User-friendly and robust paper-based device for in-field diagnostic of infectious diseases

Lead Research Organisation: University of Glasgow
Department Name: School of Engineering

Abstract

Early detection of infectious diseases requires rapid, portable and highly sensitive molecular diagnostic platforms. This project aims at creating a point-of-care (POC) device that simplifies the efforts in monitoring and eliminating infectious diseases in rural low-resource areas. Low-cost, paper-based devices based on microfluidics have been developed but none currently meet the "ASSURED" criteria for effective POC testing provided by World Health Organization (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable to end-users). Even if current tests can detect very low concentrations of infectious organisms, their limited robustness restricts their practical use in the clinics and in communities, due to the degradation of essential reagents (such as enzymes) in challenging field conditions, outside of the laboratory environment. In this project, we will develop new amplification methods, including on-board reagent storage and sample processing and integrate them onto paper substrates to deliver "ASSURED" devices. The new capabilities will be prototyped using additive manufacturing and tested using model samples (artificial DNA/RNA in buffers) to establish proof-of-concept, followed by spiked real samples. Depending on progress and international travel restrictions, the devices will potentially be brought to our partners in Africa for evaluation in the field.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513222/1 01/10/2018 30/09/2023
2385817 Studentship EP/R513222/1 02/12/2019 01/12/2023 Giulia Core
 
Description My PhD research aims at developing an ultra-low-cost, paper-based point-of-care DNA-based device that can be used outside laboratory settings, where challenging environmental conditions and untrained personnel reduce the accuracy of the results. I am creating novel methods and designs to significantly reduce the number of handling steps, thus simplifying the use by untrained personnel. I am also developing strategies to store reagents "on-board", including innovative test reagents to make the device stable at higher temperatures over the long term, into a complete sample-in-answer-out diagnostic system. Such device will transform access to low-cost accurate disease diagnosis.

During my work I have been able to deepen three main areas and make advancements on each of them.
1. Paper-based protocol to extract genomic material from pathogens present in different samples.
Escherichia coli malB gene was the DNA target used as a proof-of-concept pathogen. Initial efforts focused on the optimisation of buffers and DNA-paper contact time. Most recently, I focused on enhancing the sensitivity of the developed extraction method by using different types of paper and functionalising paper with chitosan to increase the ability to bind and release DNA on demand.
2. Easy-on-board-storage technique that also allows for long-term storage of reagents at room temperature.
I have been developing new air-drying methods using a solution of pullulan. Air-drying offers an advantage in terms of costs and preparation times compared to the currently developed freeze-drying techniques used to store and ship reagents. Some reagents have shown higher stability in pullulan, up to 54 days at 35 °C.
3. Enzyme-free amplification method integrated on paper.
Thanks to a competitive research grant I have been awarded in 2020 (Mitacs-UKRI, UK-Canada Globalink Doctoral Exchange Scheme), I had the opportunity to work with world-leading experts on the development of enzyme-free techniques for accurate detection of target genome markers from pathogens at McMaster University (Canada). The exchange allowed me to explore new complementary techniques to achieve the goals set for my PhD project. I was able to identify the strengths and weaknesses in the new enzyme-free techniques I learnt, thus gaining a wider view on strategies that can be used to detect genomic markers and to develop effective point-of-care devices. The placement has enriched my knowledge in addressing the research questions I am passionate about.
Exploitation Route My project will contribute to providing a low-cost, portable, easy to use, sensitive and specific point-of-care device that can be shipped and stored in ambient temperature. Whilst several paper-based NAATs have been developed for POC diagnostics in the past, enabling rapidity and specificity, they still involve complicated manual operations, low temperature storing and external heat sources, limiting the shipping to people's homes, for example.
Moreover, the innovations in terms of material properties and integration at the basis of my broader PhD project, have the potential to bring new ways of thinking about microfluidics devices. My research considers the 'biochips' in a full 4-dimensional view, as the materials are deformed (and folded) at different time points of an assay, to create new geometries that can carry out additional functions compared to their 2-dimensional counterparts. The integration of enzyme-free amplification techniques onto a paper-based POC device will enable a shift in the capabilities of microfluidics devices to answer current healthcare challenges.

In a long-term perspective, the device developed could also become a useful tool for the integration of environmental and healthcare management. The possibility of adjusting the same device to local needs, according to the different prevalence of diseases, would make the field evaluation easier and can be advantageous in terms of diagnostic screening. Moreover, this diagnostic test can be easily combined with a decision support system that guarantees secure data management and connectivity (system recently developed by my group, Nature Electronics, 2021, 4:615) to further facilitate data collection and intervention strategies.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description 'Lunch Talks' in life science to inspire high school students to pursue a career in research (East Sussex College, Lewes, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact I facilitated 'Lunch Talks' in life science to inspire high school students to pursue a career in research, connecting with East Sussex College (Lewes, the UK) (2021), as the Researcher Officer of the UofG PhD society.
Two classes of students attended the event online. The teacher leading this event at the East Sussex College reported increased interest in the research topics showcased.
Year(s) Of Engagement Activity 2021
 
Description 'Presentation HelpDesk' initiative to support peer PhD students rehearsing their presentations, through the UofG PhD society 
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 As the Researcher Officer of the UofG PhD society, I established, coordinated, and ran a monthly 'Presentation HelpDesk' initiative to support peer PhD students rehearsing their presentations while giving constructive feedback. 7 PhD students at the University of Glasgow rehearsed their presentations in the 4 sessions that were held. 7 further PhD students were engaged in giving feedback to the students presenting and providing a final evaluation form.
This activity helped PhD students gain confidence in delivering presentations to their research groups and at conferences.
Year(s) Of Engagement Activity 2021
 
Description Discussion about 'Biomedical Technology and Access to Healthcare' in the 'Innovation and Sustainability' series by Engineers Without Borders Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact The discussion with Engineers Without Borders Glasgow focused on Sustainable Development Goals 3 (Good health and well-being) and 10 (Reduced inequalities). The discussion was built around how to make sure that current innovations in the Biomedical Engineering sector are reducing these inequalities and closing that gap - not the opposite. I explained the diagnostic technology I am working on, how it will ease diagnostics in disadvantaged communities and the impact of my technology. I also briefly discussed the sustainability of current diagnostic methods.
Many questions arose from the audience and connections have been created through social media for future discussions and event creations.
Year(s) Of Engagement Activity 2022
 
Description Gendered Journeys Happy Hour with Angela Saini 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Through the UofG PhD Society, I co-organised a happy hour within the Gendered Journeys project and in collaboration with the FemEng society (University of Glasgow). We were able in bringing in science journalist, Angela Saini, for a short discussion on her book, Inferior. Her book, published in 2016, walks its audience through the gender bias in science research, while simultaneously questioning if any level of scientific credence can be placed in gender stereotypes.
There were 21 attendees connected from all around the world (Scotland, Nigeria and India)
Year(s) Of Engagement Activity 2021
URL https://genderedjourneys.com/2021/06/10/an-evening-with-angela-saini/
 
Description Online video call with school 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 90 primary school kids (from different schools in the UK) attended an online call to ask questions about what a career in Engineering looks like. Many questions were asked during the 1-hour session and a lot of interest sparked for topics such as Biomedical and Aeronautical Engineering.
Year(s) Of Engagement Activity 2022
 
Description Outreach event in a high school - 'Wear IT Glasgow' at the Glasgow Academy 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact In the Wear IT Glasgow event, held at the Glasgow Academy, I had the opportunity to pitch my research in 3 minutes to engage with last-year high school young women and I was part of the judging panel of diagnostic projects that the students came up with.
20/25 High-school kids took part in the two organised online events. The first event aimed at showcasing possible research topics within Engineering. Many questions arose from the students about how to access an engineering career and what a working day of an engineer looks like. The second event was a showcase of possible technologies and devices that the kids invented to support people's health. Their ideas were evaluated and a winner was established.
Year(s) Of Engagement Activity 2021
 
Description School visit (Glasgow) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A few experiments were planned to get primary school's students hands-on on engineering topics and rise their curiosity for engineering careers. Three classes attended the event. Outreach event programme with FemEng society.
Year(s) Of Engagement Activity 2019
 
Description Screening of the movie 'Picture a Scientist' within the University of Glasgow and post-screening panel discussion 
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 As the Researcher Officer of the UofG PhD society, I organised the screening of the movie 'Picture a Scientist' (205 sign-ups) within the University of Glasgow and a post-screening panel discussion to promote discussion about unconscious bias and microaggressions that minorities (with a focus on women) face in STEM careers.
Year(s) Of Engagement Activity 2020
 
Description Workshops within the DIDA project about 'Environmental sustainability of point-of-care devices' and "Privacy - integration with surveillance systems" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The DIDA diagnostic project aimed at linking professionals (both in academia and industry) to discuss the health and economic benefits of using mobile phone-enabled low-cost DNA sensor technology, based upon using paper microfluidics, in remote and under-served communities. The workshop series brought together academic, clinical practice and manufacturing experts from the UK, East Africa and Sub-Saharan Africa.
I personally coordinated one of the workshops about "Environmental sustainability of point-of-care devices" and "Privacy - integration with surveillance systems". Each workshop organised within the DIDA diagnostic project engaged with approx. 50 people each time.
Year(s) Of Engagement Activity 2020
URL https://didadiagnostics.com/index.php