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Research Projects on Imaging & Microscopy
Link to Electron Microscope Suites in Cambridge University
High magnification, high resolution microscopy is vital to the study of cells, proteins and other biological
materials, and non-invasive imaging has become incredibly important in modern medicine. Researchers in the
Cavendish Laboratory are undertaking significant work in improving microscope technology and developing new imaging techniques.
- In the Polymers and Colloids research group, led by Dr Athene Donald, there is research on the use of Environmental
Scanning Electron Microscopy (ESEM) on biological samples.
- ESEM allows high resolution microscopy in the presence of water and without the requirement for
high vacuum, significantly reducing the observation of sample preparation artifacts.
- Athene Donald's research group also work on improving methods to combine ESEM with other imaging tools such as:
- Scanning Transmission Electron Microscopy (STEM)
- Focused Ion Beam (FIB) imaging and etching
- FIB imaging can visualise different contrasts from SEM and can provide significant information about material structure.
- FIB can also be used as a dissection tool in situ for SEM imaging, or can be used in preparation of thin TEM sample foils.
- FIB is not generally suitable for imaging soft biological matter, however the combination of FIB and ESEM could provide an invaluable imaging system which, when linked with image processing software, would be capable of 3D reconstructions of biological specimens (Electron Tomography).
- Dual beam microscope systems are being tested in order to prove their value in Biological and Physical research.
Other Imaging Systems
- Dr Richard Ansorge in the Low Temperature Physics research group is working with researchers in the School of Clinical Medicine on techniques for image processing. He is also
developing a unique new scanner which will combine MRI (Magnetic Resonance Imaging) and PET (Positron Emmision Tomography) imaging.
- Medical imaging using Terahertz radiation, or T-Rays is a promising new imaging tool under development in the Semiconductor Physics research group. T-rays are electromagnetic waves (non-ionizing) between infra-red and microwave wavelengths (100GHz to 10THz) which can penetrate the surface layers of skin without
the damaging effects of X-rays. THz rays are also promising as a new spectrographic method for imaging hydrogen bond networks in proteins or large molecules. The research group led by Dr Edmund Linfield is investigatinhg the terahertz signatures of biological crystals - sugars, nucleosides and other metabolites.
This is an interdisciplinary collaboration between Semiconductor Physics, Astrophysics and Teraview
- Researchers Chris Pickard and Jonathan Yates, in the Theory of Condensed Matter research group are using theoretical studies of molecular structures from first principles - ie atomic scale interactions, to develop the interpretation of data from NMR spectroscopy. Thier software will predict the NMR
signal for a given structure which can be compared to real NMR data.
If you would like to be updated on seminars, events and new projects in this research area please send an email to Duncan Simpson with 'Update on Imaging' in the subject heading.
Links to research projects in:
Modelling Biological Systems
Physical Properties of Biological Materials
Nanotechnology
Current research projects on Imaging & Microscopy in the Cavendish Laboratory
Development of Electron Microscopy Techniques
Environmental Scanning Electron Microscopy
Professor A M Donald, Dr D J Stokes, E H C Bromley, Dr S J Williams, Dr D E Morrison, C D Nguyen, H A Houghton, N Traitler, Dr N Zakowsky - Polymers and Colloids
Sponsors: EPSRC, BBSRC, Unilever, FEI, HEFCE
Environmental Scanning Electron Microscopes are a recent entry into the family of electron microscopes.
They enable new classes of samples to be examined in their natural state, for instance wet samples and
insulators, thus opening up a new range of problems to study including dynamic ones. Systems studied
include cement, textiles, lacquers, detergent hydration, emulsions, aggregation of polymer colloids,
foods, plant systems, biomedical materials, cells and tissues. Methodological developments are also
being carried out to optimise the technique, and to understand the physics involved in image formation.
Scanning Transmission Mode Environmental Scanning Electron Microscopy
Dr BL Thiel, Dr DE Morrison - Polymers and Colloids, Cavendish Laboratory
Sponsor: EPSRC
Bright and dark field transmitted images may be recorded in the Environmental SEM using TEM type
specimens. However, as the electron beam energies used in the SEM are significantly lower than in TEM,
beam-specimen interactions are much stronger, opening the possibility of exploiting subtle contrast
mechanisms. In addition, the environment in the ESEM allows moisture-containing specimens to
remain hydrated, allowing experiments to be carried out on viable biological specimens. The project aims
to explore the contrast mechanisms and possible application areas for the technique.
CryoESEM for Biological, Pharmaceutical and Food Applications
Dr DJ Stokes - Polymers and Colloids, Cavendish Lab.
Sponsor: Royal Society
This project involves the development of cryoESEM: the use of a cryostage to view specimens over a
range of conditions, using mixtures of gases to control the stability of water present in the specimen
whilst enabling quality imaging. This will build on work previously carried out in the group, but will
involve the use of a commercially available cryo system (Alto 2500), loaned by Gatan UK. The ability
to vary relative humidity as well as temperature enables dynamic experiments to be performed. An
example where the thermodynamics and kinetics of these parameters are of key significance is the
freeze-drying process. Observation of this process in situ will give insights into the real-time dynamics of
structure development in, for example, foodstuffs and compounds for the controlled release of drugs.
Conversely, the experiment can be carried out so as to indicate the collapse temperature of such
structures upon hydration. Preliminary investigations are focusing on establishing protocols involving
temperature and gas composition (e.g. water vapour & nitrogen in varying ratios) so that water may be
selectively stabilized or sublimed, enabling controlled in situ etching of specimens. This will serve as an
essential starting point for later dynamic experiments.
3D Electron Microscopy of Soft Condensed Matter
Dr D J Stokes - Polymers and Colloids
Sponsor: FEI
Various approaches are being used for the characterisation of, for example, polymeric, biological and
food specimens in three dimensions. These include stereo-pair height map reconstruction (non-destructive)
as well as focused ion beam etching and cross-sectional milling using the latest Dual Beam ESEM technology.
New Medical Imaging Developments
Improvements in Clinical MRI and PET Imaging
Dr RE Ansorge - Low Temperature Physics Group, Cavendish Laboratory
Dr A Carpenter, University Clinical School
A number of opportunities exist for the development of novel MRI and PET imaging techniques for both
clinical and molecular imaging applications. This Biological Physics in the Cavendish Laboratory
work is a collaborative program between the Cavendish Laboratory and the University Clinical
School. One particular project will involve the development of a hybrid scanner capable of
simultaneous PET and MRI imaging. This major Research Council supported project requires the
development of novel instrumentation and data analysis methods. The group is also interested in
algorithms for improved image reconstruction with high-speed data acquisition, and advanced 3D image
visualisation. High performance parallel computing systems are available for these applications. These
projects are suitable for candidates with a Physics or similar background who have an interest in life
science applications.
The development and applications of terahertz sources
Dr EH Linfield - Semiconductor Physics Group, Cavendish Laboratory
We are developing and exploiting high-power sources of coherent terahertz (1 THz = 1012 Hz) radiation.
Such sources are potentially of considerable importance for imaging (e.g. in the medical, dental,
and electronics industries) and spectroscopy (e.g. for environmental monitoring, or screening of biological
fluids such as blood). Until recently, this significant region of the electromagnetic spectrum has not been
exploited owing to the severely limited number of sources previously available, which were bulky,
expensive, inefficient, frequently incoherent, and not at all suited to the potential applications. Research
topics include: pulsed and continuous (cw) THz generation; mechanisms for visible-to-THz
conversion; THz quantum cascade lasers; the fabrication of photonic-band-gap crystals; interactions
of THz radiation with organic and inorganic materials; spectroscopy of analytes in blood; and medical and
dental imaging. CASE awards with TeraView Limited may be available. (Linfield)
Detector Physics
Dr S Withington - Astrophysics Group, Cavendish Laboratory.
We have a major activity relating to the development of advanced superconducting detectors and their
electromagnetic and optical behaviour. This work covers the millimetre-wave-wave, THz, optical and Xray
regions of the spectrum. Although the work is aimed primarily at the development of instrumentation
for experimental astrophysics, the group is also concerned with the application of this technology in
areas such as medical physics, biochemistry, and industrial process control. A recent major JIF award,
and a major donation from Oxford Instruments Plc, is allowing a new clean room to be built and equipped.
This clean room, which will be completed March 2002, will have state of the art sputtering, reactive ion
etching, and lithography facilities. Particular devices include optical and X-ray superconducting tunnel
junction arrays and transition edge sensors, and THz superconducting tunnel junctions and transition edge
sensors.
Modelling Biological Systems from First Principles
Professor MC Payne, Dr MD Segall, Dr CJ Pickard, Dr L Colombi Ciacchi, J R Yates, S Joyce, I De Gortari, L Heady - Theory of Condensed Matter Cavendish Laboratory
Dr CE MacPhee - Biological Physics, Cavendish Laboratory.
Professor A Venkitaraman, Hutchison/MRC Research Centre
Professor R Harris, Dept. of Chemistry, Durham University
Dr N Bampos Chemical Laboratory
Sponsors: Camitro (UK) Ltd., EPSRC
Calculation of NMR chemical shifts from first principles in biological systems. This enables the
connection between experiment and structural models of biological systems to be made by providing
a unique and accurate assignment of chemical shift spectra to be made for systems containing hundreds
of atoms. A detailed picture of the electronic structure of the system studied also allows the observed
chemical shifts to be rationalised. A study of metalloporphyrin systems which can mimic the
behaviour of biological catalysis is being undertaken in collaboration with Dr N Bampos of the Department
of Chemistry.
Last updated 24 March 2004
Duncan Simpson
Partnership Development Manager
Research Services Division
16 Mill Lane
Cambridge
CB2 1SB
Email Duncan.Simpson@rsd.cam
Tel 01223 765446