Flexible Electrochemical Sensors for Detection of Neurotransmitter

Acetylcholine (ACh) functions simultaneously as a neuromodulator and neuromuscular transmitter in the brain, thus playing critical roles in learning, recognition, motivation, and muscle control. Alterations in ACh concentration in the cerebral cortex were correlated to dementia and Alzheimer's disease, psychiatric disorders, anxiety, and depression. Therefore, developing instruments for selective sensing of ACh is essential to enhance the fundamental biological understanding of the role of this neurotransmitter in disease progression, as well as the rational design and testing of therapeutics that interact with the cholinergic receptors. Here, we are developing a sensor for the in-vivo recording of ACh levels in the brain tissue to address current challenges in ACh detection, including bulky and rigid neural probes and low selectivity in biofluids.<br/>I am utilizing potentiometric sensing, which offers direct selective measurement by eliminating separation and sample processing. Potentiometric sensors offer detection in a physiologically relevant concentration range and are a passive sensing mechanism that does not consume or perturb the analyte. These characteristics make potentiometric sensing a robust analytical technique that has grown in popularity for analyzing inorganic ions, including potassium (K+) and sodium (Na+) but has⁺) and sodium (Na⁺), but has remained underutilized for detecting neurotransmitters. We developed a proof-of-concept flexible potentiometric sensor for detecting ACh with less than one-second temporal resolution based on flexible parylene electrodes via utilizing a calixarene-based ionophore for ACh.<br/>Using parylene as the structural material for developing neuroprostheses has been validated and could be compared with technologies based on other materials such as PDMS, polyimide, and silicon. However, we are reporting the first potentiometric parylene-based ACh-selective neural probe. We are utilizing parylene due to providing a pinhole-free, highly flexible, sturdy mechanical strength, and biocompatible platform to construct implantable ACh-detecting sensors consisting of a working electrode (containing an acetylcholine organic sensing membrane) and a reference electrode (having a reference membrane). The parylene C substrate encompasses three 200 nM thick Pt electrodes with a 200 μm radius. The electrical potential (emf or electromotive force) between the ACh sensor and reference electrode correlates to the activity of ACh levels in the biofluid, according to the Nernst Equation (E=E^○+(RT/zF) log a_i), where E^○ shows the standard potential, R the universal gas constant, T temperature, F the Faraday constant, z the charge of the ion, and a_i the activity of ACh. A theoretical slope of 61.5 mV/decade is expected at body temperature and is defined as the Nernstian slope. The ACh-sensing membrane will be drop-cased onto the circular area of the platinum contact. To optimize the high signal stability, we will modify the surface of platinum with the variation of carbon nanotubes (CNTs) due to CNTs' capability to generate a stable and reliable interfacial potential in potentiometric sensors with an organic sensing membrane.