Fast Detection of Single Liposomes Using a Combined Nanopore Microelectrode Sensor.

Here we report the development and characterization of a high throughput sensing device for single liposome detection. The device incorporates a quartz nanopipette positioned near a carbon-fiber microelectrode (CFE). Liposomes (∼200 nm diameter) loaded with Fe(CN)64- are driven out of the nanopipette orifice where they are sensed as a transient decrease in the measured ionic current (resistive-pulse analysis). Simultaneously, a redox signal is collected at the CFE due to the release of internalized redox molecules from translocating liposomes to the CFE surface. Interestingly, we observed that the redox signals arise coincidently with resistive-pulses, suggesting that leakage of liposome contents occurs during translocation. Further investigation suggested that liposome disruption occurs at the nanopore orifice and is not dependent on the nanopore electric field. The probability of this disruption appears to rely on the velocity of fluid flow in the nanopore as well as the nanopore geometry. The high-throughput nature of our technique may prove useful for rapid analysis of liposomal drug formulations or rapid, robust, direct measurement of neurotransmitter concentration in isolated vesicles from neurons and neuroendocrine cells.