Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells

A method for detecting a nucleic acid sequence of interest in a sample comprising the steps of:

• i) providing a first LDR primer, a Raman enhancer, a second LDR primer, and a Raman reporter, wherein the Raman enhancer is bound to the first LDR primer and the Raman reporter is bound to the second LDR primer;
• ii) performing a nucleic acid hybridization reaction on nucleic acid sequences in the sample, wherein the nucleic acid hybridization reaction is a ligase detection reaction (LDR) or a ligase chain reaction (LCR), and wherein the step of performing the nucleic acid hybridization reaction comprises the step of mixing the first LDR primer, the second LDR primer and the sample for a desired period of time;
• iii) performing surface enhanced Raman scattering (SERS) on the nucleic acid hybridization reaction, wherein the step of performing SERS comprises the step of probing the sample with a laser;
• and
• iv) analyzing the outcome of the nucleic acid hybridization reaction, wherein the analyzing step comprises detecting a SERS signal from a binding pair comprising the nucleic acid sequence of interest, wherein the SERS signal indicates the presence of the nucleic acid sequence of interest, thereby detecting the nucleic acid sequence of interest.