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

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.

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.