Raman Spectroscopy for Bladder and Prostate cancer diagnostics and multi component blood analysis.



Sponsor:

Science Foundation Ireland Starter Researcher Grant (SIRG).

Individuals:

Bryan Hennelly, Laura Kerr, ShuYu Wu, Sinead Barton, Katarina Domijan (Dept of Mathematics and Statistics, NUIM), John Lowry (Department of Chemistry, NUIM), and Ivor Cullen (consultant urologist).

Summary:

The long-term goal of this research project is the development of optoelectronic systems based on Surface Enhanced Raman Spectroscopy (SERS) and optical tweezers for spectroscopic analysis of biofluids in order to;

i)    Noninvasively diagnose presence of bladder cancer and prostate cancer based on detection of carcinoma cells shed into urine and to determine the grade of cancer with 100% sensitivity and specificity. We also intend to analyse blood serum from breast cancer patients with Principal Components Analysis to investigate the potential of SERS for diagnosing this condition.

ii)    Monitor over 20 blood and urine metabolite concentrations from a single drop of biofluid in approximately 10s. These two goals are independent but they both use the same optical system, or small variations of it and they both use statistical analysis, in different ways. Raman Spectroscopy (RS) is based on the inelastic scattering of monochromatic light, such as that emitted by a laser diode. In the case of both goals above there has been significant recent research on the use of RS for detecting cancer. In the case of bladder and prostate cancer, cells that have been shed into urine have been trapped using optical tweezers (trapped in waist of two opposing focused laser beams) and the Raman spectrum is obtained. Using multivariate statistical analysis the presence of carcinoma can be detected. In 2011 it was shown that this method demonstrated 100% sensitivity and specificity on detecting late stage bladder cancer. However for low grade cells the method was not as successful and current best practice also falls well short in diagnosis of early stage cancer (20% sensitivity) which has a significant effect on risk of mortality. We intend to use SERS, which is a method of amplifying the Raman signal by up to 1015 using aggregates of metal nanoparticles, to detect carcinoma and in all stages for the first time. We also intend to build on a study in 2011 which demonstrated that SERS and multivariate analysis applied to blood serum from colorectal cancer patients allowed for rapid diagnosis of the condition with 97% sensitivity and 100% specificity. We plan to emulate this study using serum from breast cancer patients in different stages of disease in the hope of finding a rapid and inexpensive method for screening of large populations. In the second research goal we plan to use the same SERS based system for multicomponent blood analysis, whereby we hope to improve on previous techniques using standard RS where it has been shown that up to 12 chemicals in the blood can be with clinical accuracy. The method has been shown to have a fundamental noise limit preventing detection of further analytes which we hope to overcome using SERS.

We note this is a multidisciplinary project. We are combining our extensive expertise in the optical engineering with clinicians from the Department if Urology Tallaght hospital, Dublin Ireleand, who supply us with samples from patients suffering from disease and we also work with the Dept. of Chemisty and Dept. of Maths and Statistics in the analysis of the results we obtain and with the Tyndall Institute, Cork, Ireland in designing microfluidic devices that will allow our research successes translate to the clinical environment.


Papers


Laura Kerr, Bryan Hennelly, “Review of Raman Spectroscopy as non-invasive tool for diagnosis of bladder and prostate carcinoma,” (in preparation for submission to European Journal of Urology)