Three Dimensional Multi-resolution Microscope (3DMM) for High-definition Imaging of Cell-biological Events

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Docket # 13-2834-1


The market for biological microscopes is greater than $1 billion annually. There is a high demand in the biomedical research field for microscopes which are capable of resolving ever smaller features and faster dynamics in live cells. However, currently available biological microscopes are limited in their ability to follow phenomena which evolve rapidly, in three dimensions, and over multiple length scales.


To fill this market need, researchers in the department of Chemistry at Princeton University have developed the Three Dimensional Multi-resolution microscope (3DMM), which is able to trace the 3D position of single freely diffusing nanoscale probes in real time with 10 microsecond temporal and 10 nm spatial resolution which over time delineates fine features of the 3D anatomy of interest with a resolution rivaling that of electron microscopy; all achieved with the concurrently imaged 3D context using multi-photon microscopy.


Traditional techniques observe 3D phenomena by sampling an entire volume over the length scales relevant to live cells, requiring several seconds for a full snapshot to be acquired. By using 3DMM researchers can focus on the local dynamics of a single molecule-scale particle of interest, allowing for the study of the previously impossible. Further, this groundbreaking technology is built in a modular fashion, which can be an add-on to existing optical microscopes, and is customizable and upgradeable to fit evolving research needs. The cost of 3DMM is similar to high-end multi-photon microscope, but is able to image molecular cell-biological events with high temporal, spatial, and spectral resolution. The 3D multi-resolution microscopy has been used to study the critical steps in cellular uptake of nanoscale delivery vehicles.



•       Nanoscale-resolution cellular imaging

•       Neuronal activity imaging

•       Intra- and inter-cellular processes

•       Mechanistic studies of molecular cell biology

•       Protein dynamic studies

•       In vitro imaging



•       Real-time multi-scale multi-resolution 3D imaging

•       Large-scale information of environment

•       High temporal, spatial, and spectral resolution

•       Convenient add-on system to currently used optical microscopes

•       Cost effective

•       Upgradeable


Video of 3D-CRT microscopy:



Kevin Welsher, Haw Yang. Multi-resolution 3D visualization of the early stages of cellular uptake of peptide-coated nanoparticles. Nature Nanotechnology 9, 198–203 (2014)




Professor Haw Yang

Haw Yang received his Ph.D. in Physical Chemistry from UC Berkeley in 1999, and did postdoc at Harvard University afterwards. In 2002, he joined the faculty of the University of California, Berkeley, as an Assistant Professor of Chemistry. In 2009, he moved to Princeton University as an Associate Professor of Chemistry. He is an Alfred P. Sloan Fellow, has received the CAREER award from the National Science Foundation, the Hellman Family Faculty Award, and the Camille Dreyfus Teacher-Scholar Award. His research concerns chemical dynamics in complex systems, currently focusing on (1) single-molecule protein dynamics, (2) intra-cellular local temperatures, (3) multi-scale dynamics imaging, and (4) utilizing thermal fluctuations for purposeful works. He is an Associate Editor of Chemical Science and serves on the Advisory Boards of several scientific journals.


Professor Kevin Welsher

Kevin Welsher received his undergraduate education at Emory University, majoring in chemistry and physics with a minor in mathematics. He went on to receive his Ph.D. in Chemistry from Stanford University in 2010, where he developed nanoscale materials for biological imaging under the guidance of Professor Hongjie Dai. Kevin came to Princeton in September 2010 and joined the group of Professor Haw Yang as a postdoctoral researcher. He is currently an Assistant Professor of Chemistry at Duke University.



Intellectual property and technology status:

Patent granted:


Industrial collaborators are sought for the further development and commercialization of this technology. A working prototype is available.



Laurie Tzodikov

Princeton University Office of Technology Licensing

• (609) 258-7256•

Xin (Shane) Peng

Princeton University Office of Technology Licensing

• (609) 258-5579•


Patent Information:
For Information, Contact:
Cortney Cavanaugh
New Ventures and licensing associate
Princeton University
Haw Yang
Kevin Welsher
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