Principal Investigator Scott Manalis is the David H. Koch (1962) Professor of Engineering.

Circulating tumor cells (CTCs) play a fundamental role in cancer progression, and carry a wealth of information about the state of an individual’s cancer, including response to therapy. However, in mice, limited blood volume and the rarity of CTCs in the bloodstream preclude longitudinal, in-depth studies of these cells using existing liquid biopsy techniques. To address this, the Manalis Laboratory, with collaborators from fellow Ludwig Center members in the Jacks and Vander Heiden Laboratories, developed an optofluidic system that continuously collects fluorescently labeled CTCs from mice for several hours per day over multiple days or weeks. The system is based on a microfluidic cell sorting chip that extracts individual CTCs before returning the blood to the mouse, allowing the Manalis group to scan nearly the entire blood volume of an awake and active mouse in an hour.

To demonstrate the system, the researchers profiled CTCs, isolated longitudinally from mice over four days of treatment with the drug JQ1, using single-cell RNA sequencing. They showed that their approach eliminates potential biases driven by intermouse heterogeneity that can occur when CTCs are collected across different mice, and can reveal subtle changes that occur from perturbations such as cancer therapy administration, or from tumor evolution.

This CTC isolation and sorting technology provides a research tool to help reveal details of how CTCs evolve over time, allowing studies to credential changes in CTCs as biomarkers of drug response and studies to understand the role of CTCs in metastasis. Pending additional development, the device could enable mouse studies to find associations between individual CTCs and clusters of CTCs, profile rare immune cells, monitor mesenchymal cells in a variety of contexts (eg wound healing and tumor formation), and measure induction rates of drugs or nanoparticles in circulating mononuclear cells.

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