Diagnostics and Surveillance
The Diagnostics and Surveillance theme of the CDT will focus on the development and testing of rapid diagnostic tests, digital health and improved surveillance systems
Early detection and diagnosis of AMR is critical to antimicrobial stewardship, public-health surveillance and to prevent transmission. However, there remain many critical engineering challenges. For example, to determine antimicrobial resistance and susceptibility, current “gold-standard” methods often rely on bacterial culture in centralised laboratories requiring 36- to 72-hour turnaround times after sample collection. This is too slow for effective antibiotic stewardship in emergency settings or during short clinic visits. Lateral flow tests are emerging as an important tool for public health, but many lack the sensitivity to detect early-stage infections, as well as the digital connectivity to link data into healthcare systems. Moreover, relatively little is known about the interconnectedness of AMR in animals and the environment (e.g., wastewater), since most AMR studies focus on cases in humans based on electronic patient records in hospitals.
There is an urgent need for new engineering solutions to tackle these challenges. These should cover the generation of rapid ultra-sensitive tests to detect AMR in a variety of decentralised settings (e.g.,GP surgeries, care homes, self-testing in the home, point-of-pen and wastewater surveillance), and also the need for improved surveillance of outbreaks bringing together siloed data sets between humans, animals and the environment using a One Health approach.
Research Theme Contacts:
Prof. Ingemar Cox & Dr. Mike Thomas
Available Projects for 2026 Entry
For full details on how to apply, please visit the Application Page
| Project Title | Description | Supervisors | Keywords |
|---|---|---|---|
| Dual-amplification lateral flow diagnostics for ultrasensitive, power-free detection of RTIs and AMR | Guido Bolognesi, Nguyen TK Thanh | Lateral flow assay, gold nanostars, plasmonic amplification, diffusiophoresis, respiratory tract infections, antimicrobial resistance, point-of-care diagnostics, microfluidics, nanodiagnostics | |
| Single-molecule nanopore sensors for real-time antibiotic quantification in clinical and environmental samples | Nicholas Bell, Kabir Husain | Nanopore sensing, antibiotic detection, single-molecule analysis, aptamers, AMR surveillance, point-of-care diagnostics, environmental monitoring, biosensors |
Projects in Progress
Student
Olive Giles
Supervisors
Project Details:
The MAGIC-WANDS study, which uses metagenomic sequencing to investigate antimicrobial resistance (AMR) in hospital wastewater, has already launched in Peru. The project is now expanding to the UK, where the team will apply these techniques to hospital settings for drug resistance testing and novel pathogen discovery. The student working on this project will have the opportunity to visit the Peru site to learn metagenomic methods directly from the team implementing them.
Over the past decade, both supervisors have helped establish advanced AMR surveillance systems at Great Ormond Street Hospital (GOSH). These systems screen every patient for resistance to last-line therapies and use automated reporting via a customised electronic patient record to guide treatment decisions in real time. However, hospital-wide AMR surveillance remains costly, labour intensive, and time consuming. Wastewater metagenomic surveillance offers a promising alternative, enabling cost-effective, hospital-level AMR monitoring and outbreak detection in a single test.
This project is deploying wastewater metagenomic sequencing as a screening tool for AMR in healthcare facilities. The key objectives are:
- Define the performance of hospital wastewater metagenomic sequencing for detecting resistance prevalence and mechanisms of hospital-wide AMR
- Maximise sequencing sensitivity using bait capture sets for a wide range of target pathogens
- Amplify whole genomes from target organisms using custom primers to characterise AMR at the pathogen level
The MAGIC-WANDS study, led by Professor Louis Grandjean and funded by the Wellcome Trust, currently conducts monthly wastewater sequencing in Peru using Oxford Nanopore Technologies (ONT). The team is developing pipelines for reliable and quantifiable detection of high-risk hospital-acquired drug-resistant infections. In parallel, whole genome sequencing of gram-negative isolates from GOSH inpatients is being carried out as part of the hospital’s existing AMR screening programme.
The project is supported by the Centre for the Evaluation and Treatment of Resistant Infection (CENTRI), led by Grandjean and Dr Hatcher at GOSH. CENTRI has established high-throughput DNA extraction and sample processing pipelines using the automated Hamilton Star system. A long-standing collaboration with Yale University supports the evaluation of custom bait capture sets and genome-spanning primers for detecting and characterising organisms of interest.
This project combines state-of-the-art AMR reporting at GOSH with cutting-edge wastewater genomic technology to enable sensitive, reproducible surveillance and quantification of AMR at the hospital level.
Student
Anushka Barthwal
Supervisors
Project Details:
Antimicrobial resistance (AMR) is widely recognised as one of the greatest challenges facing modern medicine, with projections estimating 10 million deaths annually by 2050 [1, 2]. Already, bacterial infections are responsible for at least one in eight deaths globally [2]. A related and even more pervasive phenomenon is antimicrobial persistence, where bacterial populations survive antibiotic treatment without genetic resistance. Despite its clinical relevance, persistence remains poorly understood.
Persistence involves a small subset of bacterial cells that temporarily halt growth, allowing them to survive antibiotic exposure and potentially resume growth later, leading to recurrent and chronic infections [3, 4]. The current gold standard for diagnosing persistence is the biphasic killing curve, based on colony counts after incubation. However, this method is slow and limits timely clinical decision-making. A major barrier to understanding persistence is the difficulty in isolating persister cells.
This project is developing advanced fluorescence imaging and cell-sorting techniques to revolutionise the detection and study of bacterial persisters. The team is mapping the metabolic state of non-growing cells using fluorescence imaging and applying optical proxies for persistence to develop protocols for isolating persisters using fluorescence-activated cell sorting (FACS). These approaches will enable detailed characterisation of the persister phenotype and exploration of strategies to inhibit regrowth, ultimately supporting the identification of treatments to prevent recurrent infections.
The project is led by the McClelland group, which focuses on experimental and quantitative microbiology, and the Blacker group, which develops fluorescence techniques for probing metabolism [5].
References
[1] Naghavi, M. et al. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. The Lancet S0140673624018671 (2024) doi:10.1016/S0140-6736(24)01867-1.
[2] Murray, C. J. L. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet 399, 629–655 (2022).
[3] Bigger, J. (1944). Treatment of Staphyloeoeeal Infections with Penicillin by Intermittent Sterilisation. Lancet, 244, 497-500.
[4] Balaban, N. Q. et al. Definitions and guidelines for research on antibiotic persistence. Nat. Rev. Microbiol. 17, 441–448 (2019).
[5] Blacker, T. S., Mann, Z. F., Gale, J. E., Ziegler, M., Bain, A. J., Szabadkai, G., & Duchen, M. R. (2014). Separating NADH and NADPH fluorescence in live cells and tissues using FLIM. Nature Communications, 5(1), 3936.
Student:
Grace Cox
Supervisors
Project Details:
Antimicrobial susceptibility testing (AST) is essential for effective antimicrobial stewardship. Traditionally, AST relies on bacterial culture, which can take between one and seven days, delaying results in urgent clinical situations. New diagnostic assays aim to detect bacterial infections earlier and more cost-effectively, often by identifying resistance genes or binding bacteria-specific proteins. Recent examples include lateral flow assays (LFAs) that target enzymatic machinery responsible for resistance, offering high sensitivity and specificity from 18 to 24-hour cultures [1]. However, faster and simpler methods are needed to support timely stewardship.
This project is designing new chemical amplification strategies to enhance the sensitivity of rapid, low-cost LFAs for AST and reduce reliance on culture. The team is scaling down bioassays in rapid test formats to minimise the amount of antibiotics and bacterial load required for detection. Model bacterial platforms such as Escherichia coli with or without inserted resistance genes are being used to probe resistance mechanisms. Reagents that respond specifically to resistance machinery are being designed and produced, and the resulting assays are being evaluated and optimised against colony-forming unit (CFU) per millilitre detection limits.
The research builds on computational models of immunoassays developed in various formats and leverages extensive experience in LFA development [2–6]. In particular, the team has expertise in LFAs responsive to chemical transformations that enhance sensitivity, positioning them well to advance rapid AST technologies
1) Hazim et al. The Journal of Molecular Diagnostics, 22(9), 1129 (2020)
2) Loynachan et al. ACS Nano 2018, 12, 1, 279.
3) Budd, J et al. Nat Rev Bioeng 1, 13-31 (2023)
4) Richards, D et al. Nanoscale, 13, 11921 (2021)
5) Miller, BS et al. Biosensors & Bioelectronics, 207, 114133 (2022).
6) Ayrton, JP et al. Nanoscale,16, 19881 (2024).