Nanowell surface enhanced Raman scattering arrays fabricated by soft-lithography for label-free biomolecular detections in integrated microfluidics

We describe a low-cost, ultrasensitive surface-enhanced Raman scattering (SERS) substrate in microfluidic biochips fabricated by soft lithography. A batch nanofabrication method is developed to create nanopillars structures on a silicon wafer as a master copy of molding, then the complementary nanowells structures on polydimethylsiloxane (PDMS) are created by soft lithography. The selective deposition of Ag thin film on the nanowells is applied to create SERS active sites before the integration with a glass-based microfluidic chip which functions as a sample delivery device and a transparent optical window for SERS spectroscopic imaging. Detections of Rhodamine 6G and adenosine SERS spectra are accomplished by using a 785nm laser with 300μW excitation power. The Raman scattering signal enhancement on the nanowell-based Ag SERS substrate is more than 107 times higher than the control sample (i.e. the smooth Ag layer on PDMS). Fabrication of ultrasensitive nanowell SERS substrate by economical and repeatable soft lithography method can contribute to the future microdevices for high throughput screening of functional genomics, proteomics, and cellular activities.