Continuous Viscoelasticity Measurement of Cell Spheroids via Microfluidic Electrical Aspiration.

Measurement of viscoelastic characteristics of cells cultured in three-dimensional (3D) is critical to study many biological processes including tissue and organ growth. In this article, we present a unique electrical aspiration method to measure the viscoelastic properties of cell spheroids. A microfluidic sensor was created to demonstrate this method. Unlike the traditional optical aspiration method, the aspiration of the cell spheroids is monitored via monitoring the dynamic electrical resistance change of a symmetrical microfluidic aspiration channel. We first used the microfluidic device to measure the viscoelastic properties of two types of biological tissues derived from calfskin and porcine left ventricular myocardium. The equilibrium elastic modulus and creep time constants were measured to be 148.1 ± 24.1 kPa and 76.7 ± 3.5 s and 64.5 ± 7.7 kPa and 31.4 ± 2.7 s respectively, which matched well with reported data. The test validated the principle of the electrical aspiration method. Next, we applied the method for measuring cell spheroids made of human mesenchymal stem cells at different culture stages. The equilibrium elastic modulus and apparent viscosity decreased with increasing culture time. Compared to optical aspiration methods, this microfluidic electrical aspiration method has no reliance on transparent materials and image processing, which thus allows simple setup, fast data acquisition and analysis. The use of a symmetric aspiration channel and the linear half-space model enable measurements of a large number of viscoelastic properties via a single measurement with higher accuracy. This method will enable high throughput, continuous viscoelastic measurement of cell spheroids as well as other 3D cell culture models in flow conditions without the need for any optical measurements.