Raman sensitivity enhancement for aqueous protein samples using a liquid-core optical-fiber cell

We have demonstrated a sensitivity enhancement factor of 500 in aqueous solutions using a liquid core optical fiber (LCOF) Raman cell made from Teflon-AF. We were able to collect a spectrum of 54 muM lysozyme with a signal-to-noise ratio of 31 in the LCOF Raman cell using 24 mW of laser power and 3 min of integration time. The lysozyme Raman intensity was only 1% of the background Raman intensity from water, but the water-subtracted lysozyme spectrum was still shot-noise-limited and essentially free of nonrandom noise. The lack of nonrandom noise indicates that it should be possible to collect good quality Raman spectra of proteins such as lysozyme at even lower concentrations. The 2.4-muL sample volume of the LCOF Raman cell is an added benefit when limited quantities of sample are available. This volume of a 54 muM lysozyme solution corresponds to only 13 nanomoles or 1.9 mug of lysozyme.