A BioMEMS device to study cell-mitochondrial physiological functionalities was developed. The pathogenesis of many diseases including obesity, diabetes and heart failure as well as aging has been linked to functional defects of mitochondria. The synthesis of Adenosine Tri Phosphate (ATP) is determined by the electrical potential across the inner mitochondrial membrane and by the pH difference due to proton flux across it. Therefore, electrical characterization by E-fields with complementary chemical testing was used here. The BioMEMS device was fabricated as an SU-8 based microfluidic system with gold electrodes on SiO²/Si wafers for electromagnetic interrogation. Ion Sensitive Field Effect Transistors (ISFETs) were incorporated for proton studies important in the electron transport chain, together with monitoring Na⁺, K⁺ and Ca⁺⁺ ions for ion channel studies. ISFETs are chemically sensitive Metal Oxide Semiconductor Field Effect Transistor (MOSFET) devices and their threshold voltage is directly proportional to the electrolytic H⁺ ion variation. These ISFETs (sensitivity ∼55 mV/pH for H⁺) were further realized as specific ion sensitive Chemical Field Effect Transistors (CHEMFETs) by depositing a specific ion sensitive membrane on the gate.

Electrodes for dielectric spectroscopy studies of mitochondria were designed as 2- and 4-probe structures for optimized operation over a wide frequency range. In addition, to limit polarization effects, a 4-electrode set-up with unique meshed pickup electrodes (7.5×7.5 μm² loops with 4 μm wires) was fabricated. Sensitivity of impedance spectroscopy to membrane potential changes was confirmed by studying the influence of uncouplers and glucose on mitochondria. An electrical model was developed for the mitochondrial sample, and its frequency response correlated with impedance spectroscopy experiments of sarcolemmal mitochondria. Using the mesh electrode structure, we obtained a reduction of 83.28% in impedance at 200 Hz. COMSOL simulations of selected electrical structures in this sensor were compared with experimental results to better understand the physical system. A broadband permittivity analysis tool consisting of lumped and distributed structures was also developed. The frequency range of this device is from 100 Hz to 40 GHz and utilizes an interdigitated capacitor and coplanar waveguide. The simultaneous measurement of membrane potential, ion concentrations and pH would enhance diagnostics and studies of mitochondrial diseases.