Date and time

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Scalable Development of Multiplexed Microparticle Technologies for Optical Single-Cell Barcoding

The biological complexity of an organism arises from the diversity and interaction of individual cells. Optical imaging techniques with single cell resolution have played an invaluable role in developing an understanding of cellular identity and function. However, current imaging techniques, although widely used to distinguish several different cell populations, are not scalable to single cells at a large scale because they rely on fluorescent molecules with broad spectral emission that results in significant spectral crosstalk. In this thesis, we develop new intracellular optical probes called ‘laser particles’ (LPs), which possess subnanometer spectral linewidth. This narrowband emission enables us to generate hundreds of unique colors well suited for cellular multiplexing. Using a top-down fabrication approach, we develop a scalable method to produce billions of micron-sized LPs from a single semiconductor wafer. Moreover, we refine the design of the particles by perturbing their optical modes using nano-scatterers to optimize their emission signal. By physically combining multiple LPs we are able to scale the number of unique optical barcodes from hundreds to tens of thousands. Using these LP barcodes, we tag thousands of mammalian cells and read out their barcode emissions using a modified microscope and a custom-developed flow cytometer. We expect that the proposed technology offers a platform to identify single cells in various single-cell measurements and allows the acquired data of same cells to be integrated using the optical barcodes.

Thesis Supervisor:
Seok-Hyun Yun, PhD
Patricia and Scott Eston MGH Research Scholar, Professor of Dermatology, HMS

Thesis Committee Chair:
Mehmet Toner, PhD
Helen Andrus Benedict Professor of Biomedical Engineering, HMS

Thesis Reader:
Ralph Weissleder, MD, PhD
Thrall Professor of Radiology, Professor of Systems Biology, HMS


Zoom invitation - 

Paul Dannenberg is inviting you to a scheduled Zoom meeting.

Topic: Paul Dannenberg Thesis Defense
Time: Tuesday, June 15, 2021 9:00 AM Eastern Time (US and Canada

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