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.
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
Liu H
(2021)
Kinetics of RNA and RNA:DNA Hybrid Strand Displacement
in ACS Synthetic Biology
Budd J
(2023)
Lateral flow test engineering and lessons learned from COVID-19
in Nature Reviews Bioengineering
Description | Co-Chair of Expert Advisory Group National Biosurveillance Network |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Machine learning and online care pathways featured in 100 days mission implementation report |
Geographic Reach | Europe |
Policy Influence Type | Contribution to a national consultation/review |
Impact | To ensure global readiness, stakeholders must embrace and embed the enablers outlined in this report into routine healthcare systems. The report recommends a coordinated approach, involving governments, international organisations, research institutions, industry and regulatory bodies, to enhance diagnostics for both epidemic and endemic diseases. Political and financial commitment to multiplexed testing, digitally connected diagnostics, and linking diagnostics to treatment, as well as the underlying framework for diagnostics R&D to meet the goals of the 100DM, are essential to keeping populations safe |
URL | https://www.finddx.org/wp-content/uploads/2023/11/20231128_rep_ipps_making_exceptional_routine_FV_EN... |
Description | Bioinspired Multiplexed Ultrasensitive Biosensing (BioSense) - ERC Advanced Grant |
Amount | € 2,496,310 (EUR) |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start |
Description | EPSRC Digital Health Hub for Antimicrobial Resistance |
Amount | £4,018,862 (GBP) |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2023 |
End | 11/2026 |
Description | Funding Decision, Subject to Contract, Wellcome Trust Affordable Innovations for Global Health Flagship Award |
Amount | £2,930,331 (GBP) |
Funding ID | 222836/Z/21/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2022 |
End | 06/2025 |
Description | Bangor University are partners on the ACE EMHP Wastewater project with the UK Health Security Agency |
Organisation | Bangor University |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Rachel McKendry's research team develop multiplexed, sensitive rapid assays to detect the low levels of biomarkers in wastewater |
Collaborator Contribution | Bangor University provide the samples for the Postpandemic sensors: Harnessing isothermal amplification and quantum nanodiamonds for wastewater epidemiology project |
Impact | The outcomes of this work will be two assays and one proof-of-concept: 1. Lateral flow assay 2. Proof-of-concept ultra-sensitive nanodiamond lateral flow assay (to reduce amplification time) 3. Proof of concept data using WBE samples |
Start Year | 2021 |
Description | University College Hospital, London |
Organisation | University College Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | Collaboration between i-sense and the Advanced Pathogen Diagnostics Unit at UCLH. Collaboration involved sharing of sample, clinical data for sequencing and dashboards |
Collaborator Contribution | Provided samples for clinical validation of new diagnostic tests Provided clinical data for analysis |
Impact | TBC |
Start Year | 2015 |
Description | A Monod model of competitive PCR |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A poster presented by John Goertz at the Integrative Collaborative Modelling in Systems Medicine 1-4 March 2021 |
Year(s) Of Engagement Activity | 2021 |
Description | CT3N - Molly Stevens - Designing bioengineering approaches for biosensing and therapeutics |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Prof Molly Stevens presented the keynote lecture "Designing bioengineering approaches for biosensing and therapeutics" at the Centre for Targeted Therapeutics and Translational Nanomedicine, Philadelphia, USA, 7 Dec 2022 |
Year(s) Of Engagement Activity | 2022 |
Description | Designing nanomaterials for ultrasensitive biosensing |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Plenary talk presented by Prof Molly Stevens to an international audience Biosensors 2021, 31st anniversary world congress on biosensors, 26-29 July, |
Year(s) Of Engagement Activity | 2021 |
Description | Exhibition Road Festival |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Public engagement event to promote scientific research of Imperial College and Exhibiiton Road museums. |
Year(s) Of Engagement Activity | 2019 |
Description | Exploring and exploiting non-ideal PCR behavior for molecular computation in the clinic |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | A virtual poster presented at the "Nucleic acids, synthetic biology and artificial life: engineering and controlling out-of-equilibrium molecular systems" workshop at Imperial College. |
Year(s) Of Engagement Activity | 2021 |
Description | Invited talk to FDA |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Invited talk to FDA |
Year(s) Of Engagement Activity | 2023 |
Description | New hybrid materials for ultrasensitive biosensing and regenerative medicine |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Plenary talk by Prof Molly Stevens IUPAC-World Polymer Congress MACRO 2020+ , Jeju, Korea and Virtual, 18 May 2021 |
Year(s) Of Engagement Activity | 2021 |
Description | Stevens Plenary Talk - MSB 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A research talk presented to an international audience |
Year(s) Of Engagement Activity | 2020 |
Description | Stevens talk - 2020 Milken Institute MEA Summit - Abu Dhabi |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A research talk presented to an international audience |
Year(s) Of Engagement Activity | 2020 |
Description | Stevens talk - Emerging technologies and medical devices event, London |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A research talk presented to an international audience |
Year(s) Of Engagement Activity | 2020 |
Description | Stevens talk - Sensors in Medicine, London, 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Lecture delivered to an international audience |
Year(s) Of Engagement Activity | 2019 |
Description | Stevens talk - World Economic Forum, Davos -2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | A research talk presented to an international audience "Biosensors and the future of diagnostics" |
Year(s) Of Engagement Activity | 2020 |