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

Here we present a novel microfluidic technique for on-chip surface enhanced Raman spectroscopy (SERS) based biomolecular detection, exploiting the use of electrokinetically active microwells. Briefly, the chip comprises of a series of microfluidic channels containing embedded microwells that, when electrically actuated, either locally attract or repulse species from solution through a combination of electrokinetic effects. We demonstrate that the approach combines the advantages of existing homogeneous (solution phase) and heterogeneous (surface phase) on-chip techniques by enabling active mixing to enhance the rate of binding between the SERS enhancers and the biomolecular targets as well as rapid concentration of the product for surface phase optical interrogation. This paper describes the chip design and fabrication procedure, experimental results illustrating the optimal conditions for our concentration and mixing processes, and a numerical analysis of the flow pattern. To demonstrate the usefulness of the device we apply it to the quantitative detection of nucleic acid sequences associated with Dengue virus serotype 2. We report a limit of detection for Dengue sequences of 30 pM and show excellent specificity against other serotypes.