Abstract: A first apparatus for sequencing a polynucleotide analyte is provided an apparatus for sequencing a polynucleotide analyte comprising: (a) a first zone for generating a flowing stream of single nucleotides by progressive pyrophosphorolysis of a molecule of the analyte attached to a particle and exposed to a flowing aqueous medium; (b) a second zone for generating a corresponding stream of aqueous droplets from the aqueous medium and the nucleotide stream and wherein at least some of the droplets contain a single nucleotide; and (c) a third zone for storing and/or for interrogating each droplet to reveal a property characteristic of the single nucleotide it may contain; wherein in that the first zone includes at least one chemically-modified substrate adapted to bind temporarily to a particle having at least two different regions adapted to bind respectively to the substrate and to the analyte.

Abstract: A method of sequencing a nucleic acid comprising the steps of (1) generating a stream of single nucleoside triphosphates; (2) producing at least one substantially double-stranded primary oligonucleotide used probe by reacting with a corresponding primary probe comprising (a) a first single-stranded oligonucleotide including a restriction endonuclease nicking-site, a single nucleotide capture site, and oligonucleotide flanking regions.

Abstract: A method of sequencing a nucleic acid such as DNA or RNA comprising (1) generating a stream of single nucleoside triphosphates; (2) producing at least one substantially double-stranded oligonucleotide used probe by reacting the single nucleoside triphosphates with a corresponding biological probe comprising (a) a first single-stranded oligonucleotide including a restriction endonuclease nicking-site, a single nucleotide capture site and oligonucleotide regions juxtaposed either side of the nicking-site having at least one fluorophore and at least one quencher and (b) second and third single-stranded oligonucleotides; (3) nicking the first oligonucleotide strand of the used probe at the nicking-site; (4) separating the first oligonucleotide components generated in step (3) from the complementary strand of the used probe and (5) detecting the fluorophores. New biological probes and probe systems for use with the method are also described.

Abstract: A method of sequencing a nucleic acid comprising the steps of (1) generating a stream of single nucleoside triphosphates; (2) producing at least one substantially double-stranded primary oligonucleotide used probe comprising (a) a first single-stranded oligonucleotide including a first restriction endonuclease nicking-site, a single nucleotide capture site, and oligonucleotide flanking regions juxtaposed either side of the capture site and (b) second and third single-stranded oligonucleotides; (3) nicking the first oligonucleotide strand of the used primary probe; (4) separating the first oligonucleotide components; (5) producing at least one substantially double-stranded secondary used probe by reacting with a corresponding secondary probe comprising (c) a complementary fourth oligonucleotide and optionally (d) a single-stranded fifth oligonucleotide; (6) nicking the fourth oligonucleotide strand of the used secondary probe to create separate fourth oligonucleotide components having fluorophores and a single

Abstract: A method of sequencing a nucleic acid comprising the steps of (1) generating a stream of single nucleotides by progressive pyrophosphorolysis; (2) producing at least one substantially double-stranded oligonucleotide used probe comprising (a) a first single-stranded oligonucleotide labelled with first and second regions of detectable element types and (b) second and third single-stranded oligonucleotides capable of hybridising to complementary regions on the first oligonucleotide; (2a) either (i) treating the used probe with a restriction endonuclease to cut the first oligonucleotide strand at the recognition site or (ii) treating the used probe with restriction endonuclease to cut the first oligonucleotide strand at the recognition site; (3) digesting the first oligonucleotide strand of the used probe with an enzyme ide; (4) reacting the fourth oligonucleotide with another first oligonucleotide to produce a substantially double-stranded oligonucleotide product corresponding to the used probe; (5) repeating th

Abstract: An apparatus for investigating a molecule comprising a channel provided in a substrate, a metallic moiety capable of plasmon resonance which is associated with the channel in a position suitable for the electromagnetic field produced by the metallic moiety to interact with a molecule passing therethrough, means to induce a molecule to pass through the channel, means to induce surface plasmon resonance in the metallic moiety; and means to detect interaction between the electromagnetic field produced by the metallic moiety and a molecule passing through the channel. Methods of investigating molecules are also provided.

Abstract: An apparatus for investigating a molecule comprising a channel provided in a substrate, a metallic moiety capable of plasmon resonance which is associated with the channel in a position suitable for the electromagnetic field produced by the metallic moiety to interact with a molecule passing therethrough, means to induce a molecule to pass through the channel, means to induce surface plasmon resonance in the metallic moiety; and means to detect interaction between the electromagnetic field produced by the metallic moiety and a molecule passing through the channel. Methods of investigating molecules are also provided.