The invention relates to an aggregate comprising metallic nanoparticles and nucleic acid molecules wherein each metallic nanoparticle is coated with a polycation. The invention also relates to a method for obtaining the aggregate of the invention and to the use of said aggregate in methods for detecting the presence of a nucleic acid in a sample, in methods for detecting the presence of a given nucleotide at a predetermined position in a target nucleic acid, in methods for detecting the presence of a modified nucleotide at a predetermined position in a target nucleic acid, methods for detecting the presence of a conjugate between a double stranded nucleic acid and a chemical in a sample comprising double stranded nucleic acid molecules, in methods for determining the content of modified nucleotides in a target nucleic acid and in a method for determining the content of modified nucleotides in a target nucleic acid.

A surface-enhanced Raman scattering (SERS) sensing system or platform and methods of using the same, where the platform comprises a graphene coated-homogeneous plasmonic metal hybrid array, which synergizes both electromagnetic mechanism (EM)- and chemical mechanism (CM)-based signal enhancement for achieving sensitive and reproducible detection of Raman signals. The system and methods of using such system or platform may be applied to the analyses of various bio/chemical molecules, such as but not limited to those found in cells, in a highly sensitive and selective manner.

A surface-enhanced Raman scattering (SERS) sensing system or platform and methods of using the same, where the platform comprises a graphene coated-homogeneous plasmonic metal hybrid array, which synergizes both electromagnetic mechanism (EM)- and chemical mechanism (CM)-based signal enhancement for achieving sensitive and reproducible detection of Raman signals. The system and methods of using such system or platform may be applied to the analyses of various bio/chemical molecules, such as but not limited to those found in cells, in a highly sensitive and selective manner.

This invention provides nucleoside polyphosphate analogues each of which comprises a tag comprising a plurality of Raman-scattering moieties; compounds comprising said nucleoside polyphosphate analogs. This invention also provides nucleotide polymerases with one or more attached and/or conjugated noble metal nanoparticles, wherein the noble metal nanoparticles are surface-enhanced Raman spectroscopy (SERS) substrates thereby creating a region of enhanced sensitivity for surface enhanced Raman spectroscopy (SERS) within or adjacent to the polymerase. This invention also provides a surface with regions of enhanced sensitivity for surface enhanced Raman spectroscopy comprising interspersed rough or nanostructured noble metal surface. This invention also provides methods for determining the sequence of a single stranded DNA or RNA polynucleotide using one or more of nucleoside polyphosphate analogues, polymerase with noble metal nanoparticles, and surface with noble metal.

This invention provides nucleoside polyphosphate analogues each of which comprises a tag comprising a plurality of Raman-scattering moieties; compounds comprising said nucleoside polyphosphate analogs. This invention also provides nucleotide polymerases with one or more attached and/or conjugated noble metal nanoparticles, wherein the noble metal nanoparticles are surface-enhanced Raman spectroscopy (SERS) substrates thereby creating a region of enhanced sensitivity for surface enhanced Raman spectroscopy (SERS) within or adjacent to the polymerase. This invention also provides a surface with regions of enhanced sensitivity for surface enhanced Raman spectroscopy comprising interspersed rough or nanostructured noble metal surface. This invention also provides methods for determining the sequence of a single stranded DNA or RNA polynucleotide using one or more of nucleoside polyphosphate analogues, polymerase with noble metal nanoparticles, and surface with noble metal.

A Surface-Enhanced Raman Spectroscopy (SERS) device to perform accurate label-free long-read DNA sequencing. A Raman sensor has a hot spot defined by plasmonic nanostructures and excited by at least one laser. An immobilized DNA polymerase can be used to pull a DNA template strand to be sequenced through the hot spot.

A Surface-Enhanced Raman Spectroscopy (SERS) device to perform accurate label-free long-read DNA sequencing. A Raman sensor has a hot spot defined by plasmonic nanostructures and excited by at least one laser. An immobilized DNA polymerase can be used to pull a DNA template strand to be sequenced through the hot spot.

Nucleic acid sequencing methods and systems, the systems including nanochannel chip including: a nanochannel formed in an upper surface of the nanochannel chip and; a roof covering the nanochannel and comprising nanopores and a field enhancement structure; and a barrier disposed in the nanochannel. The method including: introducing a buffer solution including long-chain nucleic acids to the nanochannel chip; applying a voltage potential across the nanochannel chip to drive the nucleic acids through the nanochannel, towards the barrier, and to translocate the nucleic acids through nanopores adjacent to the barrier, such that bases of each of the nucleic acids pass through the field enhancement structure one base at a time and emerge onto an upper surface of the roof; detecting the Raman spectra of the bases of the nucleic acids as each base passes through the electromagnetic-field enhancement structure; and sequencing the nucleic acids based on the detected Raman spectra.

A sensor for detecting a target pathogen (e.g., a virus or a bacterium) in a specimen is disclosed, which includes at least two sensing units one of which is configured to detect at least one protein (such as a structural protein) associated with the target pathogen and another one is configured to detect at least one genetic component (e.g., an RNA or a DNA segment) associated with that pathogen (e.g., an RNA segment that is unique to that pathogen).

A sensor for detecting a target pathogen (e.g., a virus or a bacterium) in a specimen is disclosed, which includes at least two sensing units one of which is configured to detect at least one protein (such as a structural protein) associated with the target pathogen and another one is configured to detect at least one genetic component (e.g., an RNA or a DNA segment) associated with that pathogen (e.g., an RNA segment that is unique to that pathogen).