Laser-based engineering of paper for manufacturing fluidic sensors: (Lab-flo)

Lead Research Organisation: University of Southampton
Department Name: Optoelectronics Research Centre (ORC)

Abstract

In 2013 we started work on an 18-month EPSRC feasibility grant entitled 'Laser-printable point-of-care sensors for low-cost medical diagnosis and disease monitoring', which explored laser-based printing of biological materials for applications in the healthcare sector. Our results have attracted the attention of several major international healthcare manufacturers who see the potential of laser-patterning of porous materials like paper for their future product range and who want to work with us to further develop this technology. We are submitting this follow-on proposal to (1) develop a laboratory-standard process for laser-based paper-patterning for fluidic devices, (2) use our technology in trials for a point-of-care diagnostics demonstrator sensor that allows detection of specific diseases such as tuberculosis, as well as dramatically reducing detection limits, (3) extend the technique to incorporate methodologies for fluid delay, multiplexing, and patterning of 3-D devices, and (4) explore applications beyond planar devices in paper, including 'Light-Up Paper' and functionalised fabrics for 'Smart Plasters'.

Planned Impact

With the continuously increasing strains on already over-burdened public health systems of a developed nation such as U.K, and developing countries with the low-resource settings, the role of diagnostics is proving to be crucial. On-site detection and point-of-care (POC) diagnostic testing is a trend that is emerging as one of the popular choices for such non-invasive clinical diagnostics. The reason central to the increasing approval of POC diagnostic testing at a patient's bed-side in a near-patient environment of a hospital emergency ward, or an intensive care or simply in a general practitioners clinic, is because it presents an effective modus-operandi which eliminates unnecessary communication delays between the clinical care team and external testing laboratories.

Economic Impact:
In common with most other countries, the U.K. continues to experience an economic downturn, where austerity cuts on the one hand and ever-increasing demands for increased provision in the healthcare sector on the other make for a very unhappy and unbalanced scenario. One favourable and hence a much preferred route that will enable crucial savings to the NHS (in terms of costs and staff) is the need to enable early-stage testing for disease/condition at the POC (homes, care-homes, nursing home and GP practices) thus reducing the burden on the NHS-hospitals via reduced patient trips to A&E units, emergency call outs and hospital admissions that then improves hospital bed-shortages and unnecessary occupation of these beds - all of this translates into huge financial savings for UK public health system and the economy .
The total POC diagnostics market, which comprises products outside the laboratory, used by healthcare professionals in hospital emergency, critical care, out-patient and GP surgeries, as well as consumers, to test for disease, infection, fertility, drug and alcohol abuse, was worth $13.8 billion in 2011 and is predicted to grow due to increasing interest in the adoption of these technologies to $16.5 billion in 2016. Currently, the United States accounts for almost 50% of the total POC market, however, this is followed by regions, that include Europe and Japan.
The motivation of the proposed research is the underpinning need to enable such potentially life-saving diagnostics, and hence the end-goal is to develop a methodology that will truly make possible the fabrication of such POC diagnostics devices on a paper-platform on a large-scale, which most importantly will make such devices affordable in cost, and thus allow for their wide-scale use at the POC. The UK stands to make considerable gains therefore from the economic benefits that would ensue.

Societal Impact:
POC diagnostics also facilitate prompt exchange of invaluable clinical information between healthcare professionals and their patients from the convenient comforts of their homes, which in some probabilities could be in inaccessible locations. Since a timely exchange of clinical data could potentially be very useful in early detection and prevention of life-threatening infectious diseases (such as TB, which is the focus of this research) diseases or conditions, the wide societal benefits would be not just be in the form of saving lives and but also improving the quality of life for a patient suffering from terminal illness.
For the aging population, incapacitated patients or for those suffering from illnesses such as AIDS or cancer, the possibility to remotely test themselves and send their information to the doctor, could help them from contracting possible life-threating infections from trips to the hospitals. Furthermore, the applicability of low-cost, disposable paper-based testing, the technology developed through this project, could also be extended to include testing for screening of food pathogens and environmental toxins, all of which unarguably have massive societal benefits.
 
Description We have been able to demonstrate new concepts in paper-based diagnostic performance. This work is highly relevant to new point-of-care diagnostic capability, and we are in discussion with several industries in the UK and beyond who want to use this technology for their own products. We are now in discussion with several likely investors to take the impact of this work forward via a spinout.
Exploitation Route The results will be taken forward by the healthcare and diagnostics industry in the near future, and we are actively pursing funding for formation of a spinout via the University of Southampton
Sectors Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://highfielddiagnostics.co.uk/
 
Description We are working with a range of companies in the UK and internationally to prove that our concept for rapid point-of-care paper-based diagnostics will lead to significant benefits in the global healthcare sector. it is still early days, but we are now actively engaged with several investors and likely VCs.
First Year Of Impact 2017
Sector Healthcare
Impact Types Societal,Economic

 
Description EPSRC call
Amount £1,768,136 (GBP)
Funding ID EP/P027644/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 06/2022
 
Description EPSRC standard grant
Amount £720,997 (GBP)
Funding ID EP/S003398/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 12/2018 
End 06/2021
 
Description HIPS 2017
Amount £773,734 (GBP)
Funding ID EP/P025757/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 04/2017 
End 03/2020
 
Description BBI 
Organisation BBI Solutions
Country United Kingdom 
Sector Private 
PI Contribution We worked on samples and products that they provided to try out our methodology for their applications
Collaborator Contribution They engaged in dialogue with our group in the context of commercial needs associated with out printing technique.
Impact from our contacts with BBI, we have since won further funding from EPSRC in area that directly relate to their current product lines. Having access to such internal 'knowledge' for this market sector is invaluable.
Start Year 2015
 
Description DSTL 
Organisation Defence Science & Technology Laboratory (DSTL)
Country United Kingdom 
Sector Public 
PI Contribution We are now working with DSTL to use our technique which has shown enhanced sensitivity for detection of harmful disease pathogens.
Collaborator Contribution They have provided access to their labs and facilities, and we are currently in the middle of negotiating a research contract with them.
Impact A soon-to-be submitted joint proposal for further development of our novel lateral flow technology.
Start Year 2016
 
Description GE Healthcare 
Organisation GE Healthcare Limited
Country United Kingdom 
Sector Private 
PI Contribution Collaborative discussions and soon agreements to sponsor the work and results that are coming out of this work. We intend to work with GE healthcare to benefit from their extensice experience in manufacturing the membranes we use in our laser-based patterning process.
Collaborator Contribution Time, visits, and soon entering into formal agreements and a partnership.
Impact No outputs yet, but hopefully by the end of the project
Start Year 2016
 
Description Myron 
Organisation University of Southampton
Department Faculty of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We have analysed samples that he has collected from Brazil for diagnosis of Leischmania disease
Collaborator Contribution Extensive interaction and collaboration in providing human samples for us to trial our lab-flo technique.
Impact A joint paper is about to be submitted on the results of this work and collaboration
Start Year 2016
 
Title Fluid flow device with flow control and method for making the same 
Description A method of making a fluid flow device comprises: providing a substrate of porous material (2) impregnated with a light-sensitive substance (5) in a first state and which is configured to change from the first state to a second state when exposed to light (3), the second state being a solid state that is resistant to a solvent and the first being removable with the solvent; the substrate having a fluid flow channel (7) defined therein, the channel having a depth; exposing a beam of light (3) onto an area of the substrate surface within the fluid flow channel to deliver energy to a volume of the substrate below the area to change the light-sensitive substance to the second state; during exposure, creating a partial barrier to flow of fluid along the channel by controlling the amount of energy delivered to the volume below at least part of the area to change the light-sensitive substance to the second state in a volume of the substrate within the fluid flow channel that has a depth less than the depth of the fluid flow channel; and developing the substrate in the solvent to leave the light-sensitive substance which is in the solid state and remove the light-sensitive substance which is in the other state. The device may be a medical diagnostic device, and the substrate may be a paper substrate or may be a nitrocellulose substrate 
IP Reference WO2015173543 
Protection Patent application published
Year Protection Granted 2015
Licensed No
Impact We will be using this patent as part of the basket of IP that will back up our imminent spin-out in healthcare diagnostics
 
Title Manufacture of fluid flow device involves providing stack comprising a set of layers made of porous material and impregnated with radiation-sensitive substance, and applying radiation to change state of radiation-sensitive substance 
Description A fluid flow device is manufactured by providing a stack comprising a set of layers, where greater than or equal to 1 of the layers is made of porous material and a part of greater than or equal to 1 layer is impregnated with radiation-sensitive substance; and applying radiation on a part of the stack to change the radiation-sensitive substance from a 1st state to a 2nd state through a part of the thickness of the stack. 
IP Reference WO2017207958 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact We are intending to form a spinout based on this technology and this patent, which is first of a series of three filed
 
Company Name Highfield Diagnostics ltd 
Description The company (currently registered but not yet trading) will eventually develop the healthcare impact from this EPSRC award. 
Year Established 2017 
Impact non so far...it is only just formed and not yet trading
Website https://futureworlds.com/discover-highfield-diagnostics/
 
Description CES tradeshow, Las Vegas, 2019 
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 We presented at the CES tradeshow in Las Vegas, where we showcased the results and capabilities of our diagnostic platform. many interested parties, including a follow up US company who will be visiting us in March 2019.
Year(s) Of Engagement Activity 2019
URL http://highfielddiagnostics.co.uk/
 
Description Medica Tradeshow, Germany 
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 We promoted the outputs from the research at an international tradeshow for Med Tech in Dusseldorf, Germany, where we showcased the results and new capabilities of our research, with the intention of commercialisation.
Year(s) Of Engagement Activity 2018
URL http://highfielddiagnostics.co.uk/
 
Description Medlab tradeshow, Dubai, 2019 
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 Talking directly to a range of sponsors and commercial enterprises, advertising the capabilities of our research outputs.
Year(s) Of Engagement Activity 2019
URL http://highfielddiagnostics.co.uk/