Multiparameter Assay for Profiling Susceptibility (MAPS)

Lead Research Organisation: University of York
Department Name: Physics

Abstract

Antimicrobial resistance (AMR) is the ability of microbes to evolve resistance against an antimicrobial treatment. For example, a bacterium can develop resistance to an antibiotic medicine, rendering that medicine ineffective in treating and containing the infection. The loss of effective antibiotics will have a significant impact on our lives, not only increasing the chances of developing a serious infection but also increasing the risk associated with medical procedures. The recent O'Neill review predicts "If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine".

While AMR in bacteria occurs naturally over time, the misuse and overuse of antibiotics is accelerating this process. For example, many infections such as tonsillitis are predominantly (80%) viral and can thus not be treated with antibiotics, yet antibiotics are still prescribed. An obvious solution is to introduce new drugs. However, this is not only very costly but it is also inevitable that resistance to any new medicine will develop.

A promising and sustainable solution to the AMR problem is the introduction of diagnostic tests that not only confirm a bacterial infection but also identify the best antibiotic for treating the infection. The aim of this project is to develop a diagnostic that will ensure the right drugs are prescribed at the right time. The technology, called MAPS, is based on silicon photonics. Although developed originally for use in the communications industry, we have shown that this same technology can be used to monitor biology, including bacteria and proteins, with very high sensitivity. We will exploit this technology to create a diagnostic that will identify the type of bacterium and severity of infection, the presence of resistance mechanisms and the most promising antibiotic for treatment. Working with clinical and industrial collaborators, we will demonstrate and validate the technology for the treatment of urinary tract infections and determine a route for taking it to the market.

Planned Impact

The long term vision of this proposal is to develop a test for AMR that is low cost, accurate and rapid that can be deployed at point of care, thereby addressing a major socio-economic and unmet clinical need. The project impacts on a large variety of future applications and industries, notably within healthcare, particularly focused on the challenge of AMR, but not limited to it. For example, the chirped GMR approach can be applied to many other diagnostic issues, such as wound healing or blood testing as long as there is an antibody, DNA, affimer or other binder molecule to identify the disease marker of disease. Similarly, the susceptibility test can be applied to other bacterial infections such as tuberculosis and cholera. MAPS is a true platform technology. We foresee other areas of interest, such as the monitoring of water quality, particularly for overseas development, in situ monitoring of environmental contamination or the detection of infectious agents for defence and security.

Potential stakeholders and beneficiaries include:
1. Healthcare providers (including NHS) and patients; Department of Health; Home Office; Ministry of Defense; Environment Agency/DEFRA; DFID
2. Business/industry including Medical Devices manufacturers; Diagnostics companies; Pharmaceutical/Biotech companies; Research equipment manufacturers; suppliers for the above public sector organizations.

A number of mechanisms have been put in place to engage with potential stakeholders throughout the course of the project and beyond, and to ensure the future impact of MAPS is realized. These include:

Commercialisation strategy. We already hold key IP that underpins MAPS and have carefully chosen the project partners who can support translation of our technology. IP Group will advise on the market and commercialisation opportunities. Trajan Scientific and Medical already operate in the medical devices market, so we will benefit from their experience of succeeding in a very competitive environment. Building on their extensive network and existing customer base, they have a very good insight into consumer preferences and performance requirements of any new technology aimed at the consumer healthcare market and will provide networking and contacts to other potential stakeholders. Similarly, they will provide market intelligence, especially on competing products, which will help shape the technology.

Translation strategy. Initial clinical validation of MAPS will be performed during the lifetime of the project, supported by our clinical partners at York Teaching Hospital NHS trust. We have also identified approaches for funding further clinical validation to support further adoption and commercialisation. We will be supported in this by TRANSLATE who will provide access to sector specific experts, with knowledge and experience in successfully translating medical technology from universities into commercial entities and clinical usage. TRANSLATE and IPGroup will also provide support with navigating the medical device regulatory pathway.

Wider end-user engagement strategy. At month 20, we will organise a dissemination workshop to showcase MAPS to external stakeholders. We will invite clinicians from other regions of the UK in order to capture the breadth and variety of NHS practise as well as industrial players who may be interested in adopting the technology into their products. We will be supported in this by TRANSLATE who already have established relationships with key clinical groups and organisations, coupled with experience in facilitating these discussions. In addition, we will conduct structured interviews with UTI patients and healthcare providers, which will provide information regarding characteristics of MAPS that enhance user-friendliness and end-user acceptance.

Publications

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Miller LM (2019) Surface-Bound Antibiotic for the Detection of ß-Lactamases. in ACS applied materials & interfaces

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Martins A (2020) On Metalenses with Arbitrarily Wide Field of View in ACS Photonics

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Simmons MD (2020) Aptamer-Based Detection of Ampicillin in Urine Samples. in Antibiotics (Basel, Switzerland)

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Conteduca D (2019) Monitoring of individual bacteria using electro-photonic traps. in Biomedical optics express

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Pitruzzello G (2018) Photonic crystal resonances for sensing and imaging in Journal of Optics

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Juan-Colás J (2018) Multiparameter resonant imaging for studying cell interactions in Light: Science & Applications

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Juan-Colás J (2018) Quantifying single-cell secretion in real time using resonant hyperspectral imaging. in Proceedings of the National Academy of Sciences of the United States of America

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Juan-Colás J (2017) Dual-Mode Electro-Optical Techniques for Biosensing Applications: A Review. in Sensors (Basel, Switzerland)

 
Description A key finding is that we have developed a technology that is able to detect biomarkers for infection at very low concentration and in human urine, i.e. in a clinically relevant matrix. In fact, the sensitivity is equal to or better than the laboratory standard ELISA while our technology is intrinsically simple and can be realised in a handheld instrument at low cost.
Exploitation Route Market research studies have already been conducted, funded by partner TRANSLATE (now GrowMedTech). An EPSRC IAA has been used to develop testing protocols for biomarkers also in serum. Funding applications aimed at translating the technology are being prepared.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The findings have led to the formation of the spin-out company Phorest Diagnostics Ltd.
First Year Of Impact 2022
Sector Healthcare
Impact Types Economic

 
Description IP Group 
Organisation IP Group Plc
Country United Kingdom 
Sector Private 
PI Contribution Improving sensitvity and functionality of biosensor
Collaborator Contribution Attending meetings, advising on commercial opportunity and setting performance targets
Impact Not yet.
Start Year 2017
 
Description TRANSLATE 
Organisation University of Leeds
Country United Kingdom 
Sector Academic/University 
PI Contribution Advancing biosensor research
Collaborator Contribution Supporting a 6-month feasibility study Commissioning a consultant's report on market opportunities Attending meetings & advising on progress
Impact none yet
Start Year 2017
 
Description York General Hospital NHS Trust 
Organisation York Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Conducting clinically relevant research relating to urinary track infection and antimicrobial resistance.
Collaborator Contribution Clinicians from York Hospital have advised on clinical questions and clinical practise to ensure relvance of the research. They have attended meetings at the university, have hosted meetings at the hospital and have provided access to the labs.
Impact None yet.
Start Year 2017
 
Title A CHIRPED DIFFRACTIVE ELEMENT, A SENSOR APPARATUS AND A METHOD OF DETECTING AN OPTICAL PROPERTY OF A SAMPLE USING THE CHIRPED DIFFRACTIVE ELEMENT 
Description A chirped diffractive element, a sensor apparatus and a method for determining a refractive index value of a sample using the chirped diffractive element. A chirped diffractive element (20) in the form of a grating (22) configured for supporting at least one mode resonance (54) when an optical beam is incident on the grating. The coupling position of the beam on the grating is dependent on the refractive index value of a sample on the grating as well as the wavelength of the incident beam. The incident beam is for example reflected by the grating (22) exhibiting a mode resonance (54). The reflected beam from the grating can then be detected by directly imaging the grating (22), thereby revealing the position of the exhibited mode resonance (54) in the grating (22), and thereby inferring the refractive index value of the sample. 
IP Reference WO2017216574 
Protection Patent / Patent application
Year Protection Granted 2017
Licensed Yes
Impact The IP is licensed to Phorest Diagnostics Ltd.
 
Company Name PHOREST DIAGNOSTICS LTD 
Description The company was set up to commercialise the findings from EP/V047434/1, EP/P030017/1 and EP/P02324X/1. The product to be developed is a low-cost, high performance blood test for use in the community or in the home, aimed at monitoring the immune system of patients, especially immunosuppressed patients. 
Year Established 2022 
Impact The company has secured a pre-seed investment from the Cambridge-based Life Sciences Accelerator Start Codon