Microdroplet technology - the next stage

This application is for funding a newly established microdroplets technology after the current Basic Technology grant ends. In this grant research at the two centers, at Cambridge and Imperial, was arranged to be complementary to tackle biological, chemical and physical challenges. At Imperial the focus is to create and define sophisticated optical techniques for droplet interrogation (including fluorescence, IR, Raman, RI), create functional components for droplet manipulation and to integrate these activities with the biological programmes at Cambridge. At Cambridge the focus is on developing biological applications, including DNA amplification, in vitro transcription and translation, enzymatic and cell based assays. There has also been a major effort to integrate microfluidics with mass spectrometry. At the review meeting at the end of year three, we were ahead of schedule in meeting the objectives of the grant, as we have been throughout. The research enabled us to become one of the leading groups in the emerging microdroplets area. Our output to date includes 30 publications and two patents. In this application we propose 6 proof-of-principle studies that will underpin future grant applications, and if successful, will form the foundation for a spin-out company (for which we have carried out patent landscaping and market analysis) and/or significant licensing deals. All the proposed projects are novel and outside the scope of the original BT grant. Several relate to high content screening of cell based systems, essentially screens where we get multi-parameter information out of a system over an extended period of time. Others explore the power of compartmentalisation, and the opportunities this brings to do novel experiments. The proposed studies are in: algal biofuels; analysis of secreted proteins; calcium flux assays; passive, disposable devices for DNA amplification; single cell sequencing; and separation of complex mixtures of proteins. We consider that using microdroplets will enable a transformational change in research in each of these areas, some of which are of potentially huge commercial value. In each case we have identified academic collaborators and potential commercial partners. The Translational Grant provides a funding mechanism to maintain momentum and develop this potential. It enables us to retain key personnel and support the research infrastructure funded on the BT grant. It provides the kind of flexible support we need while negotiating industrial collaborations, and also provides travel funding for us to actively collaborate with groups internationally, and for us to stimulate interaction with interested parties e.g. by encouraging extended visits by researchers keen to learn about the technology.An active programme of dissemination is planned. We have already given 84 talks, met with 11 companies and organized a major symposium to disseminate the research. Two further symposia are planned as well as a very active interaction with industry. The resources requested are primarily for six PDRAs each funded for 50% of their time, limited consumables, and a significant sum for travel and dissemination. The management of this grant will broadly follow that for the BT grant, which has been acknowledged to be very successful.

The beneficiaries from the proposed research will be individuals and organisations interested in a transformational platform for experimental science. Microdroplet technology is enabling and empowering, with applications in biology, chemistry and material science. It enables experiments to be done more quickly, is emerging as an excellent platform for high content screening, and by compartmentalising the components of a system, it opens up the possibility of new experiments. We propose to carry out proof-of-principle studies in 6 potentially high impact areas: (i) Biofuels The major energy companies and numerous start ups are actively looking to exploit algae in biofuels. These include Shell, Mobile, Joule Biotechnologies, Amyris, LS9, Solazyme, Mascoma, Gevo, Verdezyne and Codexis - to name but a few. We will work closely with members of the Algal Biofuel Consortium in the Departments of Plant Sciences and Chemical Engineering in Cambridge to optimise the impact of our research. We already have commercial interest in our future technology. (ii) Analysis of secreted proteins. The ability to quantitatively monitor protein secretion from cells will have applications in many major markets including the biopharmaceuticals, food production and diagnostics. Once we have demonstrated proof-of-principle we will identify appropriate industrial partners. (iii) Calcium flux assays. These assays are used when screening ion channels and G-coupled receptors, two of the biggest class of drug targets. We are aware of interest from the major pharmaceutical companies, biotech companies and companies involved in providing or supporting assay technology. We are well networked into these sectors and will use our connections to engage with partners at the appropriate time. (iv) Passive, disposable devices for DNA amplification. These will have applications to public health, epidemiology and medicine. The Gates Foundation have recently recognised the need to implement such new technologies in developing countries e.g. they could be used to detect acute HIV infection in nonclinical settings for early-stage HIV detection, increasing the chances of therapeutic success and allowing epidemiological data to be gathered. (v) Single cell sequencing. This is a enormous field because of potential applications in areas from cancer diagnostics, and personal medicine, to sequencing the genomes of unculturable organisms. A large number of companies are active in this area, including 454 Roche, Illumina/Solexa, Complete Genomics, Helicos Biosciences, Pacific Biosciences, and Applied Biosciences. Our approach here is to develop and patent our approach and then seek a licensing deal. (vi) Separation of complex mixtures of proteins. This research could ultimately enable single cell proteomics, and so revolutionise the protein separation market. It will facilitate the accurate detection of a single type of protein in a large population of say 10,000 others. This will be of interest to equipment and medical diagnostics companies. We have had initial discussions with Canon Life Sciences (USA) and Samsung (South Korea). We have also engaged Molecular Vision (a London company developing low-cost diagnostic devices for use in the doctor's surgery and home environments) with a view to testing segmented flow microfluidics with their patented detection technologies. In our impact plan we outline our approach to promote the research though active engagement with industry, including having industrial scientists on site to learn the technology. Beyond commercial organizations, the proposed research will be of interest to governmental research organizations e.g. the Sanger Centre (single cell sequencing); the department of energy (algal biofuels), the forensic science laboratory (protein separation, single cell sequencing). It is likely this research could ultimately impact on policy - e.g. through changes in medical practice resulting from new diagnostic tools.