Global to push GA events into
skip to main content

Title: Solid phase sequencing of biopolymers

This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Probes may be affixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.
Issue Date:
OSTI Identifier:
Sequenom, Inc. (San Diego, CA) CHO
Patent Number(s):
Application Number:
Contract Number:
Research Org:
Sequenom, Inc., San Diego, CA (USA)
Sponsoring Org:
Country of Publication:
United States

Works referenced in this record:

Magnetic bead purification of M13 DNA sequencing templates
journal, February 1992
  • Alderton, Robert P.; Eccleston, Lynne M.; Howe, Roland P.
  • Analytical Biochemistry, Vol. 201, Issue 1, p. 166-169
  • DOI: 10.1016/0003-2697(92)90190-I

Beaded polymer supports and gels: I. Manufacturing techniques
journal, November 1991

Beaded polymer supports and gels: II. Physico-chemical criteria and functionalization
journal, November 1991

Hybridization methods for DNA sequencing
journal, October 1991

Mid-infrared matrix assisted laser desorption ionization with a water/glycerol matrix
journal, May 1998

Budgeting the genome
journal, January 1992

Synthesis of an amplifiable reporter RNA for bioassays
journal, January 1986
  • Chu, Barbara C. F.; Kramer, Fred Russell; Orgel, Leslie E.
  • Nucleic Acids Research, Vol. 14, Issue 14, p. 5591-5603
  • DOI: 10.1093/nar/14.14.5591

Sequencing of megabase plus DNA by hybridization: Theory of the method
journal, February 1989

Oligonucleotides and analogues: A practical approach
journal, May 1992

Efficient preparation of short DNA sequence ladders potentially suitable for MALDI-TOF DNA sequencing
journal, January 1996
  • Fu, Dong-Jing; Broude, Natalia E.; Köster, Hubert
  • Genetic Analysis: Biomolecular Engineering, Vol. 12, Issue 3-4, p. 137-142
  • DOI: 10.1016/1050-3862(95)00125-5

Detection of oligonucleotide duplex forms by ion-spray mass spectrometry
journal, February 1993

A versatile acid-labile linker for modification of synthetic biomolecules
journal, January 1990

Advances in DNA diagnostics
journal, February 1998
  • Graber, Joel H.; O'Donnell, Maryanne J.; Smith, Cassandra L.
  • Current Opinion in Biotechnology, Vol. 9, Issue 1, p. 14-18
  • DOI: 10.1016/S0958-1669(98)80078-5

Variable-wavelength on-column fluorescence detector for open-tubular zone electrophoresis
journal, February 1986

Investigations of the metastable decay of DNA under ultraviolet matrix-assisted laser desorption/ionization conditions with post-source-decay analysis and hydrogen/deuterium exchange
journal, September 1998
  • Gross, Julia; Leisner, Arne; Hillenkamp, Franz
  • Journal of the American Society for Mass Spectrometry, Vol. 9, Issue 9, p. 866-878
  • DOI: 10.1016/S1044-0305(98)00058-0

Liquid-phase hybridization and capture of hepatitis B virus DNA with magnetic beads and fluorescence detection of PCR product
journal, December 1994

Applications of mass spectrometry to DNA sequencing
journal, December 1991
  • Jacobson, K. Bruce; Arlinghaus, Heinrich F.; Buchanan, Michelle V.
  • Genetic Analysis: Biomolecular Engineering, Vol. 8, Issue 8, p. 223-229
  • DOI: 10.1016/1050-3862(91)90032-M

Application of nested PCR and mass spectrometry for DNA-based virus detection: HBV-DNA detected in the majority of isolated anti-HBc positive sera
journal, January 1998
  • Jurinke, Christian; Zöllner, Bernhard; Feucht, Heinz-Hubert
  • Genetic Analysis: Biomolecular Engineering, Vol. 14, Issue 3, p. 97-102
  • DOI: 10.1016/S1050-3862(97)10006-7

Detection of hepatitis B virus DNA in serum samples via nested PCR and MALDI-TOF mass spectrometry
journal, September 1996
  • Jurinke, C.; Zöllner, B.; Feucht, H.-H.
  • Genetic Analysis: Biomolecular Engineering, Vol. 13, Issue 3, p. 67-71
  • DOI: 10.1016/1050-3862(95)00151-4

An oligonucleotide hybridization approach to DNA sequencing
journal, October 1989

N-acyl protecting groups for deoxynucleosides
journal, January 1981

Optimal conditions for supercoil DNA sequencing with the Escherichia coli DNA polymerase I large fragment
journal, March 1988

Direct detection of synthetic and biologically generated double-stranded DNA by MALDI-TOF MS
journal, December 1997
  • Little, Daniel P.; Jacob, Anette; Becker, Thomas
  • International Journal of Mass Spectrometry and Ion Processes, Vol. 169-170, p. 323-330
  • DOI: 10.1016/S0168-1176(97)00214-0

A 2prime;-O-thiol tether in the ribose moiety of nucleic acids for conjugation chemistry
journal, November 1994

Analytical strategies for the use of DNA probes
journal, February 1988

DNA Sequencing by Mass Spectrometry
journal, November 1996

Mass spectrometry of nucleic acids
journal, January 1996

The development of microfabricated arrays for DNA sequencing and analysis
journal, October 1996
  • O'Donnell-Maloney, Maryanne J.; Smith, Cassandra L.; Cantor, Charles R.
  • Trends in Biotechnology, Vol. 14, Issue 10, p. 401-407
  • DOI: 10.1016/0167-7799(96)10052-4

Microfabrication and array technologies for DNA sequencing and diagnostics
journal, December 1996
  • O'Donnell-Maloney, Maryanne J.; Little, Daniel P.
  • Genetic Analysis: Biomolecular Engineering, Vol. 13, Issue 6, p. 151-157
  • DOI: 10.1016/S1050-3862(96)00166-0

Initiator oligonucleotides for the combination of chemical and enzymatic RNA synthesis
journal, March 1992

Determination of oligonucleotide composition from mass spectrometrically measured molecular weight
journal, March 1993
  • Pomerantz, Steven C.; Kowalak, Jeffrey A.; McCloskey, James A.
  • Journal of the American Society for Mass Spectrometry, Vol. 4, Issue 3, p. 204-209
  • DOI: 10.1016/1044-0305(93)85082-9

A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides
journal, October 1987

Use of combined mass spectrometry methods for the characterization of a new variant of human hemoglobin: The double mutant hemoglobin villeparisis β77(EF1) His → Tyr, β 80 (EF4) Asn → Ser
journal, February 1996
  • Promé, Danielle; Deon, Catherine; Promé, Jean-Claude
  • Journal of the American Society for Mass Spectrometry, Vol. 7, Issue 2, p. 163-167
  • DOI: 10.1016/1044-0305(95)00637-0

Covalent immobilization of DNA onto polystyrene microwells: The molecules are only bound at the 5′ end
journal, October 1991
  • Rasmussen, Søren Richard; Larsen, Mette Ravn; Rasmussen, Svend Erik
  • Analytical Biochemistry, Vol. 198, Issue 1, p. 138-142
  • DOI: 10.1016/0003-2697(91)90518-X

Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin.
journal, January 1987

Expression vectors for streptavidin-containing chimeric proteins
journal, April 1991
  • Sano, Takeshi; Cantor, Charles R.
  • Biochemical and Biophysical Research Communications, Vol. 176, Issue 2, p. 571-577
  • DOI: 10.1016/S0006-291X(05)80222-0

Preparation and manipulation of large DNA molecules: advances and applications
journal, January 1987

Fluorescence detection in automated DNA sequence analysis
journal, June 1986
  • Smith, Lloyd M.; Sanders, Jane Z.; Kaiser, Robert J.
  • Nature, Vol. 321, Issue 6071, p. 674-679
  • DOI: 10.1038/321674a0

Analyzing and comparing nucleic acid sequences by hybridization to arrays of oligonucleotides: Evaluation using experimental models
journal, August 1992

Matrix-assisted Laser Desorption/Ionization for Sequencing Single-stranded and Double-stranded DNA
journal, February 1997

Coaxial continuous flow fast atom bombardment for higher-molecular-weight peptides: Comparison with static fast atom bombardment and electrospray ionization
journal, December 1991
  • Tomer, Kenneth B.; Perkins, John R.; Parker, Carol E.
  • Biological Mass Spectrometry, Vol. 20, Issue 12, p. 783-788
  • DOI: 10.1002/bms.1200201207

Rapid detection and sequencing of specific in vitro amplified DNA sequences using solid phase methods
journal, August 1990
  • Wahlberg, Johan; Lundeberg, Joakim; Hultman, Thomas
  • Molecular and Cellular Probes, Vol. 4, Issue 4, p. 285-297
  • DOI: 10.1016/0890-8508(90)90020-Z

Time of flight mass spectrometry of DNA laser-ablated from frozen aqueous solutions: applications to the Human Genome Project
journal, February 1994

Mass spectrometry and the age of the proteome
journal, January 1998