Cancer causes an increased expression of Heat Shock Protein HSP70 in the peripheral blood, at the surface of, and in cancer cells as a result of different sources of stress, including anti-cancer treatments. It was recently demonstrated that tumorigenicity, metastatic potential and resistance to chemotherapy correlated with an increased of expressed HSP70 in cancer cells.
The core goal of this project is to combine the latest advances of nano-optics, optical manipulation and microfluidics with the ultimate understanding of HSP70 to develop a novel integrated and ultra sensitive sensing platform for early cancer detection. An early detection would benefit to traditional but also new cancer therapies based on peptide aptamers, which could be delivered sooner and at lower doses.The planned sensing device, based on surface plasmon resonances supported by micro and nano-structures, will operate in a microcrofluidic circuit to minimize the volumes of analytes and increase reproducibility.
Enhanced and confined plasmonic fields will be engineered at the nanoscale to implement two main sensing schemes:
(i) ultra sensitive tracking of HSP70 proteins circulating in the peripheral blood based on resonance shift induced by specific protein/receptor binding,
(ii) individual cell optical trapping (exploiting latest generation of plasmonics tweezers) combined with scattering imaging and Surface Enhanced Raman Scattering to monitor the concentration of HSP70 proteins at the membrane surface and achieve systematic cancer cell screening.
These transduction mechanisms and plasmonic tweezers will be integrated into a compact platform to operate in a biological laboratory environment. Such a portable device should be seen as a precursor of a future device enabling point of care diagnostics in a medical environment and leading to individualized therapy.
Description of the work performed and main research achieved so far
Over the first year of the project, the collaborative efforts of the SPEDOC partners have enabled to implement skills and knowhow from the different fields of expertise and some first main achievements towards the detection of circulating HSP70 have already been accomplished.
Design and fabrication of plasmonic architectures for the detection of circulating HSP70 Based on extensive numerical simulations, we have identified and optimized geometries of coupled gold nanoparticles that feature high sensitivity to a tiny change of their shallow refractive index, as induced by the binding of HSP70. Based on the optimized designs, samples were fabricated using e-beam lithography.
Surface chemistry and preparation of gold particles We have successfully elaborated a surface chemistry protocol that enables to bind to the gold sensors receptors with high binding specificity to HSP70. This accomplishment is essential since it determines the specificity and therefore the reliability of the different HSP70 sensing schemes that will be investigated.
Design and production of microfluidic design compatible with LSP sensing. We have designed and fabricated a first microfluidic platform that is compatible with LSP sensing and could enable parallel sensing assays under a wide set of experimental conditions.
Successful demonstration of sensing of protein binding in microfluidic environment After integrating the fabricated sensors into the microfluidic platform, we have lately successfully achieved the detection of protein binding and study of the binding kinetics.
