Trevor Chan — Microfluidics

Overview

Design and fabrication of a microfluidic micropipette device for studying the mechanical behavior and invasive dynamics of single cancer cells migrating through subnuclear-diameter constrictions.

Background

Cancer metastasis requires cells to squeeze through tight pores in the extracellular matrix — a process governed by cellular mechanics. One open question is why some cells within a bulk tumor population display hyper-invasive phenotypes relative to others. This project investigates the mechanical contributors to single-cell invasion heterogeneity.

Device Design

The device is based on a microfluidic micropipette design developed by the Mak Research Lab, adapted to model in vitro conditions experienced during invasion out of the tumor stroma. Cells are flowed into the device under constant applied pressure, enabling observation of mechanical deformation in the constriction region. Equalizing inlet and outlet pressure allows observation of passive force generation and invasive behavior. After imaging, cells can be flushed and collected for genetic or mechanical analysis.

Fabrication

Devices are fabricated through a two-step process: photolithography to create a device master, followed by soft-lithography to produce the device. A silicon wafer is spin-coated with SU8 photoresist, selectively exposed to UV light through a photomask, and developed to yield the negative master. Silicone elastomer is poured and cured onto the master, then cut and bonded to a glass slide. Autoclave sterilization prevents cell contamination during loading.