A novel screening tool for cervical cancer
There are nearly 190 different strains of human papillomavirus (HPV). However, only a fraction of them can cause cervical cancer. Preventive HPV vaccination against four HPV strains is rapidly being employed by many countries worldwide as a means of eradicating cervical cancer. However, in the meantime there is an imminent need for sensitive diagnostic approaches that can detect the high-risk virus early on. The EU-funded CANCER-TECH project was focussed toward developing a new highly sensitive platform to detect HPV using a laser textured biopolymer as device substrate, functionalized with nanoparticles. “We wanted to generate an ultra-sensitive device capable of detecting high risk HPV,″ explains project coordinator Prof. Dermot Brabazon. Novel technology for nanoparticle production Researchers prepared nanoparticles specific for different HPV strains, especially strains 16 and 18 that are responsible for the majority of cervical cancers. In this context, they employed the pulsed laser ablation in liquid (PLAL) technique, a green synthesis route independent of any chemical processing. As Dr Bagga – the Marie Curie fellow who performed the experimental work – explains: “the technique produces nanoparticles with enhanced surface activity, reducing the amount of sample molecules needed for successful detection.″ In essence, this improves detection limit and time, offering a novel ultrasensitive detection assay for HPV. PLAL also overcomes certain limitations associated with traditional methods of nanoparticle production that result in a broad spectrum of chemical and physical properties and affect efficacy. In addition, it allows for fine tuning of nanoparticle size, composition, and stability, giving researchers the opportunity to control the physical and chemical properties of metal nanoparticles. The team had to address certain challenges associated with nanoparticle composition. Gold nanoparticles showed better optical properties compared to commercially available nanoparticles of similar size. They also demonstrated detection limit at the nanomolar (nM) range using the cardiac biomarker C-reactive protein as a model molecule. However, these proved to be unstable in biological media and scientists turned to molybdenum disulphide as electrode material to develop electrochemical sensor for HPV as it offers a large surface area that can enhance biosensing performance. A biomimetic platform specific for HPV The next step in the project was to functionalize the generated nanoparticles with ligands specific for HPV and attach them on a biomimetic polymer-based platform. In this context, scientists used RNA aptamers to specifically detect different HPV proteins. Cross-reactivity studies demonstrated high selectivity over potential interfering HPV species, demonstrating the potential of the approach to be used in point-of-care devices. Importantly, the aptamers functioned well in biological samples and at low target concentrations. Overall, the CANCER-TECH project made a substantial contribution to the advancement of cancer immune-sensing based on a novel on-chip immunoassay design. The novelty of the approach lies in the high-quality bio-nanostructures used for the ultrasensitive and rapid detection of HPV. The generated assay is expected to increase the sensitivity and specificity of HPV detection, relative to current state of the art. In view of the future, Prof. Brabazon believes that “the manufacturing of biomedical devices via laser processed surfaces is expected to improve numerous medical applications and enhance diagnosis.″
