Methods and apparatus for nucleic acid sequencing by signal stretching and data integration

The nucleic acid sequencing apparatus comprising:

• a first reaction chamber comprising non-labeled nucleotide precursors and only a single type of labeled nucleotide precursor being a first labeled nucleotide precursor, the first labeled nucleotide precursor consisting of labeled deoxyadenosine-5′-triphosphate (dATP), a copy of a template nucleic acid, a synthetic reagent and a primer, the first reaction chamber configured to synthesize a first labeled nucleic acid strand comprising the first labeled nucleotide precursor and complementary to the template nucleic acid;
• a second reaction chamber comprising non-labeled nucleotide precursors and only a single type of labeled nucleotide precursor being a second labeled nucleotide precursor, the second labeled nucleotide precursor consisting of labeled deoxycytosine-5′-triphosphate (dCTP), a copy of the template nucleic acid, a synthetic reagent and a primer, the second reaction chamber configured to synthesize a second labeled nucleic acid strand comprising the second labeled nucleotide precursor and complementary to the template nucleic acid;
• a third reaction chamber comprising non-labeled nucleotide precursors and only a single type of labeled nucleotide precursor being a third labeled nucleotide precursor, the third labeled nucleotide precursor consisting of labeled deoxythymidine-5′-triphosphate (dTTP), a copy of the template nucleic acid, a synthetic reagent and a primer, the third reaction chamber configured to synthesize a third labeled nucleic acid strand comprising the third labeled nucleotide precursor and complementary to the template nucleic acid;
• a fourth reaction chamber comprising non-labeled nucleotide precursors and only a single type of labeled nucleotide precursor being a fourth labeled nucleotide precursor, the forth labeled nucleotide precursor consisting of labeled deoxyuridine-5′-triphosphate (dUTP), a copy of the template nucleic acid, a synthetic reagent and a primer, the fourth reaction chamber configured to synthesize a fourth labeled nucleic acid strand comprising the fourth labeled nucleotide precursor and complementary to the template nucleic acid;
• one or more fluid channels operably coupled to the reaction chambers;
• one or more nanopores in each of the reaction chambers, each nanopore being sized to allow the passing of the labeled nucleic acid strands through the nanopore;
• a detection unit configured to detect the labeled nucleotide precursors in the labeled nucleic acid strands as the labeled nucleic acid strands pass through the nanopores.