Surface-enhanced Raman spectroscopy with single cell manipulation by microfluidic dielectrophoresis

When exposed to an alternating current (AC) electric field, a polarized microparticle is moved by the interaction between the voltage-induced dipoles and the AC electric field under dielectrophoresis (DEP). The DEP force is widely used for manipulation of microparticles in diverse practical applications such as 3D manipulation, sorting, transfer, and separation of various particles such as living cells. In this study, we propose integration of surface-enhanced Raman spectroscopy (SERS), an extremely sensitive and versatile technique based on Raman scattering of molecules supported by nanostructured materials, with DEP using a microfluidic device. The microfluidic device combines microelectrodes with gold nanohole arrays to characterize electrophysiological and biochemical properties of biological cells. The movement of particles, which varies depending on the electrical properties such as conductivity and permittivity of particles, can be manipulated by the cross-frequency change. For proof of concept, Raman spectroscopy using the DEP-SERS integration was performed for polystyrene beads and biological cells and resulted in an improved signal-to-noise ratio by determining the direction of the DEP force applied to the cells with respect to the applied AC power and collecting them on the nanohole arrays. The result illustrates the potential of the concept for simultaneously examining the electrical and biochemical properties of diverse chemical and biological microparticles in the microfluidic environment.