Microfluidic systems can revolutionize chemical detection by providing accurate chemical analysis in a fraction of the material and time requirements of current laboratory-based techniques. Due to their high surface-to-volume ratio, microfluidic systems can exploit interfacial phenomena to control mass transport and chemical processes with near molecular precision. Coupled together with a label-free detection method such as surface enhanced Raman spectroscopy (SERS), a generalizable detection scheme can be developed with countless applications.

SERS is a powerful detection method able to identify single molecules based on plasmonic enhancement of the molecule's vibrational spectrum. Appropriately nanostructured metals are necessary to achieve the high scattering cross-sections associated with SERS.

In this dissertation, engineered systems create microfluidic interfaces for the purpose of chemical detection via SERS. Mass transport across the interfaces was controlled by the interplay of advective and diffusive flows, preferential molecular partitioning between phases, and compartmentalization of chemical reactions spatially and temporally. Chemical detection was achieved by the controlled bottom-up assembly of SERS-active silver nanoparticle clusters. Chemometric analysis methods were developed for the automated identification of target analytes.

Three systems were developed to exploit different interfacial effects. Numerical studies in COMSOL were employed to investigate the relevant physical phenomena in each system. (1) In the first, concerted action of the diffusion-driven mass exchange across parallel laminar flows, and the independent control of nanoparticle aggregation enabled the detection of nanomolar concentrations of methamphetamine in saliva samples. (2) The second system used the principles of interfacial tension to produce nanoliter aqueous plugs with very high surface-to-volume ratios, and in this way achieved the 100-fold concentration of a trace vapor analyte. Quantities as low as 2 picograms of 4-amino-thiophenol were detected in real time. (3) Finally, a droplet-based system was developed that enables the encapsulation of small numbers of nanoparticles and analyte molecules within ∼10 mum diameter droplets. In this way the interactions of very small numbers of the relevant species can be investigated.

Together, SERS and microfluidics provide a powerful platform for detection of a wide range of analytes, with unparalleled specificity, precision, and accuracy.