Measuring the precise dynamics of specific neurotransmitters and neuromodulators in the brain is essential for understanding their regulation and activity at the molecular, cellular, and circuit levels. However, due to the complex nature of the central nervous system in terms of its anatomical and chemical characteristics, tracking specific neurotransmitters with high precision is extremely challenging.A general detection method would need to cover the entire spectrum of chemically diverse transmitters while still retaining the specific ability to distinguish between different transmitters.
Thanks to the development and optimization of various genetically encoded sensors in recent decades, several pioneering research tools with high cell specificity and good signal-to-noise ratio have been developed. At Creative Biolabs, we are approaching the stage of designing various tools to perceive the various characteristics of neurotransmission. These tools were reported very sensitive and specific detection for neurotransmitters and very suitable for tracking the precise dynamics of neurotransmitters and neuromodulators. Specifically, we provide multiple neurotransmitters imaging tools including genetically-encoded fluorescent sensors (e.g. PBP-based sensors, GPCR-activation Based (GRAB) Sensors), enzyme sensors and electrochemical sensors for ACh, DA, 5HT, EP, NE and GABA detection in preclinical clinical samples.
Design of Biosensors for neurotransmitter
Genetically encoded optical reporter genes are the most commonly used tools because they provide cell-specific expression and transmitter detection in the highly complex central nervous system. According to the type of neurotransmitter-binding protein, these sensors are usually classified into bacterial periplasmic binding protein (PBP)-based sensors or GPCR-based sensors. GPCR-based sensors constitute most of the receptors for neurotransmitters and neuromodulators, and have a conservative structural topology and high specificity for endogenous neurotransmitters.
In order to develop fluorescent biosensors for neurotransmitters or neuromodulators, the FRET pair FP or cpFP is combined with the corresponding binding proteins (called sensing domains). In FRET-based biosensors, the fluorescence intensity of the FRET donor and the FRET signal changes upon the neurotransmitter binding, so they are called ratiometric biosensors. In a single FP-based biosensor, the fluorescence of a single wavelength changes with the binding of neurotransmitters, so they are called intensiometric biosensors. Currently, two types of sensing domains are used in the engineering design of ratiometric and intensity biosensors.
Fig.1 Ratiometric and intensiometric biosensors. (Anna V, 2019)
Advantages of electrochemical sensors:
- Low cost, sensitive, time-saving and easy to miniaturize.
- Linear output, low power consumption requirements and good resolution.
- Excellent repeatability and accuracy.
- Simple modification based on enzymes, antibodies, DNA or polymers.
Advantages of genetically encoded optical sensors
- High sensitivity, chemical inertness and wide dynamic range.
- Minimal electromagnetic interference, no reference electrode required.
- Fast response time and high accuracy.
- Low-cost sensors and biodegradable electrodes.
- Kinetic evaluation of real-time affinity evaluation.
- Multi-analyte detection at different wavelengths.
Neurotransmitter fluorescent probe at Creative Biolabs
- Glutamate Biosensors
- Gaba Biosensors
- Acetylcholine Biosensors
- Dopamine Biosensors
- Opioid Biosensors
- ATP Biosensors
- Glycine Biosensor
In addition to ready-made neurotransmitter sensors, we also provide design and construction services for neurotransmitter sensors. If you are interested in our services, please send an email to contact us, and our team will get back to you as soon as possible.
- Leopold, A. V., Shcherbakova, D. M., & Verkhusha, V. V. (2019). Fluorescent biosensors for neurotransmission and neuromodulation: engineering and applications. Frontiers in cellular neuroscience, 13.
- Wang, H., Jing, M., & Li, Y. (2018). Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators. Current opinion in neurobiology, 50, 171-178.