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Biosensors for Mitochondrial Membrane Potential Analysis

Abstract

New generation of biosensors based on nanofabrication techniques show great promise for clinical analysis, diagnosis of diseases and drug discovery. One of the areas in which development of new techniques and technologies is crucial is the field of analysis of individual sub-cellular organelles. Mitochondria not only produce cellular energy, they are also involved in cellular signaling and control the cell fate. Mitochondrial dysfunction is implicated in many human diseases; development of new technologies for mitochondrial analysis is essential to understanding the mechanism of these illnesses and finding a cure for them.

During the course of this research, three different types of devices for analyzing mitochondria were designed, fabricated and characterized. First a miniaturized on-chip ion-selective device for mitochondrial membrane potential assays was developed. This device facilitates mitochondrial evaluations when the available mitochondrial sample is very small and therefore commercial sensors cannot be used. The second device is a Nanofluidic platform to trap individual mitochondria and is extremely useful for fluorescence microscopy studies of different characteristics of individual mitochondria. Single mitochondrion membrane potential studies were demonstrated using this device. Finally, a novel method was developed for mitochondrial studies; this method is based on capacitive sensing of individual mitochondrion's membrane potential using carbon nanotube transistors integrated into a microfluidic channel. Assays of mitochondrial membrane potential using the prototype device is presented and shows unprecedented temporal resolution compared to prior studies.

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