Nanotrap-Enhanced Raman Spectroscopy: An Efficient Technique for Trace Detection of Bioanalytes

Reliable diagnosis of disease using body fluids requires sensitive and accurate detection of disease-specific analytes present in the fluid. In recent years, there has been increasing interest in using surface-enhanced Raman spectroscopy (SERS) for this purpose. The demonstrable signal enhancement and sensitivity of SERS makes it ideally suited for detection of a trace quantity of any analyte. However, lack of reproducibility along with large spatial variability in the measured Raman intensities due to differential (and often random) distribution of surface "hot spots" limits its routine clinical use. We propose here a technique, nanotrap-enhanced Raman spectroscopy (NTERS), for overcoming these long-standing limitations and challenges of SERS. In this technique, hot spots are formed by drying up a microvolume drop of the liquid, containing the mixture of nanoparticles and analytes in the focal volume of the Raman excitation laser, and the Raman signal is detected from these spots containing the analytes localized within the nanoparticle aggregates. The performance of the technique was evaluated in detecting trace quantities of two Raman-active analytes, Rhodamine 6G (R6G) and urea. It was found that R6G and urea could be detected down to a concentration of 50 nM with signal-to-noise ratio (SNR) value of ∼75 and 4 mM with SNR value of ∼500, respectively. A comparison with SERS revealed that NTERS not only had significantly superior (around 2 orders of magnitude) signal enhancement but also had high reproducibility because of its intrinsic ability to form nanoparticle aggregates with high repetitiveness. Another advantage of NTERS is its simplicity and cost effectiveness as it does not require any specialized substrate.