We demonstrate an improvement of the sensitivity of a Raman tweezers set-up, which combines optical tweezers with Raman spectroscopy. The system was tested by taking the Raman spectrum of a 4.6 mu m diameter polystyrene sphere trapped in an aqueous solution. The improvement of sensitivity of the set-up was achieved by adjusting the trap depth for maximum signal to noise ratio (SNR). The maximum SNR was obtained by investigating the Raman peak of a trapped polystyrene sphere at 1001 cm(-1) according to trap depth. With this system, a single trapped living Schizosaccharomyces Pombe yeast cell was sensitively monitored by taking the kinetic Raman spectra for more than 2 h. The relative intensity decrease in amide I and amide III bands, frequency increase in amide I band together with alterations in tyrosine marker band around 850 cm(-1) was observed, which indicates alterations in the hydration state of protein by time progressing. (c) 2008 Elsevier B.V. All rights reserved.