Staff Scientist, Biological Nanostructures
Dr. Cohen was a postdoctoral fellow with Lily Y. Jan at the Howard Hughes Medical Institute and Department of Physiology at the University of California San Francisco. He received his Ph.D. from the Department of Chemistry at the University of California Berkeley and his A.B. from Princeton University's Department of Chemistry, where he graduated cum laude.
Nanocrystals that have unusual or exceptional optical properties have shown promise as transformative probes for biological imaging. The revolution in biology over the last decade has produced detailed blueprints for living organisms, as genomics and related studies have generated vast datasets of the molecular makeup of cells. Many of the most fundamental challenges in biology are now about understanding the localization, associations, and chemistry of these molecules within the complexity of functional cells, or in even greater detail in isolation. Imaging is critical to these studies and is able to resolve the behavior of individual components of live cells with increasing speed and resolution. Along these lines, we are developing novel nanocrystals as biosensors and single-molecule probes, improving bioconjugation and delivery methodologies, and imaging live cells with these reagents. We aim to integrate the development of novel luminescent nanomaterials into multidisciplinary efforts to address significant biological questions of cell function.
Upconverting nanocrystals (UCNCs) absorb two or more photons in the near infrared and emit one at shorter wavelengths, an unusual property unlike anything found in the cell, and one that suggests background-free imaging. Our single-particle studies have shown that UCNCs exhibit nearly ideal properties as single molecule imaging probes, including remarkable photostability and an absence of on-off blinking.
We have recently developed combinatorial methods for synthetic control of UCNC size, color, and brightness, as well as methods for advanced characterization of single nanocrystal optics. We have also developed capabilities for single-nanocrystal upconverted lifetime and spectral imaging, and using this we find that dopant concentrations optimized for single particle imaging are dramatically different than those used for ensemble imaging, which to date have been assumed to also be optimal for single particle studies. Current work is aimed at optimizing single nanocrystal brightness and targeting these probes to specific cellular targets for extended single-protein tracking in live cells.
Semiconductor nanocrystal conjugates
Many nanocrystals exhibit brightness and stability far superior to conventional fluorophores, making them ideal as the bases for biosensing reagents. We have developed quantum dot and dot-rod energy transfer-based systems for the sensitive detection of protein kinases, proteases, and intracellular temperature. We have also developed caged quantum dots, which are non-luminescent until pulsed with ultraviolet light. Current work focuses on developing bright, selective sensors for neurotransmitters that are the primary mediators of fast excitatory and inhibitory firing in the brain.
Improved bio-compatibility and targeting
An ongoing challenge in applying nanocrystals as probes for cellular imaging is improving their bio-compatibility. Nanocrystals are typically hydrophobic and must be passivated with hydrophilic organics, amphipols, or protein coatings, which can compromise optical properties or add significant bulk. Smaller stable nanoparticles are desirable because of their improved accessibility to subcellular structures and are less likely to perturb protein function and trafficking. Smaller, more stable aqueous nanocrystals, as well as simplified methods of bioconjugation and delivery, are constant goals of our work.