Issued Patents for PCT

US Patents

• Pressure cycling reactor and methods of controlling reactions using pressure

• Authors: Laugharn, J., G. Dreier, E. Rudd, and David Green
• Date Awarded: 3/14/00
• Patent Number: US 6,036,923
• Abstract: Methods and apparatus in which pressure provides precise control over the timing and preferably synchronization of chemical reactions, particularly enzymatic reactions

• Nucleic acid isolation and purification

• Authors: Laugharn, J., R. Hess, and Feng Tao
• Date Awarded: 08/29/2000
• Patent Number: US 6,111,096
• Abstract: The invention is based on the discovery that hyperbaric, hydrostatic pressure reversibly alters the partitioning of nucleic acids between certain adsorbed and solvated phases relative to partitioning at ambient pressure. The new methods and devices disclosed herein make use of this discovery for highly selective and efficient, low salt isolation and purification of nucleic acids from a broad range of sample types, including forensic samples, blood and other body fluids, and cultured cells.

• Pressure-enhanced extraction and purification

• Authors: Laugharn, J., R. Hess, and Feng Tao
• Date Awarded: 9/19/00
• Patent Number: US 6,120,985
• Abstract: Methods for cell lysis and purification of biological materials, involving subjecting a
  sample maintained at a subzero temperature to high pressure, are disclosed. Apparatus for
  practicing the methods are also disclosed. The cell or cells that are lysed may be in suspension or part of a tissue. They are lysed by a method that includes: (i) providing a frozen cell or cells under atmospheric pressure; (ii) while maintaining the cell or cells at a subzero temperature, exposing the cell or cells to an elevated pressure in a pressure chamber, the elevated pressure being sufficient to thaw the frozen cell or cells at the subzero temperature; (iii) depressurizing the pressure chamber to freeze the cell or cells at the subzero temperature; and (iv) repeating the exposing and depressurizing steps until the cell or cells are lysed. This method can lyse a cell or cells with or without cell walls; such cells include, but are not limited to, bacteria, viruses, fungal cells (e.g, yeast cells), plant cells (e.g, corn leaf tissue), animal cells, insect cells, and protozoan cells.

• Pressure modulated ion activity

• Authors: Hess, R., and J. Laugharn
• Date Awarded: 10/03/2000
• Patent Number: US 6,127,534
• Abstract: The invention is based on the discovery that pressure-induced changes in the free ion activity of a solution can be used to reversibly modulate the rate or the equilibrium position of chemical reactions, including catalytic reactions and associating/dissociating reactions. Pressure induced changes in free-ion activity can also be used to improve separation processes

• Integrated sequencing device

• Authors: Laugharn, J, and R. Hess
• Date Awarded: 06/12/2001
• Patent Number: US 6,245,506
• Abstract: The invention is based on the discovery that the sequence of monomers in a polymeric biomolecule can be determined in a self-contained, high pressure reaction and detection apparatus, without the need for fluid flow into or out from the apparatus. The pressure is used to control the activity of enzymes that digest the polymeric biomolecule to yield the individual monomers in the sequence in which they existed in the polymer. High pressures modulate enzyme kinetics by reversibly inhibiting those enzymatic processes which result in a higher average activation volume, when compared to the ground state, and reversibly accelerating those processes which have lower activation volumes than the ground state. Modulating the pressure allows the experimenter to precisely control the activity of the enzyme. Conditions can be found, for example, where the enzyme removes only one monomer (e.g., a nucleotide or amino acid) from the biomolecule before the pressure is again raised to a prohibitive level. The identity of the single released nucleotide or amino acid can be determined using a detector that is in communication with a probe in the detection zone within the reaction vessel.

• Pressure-controlled nucleic acid hybridization

• Authors: Laugharn, J., D. Green and R. Hess
• Date Awarded: 7/10/2001
• Patent Number: US 6,258,534
• Abstract: A method of hybridizing a first nucleic acid to a second nucleic acid at least partially
  complementary to the first nucleic acid by (1) providing a sample vessel and pressure controller for the vessel; and (2) contacting the first and second nucleic acids within the vessel at a pressure above ambient pressure that is effective to enhance hybridization of the first and second nucleic acids.

• Rapid cryobaric sterilization and vaccine preparation

• Authors: Laugharn, J., D. Bradley, and R. Hess
• Date Awarded: 08/07/2001
• Patent Number: US 6,270,723
• Abstract: The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e.g., from about -20.degree. C. to about 95.degree. C.). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, the decontamination of military devices, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.

• Integrated sequencing device

• Authors: Laugharn, J, and R. Hess.
• Date Awarded: 09/10/2002
• Patent Number: US 6,448,065
• Abstract: The invention is based on the discovery that the sequence of monomers in a polymeric biomolecule can be determined in a self-contained, high pressure reaction and detection apparatus, without the need for fluid flow into or out from the apparatus. The pressure is used to control the activity of enzymes that digest the polymeric biomolecule to yield the individual monomers in the sequence in which they existed in the polymer. High pressures modulate enzyme kinetics by reversibly inhibiting those enzymatic processes which result in a higher average activation volume, when compared to the ground state, and reversibly accelerating those processes which have lower activation volumes than the ground state. Modulating the pressure allows the experimenter to precisely control the activity of the enzyme. Conditions can be found, for example, where the enzyme removes only one monomer (e.g., a nucleotide or amino acid) from the biomolecule before the pressure is again raised to a prohibitive level. The identity of the single released nucleotide or amino acid can be determined using a detector that is in communication with a probe in the detection zone within the reaction vessel.

• Pressure cycling reactor

• Authors: Laugharn, J.A., G.H. Dreier, E.A. Rudd, and D.J. Green
• Date Awarded: 05/27/2003
• Patent Number: US 6,569,672
• Abstract: Methods and apparatus in which pressure provides precise control over the timing and preferably synchronization of chemical reactions, particularly enzymatic reactions.

• Pressure-mediated binding of biomolecular complexes

• Authors: Litt, G.J., J.A. Laugharn, D.J. Green
• Date Awarded: 10/21/2003
• Patent Number: US 6,635,469
• Abstract: The invention relates to (1) pressure-mediated dissociation of an analyte complexed with an endogenous binding partner to enable detection of a complex formed from the analyte and an exogenous binding factor, (2) pressure-mediated association of an analyte and an exogenous binding partner to enable more rapid and/or more sensitive detection of an analyte, and (3) pressure-mediated association and dissociation of biomolecular complexes to enable separation of one biomolecule from a complex mixture. Pressure can be used to improve assays by dissociating endogenous analyte complexes and improving assay speed and sensitivity by associating the analyte molecules with exogenously supplied binding partners. Pressure can also be used to improve the separation of compounds from contaminated mixtures. Methods of assaying an analyte in a sample having an endogenous complex between the analyte and an endogenous sample component include dissociating the analyte from the endogenous component using pressure and reacting the analyte with an exogenously supplied specific binding reagent to determine complexation between the analyte and the binding reagent.

• Rapid cryobaric sterilization and vaccine preparation

• Authors: Laugharn, J.A., D.W. Bradley, R.A. Hess
• Date Awarded: 2/24/2004
• Patent Number: US 6,696,019
• Abstract: The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e.g., from about -40.degree. C. to about 95.degree. C., or intermediate ranges). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, plant, animal, and human tissue, sputum, urine, feces, water, and ascites, the decontamination of military devices, food and beverage production, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.

• Pressure-controlled nucleic acid hybridization

• Authors: Laugharn, J., D. Green and R. Hess
• Date Awarded: 6/22/2004
• Patent Number: US 6,753,169
• Abstract: A method of hybridizing a first nucleic acid to a second nucleic acid at least partially complementary to the first nucleic acid by (1) providing a sample vessel and pressure controller for the vessel; and (2) contacting the first and second nucleic acids within the vessel at a pressure above ambient pressure that is effective to enhance hybridization of the first and second nucleic acids
.

• Pressure-enhanced extraction and purification

• Authors: James A. Laugharn, Robert Hess, and Feng Tao
• Date Awarded: 12/01/2009
• Patent Number: US 7,626,017 B2
• Abstract: Methods for cell lysis and purification of biological materials, involving subjecting a sample to high pressure. Also featured is an apparatus for practicing the methods.

Japanese Patents

• Pressure-mediated binding of biomolecular complexes

• Authors: Litt, G.J., J.A. Laugharn, D.J. Green
• Date Awarded: 03/17/2006
• Patent Number: JP 3781780
• Abstract: The invention relates to (1) pressure-mediated dissociation of an analyte complexed with an endogenous binding partner to enable detection of a complex formed from the analyte and an exogenous binding factor, (2) pressure-mediated association of an analyte and an exogenous binding partner to enable more rapid and/or more sensitive detection of an analyte, and (3) pressure-mediated association and dissociation of biomolecular complexes to enable separation of one biomolecule from a complex mixture. Pressure can be used to improve assays by dissociating endogenous analyte complexes and improving assay speed and sensitivity by associating the analyte molecules with exogenously supplied binding partners. Pressure can also be used to improve the separation of compounds from contaminated mixtures.

• Pressure cycling reactor and methods of controlling reactions using pressure

• Authors: Laugharn, J., G. Dreier, E. Rudd, and David Green
• Date Awarded: 05/15/2009
• Patent Number: JP 4308320
• Abstract: Methods and apparatus in which pressure provides precise control over the timing and preferably synchronization of chemical reactions, particularly enzymatic reactions.

European Patent

• Pressure cycling reactor

• Authors: Laugharn, J., G. Dreier, E. Rudd, and David Green
• Date Awarded: 09/12/2001
• Patent Number: EP 0814900 Same name (U.S. Patent No. 6,036,923) to European Patent Convent, Germany, France, the United Kingdom, Italy, Sweden and Switzerland.
• Abstract: Methods and apparatus in which pressure provides precise control over the timing and preferably synchronization of chemical reactions, particularly enzymatic reactions.

• Pressure-mediated binding of biomolecular complexes

• Authors: Litt, Gerald, Laugharn, J., Green, D., Hess, R., and Paulus, H.,
• Date Awarded: 10/04/2001
• Patent Number: EP 0924991
• Issued in European Patent Convention, Austria, Belgium, Switzerland, Germany, Denmark, Spain, Finland, France, United Kingdom, Greece, Ireland, Italy, Luxemburg, Monaco, Netherlands, Portugal, and Sweden.
• Abstract: The invention relates to (1) pressure-mediated dissociation of an analyte complexed with an endogenous binding partner to enable detection of a complex formed from the analyte and an exogenous binding factor, (2) pressure-mediated association of an analyte and an exogenous binding partner to enable more rapid and/or more sensitive detection of an analyte, and (3) pressure-mediated association and dissociation of biomolecular complexes to enable separation of one biomolecule from a complex mixture. Pressure can be used to improve assays by dissociating endogenous analyte complexes and improving assay speed and sensitivity by associating the analyte molecules with exogenously supplied binding partners. Pressure can also be used to improve the separation of compounds from contaminated mixtures.

• Rapid cryobaric sterilization and vaccine preparation

• Authors: Laugharn, J., D.W. Bradley, and R.A. Hess
• Date Awarded 09/17/2003
• Patent Number: EP 1112091
• Abstract: The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e.g., from about -20 DEG C to about 95 DEG C). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, the decontamination of military devices, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.

Australian Patents

• Pressure-enhanced extraction and purification

• Authors: Laugharn, J., R. Hess, and Feng Tao
• Date Awarded: 07/25/2002
• Patent Number: AU 745925
• Abstracts: Methods for cell lysis and purification of biological materials, involving subjecting a sample to high pressure. Also featured is an apparatus for practicing the methods.

• Multichamber device and uses thereof for processing of biological samples

• Authors: Laugharn James A Jr; Tao Feng; Manak Mark M; Lawrence Nathan P; Kakita Allan; Schumacher Richard T.
• Date Awarded: 11/29/2007
• Patent Number: AU 2002259017
• Abstract: Devices and methods are described for homogenization, processing, detection, and analysis of biological samples such as insects, fungi, bacteria, and plant and animal tissues. Multiple chambers in these devices permit different processing functions to be carried out at each stage, such that the resulting homogenized product can be further processed, purified, analyzed, and/or biomolecules such as metabolites, proteins and nucleic acids, or pharmaceutical products can be detected. The device can be used in a hydrostatic pressure apparatus, in which different activities, i.e. incubations, addition or renewal of reagent, and generation and detection of signal can be carried out in the appropriate chamber. The method improves the preservation of biomolecules from chemical and enzymatic degradation relative to conventional means. Additionally, this method enables automated sample preparation and analytical processes.

• Rapid sterilization and vaccine preparation

• Authors: Bradley David W; Laugharn James A Jr; Hess Robert A
• Date Awarded: 01/17/2008
• Patent Number: AU 2002367749
• Abstract: The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e.g., from about -40 DEG C to about 95 DEG C, or intermediate ranges). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, plant, animal, and human tissue, sputum, urine, feces, water, and ascites, the decontamination of military devices, food and beverage production, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.

Canadian Patents

• Pressure-mediated binding of biomolecular complexes

• Authors: Hess, R., Paulus, H., Laugharn, J., Green, D., Litt. G,
• Date Awarded: 06/26/2007
• Patent Number: CA 2259318
• Abstract: The invention relates to (1) pressure-mediated dissociation of an analyte complexed with an endogenous binding partner to enable detection of a complex formed from the analyte and an exogenous binding factor, (2) pressure-mediated association of an analyte and an exogenous binding partner to enable more rapid and/or more sensitive detection of an analyte, and (3) pressure-mediated association and dissociation of biomolecular complexes to enable separation of one biomolecule from a complex mixture. Pressure can be used to improve assays by dissociating endogenous analyte complexes and improving assay speed and sensitivity by associating the analyte molecules with exogenously supplied binding partners. Pressure can also be used to improve the separation of compounds from contaminated mixtures.

• Rapid cryobaric sterilization and vaccine preparation

• Authors: Laugharn, J.A., D.W. Bradley, R.A. Hess
• Date Awarded: 09/02/2008
• Patent Number: CA 2301067
• Summary: The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e. g., from about -20.degree.C to about 95.degree.C). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, the decontamination of military devices, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.