Advanced Diagnostics using Phononics

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.

The programme will create impact within society through improvements in diagnosis and treatment of disease, where this is presently constrained by difficulties associated with the complexity of automation of sample preparation (from blood, saliva or other biological fluids). This situation arises both in the Developed World (in primary care, point of care or in home diagnostics) or in the Developing World (in the field or in regions where infrastructure is limited). This impact will be realised in practice through the development of commercial devices and intellectual property, the delivery of which will have additional economic impacts.

Academics and commercial organizations will benefit in the short term. Academics involved in my immediate research environment will benefit from my improved understanding of this technology. These include a wide range of individuals, namely Professor Miles Padgett (School of Physics), Professor Andy Waters (Molecular Parasitology), Dr Andrew Winters (Consultant in Sexual Health & HIV Medicine and Dr Mhairi Copland (Leukaemia Research Centre and the Beatson Cancer Research). A broad range of other academics will also benefit including those involved in diagnostic instrumentation, microfluidics, microsystems, acoustics and sensors, as they will become aware of a new paradigm by which samples can be manipulated.

Commercial organisations, including diagnostic companies and microfluidic foundries will also benefit in the short term, as they discover how new tools can be used in a wide range of future applications, not only associated with diagnostics but also therapeutics and drug delivery. These will include UK based large diagnostic companies such as Alere or smaller SMEs, such as Mode Dx or Epigem. If we are able to spin-out this technology, other immediate beneficiaries will include those employed in the company.

In the longer term, as the use of phononics becomes more widespread, the range of academic users will grow and undoubtedly the methods will find broader applications outside of the fields associated with biomedical technologies (including for example environmental science and chemical processing).

Similarly, in the longer term, companies involved in the development of new diagnostic tests in the Developed World will benefit from a new technology that enables low cost, high value molecular diagnostics in crude samples. Beneficiaries will also include charitable foundations (such as the WHO, FIND and The Bill & Melinda Gates Foundation), who deliver healthcare in the Developing World, and who all will be able to perform rapid diagnostics in the field.

The relevance of the work to the proposed beneficiaries in industry, the health services and the patients is significant. Whether in the Developed or the Developing World, the most obvious way in which the cycle of infection and transmission can be broken is through rapid diagnosis, and treatment at the point of care (when the patient is present). To illustrate this, it is relevant to consider sexually transmitted infections in urban environments in the Developed World. Current testing takes too long and the patient leaves the clinic before the diagnosis is made and treatment is administered. After leaving a clinic, only 4/10 patients return, despite the use of electronic messaging/texting. Similar situations arise in the Developing World, where the patient may travel for many hours for diagnosis and may not have the opportunity to return for treatment, before the cycle of infection continues. The benefits of a rapid technology, that is low cost and able to provide detailed information, at the point of care, is significant for healthcare workers, patients and populations as a whole. It is considered that rapid point of care molecular diagnostics will underpin any strategy for infectious disease elimination, whether this be in sub-Saharan Africa or Glasgow.