Biosensor for Dielectric Spectroscopy of Mitochondria and for Monitoring Ion Activities
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Biosensor for dielectric spectroscopy of mitochondria and for monitoring ion activities. Divya Padmaraj1,2, Rohit Pande1, Wanda Zagozdzon-Wosik1, Lei-Ming Xie2, Dorota G. Pijanowska4, John H. Miller3, Piotr B. Grabiec5, Bohdan Jaroszewicz5, William Widger6, and Jarek Wosik1,2 1
Electrical and Computer Engineering, University of Houston, Houston, TX 77004, USA Texas Center for Superconductivity, University of Houston, Houston, TX 77004, USA 3 Physics Department, University of Houston, Houston, TX 77004, USA 4 Institute of Biocybernetics and Biomedical Engineering, Warsaw, Poland 5 Institute of Electron Technology, Warsaw, Poland 6 Biochemistry Department, University of Houston, Houston, TX 77004, USA
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ABSTRACT We developed a BioMEMS device to study cell- mitochondrial physiological functionalities. The pathogenesis of many diseases including obesity, diabetes, heart failure as well as aging has been linked to functional defects of mitochondria. This is understandable as the mitochondria produces up to 90% of ATP, and plays a critical role in cell signaling and apoptosis. The synthesis of ATP is determined by the electrical potential across the inner mitochondrial membrane (IMM) and by the pH difference due to proton flux across it. Therefore, electrical characterization by E-fields with complementary chemical testing was used here. Electrodes for dielectric spectroscopy studies of mitochondria were designed as 2- and 4-probe structures for optimized operation over a wide frequency range. An electrical model was developed for the mitochondrial sample, and its frequency response correlated with impedance spectroscopy experiments of sarcolemmal mitochondria. Ion Sensitive Field Effect Transistors (ISFETs) were incorporated for proton studies important in electron transport chain, together with monitoring Na+, K+, Ca++ ions. COMSOL simulations of selected electrical structures in this sensor were compared with experimental results to better understand the physical system. The simultaneous measurement of membrane potential, ion concentrations and pH would enhance diagnostics and studies of mitochondrial diseases. Studies of the electro-chemical parameters associated with mitochondrial bioenergetics may render us the significant information on different abnormalities.
INTRODUCTION Miniaturization of diagnostic tools led to the development of the domain of BioMEMS. BioMEMS allow testing and analyses of bio-samples viz. cells, organelles,
enzymes, etc towards rendering solutions to combat malignant diseases. We developed a BioMEMS device to study the mitochondrial physiological role in a non-invasive fashion. Mitochondrial involvement has been linked and cited in ageing and various genetic and neurodegenerative diseases like Pearson’s syndrome, Parkinson’s disease, Alzheimer’s disease etc. Besides being the ATP synthesizer, the central role of mitochondria in significant processes like apoptosis (programmed cell – death), cell signaling and calcium homeostasis has stimulated various researchers to study
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