Lab on a Stick: Smartphone-ready low cost rapid live microbe detection and identification using nanocoated Micro Capillary Film

Lead Research Organisation: University of Reading
Department Name: Pharmacy

Abstract

Overall project aim: simple, low cost detection of bacteria using an affordable new microfluidic technology
Bacteria are a major subtype of microbes (or germs) that cause a range of infections and can also contaminate food and medicines during manufacturing. Tools for detecting bacteria are thus vital, but current methods are often laborious and slow, and require the use of a fully-equipped microbiology laboratory. This project will develop a new bacteria testing technology- called Lab-on-a-Stick - that makes detecting and identifying live bacteria simpler, faster and more portable at an affordable price. Ultimately Lab-on-a-Stick tests can be performed without lab equipment and read using a mobile phone camera.
Technology background: Microfluidics and Lab-on-a-Chip
Research over recent decades has developed technology called "microfluidics" using tubes with dimensions smaller than 1mm, typically around 0.1-0.2 mm wide to process reagents and samples. One major aim of microfluidic research is to develop miniature tests, with advantages of the small size including faster, automatic tests and smaller samples. These are referred to as "Lab-on-a-Chip" because complex lab procedures can be performed on a tiny microchip device. However, Lab on a Chip products are expensive and difficult to manufacture and have so far been limited to specialised high value applications, and most rapid disposable tests still use a more familiar format- the dipstick- e.g. pregnancy or blood glucose tests. The great advantage of dipsticks is their extreme simplicity- just dip in sample, and wait for a colour change. Dipsticks have disadvantages, so ideally the benefits of Lab-on-a-Chip microfluidic technology should now be adapted into a dipstick form.
New technology: Lab-on-a-Stick
A collaboration between Reading and Loughborogh Universities led to the invention an entirely new approach -called Lab-on-a-Stick - that promises to deliver microfluidic properties with the simplicity and low cost of a dipstick. This technology exploits special properties of a novel microfluidic material previously studied by the applicant, but also adds a new modification that applies the science of nanotechnology - in other words a modification with dimensions around 1/10,000th of a millimeter. The resulting nano-modified microfluidic material has many beneficial properties, including the ability to perform 10 different tests after dipping into one sample, and as it is exceptionally transparent the tests results can be measured using a mobile phone camera. Remarkably it can still be produced at very low cost, using a simple, conventional manufacturing process, allowing cheap disposable tests that deliver the power of microfluidics.
Current project objectives:
Unpublished studies have already proven that the new dipstick microfluidic technology can perform three standard blood tests in a single drop of blood, and shown that bacteria testing is also feasible. This grant will build on these preliminary studies to produce fully functioning devices for detecting harmful and infectious bacteria in a smartphone-friendly dipstick format. The study will focus on developing a fundamental understanding of how to use the nanotechnology modification to perform accurate and sensitive bacteria tests using the new Lab-on-a-Stick technology platform.

Planned Impact

A Public impact
Public health benefits
This project is the start of a program to ultimately deliver new diagnostic and microbial testing products based on Lab-on-a-Stick (LoS) technology with significant public health and patient benefits. The closest to market application (~2-3 years) will be simpler, faster tests replacing current microbiology tests saving QC lab costs in food/pharma manufacturing. Clinical products for diagnosis of bacterial infection in patients will follow (~4-6 years) providing faster pathogen identification with major health benefits including rapid diagnosis and accurate antibiotic selection resulting in faster recovery. Central to MCF technology is a low manufacturing cost, which will deliver more tests for less healthcare expenditure. Long term, a broader range of LoS tests (e.g. biomarker measurement) will be developed, delivering point-of-care clinical tests that cut waiting times for results, and improving diagnostic precision and thus health outcome through personalised medication. The LoS platform has global application in real-world diagnostics, offering low-cost rapid multiple assays tests (e.g. infection screening) that can be performed in a field clinic.
Public awareness of diagnostic technology innovation
There is a public perception of a need for faster, simpler and more accurate diagnostic testing; the public must therefore be made aware of ongoing research and innovation in testing technology. Public awareness of the simple but sophisticated LoS concept will be raised via media publicity following publication of project results.
B Economic impact
IP and technology commercialisation: Project findings will support commercial uptake of LoS technology and exploitation of background and arising IP, building value in UK technology (MCF film, LoS platform). The Point of Care and microbial testing markets are both >5Bn$ and rapidly growing. Commercialisation of IP will occur through evaluation, licensing, and product development either by existing microbial testing/diagnostic companies (e.g. Alere, Roche), or through startup Capillary Film Technology Ltd, as appropriate. In addition non-patentable expertise in affordable microfluidics will arise benefiting the Health Tech community via knowledge transfer. UK manufacturing SME Lamina Dielectrics will benefit from sales of the MCF they exclusively produce.
Expanding research capacity: The PI is establishing a track record in both low-cost microfluidics and in applied microbiology. These areas of expertise will be combined and expanded by the project in the critical field of microbiology testing. The project will also train a PDRA with broad interdisciplinary expertise, but also experience of innovation, technology transfer, industrial R&D, and research translation.
R&D investment, employment and wealth creation: The project will develop new technology of commercial value, plus expertise, to the HealthTech sector, resulting in employment and economic growth. Project-derived technology, IP and expertise will release R&D expenditure in the forms of industrial R&D (evaluation, product development) and/or private investment (e.g. angel, VC) to develop Lab-on-a-Stick products. Further research investment will follow from project findings in the form of grants from charities (Wellcome Trust, Gates Foundation) to develop dipstick microfluidic tests for worldwide unmet medical need in affordable testing and diagnostics (e.g. field clinic multi-infection dipstick tests). This investment will result in employment of researchers and tech transfer experts in both the private sector (HealthTech/Biotech) and Universities.
C Scientific and academic impact
The multi-disciplinary research outputs will enhance the UK's research reputation both through publication, and by developing translational applications of current world-class UK expertise in controlled release, materials science and low-cost microfluidics
 
Description Following the completion of this project in summer 2015, at the point of reporting significant technical progress has been made, most of which was planned but with some additional insights. Specific achievements to date include:
-robust confirmation of the capabilities of our new affordable microfluidic technology for bacterial detection and identification (fermentation and enzymatic assays, plus sensitive bacterial growth detection)
-PCT filing of initial invention clearing the way for publication of new technology concept, and offering an opportunity for commercial exploitation.
-Detailed understanding of how the underlying technology works, with an unexpectedly simple mechanism of reagent loading identified.
-New and important microbiological applications of the new technology in the field of antimicrobial resistance identified and proof-of-concept that this application completed, specifically the ability to perform quantitative (MIC) and qualitative (antibiogram) antimicrobial resistance testing.

The major findings are partly published, with a major paper in summer 2016, a followup accepted in Feb 2017, and a second major publication in preparation. Major findings are continuing to be presented to potential industrial partners and clinical microbiology users. Possible investment into product development is in current discussion, as well as possible out-licensing to major international company.
Exploitation Route Our focus in the initial part of this project has been to complete the essential demonstrations of the new technology in the laboratory. Now that these technical demonstrations and scientific study has been completed, focus has now moved on to identifying the users of clinical and industrial applications of the new microfluidic dipstick microbiology testing platform. We will now not only use publications to generate academic interest, but also continue to present the technology concept to industrial and clinical audiences to generate user interest and hopefully develop partnerships to commercially and clinically develop products based on our technology. Possible industrial and clinical end-users are now involved with developing downstream applications of the technology.
Sectors Agriculture, Food and Drink,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://www.reading.ac.uk/news-and-events/releases/PR693944.aspx
 
Description Since completing the award in summer 2015 the main focus of impact activities and commercialisation has been on patent filing, scientific publication, and studying the business opportunities for this technology. A second phase focused on partnering and/or raising private investment to develop products from the technology is now ongoing, as we start to understand in detail various commercial applications. We have now completed PCT filling and entered regional phase for a new patent application which will be licensed to startup company Capillary Film Technology Ltd (subject to final license signature). The economic value to the UK life science industry of this research in generating IP with value is therefore clear, although further commercial development is required for full extent of economic impact to be defined and for products to be developed. A second strand of impact relates to eventual clinical use of the technology, and discussions with clinical end users within the UK and overseas are ongoing to identify where the technology could best benefit patients and the public. To a certain extent, this societal benefit will follow from commercial uptake and securing the required investment and time to deliver clinical products. The technology developed may be co-developed for diagnostic use with an overseas diagnostics company, but details of this partnership remain commercially sensitive and confidential. Once project findings are disseminated to industry and clinical users of analytical microbiology technology, the economic and societal impact will become more clear.
First Year Of Impact 2016
Sector Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description CFT secondment 2015
Amount £43,196 (GBP)
Organisation Capillary Film Technology Limited 
Sector Private
Country United Kingdom
Start 02/2015 
End 02/2016
 
Description EPSRC GCRF Institutional award
Amount £4,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 12/2016
 
Description Healthcare Technology Investigator Led
Amount £486,238 (GBP)
Funding ID EP/R022410/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 06/2018 
End 12/2020
 
Description Industry- CFT research project
Amount £43,552 (GBP)
Organisation Capillary Film Technology Limited 
Sector Private
Country United Kingdom
Start 09/2015 
End 02/2016
 
Description Newton Institutional LInks UK-Thailand GCRF British Council
Amount £100,000 (GBP)
Organisation British Council 
Department British Council - Newton Fund
Sector Public
Country United Kingdom
Start 03/2018 
End 02/2019
 
Description Wellcome Trust Innovations Pathfinders
Amount £100,645 (GBP)
Funding ID 204388/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 06/2018
 
Description Dengue Fever Research Unit, Bangkok, Thailand 
Organisation Mahidol University
Country Thailand 
Sector Academic/University 
PI Contribution Findings from this project have significantly improved our microcapillary film devices, especially surrounding surface modifications of fluoropolymer film and imaging methods. This led to a new type of device for immunoassay detection of viral proteins. To use this new technology, we now collaborate with the world-leading Dengue Fever Unit at Siriraj Hospitol in Bangkok, Thailand.
Collaborator Contribution The Thai partners have developed advanced tests for detecting and monitoring disease during dengue virus infection, and we are evaluating together if their tests can be combined with our improved devices to deliver low cost, high performance new diagnostic tests that will help us combat this infection that threatens >5 billion annually, and places a massive burden on health systems accross the globe.
Impact We generated vital early data showing proof of concept. This remains unpublished. We also secured joint Newton funding to take the findings further.
Start Year 2017
 
Description Industry collaboration- Capillary Film Technology Ltd 
Organisation Capillary Film Technology Limited
Country United Kingdom 
Sector Private 
PI Contribution We conduct fundamental research into analytical applications, and physicochemical properties, of micro capillary film. This material is being commercially developed for diagnostic applications by Capillary Film Technology Ltd (CFT). Note: I am a co-founder and Director of CFT.
Collaborator Contribution Capillary Film Technology (CFT) is developing point of care diagnostic products that are based upon fundamental technology development in my research group. CFT is also conducting clinical need research to understand what the most important clinical and commercial applications for micro capillary film are. CFT's employees conduct lab research on micro capillary film immunoassays, which contributes to our understanding of this novel assay technology platform.
Impact Our two latest research papers contain contributions from CFT employees.
Start Year 2012
 
Description Nuno Reis 
Organisation Loughborough University
Department Department of Chemical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution This is an equal collaboration with major contributions in both directions. My research team has pioneered the biological and clinical aspects of our new microfluidic testing technology.
Collaborator Contribution This is an equal collaboration with major contributions in both directions. Our partner has contributed expertise in fluidics, device engineering, physical chemistry.
Impact Our multi-discpilinary collaboration brings life sciences together with physical and engineering science. Outcomes include publications, IP and formation of spinout company (CFT Ltd).
Start Year 2008
 
Title CAPILLARY ASSAY DEVICE WITH INTERNAL HYDOPHYLIC COATING 
Description The present invention provides assay devices having a unitary body with an exterior surface, the unitary body being substantially transparent to visible light and formed from a material having a refractive index in the range 1.26 to 1.40, the refractive index being measured at 20 °C with light of wavelength 589 nm, and wherein the unitary body is formed from a hydrophobic material, and at least two capillary bores extending internally along the unitary body, wherein at least a portion of the surface of each capillary bore includes a hydrophilic layer for retaining an assay reagent, and wherein the hydrophilic layer is also substantially transparent to visible light to allow optical interrogation of the capillary bores through the capillary wall. The present invention also provides assay systems including such assay devices, methods of performing an assay using such assay devices and method of method for manufacturing such assay devices. 
IP Reference WO2016012778 
Protection Patent application published
Year Protection Granted 2016
Licensed Yes
Impact Securing investment in R&D.
 
Title CFTGRAV 
Description This diagnostic product will allow low skilled technicians to perform critical diagnostic tests- such as IgM and IgG serology- easily without specialist laboratory equipment to perform vital screening of large numbers of patients in a developing world healthcare setting. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2015
Development Status Actively seeking support
Impact There are economic impacts of developing this product, through partnership between UK startup CFT Ltd, and an overseas diagnostics partner. Details cannot be disclosed at this point in time due to commercial confidentiality. 
 
Title CFTPOC 
Description We have developed with spinout CFT Ltd a novel microfluidic testing platform that can perform highly sensitive rapid tests at the point of blood sampling. Based on micro capillary film technology developed by our research group, CFT is now bringing a first point-of-care testing product family. Early in 2016 CFT will launch a beta-prototype of this product, with a pre-production prototype expected to be ready for clinical testing late in 2016. Our first product will measure high sensitivity cardiac troponin, for rapid detection of myocardial infarct. Future products are planned with multiple biomarkers measured as a panel, allowing improved diagnostic sensitivity and specificity. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2015
Development Status Under active development/distribution
Impact A major impact is economic. The development process within spinout company CFT Ltd is building commercial value, with CFT's value passing various increments as the technology concept is developed into a full product prototype. Technological capability and performance is being demonstrating increasing the value of background IP, and new IP is being developed and protected. Health tech experts are being employed and developing new skills in this vital sector to our economy. 
URL https://www.capfilmtech.com
 
Company Name Capillary Film Technology Ltd 
Description Capillary Film Technology Ltd (CFT) is a technology and product development company for life sciences and clinical diagnostics. CFT is able to bring a disruptive manufacturing technique for the production of low-cost multiplex microfluidic material. Using exclusive know-how and IP, we are currently developing the next generation of lateral flow technology that allows rapid, fully quantitative multiplex immunoassays for field and bed-side/point-of-care use. 
Year Established 2012 
Impact Main activities to date are technology development, and presentation to industrial and clinical users of diagnostic technology including at international trade fairs and through academic health science network events. In 2014, CFT secured SBRI Healthcare funding, which resulted in employment of 2 full time research scientists. IN 2015, CFT secured a further £1M SBRI Healthcare funding, which resulted in employment of 3 full time research scientists, one 0.6 FTE business development employee, and significant subcontracted research in the NIHR DEC london and product development to EG Technology Ltd. In addition, CFT has secured significant private investment (commercially confidential sum). CFT also licenses IP including IP partially derived from an EPSRC-funded project.
Website http://www.capfilmtech.com/
 
Description AACC trade fair Chicago 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We had over 150 international delegates, mostly senior technical representetives in the diagnostics industry, visit our booth and see practical demonstrations of the new technology. We distributed over 100 copies of a technology summary document and a recent publication from our research group.

We are now in discussion with around 10 possible future partners who we met .
Year(s) Of Engagement Activity 2014
URL http://www.aacc.org/events/2014_annual_meeting/exhibitors/pages/default.aspx
 
Description Biotrinity 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Presented 2x posters at UK innovation showcase at Biotrinity 2015 biotech investment event, as part of Oxford AHSN event. Audience of posters included life science investors, senior health tech and pharmaceutical industry execs, and clinical innovators.
Year(s) Of Engagement Activity 2015
URL http://www.obn.org.uk/events/biotrinity-2015-london/
 
Description DSTL 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I presented capabilities and potential of our microfluidic testing technology to defence technology experts at DSTL at Porton Down, with a view to identifying military and bio defence applications of this technology both in biowarfare agent detection but also in emerging pathogen testing.
Year(s) Of Engagement Activity 2015
 
Description News about minaturisation of lab tests for antibiotic resistance 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Following latest publication, a press release from the Universities of Reading and Loughborough about our research was picked up by regional BBC broadcasters and various web news outlets including ITV news
Year(s) Of Engagement Activity 2016
URL http://www.reading.ac.uk/news-and-events/releases/PR693944.aspx
 
Description OBN Biotuesday presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Talk sparked questions and discussion afterwards from investors, health tech engineers, and industry representatives (SMEs and multinationals).

After my talk several industry experts got in touch by email to discuss possible co-development or partnering.
Year(s) Of Engagement Activity 2015
URL http://www.obn.org.uk/events/obn-biotuesday-diagnostics-precision-oxford-2/