Semiconductor nanorods as sensors for optical recording of neuronal signals

Kuo et al. describe semiconductor voltage nanosensors for optical recording of neuronal signals. These sensors operate via a unique nanoscale phenomena - the quantum confined Stark effect, whereby their emission color and intensity change upon the modulation of the neuron's membrane potential.

HFSP Program Grant holders Joerg Enderlein, Dan Oron, Antoine Triller and Shimon Weiss and colleagues
authored on Tue, 05 February 2019

“Seeing is believing” -  Kuo et al. research takes steps towards visualizing how neurons communicate and how neuronal connections in our brain function. They developed unique voltage nanosensors that one day might allow us to study large neuronal circuits with billions of neural connections. Such capabilities could eventually unravel how memories are stored in the brain, and how neuronal connections are formed or altered during the process of learning. Moreover, these unique nanosensors are so sensitive, that they could record signals from an individual synapse, hence monitoring molecular changes during memorization and learning. The surfaces of these nanosensors are functionalized such that they could ‘self-insert’ into the membranes of neurons. Neurons transmit and propagate signals via depolarizing and polarizing the membrane potential. The fluorescence of these membrane-inserted nanosensors is modulated by the changes of the membrane’s electrical potential, leading to changes in the fluorescence intensity and fluorescence wavelength (color). The tiny changes of signal from a single nanosensor can be collected via a microscope at up to 1kHz frame rate, a rate that is sufficient for recording individual action potentials (nerve impulses). This combination of sensitivity, nanoscale resolution, and speed will allow neuroscientists to monitor neural networks, composed of hundreds of neurons, in incredible detail, all in real time.

Semiconductor-based nanosensors with large quantum confined Stark effect are being developed as neural voltage sensors. The nanosensors exhibited large voltage sensitivity, fast response, long-term stability, and sufficient brightness for single-particle detection, which, in the future, could open up a new field of super-resolution detection of neural activities using single nanosensors. Supplementary Cover art from ACS Photonics 2018 5 (12). Credits: Yung Kuo and Stephen Sasaki. 

In the process of developing the nanosensors, Kuo et al. synthesized and characterized several types of semiconductor nanosensors with various material compositions, shapes, and sizes.  One of their main focuses was to optimize the nanosensor’s trigger mechanism, which relies on a unique nanoscale quantum phenomenon known as the quantum confined Stark effect.  To create nanosensors that are highly sensitive to the minute electric impulses in neurons, they designed a semiconductor nanorod, with a small spherical core embedded asymmetrically towards one end.  This highly asymmetric system forces the excited electron and hole to separate in space, which creates an excited state dipole that alters the nanosensor’s fluorescence.  The nanosensors’ performance was evaluated by several metrics at the single particle level: the emission spectra, the stability in voltage sensitivity, the half-life, the temporal response, and the correlation between applied field and the fluorescence responses.  All of these metrics will allow for further improvements in next generation voltage nanosensors.

With the collaboration established by HFSP funding, Kuo et al. (University of California, Los Angeles) closely worked with Prof. Dan Oron (Weizmann Institute, Rehovot) and Prof. Joerg Enderlein (Georg August University, Goettingen) to spectroscopically characterize these nanorods. The team has since established regular meetings and sharing of materials and research discoveries. Moreover, together with the group of Prof. Antoine Triller (IBENS / CNRS, Paris) they have made significant progress in delivering and targeting their nanorods to primary cultured neurons. The membrane inserted nanorods have shown voltage sensing capabilities at the single particle level.

Reference

Characterizing the Quantum-Confined Stark Effect in Semiconductor Quantum Dots and Nanorods for Single-Molecule Electrophysiology. Yung Kuo, Jack Li, Xavier Michalet, Alexey Chizhik, Noga Meir, Omri Bar-Elli, Emory Chan, Dan Oron, Joerg Enderlein, and Shimon Weiss, ACS Photonics 2018 5 (12), 4788-4800,  DOI: 10.1021/acsphotonics.8b00617

Other references

1. Development of a high throughput single-particle screening for inorganic semiconductor nanorods as neural voltage sensor. Yung Kuo; Kyoungwon Park; Jack Li; Antonino Ingargiola; Joonhyuck Park; Volodymyr Shvadchak; Shimon Weiss, Proc. SPIE 10352, Biosensing and Nanomedicine X, 103520L (29 August 2017); doi: 10.1117/12.2273089

2. Rapid Voltage Sensing with Single Nanorods via the Quantum Confined Stark Effect. Omri Bar-Elli, Dan Steinitz, Gaoling Yang, Ron Tenne, Anastasia Ludwig, Yung Kuo, Antoine Triller, Shimon Weiss, and Dan Oron, ACS Photonics 2018 5 (7), 2860-2867; doi: 10.1021/acsphotonics.8b00206

Link to article

Link to arXiv