Patents Represented by Attorney Stephen C. Macevicz
  • Patent number: 6818399
    Abstract: Methods for the multiplexed detection of the binding of, or interaction between, one or more ligands and target antiligands are provided. Detection involves the release of identifying tags as a consequence of target recognition. The methods include the use of electrophoretic tag probes or e-tag probes, comprising a detection region and a mobility-defining region called the mobility modifier, both linked to a target-binding moiety. In practicing the methods, target antiligands are contacted with a set of e-tag probes and the contacted antiligands are treated with a selected cleaving agent resulting in a mixture of e-tag reporters and uncleaved and/or partially cleaved e-tag probes. The mixture is exposed to a capture agent effective to bind to uncleaved or partially cleaved e-tag probes, followed by electrophoretic separation. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification.
    Type: Grant
    Filed: April 2, 2001
    Date of Patent: November 16, 2004
    Assignee: Aclara Biosciences, Inc.
    Inventors: Sharat Singh, Hossein Salimi-Moosavi, Vivian Xiao
  • Patent number: 6808609
    Abstract: Devices and methods are disclosed for moving charged molecules through a medium by the application of a plurality of electrical fields of sufficient strength and applied for sufficient amounts of time so as to move the charged molecules through the medium. The devices although preferably small in size, preferably generate large numbers (100 or more) of electrical fields to a movement area which preferably contains a liquid buffered or gel medium. Mixtures of charged molecules are pulled through the gel by the force of the electrical fields. The fields are preferably activated simultaneously or sequentially one after another at various speeds to create complex force field distributions or moving field waves along the separation medium. Charged molecules capable of moving quickly through the gel will be moved along by the faster moving field waves and be separated from slower moving molecules.
    Type: Grant
    Filed: August 30, 2000
    Date of Patent: October 26, 2004
    Assignee: Aclara Biosciences, Inc.
    Inventors: David S. Soane, Zoya M. Soane
  • Patent number: 6803019
    Abstract: A continuous form microstructure array device (20) is constructed as a flexible elongate film laminate containing microstructure arrays (26) arranged serially along the laminate. The laminate can be continuously drawn from a roll, passed through a processing and analysis device and rerolled or stacked for storage.
    Type: Grant
    Filed: June 13, 2000
    Date of Patent: October 12, 2004
    Assignee: Aclara Biosciences, Inc.
    Inventors: Torleif Ove Bjornson, Laurence R. Shea
  • Patent number: 6787015
    Abstract: Capillary electrophoresis is performed under conventional conditions in microchannels having a norbornene based polymer surface. The norbornene based polymers can be used as a solid substrate for forming the necessary features for a microfluidic device, where the entire device may be made of norbornene based polymer. Conveniently, a norbornene based polymer layer having a lower glass transition temperature may be used to adhere a cover or enclosing layer to the substrate to enclose the microchannels and provide a bottom for the reservoirs.
    Type: Grant
    Filed: July 20, 2001
    Date of Patent: September 7, 2004
    Assignee: Aclara Biosciences, Inc.
    Inventors: Hilary Lackritz, Ingrid Cruzado, Hongdong Tan
  • Patent number: 6787016
    Abstract: Compositions and methods are provided for performing capillary electrophoresis using a composition comprising in combination in an aqueous buffered medium a coating polymer and a sieving polymer, where the sieving polymer is more hydrophilic than the coating polymer and is present in greater amount. Of particular interest are uncrosslinked acrylamide polymer mixtures for coating plastic channels and providing sieving for performing DNA separations in microfluidic devices. Polyacrylamide or N,N-dimethyl acrylamide is used with a N,N-dialkyl acrylamide copolymer, either separately or together for sieving and coating, serving as the medium in capillary electrophoresis DNA separations.
    Type: Grant
    Filed: May 1, 2001
    Date of Patent: September 7, 2004
    Assignee: Aclara Biosciences, Inc.
    Inventors: Hongdong Roy Tan, Alexander Sassi, Ingrid Cruzado
  • Patent number: 6770439
    Abstract: Probe sets for the multiplexed detection of the binding of, or interaction between, one or more ligands and target antiligands are provided. Detection involves the release of identifying tags as a consequence of target recognition. The probe sets include electrophoretic tag probes or e-tag probes, comprising a detection region and a mobility-defining region called the mobility modifier, both linked to a target-binding moiety. Target antiligands are contacted with a set of e-tag probes and the contacted antiligands are treated with a selected cleaving agent resulting in a mixture of e-tag reporters and uncleaved and/or partially cleaved e-tag probes. The mixture is exposed to a capture agent effective to bind to uncleaved or partially cleaved e-tag probes, followed by electrophoretic separation. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification.
    Type: Grant
    Filed: April 2, 2001
    Date of Patent: August 3, 2004
    Inventors: Sharat Singh, Tracy Matray, Ahmed Chenna
  • Patent number: 6720179
    Abstract: The invention provides a method for constructing a high resolution physical map of a polynucleotide. In accordance with the invention, nucleotide sequences are determined at the ends of restriction fragments produced by a plurality of digestions with a plurality of combinations of restriction endonucleases so that a pair of nucleotide sequences is obtained for each restriction fragment. A physical map of the polynucleotide is constructed by ordering the pairs of sequences by matching the identical sequences among the pairs.
    Type: Grant
    Filed: April 14, 2000
    Date of Patent: April 13, 2004
    Assignee: Lynx Therapeutics, Inc.
    Inventor: Stephen C. Macevicz
  • Patent number: 6686152
    Abstract: Methods for the multiplexed detection of known, selected nucleotide target sequences are provided. Detection involves the release of identifying tags as a consequence of target recognition. The methods include the use of electrophoretic tag probes or e-tag probes, comprising a detection region and a mobility-defining region called the mobility modifier, both linked to a target-binding moiety. In practicing the methods, the target-binding moiety of the e-tag probes hybridizes to complementary target sequences followed by nuclease cleavage of the e-tag probes and release of detectable e-tags or e-tag reporters. The mixture is exposed to a capture agent which binds uncleaved and/or partially cleaved e-tag probes, followed by electrophoretic separation. In a multiplexed assay, different released e-tag reporters may be separated and detected providing for target identification.
    Type: Grant
    Filed: April 2, 2001
    Date of Patent: February 3, 2004
    Assignee: Aclara Biosciences, Inc.
    Inventors: Sharat Singh, Huan Tian
  • Patent number: 6673550
    Abstract: Electrophoretic probes comprising fluorescent compounds as detection groups and mobility modifiers are disclosed for the multiplexed detection of the binding of, or interaction between, one or more ligands and target antiligands are provided. In one embodiment, detection involves the release of identifying tags as a consequence of target recognition. Target antiligands are contacted with a set of e-tag probes and the contacted antiligands are treated with a selected cleaving agent resulting in a mixture of e-tag reporters. Typically, uncleaved or partially cleaved e-tag probes are removed and the mixture of e-tag reporters is separated by any technique that provides for separation by mass or mass to charge ratio and the like and detected to provide for target identification.
    Type: Grant
    Filed: November 9, 2001
    Date of Patent: January 6, 2004
    Assignee: Aclara Biosciences, Inc.
    Inventors: Tracy Matray, Vincent Hernandez, Sharat Singh
  • Patent number: 6654505
    Abstract: An apparatus and system are provided for simultaneously analyzing a plurality of analytes anchored to microparticles. Microparticles each having a uniform population of a single kind of analyte attached are disposed as a substantially immobilized planar array inside a flow chamber where steps of an analytical process are carried out by delivering a sequence of processing reagents to the microparticles by a fluidic system under microprocessor control. In response to such process steps, an optical signal is generated at the surface of each microparticle which is characteristic of the interaction between the analyte carried by the microparticle and the delivered processing reagent. The plurality of analytes are simultaneously analyzed by collecting and recording images of the optical signals generated by all the microparticles in the planar array. A key feature of the invention is the correlation of the sequence of optical signals generated by each microparticle in the planar array during the analytical process.
    Type: Grant
    Filed: July 17, 2001
    Date of Patent: November 25, 2003
    Assignee: Lynx Therapeutics, Inc.
    Inventors: John Bridgham, Kevin Corcoran, George Golda, Michael C. Pallas, Sydney Brenner
  • Patent number: 6649351
    Abstract: The invention provides a method for detecting a target analyte, by: (a) contacting one or more target analytes with a set of first and second binding reagents under conditions sufficient for binding of a target analyte with the first and second binding reagents, each of the first binding reagents containing a cleavage-inducing moiety and a target binding moiety, each of the second binding reagents containing a tagged probe having a mass modifier region attached to a target binding moiety by a cleavable linkage, the cleavable linkage being susceptible to cleavage when in proximity to an activated cleavage-inducing moiety; (b) activating the cleavage-inducing moiety to release a tag reporter, and (c) detecting a mass of the tag reporter, the mass uniquely corresponding to a known target analyte.
    Type: Grant
    Filed: November 9, 2001
    Date of Patent: November 18, 2003
    Assignee: Aclara Biosciences, Inc.
    Inventors: Tracy J. Matray, Vincent S. Hernandez, Ahmed Chenna, Herbert Hooper, Sharat Singh
  • Patent number: 6649598
    Abstract: Long wavelength, narrow emission bandwidth fluorecein dyes are provided for detecting specially overlapping target substances. The dyes comprise 4,7-dichlorofluoresceins, and particularly 2′,4′,5′,7′-tetrachloro-4,7-dichloro-5-(and 6-) carboxyfluoresceins. Methods and kits for using the dyes in DNA analysis are provided.
    Type: Grant
    Filed: September 7, 2001
    Date of Patent: November 18, 2003
    Assignee: Applera Corporation
    Inventors: Steven M. Menchen, Linda G. Lee, Charles R. Connell, N. Davis Hershey, Vergine Chakerian, Sam L. Woo, Steven Fung
  • Patent number: 6632606
    Abstract: Methods and compositions are provided for determining large numbers of single nucleotide polymorphisms in target DNA employing particles having (1) primers complementary to sequences in the target DNA where the next succeeding 3′-nucleotide is a potential single nucleotide polymorphism and coding composition members, where the members are unique for each primer, and (2) differentially labeled terminating nucleotides, where the label permits separation of the terminating nucleotides. Desirably the particles are separated into groups having a common prevalent next succeeding nucleotide. The particles and target DNA are combined under nucleotide extending conditions, the particles separated into groups in accordance with the terminating nucleotide and the coding members identified, so that one knows the sequence and the single nucleotide polymorphism. Various protocols are provided for the determination.
    Type: Grant
    Filed: June 12, 2000
    Date of Patent: October 14, 2003
    Assignee: Aclara Biosciences, Inc.
    Inventors: Edwin F. Ullman, Sharat Singh
  • Patent number: 6627400
    Abstract: Families of compositions are provided as labels, referred to as eTag reporters for attaching to polymeric compounds and assaying based on release of the eTag reporters from the polymeric compound and separation and detection. For oligonucleotides, the eTag reporters are synthesized at the end of the oligonucleotide by using phosphite or phosphate chemistry, whereby mass-modifying regions, charge-modifying regions and detectable regions are added sequentially to produce the eTag labeled reporters. By using small building blocks and varying their combination large numbers of different eTag reporters can be readily produced attached to a binding compound specific for the target compound of interest for identification. Protocols are used that release the eTag reporter when the target compound is present in the sample.
    Type: Grant
    Filed: October 27, 2000
    Date of Patent: September 30, 2003
    Assignee: Aclara Biosciences, Inc.
    Inventors: Sharat Singh, Tracy Matray
  • Patent number: 6614030
    Abstract: An optical detection and orientation device is provided comprising housing having an excitation light source, an optical element for reflecting the excitation light to an aspherical lens and transmitting light emitted by a fluorophore excited by said excitation light, a focussing lens for focusing the emitted light onto the entry of an optical fiber, which serves as a confocal aperture, and means for accurately moving said housing over a small area in relation to a channel in a microfluidic device. The optical detection and orientation device finds use in identifying the center of the channel and detecting fluorophores in the channel during operations involving fluorescent signals.
    Type: Grant
    Filed: May 15, 2002
    Date of Patent: September 2, 2003
    Assignee: Aclara Biosciences, Inc.
    Inventors: Kevin Maher, Timothy F. Smith, Torleif Ove Bjornson
  • Patent number: 6511802
    Abstract: The invention provides a method and materials for monitoring and isolating differentially expressed genes. In accordance with the method of the invention, differently labeled populations of DNAs from sources to be compared are competitively hybridized with reference DNA cloned on solid phase supports, e.g. microparticles, to provide a differential expression library which, in the preferred embodiment, may be manipulated by fluorescence-activated cell sorting (FACS). Monitoring the relative signal intensity of the different fluorescent labels on the microparticles permits quantitative analysis of expression levels relative to the reference DNA. The invention also provides a method for identifying and isolating rare genes. Populations of microparticles having relative signal intensities of interest can be isolated by FACS and the attached DNAs identified by sequencing, such as with massively parallel signature sequencing (MPSS), or with conventional DNA sequencing protocols.
    Type: Grant
    Filed: January 8, 1999
    Date of Patent: January 28, 2003
    Assignee: Lynx Therapeutics, Inc.
    Inventors: Glenn Albrecht, Sydney Brenner, Robert B. DuBridge
  • Patent number: 6406848
    Abstract: An apparatus and system are provided for simultaneously analyzing a plurality of analytes anchored to microparticles. Microparticles each having a uniform population of a single kind of analyte attached are disposed as a substantially immobilized planar array inside of a flow chamber where steps of an analytical process are carried out by delivering a sequence of processing reagents to the microparticles by a fluidic system under microprocessor control. In response to such process steps, an optical signal is generated at the surface of each microparticle which is characteristic of the interaction between the analyte carried by the microparticle and the delivered processing reagent. The plurality of analytes are simultaneously analyzed by collecting and recording images of the optical signals generated by all the microparticles in the planar array.
    Type: Grant
    Filed: November 16, 1999
    Date of Patent: June 18, 2002
    Assignee: Lynx Therapeutics, Inc.
    Inventors: John Bridgham, Kevin Corcoran, George Golda, Michael C. Pallas, Sydney Brenner
  • Patent number: 6352828
    Abstract: The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention comprise oligonucleotides selected from a minimally cross-hybridizing set. Preferably, such oligonucleotides each consist of a plurality of subunits 3 to 9 nucleotides in length. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports.
    Type: Grant
    Filed: April 1, 1998
    Date of Patent: March 5, 2002
    Assignee: Lynx Therapeutics, Inc.
    Inventor: Sydney Brenner
  • Patent number: 6306597
    Abstract: The present invention includes, in one aspect, a kit comprising one or more sets of oligonucleotide probes whose perfectly matched duplexes with complementary sequences have similar or substantially the same free energy of duplex formation.
    Type: Grant
    Filed: March 29, 1999
    Date of Patent: October 23, 2001
    Assignee: Lynx Therapeutics, Inc.
    Inventor: Stephen C. Macevicz
  • Patent number: 6280935
    Abstract: The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention comprise oligonucleotides selected from a minimally cross-hybridizing set. Preferably, such oligonucleotides each consist of a plurality of subunits 3 to 9 nucleotides in length. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports.
    Type: Grant
    Filed: June 4, 1998
    Date of Patent: August 28, 2001
    Assignee: Lynx Therapeutics, Inc.
    Inventor: Stephen C. Macevicz