Title: Elucidating the chemistry of biological systems through multimodal imaging and multivariate analysis
Understanding the biochemical composition of cells, organelles and body fluids is essential for uncovering both physiological and pathological processes. This requires the development of chemical tools to complement current imaging and bioanalytical techniques. We are working towards the development of a range of chemical techniques to enhance the understanding of biological systems, including multimodal imaging and sensor arrays for multivariate analysis.
Multimodal imaging is gaining traction in biomedical and clinical studies as it combines the relative advantages of two or more imaging techniques. We are interested in developing multimodal imaging agents to combine fluorescence imaging with additional modalities. One promising approach to imaging organelles is to develop dual imaging agents for fluorescence and vibrational spectroscopic imaging; the latter is highly sensitive to biochemical distributions across the cell. Organelle-targeted dual imaging agents can therefore be used to map the biochemistry of organelles. We have developed NpCN1, a bimodal fluorescence-Raman probe targeted to the lipid droplets, incorporating a nitrile as a Raman tag.1 We used NpCN1 to image lipid droplets in 3T3-L1 cells in both fluorescence and Raman modalities, reporting on the chemical composition and distribution of the lipid droplets in the cells.
Copper is an essential trace metal that participates in various physiological pathways and biological processes, including energy metabolism, neuromodulation and antioxidative defence. Imbalanced brain copper content has long been associated with neurodegenerative diseases, such as Wilson’s disease, Menkes disease, Alzheimer’s disease and Parkinson’s disease. Selective copper sensors are useful in studying biological processes,2 but their use in vivo is limited by poor tissue penetration of excitation and emission light. We have developed CyCu1, a dual fluorescence-photoacoustic imaging agent that is selective for Cu(II). It undergoes a ratiometric fluorescence change upon the addition of Cu(II), as well as a marked absorption change, which can be harnessed in photoacoustic imaging. We have shown the ability of CyCu1 to detect Cu(II) in neuroblastoma, and to image changes in Cu(II) in diseased brain tissue.
Cross-reactive sensor arrays coupled with multivariate statistical analysis are particularly useful for studying complex samples such as body fluids. We have developed a fluorescent sensor array for serum platinum levels, which can be used to gain information on the concentration of platinum drugs within clinical serum samples.3
1. J. Lin, M. E. Graziotto, P. A. Lay and E. J. New, “A bimodal fluorescence-Raman probe for cellular imaging” Cells, 10, 1699 (2021).
2. C. Shen, J. L. Kolanowski, C. Tran, A. Kaur, M. C. Akerfeldt, M. S. Rahme, T. W. Hambley and E. J. New, “A ratiometric fluorescent sensor for the mitochondrial copper pool”, Metallomics, 8, 915 (2016).
3. L. Mitchell, C. Shen, H. C. Timmins, S. B. Park and E. J. New, “A versatile fluorescent sensor array for platinum anti-cancer drug detection in biological fluids”, ACS Sensors, 6, 1261 (2021).