Patents by Inventor Larry J. Kricka
Larry J. Kricka 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).
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Patent number: 5744366Abstract: Devices and methods are provided to facilitate the rapid, accurate analysis of a sample having cells characterized by their motility. The devices feature a solid substrate microfabricated to define a flow system including one or more ports or chambers, connected by elongate channels of various shapes having a mescoscale cross-sectional dimension on the order of 0.1 .mu.m to 1000 .mu.m. In one embodiment, the devices are fitted with various flow-regulating features to facilitate unimpeded movement of the motile cells of interest along the flow channels. In another embodiment, devices are provided for conducting replicate motile cell assays, or for conducting a series of different assays using a single test sample. In another embodiment, preparative devices are provided for separating and collecting selected motile cell types of interest.Type: GrantFiled: November 14, 1994Date of Patent: April 28, 1998Assignee: Trustees of the University of PennsylvaniaInventors: Larry J. Kricka, Peter Wilding
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Patent number: 5726026Abstract: A mesoscale sample preparation device capable of providing microvolume test samples, separated into a cell-enriched fraction and a fraction of reduced cell content, for performing various analyses, such as binding assays, determinations involving polynucleotide amplification and the like. Analytical systems including such devices are also disclosed.Type: GrantFiled: November 14, 1994Date of Patent: March 10, 1998Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka
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Patent number: 5637469Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.Type: GrantFiled: November 30, 1994Date of Patent: June 10, 1997Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka, Jay N. Zemel
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Patent number: 5635358Abstract: Disclosed are devices and methods for analyzing a fluid cell containing sample. The devices are composed of a solid substrate, microfabricated to define at least one sample inlet port and a mesoscale flow system. The mesoscale flow system includes a sample flow channel, extending from the inlet port, and a cell handling region for treating cells disposed in fluid communication with the flow channel. The devices may further include a component for inducing flow of cells in the sample through the flow system. In one embodiment, the cell-handling region may include a cell lysis component to enable the lysis of cells in the sample, prior to, e.g., the detection of an intracellular component in the cell sample. In another embodiment, the cell handling region may have a cell capture region, with binding sites which reversibly bind to a specific population of cells in the cell sample, to permit the isolation of the specific cell population from the sample.Type: GrantFiled: February 14, 1994Date of Patent: June 3, 1997Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka, Jay N. Zemel
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Patent number: 5629168Abstract: Method of increasing the light output and/or signal:background ratio of light output from a chemiluminescent reaction of a dihydrophthalazinedione, a peroxidase enzyme catalyst and an oxidant, by carrying out the reaction in the presence of an enhancer which is an aromatic organo boron compound. Kits suitable for use in diagnositc assays comprising such enhancers are also described.Type: GrantFiled: June 7, 1995Date of Patent: May 13, 1997Assignee: British Technology Group LimitedInventor: Larry J. Kricka
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Patent number: 5587128Abstract: Disclosed are devices for amplifying a preselected polynucleotide in a sample by conducting a polynucleotide amplification reaction. The devices are provided with a substrate microfabricated to include a polynucleotide amplification reaction chamber, having at least one cross-sectional dimension of about 0.1 to 1000 .mu.m. The device also includes at least one port in fluid communication with the reaction chamber, for introducing a sample to the chamber, for venting the chamber when necessary, and, optionally, for removing products or waste material from the device. The reaction chamber may be provided with reagents required for amplification of a preselected polynucleotide. The device also may include means for thermally regulating the contents of the reaction chamber, to amplify a preselected polynucleotide. Preferably, the reaction chamber is fabricated with a high surface to volume ratio, to facilitate thermal regulation.Type: GrantFiled: November 14, 1994Date of Patent: December 24, 1996Assignee: The Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka
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Patent number: 5512451Abstract: In enhanced chemiluminescent (ECL) reactions of a fused aromatic diacyl cyclic hydrazide such as luminol, a peroxidase enzyme catalyst, an oxidant such as hydrogen peroxide and an enhancer, it has been found advantageous to use a combination of an organoboron enhancer such as 4-biphenylboronic acid with a non boron-containing enhancer, especially a phenolic or aromatic amine enhancer, particularly 4-iodophenol. ECL reactions are useful in diagnostic assay.Type: GrantFiled: March 25, 1994Date of Patent: April 30, 1996Assignee: British Technology Group LimitedInventor: Larry J. Kricka
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Patent number: 5498392Abstract: Disclosed are devices for amplifying a preselected polynucleotide in a sample by conducting a polynucleotide polymerization reaction. The devices comprise a substrate microfabricated to define a sample inlet port and a mesoscale flow system, which extends from the inlet port. The mesoscale flow system includes a polynucleotide polymerization reaction chamber in fluid communication with the inlet port which is provided with reagents required for polymerization and amplification of a preselected polynucleotide. In one embodiment the devices may be utilized to implement a polymerase chain reaction (PCR) in the reaction chamber (PCR chamber).Type: GrantFiled: September 19, 1994Date of Patent: March 12, 1996Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka
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Patent number: 5486335Abstract: Disclosed are devices and methods for detecting the presence of a preselected analyte in a fluid sample. The invention provides a device comprising a solid substrate, typically on the order of a few millimeters thick and approximately a 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow system. A sample is passed through the mesoscale flow system, and the restriction or blockage of flow through the flow system is detected as a positive indication of the presence of the analyte. The mesoscale flow system includes in one embodiment a primary sample flow channel extending from the inlet port, and a fractal region, in fluid communication with the flow channel, comprising bifurcations leading to plural secondary flow channels. The device may be adapted for operation in conjunction with a pump, for example, to induce flow of a sample through the flow system.Type: GrantFiled: April 24, 1995Date of Patent: January 23, 1996Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka
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Patent number: 5427946Abstract: Devices and methods are provided for the clinical analysis of a sperm sample. The devices include a solid substrate, typically on the order of a few millimeters thick and approximately 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow channel extending from the inlet port. In one embodiment, a sperm sample is applied to the inlet port, and the competitive migration of the sperm sample through the mesoscale flow channel is detected to serve as an indicator of sperm motility. In another embodiment, the substrate of the device is microfabricated with a sperm inlet port, an egg nesting chamber, and an elongate mesoscale flow channel communicating between the egg nesting chamber and the inlet port. In this embodiment, a sperm sample is applied to the inlet port, and the sperm in the sample are permitted to competitively migrate from the inlet port through the channel to the egg nesting chamber, where in vitro fertilization occurs.Type: GrantFiled: January 21, 1994Date of Patent: June 27, 1995Assignee: Trustees of the University of PennsylvaniaInventors: Larry J. Kricka, Peter Wilding
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Patent number: 5306621Abstract: An enhanced chemiluminescent assay, in which a dihydrophthalazinedione such as luminol, a peroxidase such as HRP and an oxidant such as H.sub.2 O.sub.2 are co-reacted in the presence of an enhancer such as p-iodophenol, is modified. The enhancer is generated by enzyme-catalysed reaction of a pro-enhancer, e.g. p-iodophenol phosphate is cleaved by alkaline phosphatase, enabling this enzyme to be assayed instead of peroxidase. Alternatively, the enhancer is added, an anti-enhancer such as p-nitrophenol is generated by enzymatic reaction of a pro-anti-enhancer such as p-nitrophenol phosphate and the reduction in luminescent emission is measured.Type: GrantFiled: April 1, 1992Date of Patent: April 26, 1994Assignee: British Technology Group LimitedInventor: Larry J. Kricka
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Patent number: 5304487Abstract: Devices are provided for analyzing a fluid cell containing sample. The devices comprise a solid substrate, microfabricated to define at least one sample inlet port and a mesoscale flow system. The mesoscale flow system includes a sample flow channel, extending from the inlet port, and a cell handling region for treating cells disposed in fluid communication with the flow channel. The devices may further include a structure inducing flow of cells in the sample through the flow system. In one embodiment, the cell-handling region may comprise a cell lysis structure to enable the lysis of cells in the sample, prior to, e.g., the detection of an intracellular component in the cell sample. In another embodiment, the cell handling region may comprise a cell capture region, comprising binding sites which reversibly bind to a specific population of cells in the cell sample, to permit the isolation of the specific cell population from the sample.Type: GrantFiled: May 1, 1992Date of Patent: April 19, 1994Assignee: Trustees of the University of PennsylvaniaInventors: Peter Wilding, Larry J. Kricka, Jay N. Zemel
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Patent number: 5302533Abstract: A method of increasing the light output from a chemiluminescent reaction of a dihydrophthalazinedione (DPD), and an oxidant, which comprises carrying out said reaction in the presence of at least one antibody, raised against an intermediate species of said chemiluminescent reaction.Type: GrantFiled: April 10, 1992Date of Patent: April 12, 1994Assignee: British Technology Group LimitedInventor: Larry J. Kricka
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Patent number: 5296375Abstract: Devices and methods are provided for the clinical analysis of a sperm sample. The devices comprise a solid substrate, typically on the order of a few millimeters thick and approximately 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow channel extending from the inlet port. In one embodiment, a sperm sample is applied to the inlet port, and the competitive migration of the sperm sample through the mesoscale flow channel is detected to serve as an indicator of sperm motility. In another embodiment, the substrate of the device is microfabricated with a sperm inlet port, an egg nesting chamber, and an elongate mesoscale flow channel communicating between the egg nesting chamber and the inlet port. In this embodiment, a sperm sample is applied to the inlet port, and the sperm in the sample are permitted to competitively migrate from the inlet port through the channel to the egg nesting chamber, where in vitro fertilization occurs.Type: GrantFiled: May 1, 1992Date of Patent: March 22, 1994Assignee: Trustees of the University of PennsylvaniaInventors: Larry J. Kricka, Peter Wilding
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Patent number: 5110745Abstract: The invention discloses novel methods of detecting glycated proteins in test samples of blood and methods of detecting chronic hyperglycemia. The test sample is contacted with a binder composition under conditions which allow binding of glycated protein in the test sample to at least a portion of the binder composition. The test sample is then exposed to a glycated compound affixed to a solid support under conditions which allow raction of unbound binder composition from the previous step to at least a portion of the glycated compound on the solid support. The glycated compound affixed to a solid support from the previous step which did not react with the unbound binder composition is then reacted with a detecting agent and the detecting agent is detected.Type: GrantFiled: June 1, 1989Date of Patent: May 5, 1992Assignee: The Trustees of the University of PennsylvaniaInventors: Larry J. Kricka, Peter Wilding
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Patent number: 4879097Abstract: A recording apparatus has a holder for a plurality of reaction vessels including a support plate (11) having an array of holes (15) therein for receiving an array of reaction vessels (16), a housing (10) for receiving the holder and being sealed to prevent entry of stray light, an openable cover (24, 249) for the housing, a film back (12) for holding a photographic film adjacent the underside of the plate (11), and a removable shutter (13) for interposition between the film and the support plate.Type: GrantFiled: April 4, 1986Date of Patent: November 7, 1989Inventors: Thomas P. Whitehead, Gary H. G. H. Thorpe, Larry J. Kricka, John E. C. Gibbons, Roger A. Bunce
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Patent number: 4729950Abstract: It has been a problem that the chemiluminescent emission produced by the peroxidase-catalyzed oxidation of a 2,3-dihydro-1,4-phthalazinedione is often weak or gives a poor signal-background ratio and therefore does not give the high degree of sensitivity required for assay purposes, particularly for assay of peroxidase used to label a reagent for example in ELISA. The present invention solves the problem by the finding the certain narrowly defined aromatic amines are enhancers of the reaction and accordingly provides for their use in an assay and kit. The amines are of general formula (I) ##STR1## wherein the R symbols (that is, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6) have any of the meanings (a) to (j) given below, all other R symbols in each meaning are hydrogen atoms and the fused rings are to be read in the same configurational sense as formula I:(a) R=R.sup.1 =CH.sub.3 ; R.sup.4 = ##STR2## (b) R.sup.4 = ##STR3## cyclohexyl, or alkyl or alkoxy having 1 to 4 carbon atoms (c) R.sup.2, R.Type: GrantFiled: July 29, 1985Date of Patent: March 8, 1988Assignee: National Research Development CorporationInventors: Larry J. Kricka, Angela M. O'Toole, Gary H. G. H. Thorpe, Thomas P. Whitehead
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Patent number: 4598044Abstract: A phenolic compound is used to enhance the sensitivity of a luminescent reaction such as carried out in an immunoassay between a peroxidase enzyme, an oxidant, and a chemiluminescent 2,3-dihydro-1,4-phthalazinedione. Preferably, the phenolic compound is 4-iodophenol, 4-phenylphenol or 2-chloro-4-phenylphenol. In the preferred embodiment, horseradish peroxidase is coupled to an antibody to the substance to be assayed.Type: GrantFiled: February 9, 1984Date of Patent: July 1, 1986Assignee: National Research Development CorporationInventors: Larry J. Kricka, Gary H. G. H. Thorpe, Thomas P. Whitehead
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Patent number: 4593728Abstract: A dispensing device, for dispensing reagent into an array of reaction wells (16) in a photographic recording apparatus, comprises an array of tubes (28) which are mounted in a support (23). The support (23) contains a common chamber (29) into which the tops of all the tubes (28) open. The chamber (29) is connected with atmosphere via an opening (32) which is sealable manually to retain liquid in the tubes (28) when the latter are immersed in a reservoir (40) and which is unsealed to dispense the liquid. The recording apparatus has a housing (10) closable at the top by part of the support (23). A plate (11) having an array of holes (15) therethrough rests on a shutter (13) disposed above a photographic film holder (12). The plate (11) carries the reaction wells (16) in the holes (15).Type: GrantFiled: June 27, 1984Date of Patent: June 10, 1986Inventors: Thomas P. Whitehead, Gary H. G. H. Thorpe, Larry J. Kricka, John E. C. Gibbons, Roger A. Bunce
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Patent number: 4459267Abstract: Pipette means having aspirating and expelling means and a substantially cylindrical tube connected to a pipette tip for fluid flow therebetween; the expelling means being arranged to apply pressure to the outer surface of the cylindrical tube, the diameter and wall thickness of which being chosen so that said tube is compressed elastically and substantially uniformly and circumferentially to reduce the internal volume thereof, tending to expel any liquid from the pipette tip; and the aspirating means being arranged to relieve pressure from the outer surface of said tube, allowing the tube to expand substantially circumferentially and uniformly so that liquid may thereby be drawn into the pipette tip.Type: GrantFiled: May 20, 1982Date of Patent: July 10, 1984Assignee: National Research Development CorporationInventors: Roger A. Bunce, John E. C. Gibbons, Larry J. Kricka