DNA sequencing, mapping, and diagnostic processes using hybridization and stable isotope labels of DNA
First Claim
1. A DNA sequencing, mapping, and diagnostic process using known individual isotopes, including stable isotopes and long-lived radioactive isotopes, associated with individual oligodeoxynucleotides (ODNs) or peptide nucleic acids (PNAs), said process comprising the steps of:
- labeling nucleotide segments or PNAs with said known isotopes of an element that does not normally occur in DNAs or ODNs;
causing said labeled, complementary, free nucleotide segments or PNAs to hybridize to fixed nucleotide segments or PNAs, said fixed nucleotide segments or PNAs being immobilized in distinct positions on a hybridization surface in an array such that said nucleotide segments or PNAs with known sequences define sequences of nucleotide segments or PNAs that become hybridized;
rinsing non-hybridized labeled nucleotide segments or PNAs from said hybridization array; and
using mass spectrometric methods to analyze the presence and position on said array of said hybridized, labeled complementary nucleotide segments or PNAs and identifying said isotopes.
1 Assignment
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Accused Products
Abstract
A DNA sequencing, mapping, and diagnostic process which includes the steps of labeling nucleotide segments or peptide nucleic acids (PNAs) with one or more atoms of specific stable or long-lived radioactive isotopes of a selected element that do not normally occur in DNAs, ODNs or PNAs such that the nucleotide segment or PNA has specific stable or long-lived radioactive isotope of a specified selected element at a terminal or an interior position; hybridizing the labeled nucleotide segment or PNA to complementary nucleic acid segments or PNAs which are fixed on a hybridization surface; and, using mass spectrometric techniques, including RIS, to analyze the presence and position of the labeled hybridized nucleotide segments or PNAs which are bound to the fixed nucleotide segments or PNAs.
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Citations
67 Claims
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1. A DNA sequencing, mapping, and diagnostic process using known individual isotopes, including stable isotopes and long-lived radioactive isotopes, associated with individual oligodeoxynucleotides (ODNs) or peptide nucleic acids (PNAs), said process comprising the steps of:
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labeling nucleotide segments or PNAs with said known isotopes of an element that does not normally occur in DNAs or ODNs; causing said labeled, complementary, free nucleotide segments or PNAs to hybridize to fixed nucleotide segments or PNAs, said fixed nucleotide segments or PNAs being immobilized in distinct positions on a hybridization surface in an array such that said nucleotide segments or PNAs with known sequences define sequences of nucleotide segments or PNAs that become hybridized; rinsing non-hybridized labeled nucleotide segments or PNAs from said hybridization array; and using mass spectrometric methods to analyze the presence and position on said array of said hybridized, labeled complementary nucleotide segments or PNAs and identifying said isotopes. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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26. A DNA sequencing, mapping, and diagnostic process using known individual isotopes, including stable isotopes and long-lived radioactive isotopes, associated with individual oligodeoxynucleotides (ODNs), said process comprising the steps of:
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labeling nucleotide segments with said known isotopes of an element that does not normally occur in DNAs or ODNs, said labeling nucleotides segments being one of said DNAs and said ODNs; causing said labeled, complementary, free nucleotide segments to hybridize to fixed nucleotide segments, said fixed nucleotide segment being the other of said DNAs and said ODNs, said fixed nucleotide segments being immobilized in distinct positions on a hybridization surface in an array such that said nucleotide segments of said DNAs and said ODNs with known sequences define sequences of nucleotide segments that become hybridized; rinsing non-hybridized labeled nucleotide segments from said hybridization array; and using mass spectrometric methods to analyze the presence and position on said array of said hybridized, labeled complementary nucleotide segments or ODNs and identifying said isotopes. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46)
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47. A DNA sequencing, mapping, and diagnostic process using known individual isotopes, including stable isotopes and long-lived radioactive isotopes, associated with individual oligodeoxynucleotides (ODNs) or peptide nucleic acids (PNAs), said process comprising the steps of:
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labeling nucleotide segments of PNAs with said known isotopes of an element that does not normally occur in DNAs or PNAs, said labeling nucleotide segments or PNAs being one of said PNAs and said DNAs; causing said labeled, complementary, free nucleotide segments or PNAs to hybridize to fixed nucleotide segments or PNAs, one of said fixed or free nucleotide segments or PNAs being PNAs, said fixed nucleotide segments or PNAs being immobilized in distinct positions on a hybridization surface in an array such that said PNAs with known sequences define sequences of nucleotide segments that become hybridized; rinsing non-hybridized labeled nucleotide segments or PNAs from said hybridization array; and using mass spectrometric methods to analyze the presence and position on said array of said hybridized, labeled complementary nucleotide segments or PNAs and identifying said isotopes. - View Dependent Claims (48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67)
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Specification