Resistive flow sensing of vital mitochondria with nanoelectrodes

We report label-free detection of single mitochondria with high sensitivity using nanoelectrodes . Measurements of the conductance of carbon nanotube transistors show discrete changes of conductance as individual mitochondria flow over the nanoelectrodes in a microfluidic channel . Altering the bioenergetic state of the mitochondria by adding metabolites to the flow buffer induces changes in the mitochondrial membrane potential detected by the nanoelectrodes. During the time when mitochondria are transiently passing over the nanoelectrodes, this (nano) technology is sensitive to fluctuations of the mitochondrial membrane potential with a resolution of 10 mV with temporal resolution of order milliseconds. Fluorescence based assays (in ideal, photon shot noise limited setups) are shown to be an order of magnitude less sensitive than this nano-electronic measurement technology. This opens a new window into the dynamics of an organelle critical to cellular function and fate. • The surface charge of mitochondria induces a change in the conductance of carbon nanotube transistors. • The magnitude of this conductance change depends on the energization state of the mitochondria. • Compared to fluorescence, electrical measurements of membrane potential can provide higher time resolution and accuracy.