Apparatus for single-molecule detection

1. A method of sequencing a nucleic acid, comprising the steps of:

providing a detection apparatus comprising:

a waveguide comprising:

a core layer; and

a first cladding layer made of a dielectric material; wherein

at least one nanowell is formed in at least the first cladding layer, and

an 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; and

at 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; and

processing the output signal to determine an identity of at least one base comprised by the nucleic acid.

2. The method of claim 1 , wherein the single molecule nucleic acid sequencing-by-synthesis leads to emission of light via chemiluminescence.

3. The method of claim 1 , wherein the detection apparatus further comprises a light source and the single molecule nucleic acid sequencing-by-synthesis leads to emission of light via fluorescence.