Title: A subcutaneous Raman needle probe for real time molecular spectroscopy of lymphoid tissues - application in detection and identification of malignant inclusions.
Funder: Department of Health (England)

Abstract: Here we propose to develop a tool that will uniquely probe molecular specific changes within lymph nodes and provide an immediate result based on objective criteria for the presence of disease. This project will investigate the feasibility of constructing a needle Raman probe, as a medical device for real-time decision making. We plan to demonstrate that we can develop a commercially viable device capable of rapid minimally invasive subcutaneous analysis of diseased tissue. This would have a dramatic impact on surgical procedures and would minimise the need for unnecessary surgical clearance of nodes and the associated risks. To achieve this goal we will need to undertake a carefully structured project made up of key components separated into 6 work packages. These are outlined below. WP0 Project management (0-36 months) - Monthly technical meetings to review progress and results. - Bi-monthly strategic management meetings mitigate risks to success, and to review IPR and routes to commercialisation. WP1 Probe development (0-18 months) - Model and specify new optical design. - Model and specify opto-mechanical design - Build multiple fibre design including adaptation of spectrometer interface to accept multiple inputs. - Test multiple collection fibre design for efficiency - Test new design for robustness. - Optimise filter components and light coupling to new fibre layout. M1 – Agree Final Optical design WP2 Build probes and test performance (12-18 months) - Develop robust and cost effective manufacturing process for optical subassemblies. - Incorporate optics into syringe body or custom made enclosure. - Produce 10 probes for reproducibility and repeatability testing. M2 – Deliver manufacturing process knowhow and 10 prototype units. WP3 Reproducibility and transferability testing (18-24 months) - Test 10 probes for signal and volume sampling reproducibility using standards/phantoms/tissues. - Establish spectral transferability protocols - Assess variability between probes and the implications to the specificity and sensitivity of the algorithm. - Refine design and manufacturing as appropriate. M3 – Spectral transferability protocols WP4 Clinical studies (24-36 months) - Optimise patient recruitment process - Tissue collection / sample handling - Target head and neck nodes to include primary (and secondary) malignancies: 62 patients with a 0.56 cancer to benign ratio (as found in our previous study) would provide a 90% confidence in achieving 90% sensitivity in this case and 110 patients would provide 90% confidence in 85% specificity. (We achieved 91% sensitivity and 88% specificity in a Raman microscope based study [Orr et al., Raman spectroscopy as a tool for the identification and differentiation of neoplasias contained within lymph nodes of the head and neck. SPIE 7548, DOI: 10.1117/12.848784, 2010]). - Measure needle Raman spectra at various insertion points and quality levels (vary collection time). - Build Raman spectral database (include transferability standards) - Construct and test diagnostic algorithms to distinguish node status. - Explore Raman needle tissue typing M4 – Spectral databases from human lymph nodes with associated pathology + diagnostic algorithm WP5 Pathway to Commercialisation (24-36 months) - Undertake headline health economics study using secondary data (Use NIHR SW RDS support) to provide support to commercialisation strategy. - Initiate regulatory approvals to allow in vivo trials (beyond the scope of proposal – will seek further funding with commercial partnership). - Develop commercialisation routes by identifying and engaging with key industrial partners to support the next stage of development and the in vivo clinical trial, potentially in partnership with i4i late stage. M5 – Fully developed route to commercialisation, clinical product testing and patient benefit.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS