Supervisors: Dr Kevin Read and Prof Edik Rafailov
The objective of this project was to conduct research in non-invasive multifunctional laser-based systems for assessment of drug effects in rodents.
After initial training on multifunctional laser based systems at Aston University, extensive testing and calibration of the intended device was performed. The LAZMA LAKK-M device was tested for reproducibility, sensitivity and specificity. Firstly, in vitro experiments with different fluorescing agents, naturally found in the skin tissue of animals and humans alike, showed a high variability within measurements of the same batch. This led to various approaches to try enhancing the hardware and data acquisition of the device.
The steps taken from the data acquisition side peaked in a self-developed MatLab algorithm that performed a recursive linear least square fit of the measured data. The algorithm fitted the fluorescence signals of 8 substances known to be in the skin tissue (See Figure 1). Additionally the program is able to perform a normalization on structural fluorescing biomarkers (e.g. Elastin). With this acquisition method the standard deviation between measurements was reduced by approximately 50%. Based on these good results, work progressed to the next stage which involved measuring two ex-vivo livers. While both livers were perfused with a temperate balanced salt solution one of the livers was additionally perfused with a substance that showed high toxicity during in vitro experiments. According to the literature, a change in NADH and Lipofuscin auto fluorescence during perfusion was expected. However, the only observation possible was the detection of the fluorescence of the toxic substance that was externally introduced.
In conclusion, the principle of determining autofluorescence seems promising in researching new markers for toxicity. However, the device used appears to be too unstable and has too low laser output power to be used in the detection of early signs of toxicity at an organ level. With the acquired data looking unstable and not promising the decision was taken to terminate this project.
Values shown are relative amplitude to the normalized start value. All used subspectra fitted with Gaussian functions to increase algorithm speed.
Journal and Conference Papers and Posters
[June 2015] Multifunctional laser-based systems for non-invasive assessment of drug induced toxicity. Poster presented at PHOTONEX Scotland, Glasgow, UK, 3rd June 2015.
[March 2015] Investigation of the applicability of multifunctional laser-based systems for early non-invasive assessment of drug induced toxicity in rodents. Poster presented at the College of Life Sciences Annual Research Symposium, Crieff, Scotland.