Multi-Technique Bio-Analytical Investigation at the Single / Sub-Cellular Level Using a New Lab-On-A-Chip Technology Platform

Advances in the 'silicon chip' industry during the 20th century led to the development of new microchip processing technologies that have allowed the continued miniaturisation of electronic and mechanical devices. These advances were adopted by and contributed to 'on-chip' tools to enable the massive boost in knowledge and invention within the Biotechnology area. A Biochip is a polymer, glass or silicon chip with integrated devices and features that can be used to better understand biochemical processes that occur in human beings. This new knowledge and information can be then used to develop new or better treatments for diseases.
More recently there has been a research drive to integrate 'on-chip' all the necessary sensors, micro-fluidics and analysis tools required for specific biological experiments, in this case the chip can be considered as a self contained laboratory. This technology is called Lab-On-A-Chip (LOAC) and has tremendous scope to achieve further advances in knowledge across differing scientific disciplines such as health, technology and surface science. The biotechnology industry has made highly significant contributions to health and the global economy with the invention of the DNA microarray for example.
Research groups working in the LOAC area are focusing significant research effort into various technologies that allow biological investigation at the single cell or sub-cellular level. These chips require the ability to sort cells by type, separate them and deliver them in a controlled manner to an experimental micro-site for experimentation. New tools are now becoming commercially available that can analyse the cells at the micro-site simultaneously combining 'top down' AFM force measurement and imaging with 'bottom up' advanced optical investigation. Where combined AFM and optical analytical techniques have been used the LOAC technologies used have been required to be glass based due to the required transparent characteristic. This has prevented the use of silicon chip based LOAC technology that would allow the development of new sensor functions and for example the dielectrophoretic control of cells to be performed 'on-chip' reducing size and cost.
This research program aims to design, fabricate and test a novel silicon Lab-On-A-Chip (LOAC) structure with optical transparent characteristics that allow multi-technique singular or sub-cell investigation and analysis using AFM and epi-fluorescence microscopy. The use of a Complementary Metal Oxide Semiconductor (CMOS) compatible process to fabricate the new LOAC structure enables scope for future 'on chip' integration of analytical techniques combined with the processing power of integrated silicon chip technology. This research will provide a novel technology platform that can be developed with future innovations leading to new tools and thereby better understanding of the immunological response that underpins many disease states including allergy, diabetes and cancer.

A key aim of this project is to create a new technology platform that will be compatible with the multi-billion dollar semiconductor fabrication industry. The UK is still a global powerhouse in the industry: for example 40% of the European IC Design Community is located in the UK. The UKs National Micro-electronics Institute currently has more than 200 UK member organisations operating across the semiconductor supply chain. Whilst a UK fabrication facility such as Plessey Ltd may manufacture the silicon wafers, the whole industry (materials, packaging, test, software tools and design houses) will benefit if this research project can create new technology that gains commercial favour, becomes available and hence applications come on-line.

The UK government is turning to its University's to provide new innovations and technologies to ensure long term economic stability and growth in a time of great uncertainty. As a former industrial technologist Dr Holland has been working at the boundaries between academia and industry for some time and helped create opportunities for collaborative research. This is reflected in Dr Holland's position on the steering group of the National Microelectronics Institute's "Electronics enabling the Low Carbon Economy" network where he hosted the first conference at Swansea University in September 2009 http://www.nmi.org.uk/events/event-details/27. Dr Holland has now been invited (with other academics and industrialists) by the Department for Business Innovation and Skills (BIS) to attend a two day workshop on the 8th and 9th of December to that will lead to a BIS / NMI white paper "UK National Strategy for Power Electronics" due in 2011. It is hoped this will highlight the benefits of academia and industry working together for the good of the economy. In a similar manner if this project is funded Dr Holland will seek to promote the opportunities that a vibrant bio-technology industry would create through his NMI links and in so doing generate further interest in this new and exciting research area across the public sector.

This project will provide an ideal training environment for the research assistant. The successful candidate will learn modern CMOS and MEMS fabrication techniques and use advanced semiconductor processing equipment. In addition, the biological application of the research will expose the RA to a variety of cell preparation and analysis techniques and advanced surface science analytical techniques. Working in such a multidisciplinary environment will encourage the RA to think outside of the normal academic boundaries and learn a set of skills that are very rarely combined but increasingly in demand. This will provide many opportunities for the RA to build an exciting career in either academia or industry. The PI, CoI and other interested academics are planning to build a research team around the subjects discussed in this project and this will undoubtedly result in more highly trained postgraduates and post doctoral RA's working in the CNH and further afield.

As well as potential future job creation this research will generate a novel technology platform that can be developed with future innovations. This will lead to new tools that will underpin better understanding of many disease states including allergy, diabetes and cancer. Therefore this research has the potential to be an enabler of new discoveries and treatments for disease that can have a major impact in benefit to health and therefore quality of life.