Towards successfully realising the impact of the chip-based phospholipid on mercury (Hg) device as a toxicity sensing system

Lead Research Organisation: University of Leeds
Department Name: Centre for Molecular Nanoscience

Abstract

Keywords: membrane-based sensor; membrane permeability and damage; cross-validation/demonstration; technical development; staff exchange; project workshop

This project can be divided into the following four categories of activity with the ultimate aim of transferring an interesting and unique technology to appropriate end users;SEAC, Unilever and ALcontrol Ltd and co-workers; IBMT, Fraunhofer:-

(i) Cross-validation/demonstration. The University of Leeds has developed a unique and elegant biosensor which is sensitive to compounds and particles which damage and/or are permeable in biological membranes a property defined as biomembrane activity. The aim of this task therefore is to evaluate exactly how the Leeds biosensor assay compares with those currently employed by the end users in achieving the same or similar functions. This activity will provide a clear definition of the respective advantages and disadvantages of both the Leeds and the end users' techniques. This is necessary since although the Leeds biosensor is at prototype stage, it is essential that its performance is compared with other systems in their detection of the biomembrane activity of a common group of compounds. Particular attention will be paid to the similarity and differences in the parameters being measured by each technique. The outcome of this activity is, (a) to enable end users to determine whether it is advantageous to add this technology to their measuring systems and, (b) to enable Leeds to adapt their technology to specified applications. The impact is an increasing confidence in and acceptance by the user community of the capabilities of the Leeds device.

2. Technical development. The technical development will take the Leeds biosensor from the prototype stage to a routine sensing device which can be operated by skilled technicians. This improvement will include streamlining the data analysis and extending the device from one module to three or more modules which will will enable it be used in a high-throughput automated configuration. The outcome of this activity therefore is to transform the Leeds biosensor system from a lab prototype into one which can be used by skilled technicians in the end user laboratories in a form which is specified by them. The impact is an increasingly robust biosensing device where a perceived risk in its application has been decreased allowing a more ready take up by end users.

3. Exchanges and placements. This objective will allow (a) end user scientists to operate and become completely familiar with, the Leeds biosensor and (b) scientists from Leeds to fully evaluate the end-users' methods and requirements in order to assess exactly how the end user technology fits in with the Leeds biosensor technology. The outcome of this activity is to transfer the Leeds technology to end users as a complimentary system to their own. Currently the Leeds biosensor has not been adopted by an end user. This objective will enable the Leeds biosensor to have a direct user application which not only expands the user's facility but also validates and consolidates the Leeds biosensor's applicability. The impact is a transfer of the technology to the end user.

4. Facilitated dissemination. This objective will enable the Leeds scientists to communicate the project progress to the end users and for the end users to comment on the deliverables. An end of project workshop will be held where the project's final report will be presented. The open nature of the workshop with outside participants will ensure other potential end users can assess Nelson's technology with increasing confidence and judge whether it is suitable for their needs so expanding its remit. The outcome and impact of this activity is to facilitate further knowledge transfer of the Leeds technology and its take up by other commercial users in additional to SEAC and ALcontrol.

Planned Impact

The benefits and outcomes to stakeholders will be discussed dealing with each stakeholder in turn.

(1) SEAC, Unilever: SEAC, Unilever have been investigating techniques for predicting the bioavailabilty and biomembrane permeability of their products for some time. The aim of their work is to gain some estimate of the toxicology of their products especially with respect to their impact on the environment. SEAC have been using two techniques. The first is in silico and involves estimating the lipohilicity of the product compound from its molecular structure using log P or octanol-water partition coefficient as an indicator for this. The second entails a sophisticated chromatographic technique investigating retention times of the product compound on a column where the packing is coated with phospholipid membranes, the so-called immobilised artificial membrane technique (IAM). The Leeds device has also been developed to index the permeability in biomembranes of, and damage to biomembranes from, compounds using alternative techniques of electrochemical and supported membrane technology. SEAC is extremely interested in the Leeds biosensor to see how its measurements compare in performance with their own techniques. If the Leeds biosensor measures the same or similar parameters of biomembrane activity as the SEAC technology then SEAC could adopt it in their repertoire of membrane permeability measuring methods. The Leeds technology would be very suitable for take up by the company since it is cheap to install and maintain and is high throughput in operation. This project represents a perfect opportunity to take the Leeds technology from prototype stage and transfer it to SEAC as a working system.

(2) ALcontrol: Alcontrol have 30 years experience as an evironmental agency. They have especial interest in setting environmental standards for pollutants and have a long involvement in the ecotoxicology of contaminants. ALcontrol have also been interested in the Leeds biosensor for some time. ALcontrol have been a partner on Prof Nelson's projects previously namely the Royal Society Brian Mercer project and a recent NERC Follow-On project. Currently ALcontrol focus on problems with water, food and oil and gas. They are concerned with the presence of mycotoxins in food and water. ALcontrol use an ELISA assay to detect mycotoxins. ALcontrol would benefit greatly from having a complimentary technology available to detect mycotoxins in food and water. This Innovative Project is an ideal opportunity for Nelson to bring his technology directly in line with ALcontrol's needs for screening mycotoxins. This will enable ALcontrol to assess exactly how the measurement parameters of the Leeds system align with their own ELISA testing on an interesting and hazardous group of compounds. If there is sufficient compatibility and synergy between the two technologies, ALcontrol will consider adopting the Leeds biosensor into their armoury of tests.

(3) Other stakeholders. Additional stakeholders will be invited to the project workshop held at the end of the project. The results of the project will be presented and in discussed in particular relating to the performance of the Leeds biosensor and how it compares with existing state-of-art systems. These results which show how the technology has been aligned with technologies used by high profile companies will inspire interest and confidence in the Leeds technology in the outside stakeholders. It is envisaged that following a successful workshop, new links with companies will be made togther with additional opportunities for technology transfer. Evidence based take up of the technology by SEAC, Unilever and ALcontrol is the most convincing way to transfer the technology to other users which because of the unique advantages of the technology can only benefit their companies/organisations in the long term.

Publications

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Rashid A (2017) Substituents modulate biphenyl penetration into lipid membranes. in Biochimica et biophysica acta. Biomembranes

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Sanver D (2016) Experimental Modeling of Flavonoid-Biomembrane Interactions. in Langmuir : the ACS journal of surfaces and colloids

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Vakurov A (2016) Significance of particle size and charge capacity in TiO2 nanoparticle-lipid interactions. in Journal of colloid and interface science

 
Description The Leeds newly developed toxicity sensing technology has been compared with state of art non-animal toxicity prediction methods employed by Unilever, SEAC. Most importantly the advantages and disadvantages of the Leeds technology are set against those of Unilever. It has been shown to date that the Leeds technology measures additional parameters associated with animal toxicity compared to established procedures. The work is on-going. Basically the Leeds technology measures biomembrane damage. The Unilever toxicity sensing technology measures biomembrane permeability to non-narcotic and narcotic compounds. The Leeds technology provides a rapid means of assessing the mechanism of compound interaction with biomembranes providing similar insight to the Unilever computer models. A paper on this work describing key findings has been submitted this January.
Exploitation Route The findings will be especially useful to people who wish to use the Leeds toxicity sensing technology to compliment other existing procedures. A paper is being prepared for publication in collaboration with Unilevr.
Sectors Agriculture, Food and Drink,Chemicals,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology,Security and Diplomacy

 
Description The findings are being used by Unilever to assess whether the Leeds technology can be used as a compliment to their in-house toxicity testing methods. ALcontrol Ltd are also a partner on this grant programme and will assess the findings at the end of the programme. This programme has contributed to the successful experimental initiation of the Horizon 2020 funded programme HISENTS which began April 2016. The HISENTS project has been successfully reviewed and achieved all its objectives at the half-way stage.
First Year Of Impact 2016
Sector Agriculture, Food and Drink,Chemicals,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Commercialisation of membrane-based screen on chip for natural waters and seawater
Amount £13,316 (GBP)
Funding ID NE/S008977/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 08/2018 
End 10/2018
 
Description Horizon 2020
Amount € 6,400,000 (EUR)
Funding ID 685817 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 04/2016 
End 03/2019
 
Title Development of an an electrochemical screen for biomembrane active compounds and particles. 
Description The screening platform consists of a membrane sensor element on mercury (Hg) microelectrode. The electrode is fabricated on a silicon wafer where the Hg is tightly bound to platinum (Pt). Biomembrane active compounds/particles interact with the membrane sensor element modifying its organisation in a specific and selective way. The technology now has a full performance evaluation and rivals any existing techniques for assaying biomembrane activity. The technology is also micronised and ruggedised to operate in a high throughput configuration. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Provided To Others? No  
Impact The most notable impact of this research has been the development of a collaboration with Unilever over the past year. The technology won Special Commendation by Lush Prize (2013) committee for services to the replacement of animals in testing. The research tool formed the heart and basis of the development of the EU funded HISENTS project. The research tool has formed the basis of the Option Agreement between Blueprint Product Design Ltd and University of Leeds and to the writing of three grant applications one of which to InnovateUK has been approved. 
 
Description ALcontrol Ltd 
Organisation ALcontrol Laboratories
Country United Kingdom 
Sector Private 
PI Contribution We have been working with Unilever on a NERC funded Innovation Grant. We have screened 20 compounds for Unilever and are assessing our technolgy in the context of Unilever's methods and in the toxicity sensing area in general.
Collaborator Contribution ALcontrol's contribution is mainly in the form of commenting on the final results.
Impact None as yet.
Start Year 2015
 
Description Analox Ltd 
Organisation Analox Sensor Technology
Country United Kingdom 
Sector Private 
PI Contribution We entered into a TSB funded opportunity with Analox Ltd, MicroLab Devices and PALL to develop a sensor for tricresyl phosphate in aircraft cabins. Our contribution was to develop the sensing technology.
Collaborator Contribution MicroLab Devices administered the programme and carried out some engineering work on the sensing technology.
Impact No concrete outcomes at present. Collaboration was multidisciplinary.
Start Year 2014
 
Description Blueprint Design Ltd (BPDES) 
Organisation BlueFrog Design
Country United Kingdom 
Sector Private 
PI Contribution We have had a series of meetings with the partner describing our research and applications. We took on the partner as the SME beneficiary to our EU H2020 funded HISENTS program. BPDES will lead the dissemination and exploitation work package. We have written three further grant applications with them: EU H2020 SMEinstrument application RAPPONSE submitted last January and two InnovateUK applications one of which has been approved for funding 58695 GBP coming to Leeds as subcontract.
Collaborator Contribution The partner has developed a market survey report for our technology. BPDES contributed to the writing of the three proposals above. BPDES have drawn up an Option Agreement for the IP at present owned by University of Leeds and signed by both partners.
Impact The collaboration is ongoing. Partner has joined EU HISENTS consortium where we are co-ordinators. This program began 1 April 2017. Blueprint and myself have applied for two Innovate_UK awards using the technology. One of these awards has been successful and we are awaiting formalisation. We have also applied for an H2020 SMEinstrument award. In the evaluation we passed all thresholds but did not achieve sufficient ranking to be awarded the grant. We have three more submissions this year to SMEinstrument call.
Start Year 2014
 
Description Formation of HISENTS EU consortium 
Organisation Blueprint Design Company
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation Catalan Institute of Nanoscience and Nanotechnology
Country Spain 
Sector Academic/University 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation Fraunhofer Society
Department The Fraunhofer Institute for Biomedical Engineering (IBMT)
Country Germany 
Sector Private 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation Norwegian Institute for Air Research
Country Norway 
Sector Charity/Non Profit 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation Saarland University
Country Germany 
Sector Academic/University 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation Slovak University of Technology in Bratislava
Country Slovakia 
Sector Academic/University 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation Tel Aviv University
Country Israel 
Sector Academic/University 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation University College Cork
Department Tyndall National Institute
Country Ireland 
Sector Academic/University 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation University Hospital Bratislava
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formation of HISENTS EU consortium 
Organisation Vienna University of Technology
Country Austria 
Sector Academic/University 
PI Contribution I contacted ten partners in 2015 and together we put together a grant application to H2020 which was successful. The grant programme began April 2016.
Collaborator Contribution Each partner contributed to the application in the form of describing the work that they would do in the proposed project. At present each partner is contributing to the work of the project.
Impact The outputs from this HISENTS project in the form of deliverables and mid-term report have now been provisionally accepted by the EU commission
Start Year 2015
 
Description Formed a consortium with two SMEs and one large company 
Organisation Analox Sensor Technology
Country United Kingdom 
Sector Private 
PI Contribution Prepared an application for the TSB on a direct development of the sensor to screen aircraft cabin air for toxic molecules. Stage 2 of the application to be submitted next week (10/04/2013). On second submission this grant application was successful (December 2014).
Collaborator Contribution Our technology forms the heart of the collaboration. MicroLab Devices are developing a microfluidic system to interface with our technology. Analox are developing the hybrid system to function in the field; ie within aircraft cabins. PALL are acting as end-user by selling the system to aircraft companies.
Impact Only outcome so far is winning a TSB award. The collaboration is multidisciplinary. Leeds are electrochemists. MicroLab devices are microfluidic engineers. Analox package up analytical /sensing technology and PALL manufacture filters and associated items to be used in aircraft.
Start Year 2013
 
Description Formed a consortium with two SMEs and one large company 
Organisation MicroLab devices Ltd
Country United Kingdom 
Sector Private 
PI Contribution Prepared an application for the TSB on a direct development of the sensor to screen aircraft cabin air for toxic molecules. Stage 2 of the application to be submitted next week (10/04/2013). On second submission this grant application was successful (December 2014).
Collaborator Contribution Our technology forms the heart of the collaboration. MicroLab Devices are developing a microfluidic system to interface with our technology. Analox are developing the hybrid system to function in the field; ie within aircraft cabins. PALL are acting as end-user by selling the system to aircraft companies.
Impact Only outcome so far is winning a TSB award. The collaboration is multidisciplinary. Leeds are electrochemists. MicroLab devices are microfluidic engineers. Analox package up analytical /sensing technology and PALL manufacture filters and associated items to be used in aircraft.
Start Year 2013
 
Description Formed a consortium with two SMEs and one large company 
Organisation PALL Europe
Country United Kingdom 
Sector Private 
PI Contribution Prepared an application for the TSB on a direct development of the sensor to screen aircraft cabin air for toxic molecules. Stage 2 of the application to be submitted next week (10/04/2013). On second submission this grant application was successful (December 2014).
Collaborator Contribution Our technology forms the heart of the collaboration. MicroLab Devices are developing a microfluidic system to interface with our technology. Analox are developing the hybrid system to function in the field; ie within aircraft cabins. PALL are acting as end-user by selling the system to aircraft companies.
Impact Only outcome so far is winning a TSB award. The collaboration is multidisciplinary. Leeds are electrochemists. MicroLab devices are microfluidic engineers. Analox package up analytical /sensing technology and PALL manufacture filters and associated items to be used in aircraft.
Start Year 2013
 
Description MicroLab Devices Ltd 
Organisation MicroLab devices Ltd
Country United Kingdom 
Sector Private 
PI Contribution MicroLab Devices, Analox Ltd and PALL joined with Leeds on a TSB programme to develop a sensor to determine tricresyl phosphate in aircraft cabin air. Leeds carried out the bulk of the work developing the sensing technology.
Collaborator Contribution MicroLab Devices administered the programme. MicroLab Devices made some contribution to the engineering systems of the sensing platform.
Impact None as yet.
Start Year 2014
 
Description PALL 
Organisation PALL Europe
Country United Kingdom 
Sector Private 
PI Contribution Leeds, Analox Ltd, MicroLab Devices carried out TSB funded research into a sensor technology to determine tricresyl phosphate in aircraft cabin air. Leeds carried out most of work developing sensor technology.
Collaborator Contribution MicroLab Devices administered the programme and carried out a small amount of engineering work. PALL did some market research on the need for the sensor technology.
Impact None as yet.
Start Year 2014
 
Description Platform Kinetics Ltd 
Organisation Platform Kinetics
Country United Kingdom 
Sector Private 
PI Contribution We applied jointly with Platform Kinetics Ltd (PKL) for an MoD Dstl grant and were successful. This project involved the development of a screener for antibiotic-target binding using membrane electrochemical methods. The idea was also to embed this screener within a microfluidic system.
Collaborator Contribution PKL developed a microfluidic system and automatic interrogation techniques to interface withe electrochemical screen.
Impact The main output of this collaboration is that proof of concept results have shown that the electrochemical screen for broad-based antibiotic binding with targets is entirely feasible. This has led to a collaboration with the funders the Dstl on an application for funding for a PhD studentship. Disciplines involved are: electrochemistry, microfluidics, synthetic organic chemistry and bacteriology.
Start Year 2013
 
Title BIOSENSOR 
Description The discovery relates to the deposition of thin mercury films on to fabricated platinum microelectrodes and the deposition of phospholipid monolayers on the mercury .and their use as toxicity sensors. 
IP Reference European Patent Application No. 08776089.8 
Protection Patent granted
Year Protection Granted 2016
Licensed No
Impact An Option Agreement relating to the transfer of the IP to a SME was drawn up in 2016 leading to the future licensing of the IP to the SME subject to them raising sufficient finance.
 
Title Experimental platform for screening pharmaceuticals and toxins for toxicity 
Description Innovation is an electrochemical technology of sensor element on chip-based electrode in flow system which can screen toxins and pharmaceuticals for toxicity. Technology is high throughput and on-line. A NERC Innovation Grant funded this work which finished in April 2016 and was carried out in collaboration with Unilever, SEAC. This platform led to the idea of a mulitmodule platform for screening nanomaterials, toxins and pharmaceuticals for toxicity and formed the basis of a Horizon 2020 application which was successful and began April 2016. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2014
Development Status Actively seeking support
Impact No medical impacts realised yet. 
 
Description Public lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact I give yearly lectures at Imperial College about the development of my technology. This stimulates students who wish to innovate themselves. I give talks at national KT meetings on the history of my technology and engaging with the industrial sector.
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017
 
Description Regular talks to public on impact of science on society and impact of society on scientific work 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The talks have stimulated debate and discussion and instigated invitations to give further talks.

The talks gave rise to me developing novel university courses and to be invited to other universities to give talks on this subject ie scientific impact
Year(s) Of Engagement Activity 2009,2010,2011,2012,2013
 
Description Stakeholder workshop 
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 Planned, executed and Chaired a Stakeholder conference where details of the EU HISENTS platform was disseminated and feedback from the stakeholders was obtained.
Year(s) Of Engagement Activity 2018
URL https://hisents.org/2018/02/26/hisents-stakeholder-workshop/