In t his chapter, we describe t he background of Raman spectroscopy, surface-enhanced Raman spectroscopy (SERS), a nd t he development of opto uidic systems toward producing more robust, Raman spectra. Further, applications for the device are described such as the detection of small molecules, the detection of beta amyloid for Alzheimer’s disease, the ability to detect the denaturation of proteins, and for use as a point-of-care (POC) diagnostic for acute coronary syndrome (ACS) through the detection of cardiac biomarkers, including, for example, cardiac troponin (cTn). In addition, as one speci c example, a new opto uidic platform a nd methodology i s described for early detection a nd characterization of analytes t hat c ould b e u seful i n s ensing a nd d iagnosis. is e xtremely s ensitive SERS na nochannelbased opto uidic s ystem i s b eing de veloped to p rovide en hancements e qual to o r e xceeding 1010 for small molecules at t he entrance to a na nochannel, enabling the rapid quanti cation of femtomolar or smaller levels of targets in uids.