A number of strategic scientific and technological directions identified by RCUK in the areas of applied clinical and medical sciences can be addressed using emerging Raman spectroscopy, a technique with a large untapped potential. In fact new applications for a wide range of areas are appearing on a regular basis.
The STFC is situated at the forefront of advancing Raman techniques due to its unique technology. A prime example is the ultra sensitive optical Kerr gating technique for suppression of fluorescence from Raman spectra, which is recognized worldwide as being at the leading edge of the technology development.
The Kerr gate acts as an ultra fast light shutter with opening window of 4 ps and in conjunction with impulsive laser excitation it enables the separation of instantaneous Raman signals from longer lived luminescence, the ever present bane for resonance Raman techniques. This award winning technique pioneered at STFC is currently the most powerful in existence for fluorescence rejection and has enabled observation of Raman signals buried in fluorescence backgrounds up to 106 more intense.
The Kerr gate opens new scientific opportunities to construct unique instruments of unparalleled capabilities such as Kerr gated Raman microscope and Kerr gated Raman Atomic Force Microscope (AFM) adding spatial dimension (10 nm or better resolution) to experimental observables. The viability of both of these concepts has been demonstrated recently at CLF in a series of strategic feasibility studies in collaboration with groups of Sheffield University, Oxford University and Strathclyde University.
The application fields for this technology in bio-medicine are particularly difficult to penetrate because of a wide bridge between instrumental methodology and the requirements of medical practitioners. Using the network resources we propose to establish links in the following areas, and many others, to eliminate this barrier.
Development of the gold-standard detection of cancer tissue at early stages
Raman techniques have showed great potential for providing ability to identify epithelial cancers such as those lining organs and skin. These originate from abnormal cells at a depth of several tens of microns below the tissue surface. The feasibility of the conventional Raman spectroscopy for disease detection has already been demonstrated but as a surface probe it may further benefit from Kerr gated Raman concept enabling it to suppress spurious Raman signals such as those originating from surrounding healthy tissue located at different depth as well as interfering fluorescence. This aspect is a subject of investigations performed at STFC by Dr N. Stone, Gloucestershire Hospitals NHS Trust.
Raman depth profiling in human and animal tissue
A major result has recently been produced by a pioneering experiments performed on bone tissue by Professor Allen Goodship, Dr Edward Draper (Royal Veterinary College, Hatfield), Prof M. Morris (University of Michigan) and a STFC team. The Raman Kerr gating technique was demonstrated to be capable of providing Raman depth profile in diffusely scattering media such as human or animal tissue providing thus new instrumental capability beneficial to many biomedical applications including disease recognition.
Non-invasive on-line body fluid (eg blood) analysis.
Another area of benefit is non-invasive blood content monitoring where higher contrast of signal originating from below the skin vesicles would lead to more accurate determination of blood content. Key health indicators that can be monitored include glucose, cholesterol, albumin, proteins, and urea.
One can also expect the technology to address the following areas of bioscience: design of new drugs, counter bio-terrorism, functional imaging of single living cells and cell membranes with spatial and temporal resolution, direct DNA and protein sequencing, photodynamic therapy and radiation damage repair mechanism.
Scientists both within STFC and outside have performed a number of pilot experiments in these areas demonstrating their feasibility but closer links between medical scientists and instrumental scientists must be forged to progress these new methodologies into real applications.
Whilst the facilities in this area have in the last year sought to encourage applications from the biomedical community it has been difficult to activate because of the lack of resources. BioMed Network will provide the necessary climate to turn these discussions into a practical reality. Furthermore, from the interest we stimulated over a short period of time we anticipate that many more applications will emerge. The Raman techniques will have synergy with the use of the SRS IR beamline proposed developments for medical imaging discussed below.
Current network members:
- Pavel Matousek (CLF)
- Mike Towrie (CLF)
- Tony Parker (CLF)
- Dr N Stone (Gloucester Royal Hospital NHS Trust)
- M Morris (University of Michigan)
- W E Smith (Strathclyde University)
- D Graham (Strathclyde University)
- Robin Devonshire (University of Sheffield)
- R Goodacre (UMIST)
