For many applications, multi-photon or non-linear spectroscopy can offer several advantages over one-photon excitation. In this project we explore novel spectroscopic strategies based on multi-photon excitation and their potential for multimodal two-photon sensing and imaging. This combination can provide information on morphological structures and function of biological systems along with chemical information about molecular composition, structure, and interactions.

It is possible to extend the concept of SERS to two-photon excitation in biological systems: Recently, we identified effective two-photon cross sections in surface enhanced hyper-Raman scattering (SEHRS) that exceed the largest two-photon fluorescence cross sections reported so far. We also develop multifunctional nanosensors based on SEHRS and have successfully demonstrated the potential of these nanosensors for studying live cells.

Kneipp, J.; Kneipp, H.; Kneipp, K., Two-photon vibrational spectroscopy for biosciences based on surface-enhanced hyper-Raman scattering. Proceedings of the National Academy of Sciences of the United States of America 2006, 103, (46), 17149-17153 Abstract

Kneipp, J.; Kneipp, H.; Wittig, B.; Kneipp, K., One- and two-photon excited optical pH probing for cells using surface-enhanced Raman and hyper-Raman nanosensors. Nano Letters 2007, 7, (9), 2819-2823 Abstract