New Microsystems for Antimicrobial Resistance

Lead Research Organisation: University of Glasgow
Department Name: College of Science and Engineering

Abstract

The latest estimates, published by the Government and The Wellcome Trust, predict that by 2050 antimicrobial resistance (AMR) could claim one life every three seconds, higher than the current death rates for cancer (http://amr-review.org). Many factors can be attributed to the emergence of AMR associated with medical practice, agricultural policy and deficiencies in education/global awareness. A major limitation, evidenced through the recent launch of the £10M Longitude Prize (2015-2019), is in the lack of fast and reliable diagnostic technologies. For example, current methods to identify an infection in blood are based on bacteria culture and require several days to establish a positive result. During this interim period, potentially ineffective broad-spectrum antibiotics are often administered. Consequently, the development of new diagnostic tools is now seen as one of the four main priorities to address AMR (the other being increasing public awareness, developing new drugs and decreasing the use of antibiotics in agriculture). My Fellowship aims to tackle the challenge of personalized diagnosis by engineering a suite of new advanced microsystems capable of performing a fast, user-friendly isolation of microbes for detection. I will combine improved microfluidic-based separation approaches with innovative ultrasonic concentration technologies to isolate harmful agents in volumes of fluids that are small enough to promote the use of advanced diagnostic tools such as next-generation genome sequencing. These technologies have the potential to reduce unnecessary administration of inappropriate antibiotics, enabling a targeted or personalised approach (consistent with the aims of "precision medicine").

Planned Impact

By 2020, all antibiotic prescriptions will need to be informed by up-to-date surveillance information and rapid diagnostic tests (Review on AMR, 2016). The proposed microsystems will help the UK fulfil this commitment by providing fast sample concentrating techniques that can be combined to emerging biosensors and detection techniques. Beyond the AMR threat, developing new sample processing platforms is an important topic in its own right with a wide range of applications, e.g. for water or food safety, where the presence of pathogens also needs to be detected as quickly as possible to contain potential contamination, thus extending the range of expected impacts.

The impact aims of this Fellowship are to:

1- change the landscape of diagnostics with innovative microsystems for quickly and automatically concentrating microbes without labels and ultimately improve detection procedures (thus improving patient's outcomes and helping health professionals in their choice of treatment). The focus of the project is on medical diagnostics but these microsystems can be applied to a wide range of applications relying on the concentration of a particle (pathogen or other) of interest.

2- fight against antimicrobial resistance by promoting the emergence of new diagnostic approaches by engaging with health professionals and patients, increasing awareness of this deadly growing threat and ultimately reducing the reliance on antibiotics.

3- promote the role of the UK and myself as leaders in the biomedical engineering field and foster STEM (Science, Technology, Engineering and Mathematics) in the next workforce generation

4- boost the UK economy with innovative and versatile sample preparation technologies. The market for such lab-on-a-chip technologies is projected to grow from $4.7 billion in 2015 to $18.4 billion in 2020 (Global Biochip Markets: Microarrays and Lab-on-a-Chip, BCC research, 2016)
 
Title Video PHE 
Description The product is an animated video that I developed in collaboration with Public Health England to promote interdisciplinary research, and the place of engineering, in the fight against antimicrobial resistance. 
Type Of Art Film/Video/Animation 
Year Produced 2018 
Impact The video was presented during an Antimicrobial Resistance Workshop promoting engagement between UK and Indian researchers (India, December 2017). 
 
Description The most significant achievements from the award include:

- a new understanding of the impact of standard procedures used in the bioprocessing industry (e.g. use of surfactant) on cell's morphological (size) and mechanical (deformability) properties, that led to one publication. This finding is significant as observed changes can significantly impact cell well-being and/or sorting for downstream analysis.

- new approaches to separate cells - at high throughout and without any labels (e.g. antibodies) - using microfluidic technologies and more specifically spiral channels. One additional paper has been published to highlight the capability of the technology to separate cells based on their deformability only - finding that could be used for a wide range of applications (e.g. medical, environmental diagnosis).

- a fruitful knowledge exchange with key collaborators (IMFT, France) that led to a new understanding of particle behaviour in confined environment (microfluidic channel) by combining modelling and experimental data.

- knowledge exchange with other key collaborators (NHS and Chalmers University) also shaped the development of the proposed technology to ensure relevance within a clinical workflow but also cutting-edge new detection approaches to identify infections in patients and pathogen resistance to antibiotics.

- the microfluidic technique proposed for medical diagnosis was also used during the Fellowship - and as a proof-of-concept - for the purification of parasites causing neglected tropical diseases. Preliminary data were promising and recently led to additional funding from the Royal Society. This finding could lead to an unprecedented understanding of the mode of transmission of such parasites to humans.

- a new engaging approach with teachers to promote biomedical engineering in schools. To date, 9% of Scottish Schools received tools related to the research proposed for this Fellowship. Further engagement was achieved via conferences (Engage conference, AMR SULSA conference, International Conference on Miniaturized Systems for Chemistry and Life Sciences) and science festivals.
Exploitation Route The work done during the first year of the Fellowship helped collect data for a Chief Scientist Office Translational Grant which has been awarded in 2019 in collaboration with the NHS for testing in hospitals.

The work also sparked the interest of a start-up company to characterise and optimise microfluidic channels they are developing for a wide range of applications (e.g. medical but also environmental challenges). This new collaboration was proposed for an EPSRC New Investigator Award, which has not been successful in 2019 but other routes of funding are being explored.

Other related projects also blossomed in 2019 to separate cancer cells or white blood cells for example - these projects will be further explored in 2020-2021.
Sectors Environment,Healthcare
 
Description The engagement project (ING1617/11/114) I co-led to promote medical diagnostics has demonstrated impact on the perception of engineering in secondary school students. Using clinical challenges and state-of-the-art engineering solutions - such as the ones related to the Fellowship- helped give a context to physics classes. To date, 9% of Scottish Secondary Schools volunteered to be trained to the new teaching tools that were developed during the engagement project. Engagement was also used to increase awareness on the challenge of antimicrobial resistance. In total, 150 Circuits tools were produced for 30 teachers and 60 students participated in a pilot study this year. 100% of teachers and students reported the project as enjoyable, interesting and informative. 100% of teachers who received CPD training plan to use the Circuits tools again in 2019 and 93% of students said the tools were interactive and absorbing. The 60 school students that took part in the pilot classrooms sessions were from schools located in areas that have high multiple deprivation. 70% thought that engineering was not enjoyable or interesting before the session. After the session 100% thought that engineering could be enjoyable or interesting. Findings from this project have been published in 2020 in Sensors.
First Year Of Impact 2018
Sector Education
Impact Types Cultural
 
Description Rapid new methods for sepsis diagnosis in hospitals using microsystems
Amount £296,000 (GBP)
Funding ID TCS/19/46 
Organisation Chief Scientist Office 
Sector Public
Country United Kingdom
Start 05/2020 
End 05/2022
 
Description Research Fellowship
Amount £623,625 (GBP)
Organisation Royal Academy of Engineering 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2018 
End 11/2023
 
Description Royal Society Research Grant
Amount £19,221 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2019 
End 03/2020
 
Description Chalmers University 
Organisation Chalmers University of Technology
Country Sweden 
Sector Academic/University 
PI Contribution I am proposing new technologies to concentrate pathogens that could be integrated to sensing technologies developed by Chalmers University. I spent a couple of days in Sweden presenting my technology to the group there.
Collaborator Contribution The group at Chalmers allowed me to test their sensing technology and discuss how this could be integrated with what I am proposing.
Impact Knowledge exchange at the interface of sample processing and sensing technologies.
Start Year 2018
 
Description IMFT France 
Organisation Institute of Fluid Mechanics of Toulouse
Country France 
Sector Academic/University 
PI Contribution I provided experimental data to inform the modelling tool proposed by Prof. Eric Climent at IMFT Lab
Collaborator Contribution Prof. Climent recruited and supervised a Master student for 6 months (Feb-July 2018) to work on modelling at the IMFT lab on a project related to the Fellowship. I was second supervisor for the student.
Impact • Multidisciplinary collaboration with experts in fluid mechanics and modelling. • One joint Master student supervised for 6 months • One joint paper in preparation (to be submitted in 2019) • A proposal submitted for French funding (ANR - outcome in 2019)
Start Year 2018
 
Description NHS 
Organisation Guy's and St Thomas' NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution I am developing a new approach to separate pathogens from clinical samples for rapid diagnosis of infections.
Collaborator Contribution I had the opportunity to be immersed in a microbiology lab at the NHS, have extensive discussion with health professionals on the best way forward to integrate my technology into the NHS workflow. Partners also gave access to protocols from the NHS to mimic similar protocols in our lab in Glasgow.
Impact • Multi-disciplinary collaboration with microbiologists/clinicians • A clear outline for most probable route to use the technology currently developed • Immersion in a microbiology laboratory in a hospital
Start Year 2018
 
Description Parasitologists - Glasgow 
Organisation University of Glasgow
Department Institute of Infection, Immunity and Inflammation
Country United Kingdom 
Sector Academic/University 
PI Contribution I proposed a new technology - developed during my Fellowship for medical diagnostics - to separate cells at high throughout using microfluidic technologies. I provided bespoke devices to this collaboration. I also received support from the School of Engineering to have a joint intern and supervised the intern.
Collaborator Contribution The parasitologist partner provided parasites to test with the microfluidic devices, co-supervise the intern working on the project and provided lab access for testing with parasites.
Impact This collaboration is multi-disciplinary, at the interface of engineering and parasitology and led to the following outcome in 2018: - a joint intern (summer 218) to gain preliminary data on the potential of microfluidics to separate parasites for genomic analysis - a joint master student (January 2019) to gain further data based on promising results from summer 2018 - a successful grant application submitted to the Royal Society to instal a microfluidic setup (based on the technology developed during the Fellowship) at the parasitology department (University of Glasgow).
Start Year 2018
 
Title New approaches to separate pathogens from blood 
Description The product aims at quickly isolating pathogens from clinical samples to complement existing gold-standard approaches relying on long blood cultures. Promising preliminary data were obtained during the first year of the award with model fluids (e.g. bacteria in water) and current funding is provided by the Royal Academy of Engineering for further development. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2019
Development Status Under active development/distribution
Impact Collaborations to integrate this technology to diverse sensing platform (e.g. sensors developed by Chalmers University, Sweden or by Strathclyde, Glasgow) have been strengthened/established during the award. Beyond clinical settings in the UK, the technology proposed could be integrated in the short term to projects targeting diagnosis for low and middle income countries (cf. Other Outputs section). Preliminary data have also been obtained during the first year of the award with parasites causing neglected tropical diseases as a new route for parasite purification (in collaboration with parasitologists at the University of Glasgow) and led to a Royal Society Research Grant (cf. funding section) for further development. 
 
Description Circuits Engagement project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Circuits is an engagement project that I am co-leading to promote research in medical diagnostics in secondary schools. To date, 9% of Scottish schools received training and tools co-designed by a team of researchers and physics teachers. 100% of teachers (n=30) involved are planning to use the tools in their classrooms in 2019 with impact on the curriculum and changes of perception about engineers already demonstrated (impact of the project was monitored by an independent evaluator). Circuits received funding from the RAEng (Ingenious grant ING1617/11/114) and also the Scottish Schools Education Research Centre to organise 4 CPD events for physics teachers from all over Scotland and produce (in-house) over 100 tools for them to use in schools. Last November, the Circuits team was also invited by the Institute of Physics to further extend the reach of the project by engaging with 60 more teachers. In relationship to my EPSRC Fellowship, Circuits tools were inspired by state-of-the art engineering and biomedical challenges; one of those challenges was related to the work done during my Fellowship; another one was related to the ongoing research within the EPSRC-funded project PROTEUS (with whom I am co-leading the project). In total, Circuits reached 30 teachers and 60 students who participated in a pilot study in 2018 (270 students by end of 2019). The 60 school students that took part in the pilot classrooms sessions were from schools located in areas that have high multiple deprivation. 70% of students thought that engineering was not enjoyable or interesting before the session. After the session 100% thought that engineering could be enjoyable or interesting. Over 2,000 people were also introduced to the Circuits project via engagement at engagement conference (e.g. NCCPE conference) and science festivals (e.g.Institute of Physics science festival, Young Engineers Scotland Annual STEM Challenge 2018)
Year(s) Of Engagement Activity 2018,2019
 
Description Delivery of materials for teaching sepsis in schools 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact New materials have been produced in collaboration with Sepsis Charity FEAT to increase awareness of sepsis in schools - materials have now been published on the Education Scotland Website
Year(s) Of Engagement Activity 2021
URL https://education.gov.scot/improvement/learning-resources/sepsis-teacher-resource-and-supporting-mat...
 
Description Information Day - School of Engineering 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact A talk to present the research of the Fellowship and the importance of Biomedical Engineering to undergraduate students and postgraduate students at the University of Glasgow.
Year(s) Of Engagement Activity 2018
 
Description Visit NHS hospital 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact An immersion in a microbiology lab in a hospital to better understand the NHS workflow for diagnosis of infections. The technologies I am currently developing for improving medical diagnostics were also presented to the group to discuss best implementation and knowledge exchange between engineers and health professionals.
Year(s) Of Engagement Activity 2018