High-throughput mechanophenotyping of multicellular spheroids using a microfluidic micropipette aspiration chip

TL;DR

This paper introduces a microfluidic chip that enables high-throughput, easy, and accurate measurement of the viscoelastic properties of multicellular spheroids, facilitating tissue mechanophenotyping and understanding cell mechanics.

Contribution

The authors developed a novel microfluidic device that allows parallel, high-throughput viscoelastic characterization of spheroids, overcoming limitations of traditional single-spheroid techniques.

Findings

The chip accurately measures spheroid deformation at various pressures.

Viscoelastic properties of different cell line spheroids are consistent with previous methods.

The device enables rapid, repeated measurements for tissue mechanophenotyping.

Abstract

Cell spheroids are in vitro multicellular model systems that mimic the crowded micro-environment of biological tissues. Their mechanical characterization can provide valuable insights in how single-cell mechanics and cell-cell interactions control tissue mechanics and self-organization. However, most measurement techniques are limited to probing one spheroid at a time, require specialized equipment and are difficult to handle. Here, we developed a microfluidic chip that follows the concept of glass capillary micropipette aspiration in order to quantify the viscoelastic behavior of spheroids in an easy- to-handle, high-throughput manner. Spheroids are loaded in parallel pockets via a gentle flow, after which spheroid tongues are aspirated into adjacent aspiration channels using hydrostatic pressure. After each experiment, the spheroids are easily removed from the chip by reversing the pressure and new spheroids can be injected. The presence of multiple pockets with a uniform aspiration pressure, combined with the ease to conduct successive experiments, allows for a high throughput of tens of spheroids per day. We demonstrate that the chip provides accurate deformation data when working at different aspiration pressures. Lastly, we measure the viscoelastic properties of spheroids made of different cell lines and show how these are consistent with previous studies using established experimental techniques. In summary, our chip provides a high-throughput way to measure the viscoelastic deformation behavior of cell spheroids, in order to mechanophenotype different tissue types and examine the link between cell-intrinsic properties and overall tissue behavior.