Patents Assigned to Boehringer Mannheim Corporation
  • Patent number: 5508171
    Abstract: A new electrochemical biosensor and method of its use. The electrochemical biosensor has a pair of electrodes consisting of a working electrode and a counter electrode made of the same electrically conducting materials. The counter electrode may be the same size or smaller than the working electrode. The biosensor includes a sample receiving portion wherein a portion of the electrode surfaces is covered by a reagent that includes a redox mediator and an enzyme. A fluid that contains an analyte is added to the sample receiving portion. A reaction involving the analyte, enzyme and redox mediator occurs. After this reaction is complete, an electrical potential difference is applied between the electrodes. Diffusion limited current is measured and correlated to the concentration of analyte in the fluid.
    Type: Grant
    Filed: February 22, 1994
    Date of Patent: April 16, 1996
    Assignee: Boehringer Mannheim Corporation
    Inventors: P. Douglas Walling, Joseph E. Bateson, Lance S. Kuhn, M. Luann Ochs, Kent M. Kost, Martin T. Gerber, Klaus H. Pollmann, Chi-Neng A. Han
  • Patent number: 5492813
    Abstract: Muteins of enzyme acceptor polypeptide fragments of .beta.-galactosidase are provided which exhibit substantially increased kinetic complementation activity with no significant loss in stability. A preferred enzyme acceptor fragment has an amino acid other than cysteine located at position 500 of the natural sequence. An especially preferred substitution is serine or valine. Other preferred muteins have an amino acid other than methionine located at position 443, with leucine being especially preferred, or an amino acid other than cysteine at position 76, with leucine being an especially preferred substitution. Also provided are methods for producing the novel muteins, reagent compositions comprising the novel muteins, and immunoassay methods for determining an analyte in which the novel mutein recombines with an enzyme donor polypeptide fragment to form enzymatically active .beta.-galactosidase.
    Type: Grant
    Filed: November 1, 1993
    Date of Patent: February 20, 1996
    Assignee: Boehringer Mannheim Corporation
    Inventors: Scott J. Eisenbeis, Sophie J. Boguslawski, Mark Krevolin, David J. Ledden
  • Patent number: 5492674
    Abstract: Apparatus for assaying a fluid sample with radiation capable of exciting fluorescence in fluorescent material comprises a totally internally reflecting, unitary elongated substrate transmissive to both the excitation radiation and to the fluorescence. The fluorescent material includes at least a moiety of an antibody-antigen complex that includes a tag that will provide the fluorescence when excited by an evanescent wave generated by the excitation radiation. The substrate includes an elongated fiber and an integral lens formed to guide the optical radiation into the fiber within the bounds of a critical angle to assure total internal reflectance. A hollow elongated enclosure is disposed concentrically about and spaced from the fiber so as to provide an interspace of capillary dimensions.
    Type: Grant
    Filed: March 17, 1995
    Date of Patent: February 20, 1996
    Assignee: Boehringer Mannheim Corporation
    Inventor: Peter Meserol
  • Patent number: 5488816
    Abstract: A ribbon-like flat web having a plurality of side by side depressions is fed through a horizontal slot having a downward facing surface having an aperture communicating with a reservoir of reagent containing solution. The web is urged against the downward facing surface to provide sealing as the solution is fed into the upward facing depressions. The aperture communicating with the reservoir is profiled as a parallelogram having a leading edge which is oblique to the direction of movement. After emerging from the dispensing apparatus the exposed solution is dried in hot air, followed by spray application of a second solution, further drying in hot air, and application of a backing to form capillary chambers. The method is especially useful for manufacturing coagulation assays having magnetic particles and thromboplastin.
    Type: Grant
    Filed: July 21, 1994
    Date of Patent: February 6, 1996
    Assignee: Boehringer Mannheim Corporation
    Inventors: Henry M. Grage, Jr., Stanley G. Brown, Jr., Michael W. Alderink, Elon T. Van Buren, Waring C. Lynch
  • Patent number: 5464747
    Abstract: A mutein of an enzyme acceptor polypeptide fragment of .beta.-galactosidase which is resistant to oxidation is provided. The enzyme acceptor fragment has an amino acid other than cysteine located at position 602 of the natural sequence. An especially preferred substitution is serine. Also provided are a method for producing the novel mutein, a reagent composition comprising the novel mutein, and an immunoassay method for determining an analyte in which the novel mutein recombines with an enzyme donor polypeptide fragment to form enzymatically active .beta.-galactosidase.
    Type: Grant
    Filed: October 29, 1993
    Date of Patent: November 7, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Scott J. Eisenbeis, Mark Krevolin, Christopher P. Bryant, Sophie J. Boguslawski, David J. Ledden, Scott Clark
  • Patent number: 5445933
    Abstract: The invention relates to an improvement in the strand displacement assay. Probes that are at least 20 nucleotide bases in length, but are no more than 40 bases in length, are used. These short probes permit detection and discrimination down to the order of a single base.
    Type: Grant
    Filed: September 15, 1992
    Date of Patent: August 29, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: James S. Eadie, Neil G. Balgobin, Harvey Buck
  • Patent number: 5439798
    Abstract: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;R.sub.1 =an alkyl group having 1 to 3 carbon atoms;m=an integer from 2 to 10;R.sub.2 =an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms;Z=a poly(amino acid); andn=1 to p where p=MW of Z/1000.The derivatives include maleimide conjugates of proteins or poly(amino acids), enzymes, enzyme donor polypeptides and labeling substances. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and derivatives are also disclosed.
    Type: Grant
    Filed: December 17, 1993
    Date of Patent: August 8, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Gerald F. Sigler, Charles F. Walter, Charles E. Durant, Todd Glancy, Frank E. Klein, Allan R. Dorn
  • Patent number: 5438271
    Abstract: A biosensing meter receives a biomedical sample strip or a check strip, a sample strip including electrically isolated excitation and sense electrodes. The biosensing meter includes first and second contacts that are positioned to be electrically connected by a sense electrode when a sample strip is inserted into the biosensing meter. An operational amplifier circuit has one input connected to the first contact and a second input connected to a reference potential, the one input manifesting the reference potential as a result of a feedback within the operational amplifier. A processor is coupled to the second contact and determines the presence of the reference potential at the second contact when an inserted sense electrode connects the first and second contacts.
    Type: Grant
    Filed: November 22, 1994
    Date of Patent: August 1, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Bradley E. White, Robert A. Parks, Paul G. Ritchie
  • Patent number: 5437999
    Abstract: A method for fabricating high-resolution, biocompatible electrodes is disclosed, allowing production of an electrochemical sensor which is capable of precise analyte concentration determination on a very small sample size. Electrically conducting material is affixed to a first insulating substrate. A second insulating substrate is then affixed to the electrically conducting material and patterned using photolithography to define an electrode area. Alternatively, the electrically conducting material may be screen printed directly onto a standard printed circuit board substrate in the case of a counter or reference electrode. In either case, the substrate may be rigid or flexible. When the electrodes produced in accordance with the present invention are then used in an electrochemical sensor which includes a reagent, the small and highly-defined electrode areas permit highly-accurate electrochemical analyte measurements to be performed on very small sample sizes.
    Type: Grant
    Filed: February 22, 1994
    Date of Patent: August 1, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Eric R. Diebold, Richard J. Kordal, Nigel A. Surridge, Christopher D. Wilsey
  • Patent number: 5434055
    Abstract: The invention describes a composition useful in determining sample analytes, where the determination is carried out anaerobically. The compositions include an analyte oxidizing agent, an electron transfer agent, ferric ions, and two chelators. The first chelator complexes to ferric ions, but does not have good affinity for ferrous ions. The second chelator does chelate ferrous ions, and forms a colored complex with the ion. It is the colored complex which serves as the indicator for the analyte. Different formulations of the composition are described.
    Type: Grant
    Filed: May 6, 1994
    Date of Patent: July 18, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventor: Walter Jernigan
  • Patent number: 5427912
    Abstract: An immunoassay diagnostic kit, method, and apparatus for electrochemically determining the concentration of an analyte in a sample. A mixture is formed which includes the sample, an enzyme-acceptor polypeptide, an enzyme-donor polypeptide linked to an analyte analog (enzyme-donor polypeptide conjugate), a labeled substrate, and an antibody specific for the analyte to be measured. The analyte and the enzyme-donor polypeptide conjugate competitively bind to the antibody. When the enzyme-donor polypeptide conjugate is not bound to antibody, it will spontaneously combine with the enzyme acceptor polypeptide to form an active enzyme complex. The active enzyme hydrolyzes the labeled substrate, resulting in the generation of an electroactive label, which can then be oxidized at the surface of an electrode. A current resulting from the oxidation of the electroactive compound can be measured and correlated to the concentration of the analyte in the sample.
    Type: Grant
    Filed: August 27, 1993
    Date of Patent: June 27, 1995
    Assignees: Boehringer Mannheim Corporation, Boehringer Mannheim GmbH
    Inventors: Mary E. Brown, Lance S. Kuhn, Robert J. McEnroe, Rebecca W. Muddiman, Mary L. Ochs
  • Patent number: 5413690
    Abstract: A potentiometric biosensor, test strip, reagent and a potentiometric method for detection or measurement of an analyte from a fluid sample. The biosensor includes indicating and reference electrodes, and a reagent, which overlays a portion of the surface of the indicating electrode. The reagent generally includes an enzyme and a redox mediator. When a fluid sample (e.g., blood) containing an analyte (e.g., glucose) is added to the reagent, the enzyme (e.g., glucose oxidase) catalyzes a reaction involving enzyme, redox mediator (e.g., potassium ferricyanide), and analyte.This reaction may be monitored by monitoring the electrical potential at the indicating electrode surface. (Electrical potential at the indicating electrode surface changes as the concentration of oxidized and reduced forms of the redox mediator change at the indicating electrode surface.
    Type: Grant
    Filed: July 23, 1993
    Date of Patent: May 9, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Kent M. Kost, Thomas J. Lindsay, John F. Price
  • Patent number: 5405511
    Abstract: A biosensing meter is provided that determines a value of an analyte in a biological sample. The meter employs an algorithm for determining the analyte value, which value is dependent upon ambient temperature about the biological sample when it is present in a reaction zone. The biosensing meter includes a processor and a temperature sensor. The temperature sensor is positioned within the meter's structure and thereby exhibits a delayed response to changes in the ambient temperature. The meter performs a temperature estimation method to overcome the delayed temperature response. The method commences by the meter repetitively and periodically acquiring temperature readings from the temperature sensor when the biosensing meter is both in an on state and in an off state. When the meter is in the on state, the algorithm estimates the ambient temperature by employing at least two most recent temperature readings and extrapolating therefrom to achieve an ambient temperature estimate.
    Type: Grant
    Filed: June 8, 1993
    Date of Patent: April 11, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Bradley E. White, Michael L. Brown, Paul G. Ritchie, Vladimir Svetnik, Robert A. Parks, Stefan Weinert
  • Patent number: 5389515
    Abstract: Isolated nucleic acid molecules capable of hybridizing to rRNA sequences of Neisseria Gonorrhoeae and not to rRNA sequences of non-Neisseria Gonorrhoeae along with methods utilizing such probes for the detection of Neisseria Gonorrhoeae in clinical and other biological samples.
    Type: Grant
    Filed: September 15, 1992
    Date of Patent: February 14, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Rich Chmelo, Lisa Foltz
  • Patent number: 5385844
    Abstract: Described are control reagents useful in analyte determination. The reagents contain a known concentration or amount of the analyte to be assayed, and a polymer. The polymer is made up of monomers of either water soluble acrylic monomers, water soluble quaternary amines, or mixtures of these two types of molecules. Various control reagent formulations, as well as new polymers useful in control reagents, are disclosed.
    Type: Grant
    Filed: April 22, 1993
    Date of Patent: January 31, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Jim Kennamer, Arthur Usmani
  • Patent number: 5385846
    Abstract: A biosensor and method for determining the hematocrit level of a whole blood sample using electrochemistry. The biosensor includes working and counter electrodes. A porous membrane is impregnated with an electroactive compound and is spatially displaced from the surface of the electrodes. When a whole blood sample is applied to the porous substrate, a mixture of the electroactive compound and the blood is formed. The mixture settles on the electrodes and a potential difference is applied sufficient to oxidize or reduce the electroactive compound and generate a current. This current can be measured and correlated to hematocrit level.
    Type: Grant
    Filed: June 3, 1993
    Date of Patent: January 31, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Lance S. Kuhn, Mary L. Ochs, Gilbert C. Morris
  • Patent number: 5379214
    Abstract: A method of communicating with one or more microcomputer (200) controlled instruments (10) for determining the concentration of a medically significant component of a body fluid. Each instrument (10) includes a port (220) through which instructions and data can be received from, and transmitted to, an external device. The method comprises the steps of transmitting to each instrument (10) an attention protocol for advising each instrument (10) that a further instruction is to be transmitted, transmitting one of a global address to all of such instruments (10) and an address unique to one of such instruments (10), and transmitting an instruction to all of the instruments (10) or to the above-mentioned one instrument (10).
    Type: Grant
    Filed: October 21, 1993
    Date of Patent: January 3, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Steven R. Arbuckle, Michael E. Grant, Richard Riedel, Roger L. Hammer
  • Patent number: 5376063
    Abstract: A self-balancing apparatus for a centrifuge is disclosed which employs two arcuately movable counterweights. The centrifuge has a plurality of receptacles for receiving one or more assay cartridges. Control apparatus in the centrifuge determines the location and number of received cartridges. Desired counterweight positions are then calculated which will substantially balance the centrifuge. The counterweights are moved into these positions prior to the centrifuge being operated at high speeds.
    Type: Grant
    Filed: February 18, 1993
    Date of Patent: December 27, 1994
    Assignee: Boehringer Mannheim Corporation
    Inventor: Alan P. Greenstein
  • Patent number: D361129
    Type: Grant
    Filed: November 2, 1993
    Date of Patent: August 8, 1995
    Assignee: Boehringer Mannheim Corporation
    Inventors: Rick L. Collins, Martin T. Gerber, Daniel L. Kennedy, Brett S. Lewis, James D. Morrow, Peter L. Sebastian, David E. Storvick, Charles L. Thomeczek, Jr.
  • Patent number: D368967
    Type: Grant
    Filed: October 22, 1993
    Date of Patent: April 16, 1996
    Assignee: Boehringer Mannheim Corporation
    Inventors: Dale A. Keiser, Charles A. Jackson