Viral infections pose one of the biggest global threats to human populations and agriculture. Successful prevention, monitoring and treatment of viral infections requires the availability of fast and reliable diagnostic methods which can not only sensitively, but rapidly detect a viral infection of interest and differentiate between viral infections. This is particularly important in the winter months where rapid diagnosis of viral infections emerging from SARS-Cov-2 relative to influenza strains is essential in order to assist medical practitioners to suggest the most appropriate interventions and treatment. At present, methods do not exist which can rapidly detect viral infections in a low-cost, point-of-care device. We propose to develop a biosensing technology which can not only detect viral components, but also has the potential for the platform to be reusable and regeneratable. Central to these developments is the use of fluorous technology as a tool to immobilise elements which detect viral components. Much akin to Teflon, fluorous technology has the dual advantage as a method which can immobilise molecular components which have a complementary fluorous tag, and reduces non-specific binding to non-fluorous biomolecules, thus improving the sensitivity of the approach. Furthermore, the fluorous-directed immobilisation event is inherently reversible by a simple washing step with organic solvent. In this proposal, we will demonstrate the modularity of the strategy to detect viral RNA (by RT-PCR) or protein (by direct detection of intact viral particles). This will provide a powerful new tool for the biosciences which has the potential to be used for any application which requires rapid detection of pathogenic infections.

The research, which will be carried out in the School of Engineering at the University of Glasgow, will underpin a completely new paradigm in the handling of liquids. It involves the control of the mechanical interactions between fluids and microfabricated structures, with acoustic waves. Notwithstanding its potential impact on a wide range of areas (e.g. physics and chemistry), my focus in this Fellowship will be in enabling advanced diagnostics both in remote areas in developing countries and in the developed world, by integrating complex biological sample processing on low cost portable devices. Acoustic waves carry a mechanical energy that has been successfully used to actuate a wide range of liquid functions. In particular, Surface Acoustic Waves (SAW) propagated on piezoelectric surfaces, using transducers commonly found in electronics, can refract in a liquid, leading to recirculation flows. I have pioneered and enhanced a technique to control SAW and their interactions with the liquid and particles, enabling more complex manipulations. The new platform is based on micromanufactured, disposable phononic lattices, that scatter or reflect the acoustic waves in a frequency dependent manner. These structures shape the acoustic waves, in a manner analogous to that of holograms shaping light. The structures rely on mechanical contrast when holograms are based on refractive index. Geometric aspects of the hologram's design provide colours of different frequencies; here, the phononic lattice geometry determines the frequency at which the sound is scattered. The different frequencies of ultrasound interact with different phononic structures to give different functions, providing a "tool-box" of different diagnostic processes (sample processing, cell separation, detection), which, when combined, form a fluidic circuit, a complete diagnostic assay. Contrary to the established microfluidic systems used in point-of-care devices, which rely on flow through channels to carry out different functions at different positions within the channels, I will design, fabricate, characterise and use new phononic lattices to combine different functions in the frequency domain, on a stationary sample. Others involved in the research include Professor Miles Padgett (School of Physics), Professor Andy Waters (Welcome Centre for Molecular Parasitology), Dr Andrew Winters (Consultant in Sexual Health & HIV Medicine and Joint Clinical Director at The Sandyford Clinic, NHS Greater Glasgow and Clyde) and Dr Mhairi Copland (Paul O'Gorman Leukaemia Research Centre and the Beatson Cancer Research. My research will have three potential outcomes in diagnostics and sensing, namely the development of new Microsystems technologies for: 1. Drug resistant malaria diagnostics. I will develop phononic geometries to carry out a complete nucleic acid based test, including sample preparation, amplification, and detection in whole blood. These will be fabricated in low cost materials (e.g. glass, composites) and could transform malaria diagnostics in the Developing World. 2. Multiplexed detection of a panel of sexually transmitted diseases, working with the NHS. The ability to perform complex sample preparation has the potential to integrate multiplexed analysis in an expert system, where instead of a diagnostic test centered around a pathogen, the test has the capability to analyse a set of symptoms, a decisive shift in diagnostics. 3. Stratification of leukemia cells' aggressiveness. I will explore how the combination of the cells mechanical information probed using acoustics, and coupled with electrical information on cell membranes, could enable a multidimensional analysis of cells. This research will have the potential to create devices to carry out diagnostics anywhere.