Microfluidics for Cancer: exploring tumour cell transit, enabling clinical practice and optimising T cell immunotherapies

Sam Au, Imperial College London

Our ability to control fluids and geometries at the nanometer-micrometer scale in microfluidics allow us to tailor microfluidic devices for diverse applications in cancer. In this talk I will present three different microfluidic platforms we have designed to address needs in the cancer space from fundamental research into the mechanisms responsible for metastasis to new methods for identifying optimal immuno-therapy candidates.

• Multicellular aggregates of circulating tumour cells (CTC clusters) are potent initiators of distant organ metastases yet we have a poor fundamental understanding of their behaviour in the body. To explore the ability of CTC clusters to traverse the microcirculation, we developed organ-on-chip microfluidic devices designed to mimic human capillaries. We used hydrodynamic analyses to explain how CTC clusters of 20+ cells are capable of traversing capillaries under physiological conditions even in whole blood by reversibly reorganizing into single-file chains.
• Given the potency of CTC clusters, their isolation from patient blood may improve our diagnostic, prognostic and predictive capabilities in oncology. Towards this end, we developed a two-stage lab-on-chip platform for isolating CTC clusters out of the circulation based on the greater size and inherent asymmetry of CTC clusters. This technology is capable of the high purity extraction of both large and small clusters with high viabilities by operating under physiological shear.
• Adoptive cell therapies hold great promise for cancer management, but are hindered by the in vitro selection and identification of T cells. Current methods of T cell receptor (TCR) selection that use MHC tetramers have difficulty identifying TCRs that are most effective in patients. To address this, we have developed a microfluidic device that probes the avidity between T cells and antigen presenting tumour cells by applying known levels of uniform shear stress. Importantly, our device evaluates the avidity generated by the numerous cell-cell interactions involved in T cell responses, allowing us to identify TCRs that are most likely to be effective patients.

Bio:

Sam Au joined the Department of Bioengineering at Imperial College London in 2017. Prior to Imperial, Sam was a Tosteson Postdoctoral Fellow in the lab of Professor Mehmet Toner at Harvard Medical School and Massachusetts General Hospital where he developed microfluidic models of the microvasculature to investigate how circulating tumour cell clusters traversed the narrow vessels of the body. Sam obtained a PhD in Biomedical Engineering while in Professor Aaron Wheeler's group at the University of Toronto in 2013 and a BSc in Chemical Engineering in 2008. 

https://rochester.zoom.us/j/92910356167