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.
Highlights
Detection and quantification of cell viability and growth in two-dimensional (2D) and three-dimensional (3D) cell cultures commonly involve harvesting of cells and requires a parallel set-up of several replicates for time-lapse or dose–response studies
Biosensors are widely used in cancer biomarker detection and bio-agent detection
Shear horizontal-surface acoustic waves (SH-SAW) with the substrate polarized normal to wave propagation are most commonly used in sensor applications that involve fluidics
Summary
Detection and quantification of cell viability and growth in two-dimensional (2D) and three-dimensional (3D) cell cultures commonly involve harvesting of cells and requires a parallel set-up of several replicates for time-lapse or dose–response studies. Shear horizontal-surface acoustic waves (SH-SAW) with the substrate polarized normal to wave propagation are most commonly used in sensor applications that involve fluidics. Because of its high electroacoustic coupling coefficient, the 36 ̋Y-cut LiTaO3 generates more stable signals when the SH-SAWs travel through polydimethylsiloxane (PDMS), which absorbs the majority of the energy generated by the interdigital transducers [13,14]. We reasoned that SH-SAW using 36 ̋Y-cut LiTaO3 wafers coated with ZnO might have the potential to measure and quantify cellular mass changes. To test this idea, we utilized a PDMS channel/well and surface acoustic wave transducers coated with a ZnO layer to measure mass changes due to increasing cell numbers in normal murine RAW264.7 macrophages and human A549 lung adenocarcinoma cell lines. Our results indicate that the proposed microfluidic SAW device is capable of monitoring and quantifying cell density of both cell lines in suspension as well as cultured on a 3D-nanofiber scaffold
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
