Detecting ultra-low fluorescence with a new light-sensing device

In a nutshell: An organic photodetector measures the activity of brain cells at high resolution, overcoming the limitations of existing techniques ⎮ 1 min read
Published in Neuroscience
Detecting ultra-low fluorescence with a new light-sensing device
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Direct Detection of Neuronal Activity Using Organic Photodetectors

Calcium- and voltage-sensitive indicators allow for the optical monitoring of neuronal activity at both cellular and population levels. However, conventional approaches for the optical detection of electrical activity in an intact brain typically involve a trade-off between tissue depth and resolution. Cameras of high temporal and spatial resolution can detect activity with single-cell resolution, but are restricted to more superficial structures such as the neocortex and require elaborate optical setups. In contrast, optical fibers can collect fluorescent neural activity from deeper brain areas, but with low spatial resolution. Here, we present a new class of high-resolution, light-sensing devices that are capable of detecting ultralow changes in fluorescent neuronal activity without the need for an optical setup. We show that organic photodetectors (OPDs) based on rubrene and fullerene feature a photovoltage responsivity of 2 V m2 W–1 and that can directly detect changes in fluorescent neuronal activity as low as 2.3 nW cm–2. Primary cortical neurons were loaded with the fluorescent calcium indicator Cal-520, and neuronal activity was evoked with brief pulses of electrical field stimulation. During simultaneous sCMOS camera acquisition, the OPD was observed to reliably detect electrically evoked fluorescent activity with high fidelity and signal-to-noise ratio. The device also detected time-locked spontaneous fluorescent transients, demonstrating sufficient sensitivity for the detection of physiological events. Our results pave the way for a new class of subdermally implanted stereotactic sensors, representing a capacity for minimally invasive, high-resolution in vivo recordings, which are especially suited to record neuronal populations in behaving animals.

To study the brain, researchers often need to measure the activity of brain cells. They can do this by tagging specific components with fluorescent indicators, then using optical techniques to detect the fluorescence.

But using optical techniques in a living brain typically involves a trade-off between tissue depth and resolution. Cameras can detect activity within a single cell, but only in areas of the brain that are close to the surface. Optical fibres can measure activity deeper in the brain, but not at high resolution.

To solve this problem, Brain Function CoE researchers have developed a new type of high-resolution light-sensing device. Their organic photodetector can detect very small changes in fluorescence without the need for optical techniques. In experiments involving evoked and spontaneous brain-cell activity, the device directly detected ultra-low fluorescence with high accuracy and reliability.

The research was led by Marcin Kielar and Helen Gooch from Pankaj Sah’s group at the Queensland Brain Institute, in close collaboration with Ajay K. Pandey from Queensland University of Technology.

The device uses a new method of light detection, recently developed by the same research team, that overcomes the challenges posed by low levels of light.

The photodetector is built from rubrene and fullerene, two organic semiconductors with excellent mechanical, optical and electrical properties. It measures less than 300 nanometers across – 300 times thinner than a human hair. This small size is useful, as it means the device can be more easily implanted under the scalp for long-term recording. As the organic materials are biocompatible, implanting the device would not trigger an immune response.

These findings demonstrate the potential of organic photodetectors as a new type of high-resolution sensor for medical and biological imaging.

Next steps:
The researchers plan to use the organic photodetector to measure the activity of brain cells using voltage-sensitive indicators instead of calcium sensors. This would allow the activity of a single cell to be tracked at an unprecedented speed.

Reference:
Kielar, M., Gooch, H., Xu, L., Pandey, A. K., & Sah, P. (2021). Direct detection of neuronal activity using organic photodetectors. ACS Photonics, 8(1), 228–237. doi: 10.1021/acsphotonics.0c01378


This article originally appeared on The Brain Dialogue. Read the original article https://www.cibf.edu.au/light-sensing-device, available under CC-BY 4.0.

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