Multiple-layer guided surface acoustic wave (SAW)-based pH sensing in longitudinal FiSS-tumoroid cultures

Abstract

A constitutively increased intracellular pH that is higher than the extracellular pH is emerging as a hallmark of cancer and determining pH could play a significant role in the measurement of drug responsiveness of tumor cells. However, a non-invasive, touch-free and real-time pH sensing as a research tool is lacking and remains a major unmet need. The purpose of the current study is to investigate a microfluidic surface acoustic wave (SAW) sensor platform capable of monitoring pH in cell and tumoroid cultures. A novel multi-layer guided SAW sensor integrated into a microfluidic channel was investigated theoretically and experimentally in detail for pH bio-sensing. Sensitivity and capability of the layer guided Love wave device was modeled using the finite element simulation. The model was verified experimentally, and a study monitoring pH of cell growth media is presented. This novel pH sensor is based on a 13.91 MHz center frequency SAW device coated with ZnO (500 nm) and IrO2 (30 nm) layers to increase the sensitivity. A change in mechanical and electrical properties of the conductive IrO2 layer was observed resulting from electrical corrosion induced by pH solutions affecting the charge distribution, SAW phase velocity and attenuation. By measuring the frequency shift induced by the change in SAW phase velocity between the test group and control group, the pH value of cell culture media from H460 cancer cell culture plates from day 0 to day 5 can easily be determined. To improve the sensitivity and stability of the sensor, a finite element method was used to optimize the layer thicknesses. Taken together, the results of experiments show the potential application of this device to be integrated with microfluidic channels and used in determining pH changes in longitudinal tumor cell cultures.