noninvasive applications such as sweat sensing. [18] To this end, we develop a novel ion-selective microelectrode array platform with high spatial resolution. We fabricate the platform using photolithography for patterning electronic wiring and insulation, electrodeposition for surface modification, and ISMs through an advanced process involving temporary polydimethylsiloxane (PDMS) microfluidic channels. As a proof of concept, we apply this device to detect the ion concentration change in culture medium. [36,37] Figure 1 comprises schematic views and the working mechanism for this device. Figure 1a describes the schematic view of the device with multiple ion sensors, including the K + -sensor, Na + -sensor, and Cl − -sensor. The inner electrode for each ion is 500 µm × 500 µm, and the space between two electrodes is 400 µm. With multiple ion sensors, the device enables to simultaneously monitor [K + ], [Na + ], and [Cl − ] in electrolyte solutions. We fabricate the sensor array on a silicon wafer with a process that combines photolithography for connectors, electrochemical deposition for electrodes, and microfluidics for ISM patterning ( Figure S1, Supporting Information). Figure 1b illustrates the working principle of the sensor array. When the device is placed in an electrolyte solution (e.g., KCl, NaCl, and KNO 3 ), the target ion will diffuse across a polymer membrane that is made selective with the addition of an ionophore. Diffusion continues until the concentration of the target ion is in equilibrium between the outside of the membrane in contact with the electrolyte solution and the inside of the membrane in contact with the electrode. The concentration of the target ion on the electrode surface affects the electrode potential and the corresponding ionic concentration can be can be calculated from the electrode voltage using Nernst equation. Figure 2 displays a microfluidic-based method for the PVCbased polymer membrane patterning on a substrate that already includes Au wires. A parylene thin film coated on top acts as the encapsulation layer and creates windows for electrode electrodeposition (Figure 2a). For electrodes, we use poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) to create electrodes with high capacitance. [38,39] As shown in Figure 2b, we deposit PEDOT:PSS from electrochemical polymerization of a solution containing 0.01 m EDOT and 0.1 m NaPSS. [38][39][40] The PEDOT:PSS coated electrodes have higher capacitance than the bare Pt electrodes ( Figure S2, Supporting Information), which is important for sensor performance. To selectively pattern the ISMs, we use a PDMS mold as template (Figure 2c,g). We then position the mold onto the substrate, align it to the electrodes, A balanced concentration of ions is essential for biological processes to occur. For example, [H + ] gradients power adenosine triphosphate synthesis, dynamic changes in [K + ] and [Na + ] create action potentials in neuronal communication, and [Cl − ] contributes to maintaining appropriate cell membrane...