Surface Acoustic Waves (SAW)-Based Biosensing for Quantification of Cell Growth in 2D and 3D Cultures

Abstract

Detection and quantification of cell viability and growth in two-dimensional (2D) and three-dimensional (3D) cell cultures commonly involve harvesting of cells and therefore requires a parallel set-up of several replicates for time-lapse or dose–response studies. Thus, developing a non-invasive and touch-free detection of cell growth in longitudinal studies of 3D tumor spheroid cultures or of stem cell regeneration remains a major unmet need. Since surface acoustic waves (SAWs) permit mass loading-based biosensing and have been touted due to their many advantages including low cost, small size and ease of assembly, we examined the potential of SAW-biosensing to detect and quantify cell growth. Herein, we demonstrate that a shear horizontal-surface acoustic waves (SH-SAW) device comprising two pairs of resonators consisting of interdigital transducers and reflecting fingers can be used to quantify mass loading by the cells in suspension as well as within a 3D cell culture platform. A 3D COMSOL model was built to simulate the mass loading response of increasing concentrations of cells in suspension in the polydimethylsiloxane (PDMS) well in order to predict the characteristics and optimize the design of the SH-SAW biosensor. The simulated relative frequency shift from the two oscillatory circuit systems (one of which functions as control) were found to be concordant to experimental data generated with RAW264.7 macrophage and A549 cancer cells. In addition, results showed that SAW measurements per se did not affect viability of cells. Further, SH-SAW biosensing was applied to A549 cells cultured on a 3D electrospun nanofiber scaffold that generate tumor spheroids (tumoroids) and the results showed the device's ability to detect changes in tumor spheroid growth over the course of eight days. Taken together, these results demonstrate the use of SH-SAW device for detection and quantification of cell growth changes over time in 2D suspension cultures and in 3D cell culture models, which may have potential applications in both longitudinal 3D cell cultures in cancer biology and in regenerative medicine.

Surface acoustic wave devices for chemical sensing and microfluidics: a review and perspective

“…To date, a wide variety of biological targets have been studied, including proteins 86,87 , DNA 88 , and large cells and bacteria 89,90,91,92 , as well as biological warfare agents (BWAs) 93 and aflatoxins. 94 From a diagnostic and therapeutic perspective, there are multiple approaches that have been explored.…”

Microfluidic Technology for the Generation of Cell Spheroids and Their Applications

“…The application of external forces has long been employed to induce cell aggregation and compaction to form 3D structure. Widely used actuation concepts are dielectrophoresis [ 57 ], magnetism [ 58 ] and acoustic waves [ 59 ]. However, these methods are fairly complex, offer little access for visualization of spheroid formation and require specialized equipment.…”

Dynamic Cultivation of Mesenchymal Stem Cell Aggregates

“…As an example double-emulsion droplets were used to generate picoliter-sized bioreactors for the self-assembly of MSC spheroids [ 86 ]. External forces such as magnetic force [ 87 ], electric field [ 88 ], or ultrasound wave traps [ 89 ] to concentrate cells for aggregation are not as common, and only magnetic force has been used for the aggregation of MSCs so far [ 90 , 91 ].…”