Patents Represented by Attorney Joseph H. Smith
  • Patent number: 5240576
    Abstract: an apparatus is disclosed for providing capillary electrophoresis, which includes an electronically controlled valve system for automatically introducing a sample into the capillary by means of a vacuum at the end of the capillary tube. This approach of sucking in the sample is extremely accurate and reproducible, and results in a minimum of band broadening. Furthermore, it enables the entire capillary electrophoresis sytem to be easily automated. An automated temperature control system is provided which enables the temperature of the capillary tube (and hence the solvent/solute system) to be controlled during electrophoresis, thereby very directly controlling pH and electrophoretic mobility. In another embodiment, the capillary is prewashed and equilibrated to achieve substantially zero charge on the capillary wall, thereby essentially eliminating electroosmotic flow and substantially improving resolution.
    Type: Grant
    Filed: January 5, 1990
    Date of Patent: August 31, 1993
    Assignee: Applied Biosystems, Inc.
    Inventors: Henk H. Lauer, Paul D. Grossman, Dennis E. Mead
  • Patent number: 5239360
    Abstract: An apparatus for enhancing signal to noise ratio in the detection of electromagnetic radiation traversing a capillary tube includes a ball lens and a holding element for holding the ball lens and the capillary tube, the holding element having an aperture so that the aperature and the lens together define an optic axis. The holding element is configured to hold the capillary tube such that the center of the capillary tube traverses the optic axis. The lens has a focal length and is held at such a position relative to that focal length by the holding element such that electromagnetic radiation incident on the aperature is focussed to pass radially through the capillary tube. Thus, the effective path length is 100% of the inside diameter of the capillary tube.
    Type: Grant
    Filed: July 31, 1990
    Date of Patent: August 24, 1993
    Assignee: Applied Biosystems, Inc.
    Inventors: Stephen E. Moring, Dennis E. Mead
  • Patent number: 5231191
    Abstract: The invention provides a novel cleavage reagent for hydrolysing base-labile linking groups between a solid phase support and oligonucleotides. The cleavage reagent comprises a lower alkyl alcohol, water, and a non-nuccleophilic hindered alkylamine containing from 3 to 6 carbon atoms in a ratio of about 1:1:1 to about 1:3:1, respectively. An important property of the cleavage reagent is that it preserves the fluorescent characteristics of rhodamine dyes during cleavage, thereby making it possible to completely synthesize rhodamine-labeled oligonucleotides by solid phase methods. Rhodamine phosphoramidites are provided to further enhance the efficiency of synthesizing rhodamine-labeled oligonucleotides by such methods.
    Type: Grant
    Filed: October 22, 1990
    Date of Patent: July 27, 1993
    Assignee: Applied Biosystems, Inc.
    Inventors: Sam L. Woo, Steven M. Menchen, Steven Fung
  • Patent number: 5207886
    Abstract: An apparatus is disclosed for providing capillary electrophoresis, which includes an electronically controlled valve system for automatically introducing a sample into the capillary by means of a vacuum at the end of the capillary tube. This approach of sucking in the sample is extremely accurate and reproducible, and results in a minimum of band broadening. Furthermore, it enables the entire capillary electrophoresis system to be easily automated. An automated temperature control system is provided which enables the temperature of the capillary tube (and hence the solvent/solute system) to be controlled during electrophoresis, thereby very directly controlling pH and electrophoretic mobility. In another embodiment, the capillary is prewashed and equilibrated to achieve substantially zero charge on the capillary wall, thereby essentially eliminating electroosmotic flow and substantially improving resolution.
    Type: Grant
    Filed: September 27, 1991
    Date of Patent: May 4, 1993
    Assignee: Applied Biosystems, Inc.
    Inventors: Henk H. Lauer, Paul D. Grossman, Dennis E. Mead
  • Patent number: 5188934
    Abstract: Long wavelength, narrow emission bandwidth fluorecein dyes are provided for detecting spacially overlapping target substances. The dyes comprise 4,7-dichlorofluoresceins, and particularly 1',2',7',8'-dibenzo-4,7-dichlorofluoresceins. Methods of using the dyes in automated DNA sequencing are described.
    Type: Grant
    Filed: November 14, 1989
    Date of Patent: February 23, 1993
    Assignee: Applied Biosystems, Inc.
    Inventors: Steven M. Menchen, Linda G. Lee, Charles R. Connell, N. Davis Hershey, Vergine Chakerian, Sam Woo, Steven Fung
  • Patent number: 5186898
    Abstract: An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel.
    Type: Grant
    Filed: March 24, 1989
    Date of Patent: February 16, 1993
    Assignee: Applied Biosystems, Inc.
    Inventors: John Bridgham, Timothy G. Geiser, Michael W. Hunkapiller, Stephen B. H. Kent, Mark P. Marriott, Paul O. Ramstad, Eric S. Nordman
  • Patent number: 5124041
    Abstract: A filter system for separating and binding biomolecules contained in a solution includes a first filter means for selectively passing components of the solution that are smaller than the biomolecules, thereby concentrating the biomolecules in the solution. Also included is a binding membrane means having an affinity for the biomolecules for binding the biomolecules to the binding membrane means, with the binding membrane means being located where the biomolecules are concentrated by the first filter means. In the preferred mode, the binding membrane means is chosen to selectively bind the biomolecule of interest. According to a preferred method of the invention, biomolecules from a sample volume are bound to a binding membrane by urging the sample volume against a biomolecule-binding support membrane that is in contact with a cut-off filter membrane such that the sample volume will pass through the biomolecule-binding support membrane before passing through the cut-off filter membrane.
    Type: Grant
    Filed: May 1, 1991
    Date of Patent: June 23, 1992
    Assignee: Applied Biosystems, Inc.
    Inventors: Donald G. Sheer, Michael L. Kochersperger
  • Patent number: 5113507
    Abstract: A computer memory includes K hard memory locations, hereinafter HMLs, each HML having M counters. A reference address element stores a reference address sequence of N bits. A data register stores data as a sequence of M integers. The memory has a processor system for determining a subset of HMLs to access for each reference address during read and write operations. For each HML, the processor system receives a subset of the reference address bits equal in number to q. The subset of reference address bits is chosen by selecting, for each HML, q integers between 1 and N as selected coordinates, hereinafter SCs, each SC corresponding to a bit position within the reference address, and for each SC for each HML, assigning a 0 or 1 as an assigned value for that SC. The processor system then stores the SCs and the assigned values and, for each of the SCs for each of the HMLs, compares the assigned value for the SC with the value of the corresponding bit in the reference address bits.
    Type: Grant
    Filed: May 3, 1989
    Date of Patent: May 12, 1992
    Assignee: Universities Space Research Association
    Inventor: Louis A. Jaeckel
  • Patent number: 5107508
    Abstract: A tunable generator or amplifier of intense, collimated, monochromatic electromagnetic radiation includes primarily of a relativistic electron beam, a periodic medium, a periodic magnet or electromagnetic field, a vacuum housing, and, in the primary embodiment, a ring resonator. An accelerator provides a high current, relativistic electron beam which interacts with an electromagnetic wave in a periodic magnetic field and a periodic medium to achieve periodic phase synchronizism between the phase velocity of the electromagnetic wave and the velocity of the said electron beam. The said periodic phase synchronization results in the bunching of the electron beam and the amplification of the electromagnetic wave. In the primary embodiment the growing wave is returned back to the interaction region via Bragg reflectors. The wave continues to grow on each pass through the interaction region formed by the periodic medium and magnetic field.
    Type: Grant
    Filed: November 16, 1990
    Date of Patent: April 21, 1992
    Assignee: Adelphi Technology
    Inventor: Melvin A. Piestrup
  • Patent number: 5106583
    Abstract: Protein analysis apparatus has porous sample supports enclosed in holes in a sample slide. Slides are delivered to hydrolysis and derivatizer stations by a rotating turret such that moveable heads at the stations form closed reaction chambers with the slides, sealing around the holes in the slides and enclosing the sample supports. Tubings connected to the heads deliver substances for reaction, derivatization and cleaning. Protein samples applied to sample supports at one position on the turret are delivered sequentially to hydrolysis and derivatizer stations, and operations are computer controlled. Derivatives are automatically delivered for chromatographic analysis, and supports are automatically cleaned with solvents and purge gas after derivatization and before return to a sample load position. Closed reaction chambers formed by the moveable heads can be heated and pressurized as required for processing.
    Type: Grant
    Filed: March 8, 1989
    Date of Patent: April 21, 1992
    Assignee: Applied Biosystems, Inc.
    Inventors: Yefim M. Raysberg, David R. DuPont, Eric Shulse, Jan K. Hughes
  • Patent number: 5096554
    Abstract: A method of fractionating nucleic acid fragments is disclosed. The method is based on counter migration of the fragments in an upstream direction through a polymer solution which is moving by electroosmotic flow in a downstream direction. Fractionation of selected-size nucleic acid fragments can be enhanced by reducing the difference between the electroosmotic flow rate and the migration rates of the selected-size fragments.
    Type: Grant
    Filed: August 7, 1989
    Date of Patent: March 17, 1992
    Assignee: Applied Biosystems, Inc.
    Inventor: Allan M. Chin
  • Patent number: 5094885
    Abstract: An apparatus for preventing edge and backside coating during CVD processing supports a wafer on flexible supports within a purge cavity in a pedestal such that a movable clamp ring deforms the supports, forms a slot with the frontside of the wafer around the periphery of the wafer and by contacting the pedestal isolates the purge cavity from the coating chamber except for a the slot. The wafer is heated by a pyrolytic carbon heater in the cavity and purge gas is fed to the purge cavity to flow through the slot and purge coating gas from diffusing into the purge cavity to coat the heater or the edge or backside of the wafer. In an alternative embodiment plural pedestals allow processing of plural wafers in a single cycle, and a vacuum lock and automatic handling devices are provided.
    Type: Grant
    Filed: October 12, 1990
    Date of Patent: March 10, 1992
    Assignee: Genus, Inc.
    Inventor: Steven C. Selbrede
  • Patent number: 5078361
    Abstract: A solenoid operated pinch valve has a flexible conductor with extensions on each side of the fluid passage for connecting to the valve frame and to a solenoid plunger. In a preferred mode the valve is normally closed by a spring and actuated open. In a preferred embodiment, the flexible fluid conductor is held in the frame at the ends to prevent transferral of stress from connectors and tubings to the pinch area of the valve. A portion of the fluid passage at the pinch area is especially shaped to reduce stress and fatigue on the flexible material. In other embodiments, valves may be normally open or actuated in both directions.
    Type: Grant
    Filed: December 4, 1990
    Date of Patent: January 7, 1992
    Assignee: Applied Biosystems Inc.
    Inventor: Eric S. Nordman
  • Patent number: 5077774
    Abstract: A high-intensity, inexpensive X-ray source for X-ray lithography for the production of integrated circuits. Foil stacks are bombarded with a high-energy electron beam of 25 to 250 MeV to produce a flux of soft X-rays of 500 eV to 3 keV. Methods of increasing the total X-ray power and making the cross section of the X-ray beam uniform are described. Methods of obtaining the desired X-ray-beam field size, optimum frequency spectrum and elminating the neutron flux are all described. A method of obtaining a plurality of station operation is also described which makes the process more efficient and economical. The satisfying of these issues makes transition radiation an exellent moderate-priced X-ray source for lithography.
    Type: Grant
    Filed: August 21, 1990
    Date of Patent: December 31, 1991
    Assignee: Adelphi Technology Inc.
    Inventors: Melvin A. Piestrup, David G. Boyers, Cary Pincus
  • Patent number: 5071712
    Abstract: A four quadrant leadframe, base and window assembly and assembly method therefor are disclosed which are suited for fabrication of leaded integrated circuit (IC) chip carriers having electrical contacts on all four sides of the package, lead spacing as small as 0.020 inch, and lead counts exceeding 164 total leads.
    Type: Grant
    Filed: April 25, 1990
    Date of Patent: December 10, 1991
    Assignee: Diacon, Inc.
    Inventor: Tom J. Frampton
  • Patent number: 5052806
    Abstract: Apparatus is provided for measuring non-absorptive scattering with an exceptionally high degree of accuracy. In the preferred mode, the apparatus can also be used to measure absorptive scattering, thus providing a method of distinguishing absorptive scattering from scattering due to transparent moieties (i.e. non-absorptive scattering). The approach of the invention promises to significantly expand the use of optical systems in quality control. The general concept of the invention relies on symmetric heterodyne scattering. Specifically, two beams at slightly differing optical frequencies are directed to intersect at some arbitrary angle. Transparent objects within the intersection volume scatter light from each beam into the other. After intersecting, the two beams are directed to separate photodetectors which mix each transmitted beam with the scattered light from the other beam.
    Type: Grant
    Filed: May 21, 1990
    Date of Patent: October 1, 1991
    Assignee: Blue Sky Research, Inc.
    Inventor: James J. Snyder
  • Patent number: 5050384
    Abstract: A power plant has an internal combustion engine with piston backside pumping and a stroke of sufficient length to reduce the pressure of the combustion gases at the end of the power stroke to substantially a common inlet and exhaust pressure, extracting maximum power from the combustion gas expansion and reducing both power loss from expansion into the exhaust manifold and exhaust noise. For a cylinder the exhaust valve is opened at a specific time relative to the engine cycle, but exhaust closing is variable to account for changes in operating conditions and power settings. In a preferred embodiment the engine is a two-cycle compression-firing engine, and an exhaust valve for a cylinder is opened by cam action but closed at a variable time by an actuator controlled by a computer.
    Type: Grant
    Filed: November 8, 1989
    Date of Patent: September 24, 1991
    Inventor: Ivan L. Crockett
  • Patent number: 5047524
    Abstract: A method and system for polynucleotide synthesis and purification are provided which employ solid phase synthesis on a nonswellable porous polystyrene support by phosphoramidite or hydrogen phosphonate chemistries. The polystyrene support gives rise to fewer tritylated failure squences caused by chain growth from extraneous support sites. Consequently, currently used rapid purification techniques depending on trityl hydrophobicity give a more highly purified product. The method and system also employ nucleoside intermediates whose exocyclic amines are protected by base-labile groups which permit simultaneous cleavage and deprotection of the completed polynucleotide chain in the presence of the solid phase support. This latter feature allows practical automation of both the synthesis and purification of polynucleotides.
    Type: Grant
    Filed: December 21, 1988
    Date of Patent: September 10, 1991
    Assignee: Applied Biosystems, Inc.
    Inventors: William A. Andrus, Christie D. McCollum, Gerald Zon
  • Patent number: 5020793
    Abstract: A ski exercising apparatus has a carriage restrained by resilient elements to restore the carriage toward a middle position when displaced by a user simulating parallel skiing, and a single foot platform arranged on the carriage as a swing, so the force applied by a user causes the foot surface of the platform to swing to a position with the surface at substantially a right angle with the direction of the force.
    Type: Grant
    Filed: October 24, 1989
    Date of Patent: June 4, 1991
    Inventor: R. Joel Loane
  • Patent number: 5015350
    Abstract: A method for achieving desired electroosmotic flow characteristics in a capillary tube having charged surface groups. An electrolyte solution containing a compound effective to stably alter the charge of the tube walls is drawn into and through the tube during while the electroosmotic flow rate in the tube is being monitored, until a desired electroosmotic flow rate is achieved. The method can be used to optimize electrophoretic separation of charged protein or nucleic acid species in a capillary tube, and to produce capillary tubes with desired charge density properties.
    Type: Grant
    Filed: November 6, 1989
    Date of Patent: May 14, 1991
    Assignee: Applied Biosystems, Inc.
    Inventor: John E. Wiktorowicz