Apparatus for single-molecule detection

A method of sequencing a nucleic acid, comprising the steps of:nproviding a detection apparatus comprising:na waveguide comprising:na core layer; anda first cladding layer made of a dielectric material; whereinat least one nanowell is formed in at least the first cladding layer, andan upper opening of the at least one nanowell is larger than a bottom of the at least one nanowell;a first opaque protection layer arranged over the first cladding layer without extending into the at least one nanowell;a second opaque protection layer arranged below the waveguide, the second opaque protection layer having a nanostructured metal pattern; andat least one light detector;providing at least one nucleic acid molecule;locating the at least one nucleic acid molecule individually within the at least one nanowell;performing single molecule sequencing-by-synthesis of the at least one nucleic acid molecule, wherein the single molecule nucleic acid sequencing-by-synthesis leads to emission of light correlated to the identity of at least one base in the nucleic acid;detecting the light with the detector, resulting in an output signal; andprocessing the output signal to determine an identity of at least one base comprised by the nucleic acid.