In-vivo real-time monitoring of neurotransmitter in mouse brain for study of neurodevelopmental disorders

Real-time monitoring of brain neurotransmitters, such as dopamine and serotonin is the key in understanding the biological bases of neurodevelopmental disorders and also in the development of novel therapeutic agents for the treatment. Current method for detecting brain neurotransmitters such as HPLC requires large sample volume and takes long time for sample collection. Dr. Wang has been developing a novel label-free biosensor based on ultraviolet plasmonic enhanced native fluorescence. The UV plasmonic sensor is label-free and does not require signal enhancement from enzyme or nanoparticles, thus can significantly improve the detection speed. The sensor requires very small sample volume and can be integrated into the microdialysis apparatus to realize real-time monitoring of brain neurotransmitters.
The project will be a new cross campus collaboration between the College of Engineering (Drs. Yunshan Wang, Steve Blair and Jules Magda), College of Pharmacy (Dr. Marco Bortolato). The proposal addresses the University’s four strategic goals: 1) Generate new knowledge regarding to plasmonic enhancement of native fluorescence of neurochemicals. 2) Provide experience to graduate students and undergraduate students working in an interdisciplinary environment 3) Contribute our understanding in neurodevelopmental disorders and facilitate the development of treatment methods. 4) Cultivate One U partnerships across campus and within our communities.

Current Status

2021-09-13
Abstract:
Neurotransmitters are electrochemical signaling molecules which are essential for proper brain function and crucial for signal transmission in the neuronal system. Current methods for measuring neurotransmitters such as HPLC and ELISA can detect concentration at pM range; however, they require large sample volume and take a long time for sample collection (hours long), providing no-way for continuous, real-time detection. On the other hand, electrochemical sensors and SPR sensors provide better resolution but suffer from poor sensitivity (typically in the nM range or higher). Therefore, methods/assays that can detect and quantitate neurotransmitters at their physiological levels in a continuous, real-time fashion are highly demanded. We propose to develop a novel sensor that is expected to achieve continuous, real-time detection of neurotransmitters with high sensitivity (10 pM concentration range), better temporal resolution and high selectivity. We fabricated and tested an aluminum nanohole arrays and achieved an enhanced fluorescence emission spectrum with a limit of detection (LOD) on the order of 10 pg/mm2. Also, we investigated the selectivity of the sensor against similarly structured biomolecules such as dopamine and norepinephrine. The photobleaching rates for these two molecules are significantly different, which implies that they can be differentiated without recognition elements such as antibodies.

Publications

Lee, J.Y., Cheng, X. and Wang, Y., 2021. Ultraviolet plasmonic enhancement of the native fluorescence of tryptophan on aluminum nano-hole arrays. Journal of Physics D: Applied Physics, 54(13), p.135107.