This Report is designed to summarise the data presented at the 3rd BioNano-Switch Workshop, held at ENS in Paris on 3rd September 2008 and to provide direction to the Consortium for the final stages of the Project during Year 3. This Project was developed from initial work carried out during the Mol Switch Project (IST-2001-38036), which demonstrated that biological molecular motors could be used to manipulate micron-sized objects including magnetic particles. This led the way to the concept of developing a nanoactuator device that could act as a molecular dynamo and provide a dynamic signalling system, or transducer, with electronic output from biological input. In this Project we propose to use such a nanoactuator within a generic biosensor system. The application of Synthetic Biology, within the Project, manifests itself in two ways:
At the outset of the Project it was imagined that this Synthetic Biology approach would provide a means for generating both useful biomaterial, which could be used in biosensing and provide an engineering / fabrication background for design and construction of a generic biosensor. This was an ambitious Project with the concept of using a single molecule system to report positive biosensing. At the end of Year 1 (as already reported) significant progress had been made on both Module 2 and Module 3 and Proof of Concept for the proposed Module 3 device was already established. Module 1 was dependent upon the outcome of the genetic engineering work, to produce a variety of modified proteins, and has now progressed close to completion with only two outstanding recombinant proteins to produce – biotinylated PrescissionTM Protease and a novel FtsK motor protein construct. This work is now a shared Project between IMIC and UoP. With one year remaining, the bulk of the residual work will focus on production of prototype device based around the two, slightly altered, pre-prototypes developed by INESC-MN. This requires integration of all three modules into a single Lab-on-a-Chip device and this, in turn, is somewhat dependent upon the availability of the biomaterial used in each Module. An important Milestone, completed at the end of Year 2, was a discussion with regard to which magnetic sensor technology to use in the final prototype and a decision was made and agreed by all concerned. Therefore, everything is in place for WP4 – prototype design and production – work on which was originally planned to commence in month 27. It is planned that a Meeting of key Partners will be arranged in early 2009, at which the design and construction timetable for this prototype will be discussed and planned. Coordination of these efforts will be carried out by NPLML; as their metrology input to the Project is a significant aspect of this Workpackage. In parallel, the biomaterial will be made available for use in the prototype device. We envision, therefore, production of a prototype generic biosensor, incorporating a single molecule transducer/nanoactuator, as the output of this Project. The biomaterial produced by the Project could also be made available to a Synthetic Biology "database of parts", if appropriate. Proof of Concept for the use of a variety of highly significant molecular motors within the device, which are also potential targets within the area of drug discovery, suggests a commercial market for the platform technology. This would be alongside the more generic biosensing capabilities of the device. The commercial potential for the device is now being explored by UoP; who have the agreement of all Partners to lead this development on their behalf.
In summary, the BioNano-Switch Project is progressing extremely well, with major progress in all Deliverables. A clear plan for Year 3 is in place and will comprise a Meeting of key Partners to design a prototype device. The final year should provide all material and components for the proposed device – a generic biosensor. Commercial exploitation of this technology is a real possibility and funds for such have been acquired by UoP. Protection of the generated Intellectual Property (IP) is now a key aspect of the background to the Project and progress is being made toward an Agreement that will enable UoP to lead this process.