A Single-Cell Micromanipulation Platform Relying on Optoelectronic Tweezers

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***We have entered an age of research that is increasingly dependent upon the capacity to manipulate individual biological cells. Whether these techniques are applied to clonal expansion of individual genomes, to in vitro fertilization of oocytes, or simply to study the cell-to-cell heterogeneity that underpins the behaviour of all biological systems, single-cell micromanipulation has become indispensable in modern biomolecular research. ******There are many techniques that are being refined to support the “next generation” of single-cell manipulation, including optical tweezers, dielectrophoresis, and microfluidics. A relatively new member of this group, optoelectronic tweezers (OET), has not been implemented in Canada before. Here, PI Aaron Wheeler (U of T Chemistry), co-PI Nazir Kherani (U of T Electrical and Computer Engineering), and collaborator Peter Zandstra (UBC Biomedical Engineering) propose to build a one-of-its-kind-in-Canada OET system to manipulate single cells and small groups of cells for long-term culture and analysis. ******A team of three Ph.D. students and a postdoc will work together to build and validate an integrated system coupling precision optoelectronic tweezers with long-term cell culture and microfluidic control. The team will then apply the system to a long list of projects requiring high-precision manipulation of single cells, including a systematic evaluation of entosis, a recently observed phenomenon in which particular cells are triggered to invade the cytoplasms of their neighbors. Not much is known about entosis, but it is believed to be a key stage in some types of tumorigenesis, making it imperative that we learn more about how and why it happens. This work will be highly interdisciplinary, and will result in marketable skills and experience with microscopy, microfluidics, materials characterization, next generation genome sequencing, single-cell biology, and beyond. ******There is great urgency for this proposal, given the surging popularity of single cell manipulation research (e.g., the 2018 Nobel Prize in Physics to Arthur Ashkin for optical tweezers). If granted, the work proposed here represents a unique opportunity to establish Canada as an emerging leader in OET technology and single-cell micromanipulation, and to train the next generation of Canadian researchers, inventors, and job creators.*****