University of California, Irvine – Pharmaceutical Sciences
Laboratory for Fluorescence Dynamics
Optical Detection of Rare Space Time Events for Precision Medicine
Finding low-abundance bioparticles and rare events in clinically relevant samples is an unresolved but very important issue in biomedicine, specifically for rapid identification of infections and malignant tissues and the development of personalized cancer immunotherapeutics. Optical methods are minimally invasive and have the potential to identify targets and screen large samples within short periods of time with the capability to enable detailed analyses.
High resolution quantification of rare interactions including immune cell interactions and circulating tumor cells invading healthy tissues could significantly advance the development of precision medicine treatments and personalized therapeutics. For this purpose, we are developing an intelligent, high throughput light sheet microscopy platform that can screen large complex structures in physiologically relevant 3D cell/tissue culture models and patient derived organoids. While nanoscale imaging with millisecond time resolution can map the dynamic spatial organization of biomolecules, the same platform enables hyperspectral and fluorescence lifetime-based metabolic imaging. This technology has the potential to study treatment effectiveness in patient derived tissues/organoids to develop highly personalized therapeutics for cancer treatment.
At the same time, rapid and accurate optical identification of viruses and bacteria in fluids and on surfaces could significantly advance diagnosis of infectious diseases, detect contaminants in medical supplies, identify circulating tumor cells, and discover antibody-producing B cells and antigen-specific T cells, to name a few. Existing biochemical or microfluidic methods take many hours or are not sensitive enough to detect highly dilute, single targets. To address this issue, we are developing a revolutionary 3D particle detection approach to find and isolate rare targets (1-100 per mL) directly from larger volumes of fluid (1-10 mL) within minutes.
Per Niklas Hedde, Ph.D., is a researcher at the University of California, Irvine where he develops camera-based fluorescence fluctuation spectroscopy techniques, devices for the isolation of rare bioparticles from turbid media, and optical methods for medical diagnosis and antibody discovery using non-linear excitation with lifetime and hyperspectral detection. He studied physics at the University of Ulm, Germany, with a master thesis project on ultrafast analysis of super-resolution microscopy data. He completed his Ph.D. in physics at the Karlsruhe Institute of Technology where he built an instrument for super-resolved image correlation spectroscopy to study the dynamics of cell membrane receptors and developed localization microscopy techniques to image protein mutations and receptor interactions related to heart disease and allergy. For his thesis work he received the Karlsruhe Institute of Technology Award for Outstanding Doctoral Research Work in the Area of Applied Life Sciences 2014 and the Gregorio Weber International Prize 2014. He then accepted a postdoctoral position at the Laboratory for Fluorescence Dynamics at UC Irvine to broaden his skills including fluorescence lifetime, spectral and polarization imaging. During this time, he also visited and collaborated with the Karolinska Institute in Stockholm, Sweden to learn about natural killer cells, their value for cancer immune therapy and to establish fluctuation spectroscopy methods at the KI Department of Microbiology, Tumor and Cell Biology. So far, he has published 30 peer-reviewed journal articles and is member of the Biophysical Society (US and Germany), the American Association for Cancer Research, and the UC Irvine Center for Complex Biological Systems. Most recently, he received an R21 award from NIH for the development of “Fluctuation Spectroscopy with Light Sheet Microscopy”.
Sponsored by the Michael and Roberta Berns Laser Microbeam Program