Surface enhanced Raman scattering (SERS) spectroscopy is molecular structure specific, sensitive and ideal for multiplexed detection. This thesis presents the development of SERS based biosensing techniques for rapid, sensitive and high throughput detection of oligonucleotides and pathogenic bacteria and discusses the potential of tunable transition metal substrates for UV/ blue SERS application.

The first part of this research describes the development of gold-based SERS beacons for multiplexed DNA sequence detection in a wash-free, separation-free and non-arrayed format. These beacons consist of a simple stem-loop oligonucleotide probe in its native form with one end attached to a SERS active dye molecule and the other to a gold nanoparticle, approximately 50 nm in diameter. When the target sequence is hybridized to the probe, which results in an open conformation, its respective reporter dye is separated from the gold nanoparticle, producing diminished SERS signal.

The second part of the thesis introduces an immuno-microwell array based SERS assay platform for pathogenic bacteria detection which couples the quickness of the immuno-magnetic separation of bacteria with the multiplexed ability of SERS-detection. Specifically this part describes the fabrication and characterization of optical addressable immuno-magnetic beads (IMBs) for bacteria separation, immuno-microwell array based uniform and sensitive SERS substrates and the coupling between IMS and SERS detection. The potential for multiplexed detection is demonstrated by differentiable characteristic SERS bands of the corresponding Raman label of IMB mixtures.

The third part of the thesis discusses the fabrication and characterization of tunable transition metal substrates. The surface plasmon bands of these substrates can be tuned from near UV through the whole visible spectral range, showing the potential for UV/ blue SERS applications.