Towards new sensors for prostate cancer detection : combining Raman spectroscopy and resonance sensor technology

Sammanfattning: Prostate cancer (PCa) is the most common male cancer in Europe and the US, and only lung and colorectal cancer have a higher mortality among European men. In Sweden, PCa is the most common cause of cancer-related death for men.The overall aim of this licentiate work was to explore the need for new and complementary methods for PCa detection and to take the first step towards a novel approach: combining Raman spectroscopy and resonance sensor technology. Firstly, the main methods for PCa detection were reviewed. Secondly, to establish a robust protocol for Raman experiments in vitro, the effects of snap-freezing and laser illumination on porcine prostate tissue were studied using Raman spectroscopy and multivariate statistics. Thirdly, measurements on pork belly tissue using both a resonance sensor and a Raman fiberoptic probe were evaluated regarding correlation of the data.It was concluded that the gold standard for PCa detection and diagnosis, the prostate specific antigen test and systematic biopsy, have low sensitivity and specificity. Indolent and aggressive tumors cannot be reliably differentiated, and many men are therefore treated either unnecessarily or too late. Clinical benefits of the state-of-the-art in PCa imaging - advanced ultrasound and MR techniques - have still not been convincingly shown. There is a need for complementary and cost-effective detection methods. Raman spectroscopy and resonance sensor technology are promising alternative techniques, but hitherto their potential for PCa detection have only been investigated in vitro.No evidence of tissue degradation due to 830 nm laser illumination at an irradiance of 3 1010 W/m2 were found. Snap-freezing and subsequent storage at -80◦C gave rise to subtle but significant changes in Raman spectra, most likely related to alterations in the protein structure. The major changes in cancerous prostate tissue do not seem to be related to the protein structure, hence snap-freezing may be applied.The combined measurements on pork belly tissue showed that Raman spectroscopy provided additional discriminatory power to the resonance sensor. The Raman data explained 67% of the variability of the stiffness parameter. The differentiation of tissue types using the resonance sensor was relatively poor, likely due to its large sample volume compared to the Raman sensor. A smaller resonance sensor tip may improve the results.In summary, this work indicates that an instrument combining Raman spectroscopy and resonance sensor technology is a promising complementary method for PCa detection. Snap-freezing of samples may be used in future Raman studies of PCa. A combined instrument could potentially be used to guide prostate biopsies towards lesions suspicious for cancer, and for tumor-border demarcation during surgery. All of this should provide a more secure diagnosis and consequently more efficient treatment of the patient.