elastomeric layer on top of a planar substrate such that a flow channel forms in the first recess between the first elastomeric layer and the planar substrate.
    Type: Grant
    Filed: August 13, 2009
    Date of Patent: January 31, 2012
    Assignee: California Institute of Technology
    Inventors: Marc A. Unger, Hou-Pu Chou, Todd A. Thorsen, Axel Scherer, Stephen R. Quake
  • Publication number: 20120009663
    Abstract: The present invention provides microfluidic devices and methods using the same in various types of thermal cycling reactions. Certain devices include a rotary microfluidic channel and a plurality of temperature regions at different locations along the rotary microfluidic channel at which temperature is regulated. Solution can be repeatedly passed through the temperature regions such that the solution is exposed to different temperatures. Other microfluidic devices include an array of reaction chambers formed by intersecting vertical and horizontal flow channels, with the ability to regulate temperature at the reaction chambers. The microfluidic devices can be used to conduct a number of different analyses, including various primer extension reactions and nucleic acid amplification reactions.
    Type: Application
    Filed: November 16, 2010
    Publication date: January 12, 2012
    Applicant: California Institute of Technology
    Inventors: Markus M. Enzelberger, Carl L. Hansen, Jian Liu, Stephen R. Quake, Chiem Ma
  • Publication number: 20110319272
    Abstract: Disclosed is a method to achieve digital quantification of DNA (i.e., counting differences between identical sequences) using direct shotgun sequencing followed by mapping to the chromosome of origin and enumeration of fragments per chromosome. The preferred method uses massively parallel sequencing, which can produce tens of millions of short sequence tags in a single run and enabling a sampling that can be statistically evaluated. By counting the number of sequence tags mapped to a predefined window in each chromosome, the over- or under-representation of any chromosome in maternal plasma DNA contributed by an aneuploid fetus can be detected. This method does not require the differentiation of fetal versus maternal DNA. The median count of autosomal values is used as a normalization constant to account for differences in total number of sequence tags is used for comparison between samples and between chromosomes.
    Type: Application
    Filed: August 25, 2011
    Publication date: December 29, 2011
    Applicant: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Hei-Mun Christina Fan, Stephen R. Quake
  • Publication number: 20110306522
    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.
    Type: Application
    Filed: April 15, 2011
    Publication date: December 15, 2011
    Applicant: California Institute of Technology
    Inventors: Carl L. Hansen, Morten Sommer, Stephen R. Quake
  • Patent number: 8052792
    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.
    Type: Grant
    Filed: May 15, 2007
    Date of Patent: November 8, 2011
    Assignees: California Institute of Technology, The Regents of the University of California
    Inventors: Carl L. Hansen, Stephen R. Quake, James M. Berger
  • Patent number: 8039269
    Abstract: The invention provides devices and methods for surface patterning the substrate of a microfluidic device, and for detection and analysis of interactions between molecules by mechanically trapping a molecular complex while substantially expelling solvent and unbound solute molecules. Examples of molecular complexes include protein-protein complexes and protein-nucleic acid complexes.
    Type: Grant
    Filed: January 26, 2007
    Date of Patent: October 18, 2011
    Assignee: California Institute of Technology
    Inventors: Sebastian J. Maerkl, Stephen R. Quake
  • Publication number: 20110246083
    Abstract: Disclosed is a method to achieve digital quantification of DNA (i.e., counting differences between identical sequences) using direct shotgun sequencing followed by mapping to the chromosome of origin and enumeration of fragments per chromosome. The preferred method uses massively parallel sequencing, which can produce tens of millions of short sequence tags in a single run and enabling a sampling that can be statistically evaluated. By counting the number of sequence tags mapped to a predefined window in each chromosome, the over- or under-representation of any chromosome in maternal plasma DNA contributed by an aneuploid fetus can be detected. This method does not require the differentiation of fetal versus maternal DNA. The median count of autosomal values is used as a normalization constant to account for differences in total number of sequence tags is used for comparison between samples and between chromosomes.
    Type: Application
    Filed: May 6, 2011
    Publication date: October 6, 2011
    Applicant: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Hei-Mun Christina Fan, Stephen R. Quake
  • Patent number: 8021480
    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.
    Type: Grant
    Filed: April 16, 2010
    Date of Patent: September 20, 2011
    Assignees: California Institute of Technology, The Regents of the University of California
    Inventors: Carl L. Hansen, Stephen R. Quake, James M. Berger
  • Patent number: 8017353
    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.
    Type: Grant
    Filed: July 29, 2008
    Date of Patent: September 13, 2011
    Assignee: California Institute of Technology
    Inventors: Frederick Balagadde, Carl L. Hansen, Emil Kartalov, Stephen R. Quake
  • Patent number: 8002933
    Abstract: A method of fabricating an elastomeric structure, comprising: forming a first elastomeric layer on top of a first micromachined mold, the first micromachined mold having a first raised protrusion which forms a first recess extending along a bottom surface of the first elastomeric layer; forming a second elastomeric layer on top of a second micromachined mold, the second micromachined mold having a second raised protrusion which forms a second recess extending along a bottom surface of the second elastomeric layer; bonding the bottom surface of the second elastomeric layer onto a top surface of the first elastomeric layer such that a control channel forms in the second recess between the first and second elastomeric layers; and positioning the first elastomeric layer on top of a planar substrate such that a flow channel forms in the first recess between the first elastomeric layer and the planar substrate.
    Type: Grant
    Filed: November 2, 2007
    Date of Patent: August 23, 2011
    Assignee: California Institute of Technology
    Inventors: Marc A. Unger, Hou-Pu Chou, Todd A. Thorsen, Axel Scherer, Stephen R. Quake
  • Publication number: 20110201009
    Abstract: A microfluidic device for analyzing and/or sorting biological materials (e.g., molecules such as polynucleotides and polypeptides, including proteins and enzymes; viruses and cells) and methods for its use are provided. The device and methods of the invention are useful for sorting particles, e.g. virions. The invention is also useful for high throughput screening, e.g. combinatorial screening. The microfluidic device comprises a main channel and an inlet region in communication with the main channel at a droplet extrusion region. Droplets of solution containing the biological material are deposited into the main channel through the droplet extrusion region. A fluid different from and incompatible with the solution containing the biological material flows through the main channel so that the droplets containing the biological material do not diffuse or mix.
    Type: Application
    Filed: December 15, 2010
    Publication date: August 18, 2011
    Applicant: California Institute of Technology
    Inventors: Stephen R. Quake, Todd Thorsen
  • Publication number: 20110177499
    Abstract: This invention relates in general to a method for molecular fingerprinting. The method can be used for forensic identification (e.g. DNA fingerprinting, especially by VNTR), bacterial typing, and human/animal pathogen diagnosis. More particularly, molecules such as polynucleotides (e.g. DNA) can be assessed or sorted by size in a microfabricated device that analyzes the polynucleotides according to restriction fragment length polymorphism. In a microfabricated device according to the invention, DNA fragments or other molecules can be rapidly and accurately typed using relatively small samples, by measuring for example the signal of an optically-detectable (e.g., fluorescent) reporter associated with the polynucleotide fragments.
    Type: Application
    Filed: April 4, 2011
    Publication date: July 21, 2011
    Applicant: California Institute of Technology
    Inventors: Stephen R. Quake, Hou-Pu Chou
  • Publication number: 20110151442
    Abstract: Methods and materials for detection of aneuploidy and other chromosomal abnormalities using fetal tissue are disclosed. Results can be obtained rapidly, without cell culture. The method uses digital PCR for amplification and detection of single target sequences, allowing an accurate count of a specific chromosome or chromosomal region. Specific polynucleic acid primers and probes are disclosed for chromosomes 1, 13, 18, 21, X and Y. These polynucleic acid sequences are chosen to be essentially invariant between individuals, so the test is not dependent on sequence differences between fetus and mother.
    Type: Application
    Filed: December 22, 2009
    Publication date: June 23, 2011
    Applicant: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Hei-Mun Christina Fan, Stephen R. Quake
  • Publication number: 20110151498
    Abstract: The present invention provides microfluidic devices and methods for using the same. In particular, microfluidic devices of the present invention are useful in conducting a variety of assays and high throughput screening. Microfluidic devices of the present invention include elastomeric components and comprise a main flow channel; a plurality of branch flow channels; a plurality of control channels; and a plurality of valves. Preferably, each of the valves comprises one of the control channels and an elastomeric segment that is deflectable into or retractable from the main or branch flow channel upon which the valve operates in response to an actuation force applied to the control channel.
    Type: Application
    Filed: February 14, 2011
    Publication date: June 23, 2011
    Applicant: California Institute of Technology
    Inventors: Stephen R. Quake, Marc A. Unger, Hou-Pu Chou, Todd A. Thorsen, Axel Scherer
  • Publication number: 20110151499
    Abstract: The present invention provides microfluidic devices and methods for using the same. In particular, microfluidic devices of the present invention are useful in conducting a variety of assays and high throughput screening. Microfluidic devices of the present invention include elastomeric components and comprise a main flow channel; a plurality of branch flow channels; a plurality of control channels; and a plurality of valves. Preferably, each of the valves comprises one of the control channels and an elastomeric segment that is deflectable into or retractable from the main or branch flow channel upon which the valve operates in response to an actuation force applied to the control channel.
    Type: Application
    Filed: February 15, 2011
    Publication date: June 23, 2011
    Applicant: California Institute of Technology
    Inventors: Stephen R. Quake, Marc A. Unger, Hou-Pu Chou, Todd A. Thorsen, Axel Scherer
  • Patent number: 7964139
    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. N2 independent 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.
    Type: Grant
    Filed: July 23, 2009
    Date of Patent: June 21, 2011
    Assignee: California Institute of Technology
    Inventors: Jian Liu, Carl L. Hansen, Stephen R. Quake
  • Patent number: 7927422
    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.
    Type: Grant
    Filed: December 2, 2008
    Date of Patent: April 19, 2011
    Assignees: National Institutes of Health (NIH), The United States of America as represented by the Dept. of Health and Human Services (DHHS), U.S. Government NIH Division of Extramural Inventions and Technology Resources (DEITR)
    Inventors: Carl L. Hansen, Morten Sommer, Stephen R. Quake
  • Patent number: 7887753
    Abstract: The present invention provides microfluidic devices and methods for using the same. In particular, microfluidic devices of the present invention are useful in conducting a variety of assays and high throughput screening. Microfluidic devices of the present invention include elastomeric components and comprise a main flow channel; a plurality of branch flow channels; a plurality of control channels; and a plurality of valves. Preferably, each of the valves comprises one of the control channels and an elastomeric segment that is deflectable into or retractable from the main or branch flow channel upon which the valve operates in response to an actuation force applied to the control channel.
    Type: Grant
    Filed: May 27, 2008
    Date of Patent: February 15, 2011
    Assignee: California Institute of Technology
    Inventors: Stephen R. Quake, Marc A. Unger, Hou-Pu Chou, Todd A. Thorsen, Axel Scherer
  • Patent number: 7833708
    Abstract: The present invention provides microfluidic devices and methods using the same in various types of thermal cycling reactions. Certaom devices include a rotary microfluidic channel and a plurality of temperature regions at different locations along the rotary microfluidic channel at which temperature is regulated. Solution can be repeatedly passed through the temperature regions such that the solution is exposed to different temperatures. Other microfluidic devices include an array of reaction chambers formed by intersecting vertical and horizontal flow channels, with the ability to regulate temperature at the reaction chambers. The microfluidic devices can be used to conduct a number of different analyses, including various primer extension reactions and nucleic acid amplification reactions.
    Type: Grant
    Filed: May 19, 2005
    Date of Patent: November 16, 2010
    Assignee: California Institute of Technology
    Inventors: Markus M. Enzelberger, Carl L. Hansen, Jian Liu, Stephen R. Quake, Chiem Ma