Patents by Inventor Lloyd M. Smith

Lloyd M. Smith 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).

  • Patent number: 9651487
    Abstract: SPR-compatible substrates for high density microarray fabrication and analyses are provided. Novel carbon-on-metal thin film substrate architecture permits the integration of surface plasmon resonance detection with photolithographically fabricated biomolecule arrays for the analysis of biomolecular interactions. The utility of the technology is shown in the analysis of specific DNA-DNA, DNA-RNA and DNA-protein binding interactions. These new substrates may be used to determine the secondary structure of RNA molecules, to probe the sequence-specific binding kinetics and affinity of proteins and small molecules, and as substrates for small-molecule combinatorial chemistry platforms for drug discovery applications.
    Type: Grant
    Filed: February 26, 2008
    Date of Patent: May 16, 2017
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Lloyd M. Smith, Matthew R. Lockett, Michael R. Shortreed, Robert M. Corn, Stephen Weibel, Robert J. Hamers, Bin Sun
  • Patent number: 8686375
    Abstract: An active detector and methods for detecting molecules, including large molecules such as proteins and oligonucleotides, at or near room temperature based on the generation of electrons via field emission (FE) and/or secondary electron emission (SEE). The detector comprises a semiconductor membrane having an external surface that is contacted by one or more molecules, and an internal surface having a thin metallic layer or other type of electron emitting layer. The kinetic energy of molecules contacting the semiconductor membrane is transferred through the membrane and induces the emission of electrons from the emitting layer. An electron detector, which optionally includes means for electron amplification, is positioned to detect the emitted electrons.
    Type: Grant
    Filed: September 24, 2012
    Date of Patent: April 1, 2014
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Robert H. Blick, Lloyd M. Smith, Michael Westphall, Hua Qin
  • Patent number: 8628974
    Abstract: A fast and sensitive method and device for protein sequencing are disclosed. The method uses a combination of Edman degradation chemistry and mass spectrometry to sequence proteins and polypeptides. A peptide degradation reaction is performed on a polypeptide or protein ion reactant in the gas phase. The reaction yields a first ion product corresponding to a first amino acid residue of the polypeptide or protein reactant and a polypeptide or protein fragment ion. The mass-to-charge ratio for the first ion product, or the polypeptide or protein fragment ion, or both, is then determined. The first amino acid residue of the polypeptide or protein reactant is then identified from the mass-to-charge ratio so determined.
    Type: Grant
    Filed: July 15, 2005
    Date of Patent: January 14, 2014
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Xiaoyu Chen, Michael S. Westphall, Lloyd M. Smith, Brian L. Frey
  • Patent number: 8592216
    Abstract: The present invention provides methods for enhancing the fragmentation of peptides for mass spectrometry by modifying the peptides with a tagging reagent containing a functional group, such as a tertiary amine, having a greater gas-phase basicity than the amide backbone of the peptide. These high gas-phase basicity functional groups are attached to a peptide by reacting the tagging reagent to one or more available carboxylic acid groups of the peptide. Linking these high gas-phase functional groups to the peptides leads to higher charge state ions from electrospray ionization mass spectrometry (ESI-MS), which fragment more extensively during fragmentation techniques, particularly non-ergodic fragmentation techniques such as electron capture dissociation (ECD) and electron transfer dissociation (ETD).
    Type: Grant
    Filed: April 14, 2010
    Date of Patent: November 26, 2013
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Brian L. Frey, April L. Jue, Casey J. Krusemark, Lloyd M. Smith, Joshua J. Coon
  • Patent number: 8563777
    Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic compositions facilitate relative quantification. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. The labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.
    Type: Grant
    Filed: June 8, 2011
    Date of Patent: October 22, 2013
    Assignees: Wisconsin Alumni Research Foundation, The Board of Trustees of the University of Illinois
    Inventors: Lloyd M. Smith, Michael R. Shortreed, Brian L. Frey, Margaret F. Phillips, Joshua J. Coon, Shane M. Lamos, Casey J. Krusemark, Peter J. Belshaw, Madhusudan Patel, Neil L. Kelleher
  • Publication number: 20120022230
    Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic compositions facilitate relative quantification. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. The labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.
    Type: Application
    Filed: June 8, 2011
    Publication date: January 26, 2012
    Applicant: Wisconsin Alumni Research Foundation
    Inventors: Lloyd M. SMITH, MICHAEL R. SHORTREED, BRIAN L. FREY, MARGARET F. PHILLIPS, JOSHUA J. COON, SHANE M. LAMOS, CASEY J. KRUSEMARK, PETER J. BELSHAW, MADHUSUDAN PATEL, NEIL L. KELLEHER
  • Patent number: 7982070
    Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.
    Type: Grant
    Filed: March 21, 2007
    Date of Patent: July 19, 2011
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Lloyd M. Smith, Michael R. Shortreed, Brian L. Frey, Margaret F. Phillips, Joshua J. Coon, Shane M. Lamos, Casey J. Krusemark, Peter J. Belshaw, Madhusudan Patel, Neil L. Kelleher
  • Patent number: 7884324
    Abstract: The present invention provides systems, devices, device components and structures for modulating the intensity and/or energies of electrons, including a beam of incident electrons. In some embodiments, for example, the present invention provides nano-structured semiconductor membrane structures capable of generating secondary electron emission. Nano-structured semiconductor membranes of this aspect of the present invention include membranes having an array of nanopillar structures capable of providing electron emission for amplification, filtering and/or detection of incident radiation, for example secondary electron emission and/or field emission. Nano-structured semiconductor membranes of the present invention are useful as converters wherein interaction of incident primary electrons and nanopillars of the nanopillar array generates secondary emission.
    Type: Grant
    Filed: May 30, 2008
    Date of Patent: February 8, 2011
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Robert H. Blick, Michael S. Westphall, Hua Qin, Lloyd M. Smith
  • Publication number: 20100330680
    Abstract: The present invention provides methods for enhancing the fragmentation of peptides for mass spectrometry by modifying the peptides with a tagging reagent containing a functional group, such as a tertiary amine, having a greater gas-phase basicity than the amide backbone of the peptide. These high gas-phase basicity functional groups are attached to a peptide by reacting the tagging reagent to one or more available carboxylic acid groups of the peptide. Linking these high gas-phase functional groups to the peptides leads to higher charge state ions from electrospray ionization mass spectrometry (ESI-MS), which fragment more extensively during fragmentation techniques, particularly non-ergodic fragmentation techniques such as electron capture dissociation (ECD) and electron transfer dissociation (ETD).
    Type: Application
    Filed: April 14, 2010
    Publication date: December 30, 2010
    Inventors: Brian L. Frey, April L. Jue, Casey J. Krusemark, Lloyd M. Smith, Joshua J. Coon
  • Patent number: 7820387
    Abstract: The present invention relates to compositions and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for forming a nucleic acid cleavage structure on a solid support and cleaving the nucleic acid cleavage structure in a site-specific manner. For example, in some embodiments, a 5? nuclease activity from any of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.
    Type: Grant
    Filed: October 28, 2007
    Date of Patent: October 26, 2010
    Assignee: Third Wave Technologies, Inc.
    Inventors: Bruce P. Neri, Jeff G. Hall, Victor Lyamichev, Lloyd M. Smith
  • Publication number: 20090321633
    Abstract: The present invention provides systems, devices, device components and structures for modulating the intensity and/or energies of electrons, including a beam of incident electrons. In some embodiments, for example, the present invention provides nano-structured semiconductor membrane structures capable of generating secondary electron emission. Nano-structured semiconductor membranes of this aspect of the present invention include membranes having an array of nanopillar structures capable of providing electron emission for amplification, filtering and/or detection of incident radiation, for example secondary electron emission and/or field emission. Nano-structured semiconductor membranes of the present invention are useful as converters wherein interaction of incident primary electrons and nanopillars of the nanopillar array generates secondary emission.
    Type: Application
    Filed: May 30, 2008
    Publication date: December 31, 2009
    Inventors: Robert H. BLICK, Michael S. WESTPHALL, Hua QIN, Lloyd M. SMITH
  • Patent number: 7582422
    Abstract: Chemically-modified surfaces on unoxidized carbon, silicon, and germanium substrates are disclosed. Ultraviolet radiation mediates the reaction of protected ?-modified, ?-unsaturated aminoalkenes (preferred) with hydrogen-terminated carbon, silicon, or germanium surfaces. Removal of the protecting group yields an aminoalkane-modified silicon surface These amino groups can be coupled to terminal-modified oligonucleotides using a bifunctional crosslinker, thereby permitting the preparation of modified surfaces and arrays. Methods for controlling the surface density of molecules attached to the substrate are also disclosed.
    Type: Grant
    Filed: October 11, 2002
    Date of Patent: September 1, 2009
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Todd C. Strother, Lloyd M. Smith, Robert J. Hamers
  • Publication number: 20090141376
    Abstract: SPR-compatible substrates for high density microarray fabrication and analyses are provided. Novel carbon-on-metal thin film substrate architecture permits the integration of surface plasmon resonance detection with photolithographically fabricated biomolecule arrays for the analysis of biomolecular interactions. The utility of the technology is shown in the analysis of specific DNA-DNA, DNA-RNA and DNA-protein binding interactions. These new substrates may be used to determine the secondary structure of RNA molecules, to probe the sequence-specific binding kinetics and affinity of proteins and small molecules, and as substrates for small-molecule combinatorial chemistry platforms for drug discovery applications.
    Type: Application
    Filed: February 26, 2008
    Publication date: June 4, 2009
    Inventors: Lloyd M. Smith, Matthew R. Lockett, Michael R. Shortreed, Robert M. Corn, Stephen Weibel, Robert J. Hamers, Bin Sun
  • Patent number: 7527928
    Abstract: The present invention relates to compositions and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for forming a nucleic acid cleavage structure on a solid support and cleaving the nucleic acid cleavage structure in a site-specific manner. For example, in some embodiments, a 5? nuclease activity from any of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.
    Type: Grant
    Filed: December 4, 2002
    Date of Patent: May 5, 2009
    Assignee: Third Wave Technologies, Inc.
    Inventors: Bruce P. Neri, Jeff G. Hall, Victor Lyamichev, Lloyd M. Smith
  • Patent number: 7518108
    Abstract: This invention provides methods, devices and device components for preparing ions from liquid samples containing chemical species and methods and devices for analyzing chemical species in liquid samples. The present invention provides an ion source for generating analyte ions having a selected charge state distribution, such as a reduced charged state distribution, that may be effectively interfaced with a variety of charged particle analyzers, including virtually any type of mass spectrometer.
    Type: Grant
    Filed: November 10, 2005
    Date of Patent: April 14, 2009
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Brian L. Frey, Lloyd M. Smith, Michael S. Westphall
  • Publication number: 20080248585
    Abstract: A fast and sensitive method and device for protein sequencing are disclosed. The method uses a combination of Edman degradation chemistry and mass spectrometry to sequence proteins and polypeptides. A peptide degradation reaction is performed on a polypeptide or protein ion reactant in the gas phase. The reaction yields a first ion product corresponding to a first amino acid residue of the polypeptide or protein reactant and a polypeptide or protein fragment ion. The mass-to-charge ratio for the first ion product, or the polypeptide or protein fragment ion, or both, is then determined. The first amino acid residue of the polypeptide or protein reactant is then identified from the mass-to-charge ratio so determined.
    Type: Application
    Filed: July 15, 2005
    Publication date: October 9, 2008
    Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATION
    Inventors: Xiaoyu Chen, Michael S. Westphall, Lloyd M. Smith, Brian L. Frey
  • Patent number: 7432048
    Abstract: The present invention relates to compositions and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for forming a nucleic acid cleavage structure on a solid support and cleaving the nucleic acid cleavage structure in a site-specific manner. For example, in some embodiments, a 5? nuclease activity from any of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.
    Type: Grant
    Filed: December 8, 2000
    Date of Patent: October 7, 2008
    Assignee: Third Wave Technologies, Inc.
    Inventors: Bruce P. Neri, Jeff G. Hall, Victor Lyamichev, Lloyd M. Smith
  • Publication number: 20080188375
    Abstract: The present invention relates to compositions and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for forming a nucleic acid cleavage structure on a solid support and cleaving the nucleic acid cleavage structure in a site-specific manner. For example, in some embodiments, a 5? nuclease activity from any of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.
    Type: Application
    Filed: October 28, 2007
    Publication date: August 7, 2008
    Applicant: THIRD WAVE TECHNOLOGIES, INC.
    Inventors: Bruce P. Neri, Jeff G. Hall, Victor I. Lyamichev, Lloyd M. Smith
  • Patent number: 7303869
    Abstract: The present invention relates to systems, compositions, and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for attaching nucleic acids to solid supports and modifying nucleic acids. For example, in some embodiments, the 5? nuclease activity of a cleavage agent is used to cleave a cleavage structure formed on the solid support, the occurrence of the cleavage event indicating the presence of specific nucleic acid sequences.
    Type: Grant
    Filed: October 11, 2002
    Date of Patent: December 4, 2007
    Assignee: Northwestern University
    Inventors: Priscilla Wilkins Stevens, David Kelso, Victor Lyamichev, Jeff Hall, Bruce P. Neri, Robert W. Kwiatkowski, Jr., Lloyd M. Smith
  • Patent number: RE43096
    Abstract: This invention provides a duplex comprising an oligonucleotide primer and a template, wherein the primer is coupled chemically to a chromophore or fluorophore so as to allow chain extension by a polymerase. In one embodiment, the primer is extended by a polymerase to generate the complement of the template. In a further embodiment, the extended primer is separated from the template for use in a number of methods, including sequencing reactions. Methods of generating these compositions of matter are further provided.
    Type: Grant
    Filed: March 13, 2003
    Date of Patent: January 10, 2012
    Assignee: California Institute of Technology
    Inventors: Lloyd M. Smith, Leroy E. Hood, Michael W. Hunkapiller, Timothy Hunkapiller, Charles R. Connell