Insights into Biocompatible and Bioorthogonal Fluorous-Phase Neural Probe for In Vivo Detection of Acetylcholine

Acetylcholine (ACh) is one of the least understood neurotransmitters, mainly due to difficulty in its selective detection in biological matrices. ACh appears in the brain and body of mammalians, and is released as a messenger by the nerve cells to communicate with other nerve cells, muscle cells, and gland cells. In the brain, ACh functions both as a neuromuscular transmitter and neuromodulator, and thus plays key roles in learning and memory, motivation, and muscle control. Alterations in ACh concentration in the cerebral cortex was correlated to dementia and Alzheimer's disease, psychiatric disorders such as schizophrenia and major depressive disorder, as well as anxiety and depression. Tools for selective sensing of ACh are crucial for better understanding the role of this neurotransmitter in disease progression, as well as rational design and testing of therapeutics that interact with the cholinergic receptors.<br/>For successful in-vivo recording of ACh levels, the neural probe (1) should have high selectivity to enable detection of ACh in the large background of other species in the complex brain environment, (2) should be flexible to minimize tissue scaring during probe insertion, (3) should be resistant to biofouling and remain functional after implantation, and (4) should be non-toxic and safe. This talk will discuss the strategies we have take to address these requirements for an ACh in-vivo probe through development of new materials for sensing and for electrode fabrication. We detect ACh using its permanent positive charge and a potentiometric sensing membrane. This membrane is made of a unique fluorous-phase material that provides outstanding selectivity and biocompatibility to the electrode. Fluorous compounds (not to be mistaken with fluorescent compounds) are molecules with high content of fluorine atoms. They are extremely non-polar to the extent that they are NOT miscible with oil and water. In fact, mixing water, hexanes, and perfluorohexane results in formation of three distinct phases. That is, fluorinated compounds are both hydrophobic and lipophobic. This sets apart fluorocarbons for novel biomedical applications. As a matter of fact, living systems are made of water and lipophilic compounds, making fluorocarbons bio-orthogonal, meaning that they do not interfere with biology. This work will show how the low polarity of the fluorous phase can enhance the selectivity and biocompatibility of our ACh sensor by orders of magnitude. We integrate this fluorous sensing membrane with a porous graphene electrode that is engraved on a flexible polyimide film using a CO₂ laser. This talk will discuss integration of laser-induced graphene electrodes (LIGs) with fluorous-phase sensing membranes to produce a new generation of highly selective, biocompatible, and resilient neural probes.