基于多层导波面波（SAW）的 FiSS 肿瘤纵向培养物 pH 传感。

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

机构信息

Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Microfluidics and Acoustics Laboratory, Department of Mechanical Engineering, College of Engineering, University of South Florida, Tampa, FL 33612, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; James A Haley VA Hospital, Tampa, FL 33612, USA.

Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.

出版信息

Biosens Bioelectron. 2019 Jan 15;124-125:244-252. doi: 10.1016/j.bios.2018.10.011. Epub 2018 Oct 12.

DOI:10.1016/j.bios.2018.10.011

PMID:30390467

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 IrO (30 nm) layers to increase the sensitivity. A change in mechanical and electrical properties of the conductive IrO 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.

摘要

细胞内 pH 值持续升高且高于细胞外 pH 值，这正成为癌症的一个特征，而测定 pH 值可能在测量肿瘤细胞对药物的反应方面发挥重要作用。然而，目前缺乏一种非侵入性、无需接触且实时的 pH 感测技术，这仍然是一个未满足的主要需求。本研究旨在探索一种能够监测细胞和类器官培养物中 pH 值的微流控表面声波（SAW）传感器平台。一种新型多层导波 SAW 传感器被集成到微流道中，从理论和实验两方面对其进行了详细研究，以实现 pH 值生物传感。采用有限元模拟对层导声表面波器件的灵敏度和性能进行了建模。对模型进行了实验验证，并展示了一项监测细胞生长培养基 pH 值的研究。这种新型 pH 传感器基于一个中心频率为 13.91 MHz 的 SAW 器件，该器件涂有 ZnO（500nm）和 IrO（30nm）层，以提高灵敏度。观察到 IrO 导电层的机械和电气特性发生变化，这是由 pH 溶液引起的电腐蚀导致电荷分布、SAW 相速度和衰减发生变化所致。通过测量实验组和对照组之间 SAW 相速度变化引起的频率偏移，可以轻松确定 H460 癌细胞培养板从第 0 天到第 5 天的细胞培养介质的 pH 值。为了提高传感器的灵敏度和稳定性，采用有限元法对层厚度进行了优化。总的来说，实验结果表明，该设备具有与微流道集成并用于确定纵向肿瘤细胞培养物中 pH 值变化的潜在应用。