COF-Coated Microelectrode for Space-Confined Electrochemical Sensing of Dopamine in Parkinson’s Disease Model Mouse Brain

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder causing the loss of dopaminergic neurons in the substantia nigra and the drastic depletion of dopamine (DA) in the striatum; thus, DA can act as a marker for PD diagnosis and therapeutic evaluation. However, detecting DA in the brain is not easy because of its low concentration and difficulty in sampling. In this work, we report the fabrication of a covalent organic framework (COF)-modified carbon fiber microelectrode (cCFE) that enables the real-time detection of DA in the mouse brain thanks to the outstanding antibiofouling and antichemical fouling ability, excellent analytical selectivity, and sensitivity offered by the COF modification. In particular, the COF can inhibit the polymerization of DA on the electrode (namely, chemical fouling) by spatially confining the molecular conformation and electrochemical oxidation of DA. The cCFE can stably and continuously work in the mouse brain to detect DA and monitor the variation of its concentration. Furthermore, it was combined with levodopa administration to devise a closed-loop feedback mode for PD diagnosis and therapy, in which the cCFE real-time monitors the concentration of DA in the PD model mouse brain to instruct the dose and injection time of levodopa, allowing a customized medication to improve therapeutic efficacy and meanwhile avoid adverse side effects. This work demonstrates the fascinating properties of a COF in fabricating electrochemical sensors for in vivo bioanalysis. We believe that the COF with structural tunability and diversity will offer enormous promise for selective detection of neurotransmitters in the brain.

Biosensor Strip for Rapid On‐site Assessment of Levodopa Pharmacokinetics along with Motor Performance in Parkinson's Disease

“…We envision that this technology can eventually be used in the ambulatory setting by PwP to detect L‐Dopa levels with rapid turnaround times and pre‐empt motor fluctuations, by allowing adjustments to therapy accordingly, towards personalized, optimal, and accessible management of PD symptoms. Additionally, in vivo probing of the dopamine dynamics, [38][39] in correlation with L‐Dopa intake will offer better understanding of the real‐time dynamics of the brain functioning of PwPs [40] . Overall, obtaining the temporal L‐Dopa capillary blood concentration profiles, along with the corresponding motor performance, in a decentralized clinical setting, offers tremendous potential for addressing the current shortcomings in personalized PD symptom management, including the narrow and variable therapeutic ranges across patients, toward optimizing L‐Dopa dosing regimens and improving the management of PD.…”

“…Additionally, in vivo probing of the dopamine dynamics, [38][39] in correlation with L-Dopa intake will offer better understanding of the real-time dynamics of the brain functioning of PwPs. [40] Overall, obtaining the temporal L-Dopa capillary blood concentration profiles, along with the corresponding motor performance, in a decentralized clinical setting, offers tremendous potential for addressing the current shortcomings in personalized PD symptom management, including the narrow and Angewandte Chemie variable therapeutic ranges across patients, toward optimizing L-Dopa dosing regimens and improving the management of PD.…”

Electrochemical Characterization of Neurotransmitters in a Single Submicron Droplet

“…Graphene-coated microelectrodes [12] Carbon fiber Covalent organic framework modified electrode [13]…”

A novel Cu-Cu2O hetero-structure for ultrasensitive detection of dopamine

“…Dopamine (DA) is an important catecholamine neurotransmitter that exists in the brain and peripheral nervous system (Amani et Zhou et al 2023). Abnormal levels of DA can lead to various neurodegenerative diseases, such as Parkinson's disease, Huntington's disease, schizophrenia, and epilepsy have been reported to mediate HIV replication in human macrophages (He et al 2022;Lakard et al 2021).…”