Surface-enhanced Raman scattering (SERS) spectroscopy is presented as a sensitive and speci fic molecular tool for clinical diagnosis and prognosis monitoring of various diseases including cancer. In order for clinical application of SERS technique, an ideal method of bulk synthesis of SERS nanoparticles is necessary to obtain sensitive, stable and highly reproducible Raman signals. In this contribution, we determined the ideal conditions for bulk synthesis of Raman reporter (Ra) molecules embedded silver-gold core-shell nanoparticles (Au@Ra@ AgNPs) using hydroquinone as reducing agent of silver nitrate. By using UV-Vis spectroscopy, Raman spectroscopy and transmission electron microscopy (TEM), we found that a 2:1 ratio of silver nitrate to hydroquinone is ideal for a uniform silver coating with a strong and stable Raman signal. Through stability testing of the optimized Au@Ra@AgNPs over a two-week period, these SERS nanotags were found to be stable with minimal signal change occurred. The stability of antibody linked SERS nanotags is also crucial for cancer and disease diagnosis, thus, we further conjugated the as-prepared SERS nanotags with anti-EpCAM antibody, in which the stability of bioconjugated SERS nanotags was tested over eight days. Both UV-Vis and SERS spectroscopy showed stable absorption and Raman signals on the anti-EpCAM conjugated SERS nanotags, indicating the great potential of the synthesized SERS nanotags for future applications which require large, reproducible and uniform quantities in order for cancer biomarker diagnosis and monitoring.

Surface enhanced resonance Raman scattering (SERRS) is a physical phenomenon that occurs when the energy of incident light is close to that of electronic excitation of reporter molecules (RMs) attached on substrates. SERRS has showed great promise in healthcare applications such as tumor diagnosis, image-guided tumor surgery and real-time evaluation of therapeutic response due to its ultra-sensitivity, manipulating convenience and easy accessibility. As the most widely used organic near-infrared (NIR) fluorophore, heptamethine cyanines possess the electronic excitation energy that is close to the plasmon absorption energy of the gold nano-scaffolds, which results in the extraordinary enhancement of the SERRS signal. However, the effect of heptamethine cyanine structure and the gold nanoparticle morphology to the SERRS intensity are barely investigated. This work developed a series of SERRS nanoprobes in which two heptamethine cyanine derivatives (IR783 and IR780) were used as the RM and three gold nanoparticles (nanorod, nanosphere and nanostar) were used as the substrates. Interestingly, even though IR780 and IR783 possess very similar chemical structure, SERRS signal produced by IR780 was determined as 14 times higher than that of IR783 when the RM concentration was 6:5 × 10⁶ M. In contrast, less than 4.0 fold SERRS signal intensity increase was measured by changing the substrate morphologies. Above experimental results indicate that finely tuning the chemical structure of the heptamethine cyanine could be a feasible way to develop robust SERRS probes to visualize tumor or guide tumor resection with high sensitivity and target to background ratio.