Apparatus and method

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.

1 - 33 . (canceled) 
     
     
         34 . An apparatus for sequencing a nucleic acid molecule, the apparatus comprising:
 an array of nanopores provided in a substrate;   a first reservoir suitable for receiving a sample including molecules of the nucleic acid;   a second reservoir separated from the first reservoir by the substrate;   means to induce a plurality of the nucleic acid molecules to move simultaneously from the first reservoir to the second reservoir via the nanopores;   a metallic nanostructure disposed around or adjacent to each of the nanopores facing the second reservoir, each of the metallic nanostructures producing, by particle plasmon resonance, a localized electromagnetic field around or adjacent to the corresponding nanopore facing the second reservoir;   means to induce the particle plasmon resonance in each of the metallic nanostructures;   means to detect Raman-scattered photons produced by the interaction of (i) the localized electromagnetic fields produced by the metallic nanostructures and (ii) a nucleic acid molecule moving from the first reservoir to the second reservoir via each of the nanopores and in close proximity to the corresponding metallic nanostructure;   control means to control the velocity, direction, position or conformation of the nucleic acid molecules through the nanopores; and   means to multiplex a plurality of signals derived from the Raman-scattered photons produced in each of the electromagnetic fields.   
     
     
         35 . The apparatus according to  claim 34 , wherein the control means controls the speed of passage of the nucleic acid molecules through the nanopores. 
     
     
         36 . The apparatus according to  claim 34 , wherein the control means holds the nucleic acid molecules in a linear conformation through the nanopores. 
     
     
         37 . The apparatus according to  claim 34 , wherein the Raman-scatters photons are SERS photons. 
     
     
         38 . The apparatus according to  claim 34 , wherein the means to detect the Raman-scattered photons comprises a photon detector. 
     
     
         39 . The apparatus according to  claim 34 , wherein the means to detect the Raman-scattered photons includes a Raman spectrometer. 
     
     
         40 . The apparatus according to  claim 38 , further comprising an array of voltage modulators linked to the photon detector. 
     
     
         41 . The apparatus according to  claim 38 , further comprising an array of voltage supplies based on input from the photon detector. 
     
     
         42 . The apparatus according to  claim 34 , wherein each of the nanopores has a diameter of from approximately 0.5 nm to 100 nm. 
     
     
         43 . The apparatus according to  claim 34 , wherein each of the nanopores has a diameter of from approximately 1 nm to 50 nm. 
     
     
         44 . The apparatus according to  claim 34 , wherein each of the nanopores has a diameter of from approximately 1 nm to 30 nm. 
     
     
         45 . The apparatus according to  claim 34 , wherein each of the nanopores has a diameter of from 1 nm to 5 nm. 
     
     
         46 . The apparatus according to  claim 34 , wherein each of the nanopores is conical. 
     
     
         47 . The apparatus according to  claim 34 , wherein each of the nanopores is organic. 
     
     
         48 . The apparatus according to  claim 34 , wherein the substrate further comprises a waveguide to control the emission of Raman-scattered photons from the nucleic acid molecules. 
     
     
         49 . The apparatus according to  claim 34 , wherein the substrate is a film. 
     
     
         50 . The apparatus according to  claim 34 , wherein each of the nanopores is formed from a nanoporous material selected from the group consisting of porous gold, a colloidal crystal, a colloidal cavity and a metal toroid. 
     
     
         51 . The apparatus according to  claim 34 , wherein each of the metallic nanostructures comprises gold, silver, copper or aluminium. 
     
     
         52 . The apparatus according to  claim 34 , wherein each of the metallic nanostructures is substantially spherical. 
     
     
         53 . The apparatus according to  claim 34 , wherein each of the metallic nanostructures is substantially annular. 
     
     
         54 . The apparatus according to  claim 34 , wherein each of the metallic nanostructures is a polygonal prism. 
     
     
         55 . The apparatus according to  claim 34 , wherein each of the metallic nanostructures has a diameter of from 50 nm to 150 nm. 
     
     
         56 . The apparatus according to  claim 34 , wherein the metallic nanostructures are disposed facing the second reservoir so that the metallic nanostructures are 50 nm or less from the nucleic acid molecules as the nucleic acid molecules move from the first reservoir to the second reservoir via the corresponding nanopores. 
     
     
         57 . The apparatus according to  claim 34 , wherein the control means comprises laser trapping. 
     
     
         58 . The apparatus according to  claim 34 , wherein the control means comprises a porous matrix through which the nucleic acid molecules pass, the porous matrix lying immediately adjacent to the entrance to the nanopores. 
     
     
         59 . The apparatus according to  claim 34 , wherein the means to detect Raman-scattering photons comprises at least one photomultiplier or avalanche photodiode. 
     
     
         60 . The apparatus according to  claim 34 , wherein the nucleic acid is DNA or RNA. 
     
     
         61 . The apparatus according to  claim 34 ,
 wherein the metallic nanostructures are pairs of metallic nanostructures, the localized electromagnetic field being produced, by the particle plasmon resonance, between each of the pairs of metallic nanostructures, and   wherein each of the pairs of metallic nanostructures is disposed around or adjacent to a nanopore facing the second reservoir so that the nucleic acid molecules pass through the localized electromagnetic field being produced between each of the pairs of metallic nanostructures as the nucleic acid molecules move from the first reservoir to the second reservoir via the nanopores.