2010 Poster Sessions : Miniature and Mass-Producible Fluorescence Microscopes for Biomedical Imaging

Student Name : Kunal Ghosh
Advisor : Abbas El Gamal
Research Areas: Information Systems
Fluorescence microscopy has emerged as a workhorse of modern biology and medicine.
Fluorescence microscopes are indispensable as tools for basic research in the biological sciences, enable platforms for drug discovery in the biotechnology and pharmaceutical industries, and are increasingly aiding in several clinical diagnostic applications. However, state‐of‐the‐art fluorescence microscopes remain bulky and expensive benchtop instruments with an architecture that impedes usage in certain applications and a cost that precludes adoption in large numbers. For example existing benchtop fluorescence microscopes are not amenable for in vivo imaging in animals, with the mouse being a common animal subject, especially during awake, active behavior. For the field of neuroscience in particular, such an experimental capability permits correlating causal cellular processes with animal behavior – a longstanding goal.
Inspired by this need, we have designed a miniature fluorescence microscope that can be
borne by a mouse during active behavior. We have fabricated several such microscopes, each less
than 2 g in mass, perhaps heralding a transformation in fluorescence microscopy from today’s bulky and expensive benchtop paradigm towards miniature and mass‐producible devices. Our fabricated microscopes achieve 2.5 μm spatial resolution imaging fields‐of‐view up to 800 μm x 600 μm at 36 Hz, suitable for cellular‐level imaging at high temporal resolution.
We have experimentally validated fabricated microscopes for in vivo brain imaging in freely behaving mice, specifically using them for: 1) Imaging cerebellar vasculature and hemodynamics during activity; and 2) Imaging cerebellar Purkinje cell Calcium dynamics, analyzing spiking activity of populations of neurons with single neuron specificity during different motor behaviors. We also show how several of these microscopes imaging in parallel can enable new highthroughput imaging solutions with the potential to achieve broad impact, specifically
demonstrating high‐throughput image‐based assays for: 1) Mutant phenotype screening in genetic
model species such as the zebrafish; and 2) Multiple well plate cell analyses.

Kunal Ghosh is currently working towards completing his Ph.D. at Stanford University. His thesis
work described above is the result of an interdisciplinary collaboration between the group of Prof. Abbas El Gamal, Department of Electrical Engineering, and the lab of Prof. Mark J. Schnitzer,
Departments of Biology and Applied Physics. Prior to undertaking this work, he was involved in circuit design and validation in silicon of architectures for high speed and high dynamic range CMOS image sensors. Kunal received the M.S. in Electrical Engineering in 2006, also from Stanford. He graduated from the Jerome Fisher Program in Management and Technology at the University of Pennsylvania in 2004 with a B.S.E. in Electrical Engineering and a B.S. from the Wharton School. He has spent summers at Agere Systems (formerly part of AT&T Bell Labs, now part of LSI) and at McKinsey & Company.