研究领域
Physical and Biophysical Chemistry, Bio-Imaging, Medical Diagnostics
The research in Prof. Diem’s laboratory is centered on the development of optical methods for medical diagnosis. In contrast to standard pathology, where stained cells and tissues are examined visually under a microscope, we measure changes in cellular composition using molecular fingerprint techniques, such as infrared and Raman micro-spectroscopy.
The research being carried out is divided into three major areas. In Prof. Diem’s work on tissue diagnostics, he has developed methods for the detection and diagnosis of secondary (metastatic) tumors in lymph nodes (Figure 1) by methods of infrared spectral imaging. Prof. Diem’s lab is working on producing instrumentation and software that can diagnose and classify tissue sections, and provide the physician with an objective diagnosis of disease. Similarly, he is using the infrared spectral signatures of individual exfoliated cells to determine pre-cancer and viral infection (Figure 2). The infrared methods have been licensed to a start-up company to commercialize the diagnostic methodologies.
Prof. Diem’s lab also uses Raman micro-spectroscopy, in conjunction with multivariate imaging analysis al-gorithms, to follow cellular processes and drug uptake into cells by a minimally invasive method.
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Diem, M.; Miljković, M.; Bird, B.; Chernenko, T.; Schubert, J.; Marcsisin, E. J.; Mazur, A. I.; Kingston, E.; Zuser, E.; Papamarkakis, K.; Laver, N., Applications of Infrared and Raman Micro-spectroscopy of Cells in Medical Diagnostics: Present Status and Future Promise. Spectroscopy – Biomedical Applications 2012, (26), (In Press).
Marcsisin, E. J.; Uttero, C. M.; Mazur, A. I.; Miljković, M.; Bird, B.; Diem, M., Noise Adjusted Principal Component Reconstruction to Optimize Infrared Microspectroscopy of Individual Live Cells. Analyst 2012, (In Press).
Diem, M; Laver, N.; Bedrossian, K.; Schubert, J.; Papamarkakis, K.; Bird, B.; Miljković, M., “Detection of Viral Infection in Epithelial Cells by Infrared Spectral Cytopathology”, Handbook of Biophotonics, Popp, J., Ed, Wiley, Vol. 2, Chap 17, pp 251-261.
Bird, B.; Miljković, M.; Laver, N.; Diem, M., “Spectral Detection of Micro-Metastases and Individual Metastatic Cells in Lymph Node Histology”, (2011) Techn. Cancer Res. Treatment (TCRT), 10(2), 135-144.
Matthäus, C.; Chernenko, T.; Miljković, M.; Quintero, L.; Amiji, M.; Torchilin, V.; Diem, M., “Raman Micro-spectral Imaging of Cells, and Applications Monitoring the Uptake of Drug Delivery Systems”, in “Confocal Raman Imaging”, Hollricher and Dieing, Ed, Springer Verlag, Heidelberg, Germany, 2011, 137-162.
Whelan, D. R.; Bambery, K. R.; Heraud, P.; Tobin, M. J.; Diem, M.; McNaughton, D.; Wood, B. R., Monitoring the reversible B to A-like transition of DNA in eukaryotic cells usint Fourier transform Infrared spectroscopy. Nucleic Acids Research 2011, 39, (13), 5439-5448.
Mazur, A. I.; Marcsisin, E. J.; Bird, B.; Miljković, M.; Diem, M., Evaluating Different Fixation Protocols for Spectral Cytopathology, Part I. Analytical Chemistry 2012, 84, 1259-1266.
Lin, C. Y.; Suhalim, J. L.; Nien-Shy, C.; Miljković, M.; Diem, M.; Jester, J. V.; Potma, E. O., Picosecond spectral CARS imaging with principal component analysis of meibomian glands. J. Biomed. Optics 2011, 16, (2), 1-9.
Hedegaard, M.; Matthäus, C.; Hassing, S.; Krafft, C.; Diem, M.; Popp, J., Spectral unmixing and clustering algorithms for assessment of single cells by Raman microscopic imaging. Theor. Chem. Acc. 2011, 130, 1249-1260.
Cherchi, C.; Chernenko, T.; Diem, M.; Gu, A. Z., Impact of Nano Titanium Dioxide Exposure on Cellular Structure of Anabaena Variabilis and Evidence of Internalization. Environmental Toxicology and Chemistry 2011, 30, (4), 861-869.
Chernenko, T.; Sawant, R.; Matthäus, C.; Quintero, L.; Torchilin, V.; Diem, M., “A Novel Approach to Follow the Intracellular Fate of Pharmaceutical Nanocarriers”, (2010) Controlled Release Newsletter, 27(3), 18-19.
Zuser, E.; Chernenko, T.; Newmark, J.; Miljković, M.; Diem, M., Confocal Raman microspectral imaging (CRMI) of murine stem cell colonies. Analyst 2010, 135, (12), 3030-3033.
Schubert, J. M.; Mazur, A. I.; Bird, B.; Miljković, M.; Diem, M., Single point vs. mapping approach for spectral cytopathology (SCP). J Biophotonics 2010, 3, (9), 588-596.
Schubert, J. M.; Bird, B.; Papamarkakis, K.; Miljković, M.; Bedrossian, K.; Laver, N.; Diem, M., Spectral cytopathology of cervical samples: detecting cellular abnormalities in cytologically normal cells. Lab Invest 2010, 90, (7), 1068-1077.
Quintero, L.; Miljković, M.; Hunt, S.; Matthäus, C.; Diem, M., Impulsive Noise Reduction in Raman Spectroscopy Images. Proc. of SPIE 2010, 7568.
Quintero, L.; Matthäus, C.; Hunt, S.; Diem, M., Denoising Single Scan Raman Spectroscopy Signals. Proc. of SPIE 2010, 7568.
Papamarkakis, K.; Bird, B.; Schubert, J. M.; Miljković, M.; Wein, R.; Bedrossian, K.; Laver, N.; Diem, M., Cytopathology by optical methods: spectral cytopathology of the oral mucosa. Lab Invest 2010, 90, (4), 589-598.
Miljković, M.; Chernenko, T.; Romeo, M. J.; Bird, B.; Matthäus, C.; Diem, M., Label-free imaging of human cells: algorithms for image reconstruction of Raman hyperspectral datasets. Analyst 2010, 135, (8), 2002-2013.
Mariani, M. M.; Maccoux, L. J.; Matthäus, C.; Diem, M.; Hengstler, J. G.; Deckert, V., Micro-Raman detection of nuclear membrane lipid fluctuations in senescent epithelial breast cancer cells. Anal Chem 2010, 82, (10), 4259-63.
Marcsisin, E. J.; Uttero, C. M.; Miljković, M.; Diem, M., Infrared microspectroscopy of live cells in aqueous media. Analyst 2010, 135, (12), 3227-32.