Dr Elisabetta Canetta
Modulated Raman spectroscopy for enhanced cancer screening
A variety of diagnostic tests are used to detect cancer. However, they are costly and time consuming. Raman spectroscopy is a non-invasive technique with a considerable potential as a diagnostic tool. However, its use is dramatically limited by the presence of strong fluorescence signals. A way to overcome this problem is to use modulated Raman spectroscopy (MRS) (http://photon.st-andrews.ac.uk/manipulation/) to filter out the Raman spectra from the fluorescence background.
Together with Prof K. Dholakia, Dr M. Mazilu, Profs A. Riches and S. Herrington from the University of St Andrews, I have successfully applied MRS to the identification of fixed urothelial (SV-HUC-1) and bladder tumour (MGH) cells exposed to urine (Fig. 1).
We have also applied, for the first time, MRS to the identification of fixed normal and tumour bladder cells in voided urine samples collected from cancer patients. Principal Component Analysis (PCA) showed that bladder cancer cells could be distinguished from normal bladder cells (Fig. 2) with 98% specificity and 94% sensitivity.
 Fig 1 |  Fig 2 |
Ultrastructural and nanomechanical properties of living cells
Atomic Force Microscopy (AFM) is one of the most powerful nanotools in biology that allows studying the structure, function, properties, and interaction of biological samples in their native state under physiological buffer conditions. In collaboration with Prof A.K. Adya of the University of Abertay Dundee, I have investigated the ultrastructural and nanomechanical properties of a variety of biological samples, such as proteins, and yeast and mammalian cells. Recently, we investigated the morphological differences between normal (Fig. 3 left) and cancer (Fig. 3 right) bladder cells. Tumour cells were found to be smaller in dimensions and thicker than the normal cells. Their anomechanical properties showed cancer cells to be more compliant and their cell walls softer than the normal cells.
Prof Adya and I along with our collaborators are currently developing new protocols for separating undifferentiated and differentiated embryonic stem cells based on their morphological (Fig. 4), nanomechanical (AFM), and biochemical (Raman) properties, without resort to the use of antibodies as specific lineage markers. We found undifferentiated cells to be rounder in shape and having a stiffer cell wall than differentiated stem cells.
Future research plans
- Design and development of new ultrasensitive instruments for nanomechanics and nanomanipulation experiments;
- Investigation of cell nanostructure, nanomechanics, and bio-signature for cell screening and sorting;
- Study of cell nanoadhesion to a substrate for cell-biomaterial interactions.
Other research interests
- Study of the physical, mechanical, and structural properties of adhesive nanocomposite polymeric films;
- Investigation of the ultrastructural and nanomechanical features of colloidal nanoparticles;
- Interaction of nanoparticles with biological systems;
- Study of the structures of polymers, biomolecules, and viruses by using neutron/X-ray scattering techniques (e.g., Liquid and Powder Neutron Diffraction, Small Angle Neutron Scattering (SANS), and Neutron Reflectivity (NR)) complementarily to nano- and micro-scopic techniques, and biological assays.
Collaborators
Prof Ashok K Adya
(Biotechnology and Forensic Science Division, University of Abertay Dundee)
Prof Joseph L Keddie
(Department of Physics, University of Surrey)
Prof Costantino Creton
(ESPCI ParisTech, France)
Prof José M. Asua
(POLYMAT, Spain)
Prof Kishan Dholakia
(School of Physics and Astronomy, University of St Andrews)
Prof Andrew Riches
(School of Medicine, University of St Andrews)
Prof Simon Herrington
(School of Medicine, University of St Andrews)
Prof Paola Borri
(School of Biosciences, University of Cardiff)
Prof Wolfgang Langbein
(Optoelectronics School of Physics and Astronomy, University of Cardiff)