IRC Next Steps Plus: A Smartphone Powered mRNA Sequence Detector

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

South Africa's leading cause of death is tuberculosis (TB). The country is inflicted by the world's highest incidence rate of TB. Diagnosing TB is notoriously challenging and requires long testing times, costly equipment or false negatives. Of the currently available diagnostic tests, culture tests of sputum samples are the most sensitive but require at least 10 days prior to results. Sputum is often inaccessible, in children or patients co-infected with HIV. More powerful available techniques are costly, bulky or require specially trained staff, inhibiting their implementation in rural healthcare clinics. Point-of-care (POC) tests have transformed diagnoses of several diseases, including HIV in developed regions, and we aim to create innovative POC tests designed to be implemented in South Africa and are rapid, accurate, and cost-effective for the diagnosis of TB. Our design incorporates nanomaterial-based approaches to enable sensitive and specific detection, while microfluidic engineering will support sample processing and signal amplification to give optimal readouts. We will also incorporate a smartphone-based component with the intention to immediately report results and enable rapid linking with remote healthcare units or global healthcare organisations to improve TB monitoring. We will validate our device by analysing samples deriving from patients in South Africa and Malawi. We will perform validation studies in a small pilot study with the Africa Health Research Institute (AHRI), located in KwaZulu-Natal, a rural region of South Africa that hosts the epicentre of TB and HIV endemics. This Plus Award will directly support and feed into the main goals of the "i-sense2" Interdisciplinary Research Centre (IRC), which aims to exploit research strategies to design and promote smartphone-based biosensing technologies within resource-constrained settings, for (re)emerging infectious diseases, influenza-like illnesses, sexually transmitted infections and antimicrobial resistance.

Planned Impact

This Plus Award will bring maximum impact through our leadership in TB diagnostics, biosensing technologies, smartphone-based diagnostic tool designs, analyses of patient samples from Malawi and South Africa (in our labs in ICL), as well as field demonstration in in KwaZulu-Natal, South Africa.

We are targeting a technology with potential for showing improved diagnostic capabilities for TB at the point-of-care. The smartphone component aims to enable streamlined activities with larger healthcare systems to better track, monitor and treat existing or (re)emerging TB, while local healthcare units within South Africa can be equipped with a more powerful tool. The potential impact of such a technology cannot be understated for the hundreds of thousands affected in South Africa and millions around the globe.

Our technology aims to revolutionise the options available for detecting TB at the point-of-care. A successful device will be a powerful diagnostic tool for healthcare officials and possible self-administration. Our engineering approaches can potentially be exploited for engineering point-of-care technologies targeting other biomarkers and against various disease states.

This Plus Award features a unique multidisciplinary approach to design a transformative diagnostic technology. With features from traditionally distinct areas such as nanotechnology, molecular diagnostics, microfabrication and smartphone-driven data linking, this Plus Award is an extremely multidisciplinary approach to a real, tangible problem present when diagnosing TB in South Africa. This project will exploit the most state-of-the-art components and engineering strategies towards an innovative diagnostic tool specific for TB. An exciting feature of this approach is its platform capacity: in creating a technology capable of detecting mRNA in clinically relevant samples, we can build upon this in alternate projects focusing on similar nucleic acid-based molecular targets. We will also support the early career researchers involved in this project, providing them with the highest level of multidisciplinary training and international experience. They will also have full access to workshops, biannual meetings and the Education Alliance supported within the Core Award. We have an excellent track record of completing successful postdoctoral research projects and PhD studies within the framework of "i-sense" and we will continue this within this Plus Award.

In addition to the team's strong track record of delivering high impact results, they have delivered a number of translated designs. The Stevens programme recently filed a patent application for nanomaterial-based components showing amplified signal readouts in lateral flow assays for the detection of p24, a biomarker for HIV. This achievement was based on activities from within "i-sense" and demonstrates the rational approaches we utilise to achieve translationally feasible technologies. Our team has also received recognition and interest form numerous industrial partners, including Google, Oxford Nanopore, Mologic, BBI, Cambridge Life Sciences, Surrey 5G and Telefonica O2. Many of these industrial partners are based in UK and will be active partners within the Core Award. We will communicate with UK-based industrial partners such as Mologic and BBI about upscaling and manufacturing protocols. We already have several examples of successful projects with Mologic, such as our recent successful EPSRC GCRF award and TSB-funded project, where we engineered lateral flow tests against the Ebola virus and phospholipase-A2, a biomarker for acute pancreatitis and rheumatoid arthritis. This Plus Award will support industrial activities with partners of the Core Award, from which we will improve and streamline our design to optimise its marketability. We will perform market landscaping studies as part of this Plus Award to guide translation towards larger healthcare organisations.

Publications

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