Towards commercialising a hybrid nanosensor for screening dispersed nanoparticles and heavy metal ions in natural waters

Lead Research Organisation: University of Leeds
Department Name: Sch of Chemistry

Abstract

The problem:

The use of engineered nanoparticles (NP) in cosmetics, pharmaceuticals, sensors and many other commercial applications has been growing exponentially over the past decade. Because of their increasing application many NP are discharged to the watercourse both by industrial companies and through domestic use. The technology for monitoring the environmental impact of these materials, particularly in aquatic systems, is not well developed. It is not only sufficient to be able to determine the NP in water but also it is crucial to have some understanding of their toxicity or biological activity. At the same time, a high throughput screener is urgently required to report on the biomembrane activity (ability to bind to/adsorb on/penetrate biological membranes) of different NP and/or products containing NP dispersed in water. A screening system for NP is therefore required which reports routinely on the level of biologically active NP in raw, waste and drinking waters. At the same time the presence of heavy metal ions in water is always a concern due to their implicit toxicity. These heavy metal ions can be derived from industrial and/or domestic use and in spite of the tremendous advances in the analysis of heavy metal ions in water in the past 50 years, there is currently no routine heavy metal ion screener available for natural and potable waters. A combined NP and heavy metal ion screener therefore would have immediate application in any organisation concerned about the quality of water which comes into contact with human activity.

Addressing the problem:

The proposed technology offers a device which has a dual capability as follows: (1) To screen waters for NP which are biomembrane active and hence are putatively toxic and, (2) To detect toxic heavy metal ions (Cu2+, Pb2+, Cd2+ and Zn2+) in water. The system can also be used to test samples of NP or products containing NP dispersed in water for biomembrane activity. The screening for NP in water is rapid, on-line and high throughput and takes 10 minutes to test each sample. Similarly heavy metal ions in the water can be measured together simultaneously and quantitatively. The NP screener works by looking at the interaction of NP with a phospholipid layer coated on a chip based Pt/Hg microelectrode in a flow cell. This is a development of a previous technology which uses the same device to screen waters for biomembrane active compounds. The heavy metal ions are determined using anodic stripping voltammetry which is a well established analytical technique. The development of the chip-based Pt/Hg electrode in flow cell with flow injection techniques enables both techniques to be used in a high throughput configuration. The switchover from one technique to the other can be readily software controlled.

Benefits which end-users will derive by adopting it:

(1) Screening waters for the presence of biomembrane active NP
(2) Screening products containing NP dispersed in water for biomembrane activity
(3) Screening commercially produced NP dispersed in water for biomembrane activity
(4) Detecting, identifying and quantitatively measuring toxic heavy metal ions in water

Planned Impact

The hybrid nanosensor will be of direct benefit to the following:-

(a) Water industry for screening metal/metal oxide nanoparticles (NP) and heavy metal ions in drinking waters and river waters. One of the major applications would be to introduce this technology as a routine test for the presence of these materials in drinking waters at various stages of purification. This will become increasingly important with the use of nanosized materials in water treatment.
(b) Marine agencies to screen NP and heavy metal ions in seawater and assess their putative toxicity. NERC through Plymouth Marine Laboratory funded the science underlying this technology development 1985-2001.
(c) Security and defence to detect presence of toxic NP and heavy metal ions in urban atmospheres and drinking waters. This is a key growth area in the post 9/11 world, although this market has chiefly been driven by US companies.
(d) Pharmaceutical companies for screening biomembrane activity of new bionanomaterials. Pharmaceutical companies normally use cell culture procedures to assay biocompatibility. The proposed current technology has shown proof of principle to measure membrane activity of bionanomaterials e.g peptide bionanomaterials far more rapidly and cheaply than the "conventional" methods.
(e) Biomaterials fabrication to test the biomembrane compatibility of newly fabricated materials especially at the nanometer dimension. NERC have already "start-up" funded the proposer using the older technology to look at the biological activity of engineered nanoparticles (NE/F011830/1).
(f) Consumer products: Unilever and Proctor and Gamble (P & G) would have an interest. Using a sensor like the one proposed would help them not only design better products, but would help them to better understand the chemistry of their activities in-situ and give the public greater confidence in their products.
(g) Health care: The proposed sensor would offer a rapid means of screening preparations intended for applications in health care.

By combining two technologies (NP and heavy metal ions) into one device, the marketing potential of either technology will be greatly enhanced in its appeal to an end user. The project through its various objectives will take the device to the point of (a) licensing to an end user who is prepared to use their resources to commercialise the device, (b) selling the product as a stand-alone item or (c) operating a fees for service consultancy using the technology.

The project will improve the prospect of commercialisation and increase the value of the technology by:-

(a) taking the device from a lab based system to one which can be used in the field with all the technical modifications implemented therein.
(b) carrying out a full performance evaluation of the system to improve its credibility rating.
(c) integrating the very novel NP screening technology with a heavy metal ion detection system founded on well established science (as a continuation of the NERC Pathfinder Funded programme). In this way the risk factor of the technology as perceived by the potential client would be decreased.
(d) focusing the technical and coupled commercial development on licensing the technology to a partner in the Water Industry or a closely associated grouping.
(e) Packaging the system so that it can be sold as a stand-alone product.

Publications

10 25 50

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Mohamadi S (2014) Electrochemical screening of biomembrane-active compounds in water. in Analytica chimica acta

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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

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Vakurov A (2013) ZnO nanoparticle interactions with phospholipid monolayers. in Journal of colloid and interface science

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Zhang S (2014) Electrochemical modelling of QD-phospholipid interactions. in Journal of colloid and interface science

 
Description We consolidated the development of a hybrid sensor for screening heavy metal ions, nanoparticles and additionally organic contaminants in water together with carrying out an extensive performance evaluation. The grant also funded extensive discussions with potential end-users of the technology. These discussions enabled us to secure additional funds through the TSB to develop a sensor for volatile organic compounds in air-cabin air. We were also able to win funds from the MoD-Dstl to develop our sensing technology for antibiotic-target screening. We have subsequently linked up with 10 partners throughout Europe and Israel to secure a H2020 grant (HISENTS) which is building a third generation multimode toxicity sensor for nonmaterial dispersions and also soluble chemical toxicants. Project is already at half way stage and has satisfied all objectives for our client, the EU.
Exploitation Route The findings could be taken forward to run a toxicity testing service for organisations interested in testing environmental matrices and/or contaminants for potential toxicity prior to engaging on the more lengthy in vitro and in vivo tests. Another application of the work is to transfer the technology/product to a company in the toxicity testing business who will add it to their testing strategy.
Sectors Aerospace, Defence and Marine,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology,Security and Diplomacy

 
Description The findings enabled us to link with three companies to win a TSB grant for developing the sensor to detect volatile organic compounds in aircraft cabins. At the same time we have formed a collaboration with Unilever with whom we have carried out a cross validation of our sensing system on a number of compounds.
First Year Of Impact 2013
Sector Aerospace, Defence and Marine,Manufacturing, including Industrial Biotechology
Impact Types Societal,Economic

 
Description Winter School at University of Plymouth. on nanotechnology
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Ran an international winter school for practitioners in nanotechnology for one week in Plymouth January 2012 on the characterisation, behaviour and safety assessment procedures regarding nanomaterial dispersions
 
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
 
Description Knowledge exchange grant
Amount £20,000 (GBP)
Funding ID NE/L01274X/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 01/2014 
End 03/2014
 
Description MoD CDE
Amount £40,000 (GBP)
Organisation Defence Science & Technology Laboratory (DSTL) 
Sector Public
Country United Kingdom
Start 12/2013 
End 05/2014
 
Description Technology Strategy Board
Amount £80,000 (GBP)
Funding ID TS/L007835/1 
Organisation Technology Strategy Board (TSB) 
Sector Public
Country United Kingdom
Start 06/2014 
End 01/2015
 
Description Towards successfully realising the impact of the chip-based phospholipid on mercury (Hg) device as a toxicity sensing system
Amount £96,173 (GBP)
Funding ID NE/M021378/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 06/2015 
End 04/2016
 
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 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
 
Description Unilever 
Organisation Unilever
Department Unilever Research and Development
Country United Kingdom 
Sector Private 
PI Contribution We have been developing a liaison with Unilever over a year. We shall now screen some compounds for Unilever as a cross validation exercise for our technology. This will consolidate our collaboration. We have now been successful and obtained an Innovation grant from NERC started last June to work with Unilever, SEAC assessing how our technology compared with Unilever's in-house procedures.
Collaborator Contribution Unilever have supplied us with twenty calibration compounds. We have had regular communication with Unilever since June last year comparing our data sets. Unilever has given us sight of numerous data sets using different toxicity sensing technologies.
Impact Collaboration is multidisciplinary and joint paper is in preparation
Start Year 2014
 
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 Biosensor 
Description This patent describes a high throughput on line screener for biomembrane activity of organic compounds. 
IP Reference Application number PCT/GB2008/002591 
Protection Patent application published
Year Protection Granted 2007
Licensed Yes
Impact The IP was licensed to Modern WaterPLC in 2010. The license was revoked in 2012. The main impact of this patent is the forming of successful on-going collaboration with Unilever and also the continuing collaborations with MicroLab Devices Ltd, Analox Ltd and PALL (Europe). The patent technology formed the basis of a recent successful Horizon 2020 bid with 10 other partners due to start April 1 this year.
 
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