title: Oleyl group-functionalized insulating gate transistors for measuring extracellular pH of floating cells.
abstract: The extracellular ionic microenvironment has a close relationship to biological activities such as by cellular respiration, cancer development, and immune response. A system composed of ion-sensitive field-effect transistors (ISFET), cells, and program-controlled fluidics has enabled the acquisition of real-time information about the integrity of the cell membrane via pH measurement. Here we aimed to extend this system toward floating cells such as T lymphocytes for investigating complement activation and pharmacokinetics through alternations in the plasma membrane integrity. We functionalized the surface of tantalum oxide gate insulator of ISFET with oleyl-tethered phosphonic acid for interacting with the plasma membranes of floating cells without affecting the cell signaling. The surface modification was characterized by X-ray photoelectron spectroscopy and water contact angle measurements. The Nernst response of -37.8 mV/pH was obtained for the surface-modified ISFET at 37 °C. The oleyl group-functionalized gate insulator successfully captured Jurkat T cells in a fluidic condition without acute cytotoxicity. The system was able to record the time course of pH changes at the cells/ISFET interface during the process of instant addition and withdrawal of ammonium chloride. Further, the plasma membrane injury of floating cells after exposure by detergent Triton™ X-100 was successfully determined using the modified ISFET with enhanced sensitivity as compared with conventional hemolysis assays.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Imaizumi
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Goda
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Toya
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyahara
keywords: 101 Self-assembly/Self-organized materials; 201 Electronics/Semiconductor/TCOs; 208 Sensors and actuators; 212 Surface and interfaces; 30 Bio-inspired and biomedical materials; 502 Electron spectroscopy; Ion-sensitive field-effect transistors; T lymphocytes; biocompatible anchor for cell membrane; hemolysis; plasma membrane injury; self-assembled monolayer