Zwitterionic Polymer Coated and Aptamer Functionalized Flexible Micro-Electrode Arrays for In Vivo Cocaine Sensing and Electrophysiology

Abstract

The number of people aged 12 years and older using illicit drugs reached 59.3 million in 2020, among which 5.2 million are cocaine users based on the national data. In order to fully understand cocaine addiction and develop effective therapies, a tool is needed to reliably measure real-time cocaine concentration and neural activity in different regions of the brain with high spatial and temporal resolution. Integrated biochemical sensing devices based upon flexible microelectrode arrays (MEA) have emerged as a powerful tool for such purposes; however, MEAs suffer from undesired biofouling and inflammatory reactions, while those with immobilized biologic sensing elements experience additional failures due to biomolecule degradation. Aptasensors are powerful tools for building highly selective sensors for analytes that have been difficult to detect. In this work, DNA aptamer-based electrochemical cocaine sensors were integrated on flexible MEAs and protected with an antifouling zwitterionic poly (sulfobetaine methacrylate) (PSB) coating, in order to prevent sensors from biofouling and degradation by the host tissue. In vitro experiments showed that without the PSB coating, both adsorption of plasma protein albumin and exposure to DNase-1 enzyme have detrimental effects on sensor performance, decreasing signal amplitude and the sensitivity of the sensors. Albumin adsorption caused a 44.4% sensitivity loss, and DNase-1 exposure for 24 hr resulted in a 57.2% sensitivity reduction. The PSB coating successfully protected sensors from albumin fouling and DNase-1 enzyme digestion. In vivo tests showed that the PSB coated MEA aptasensors can detect repeated cocaine infusions in the brain for 3 hrs after implantation without sensitivity degradation. Additionally, the same MEAs can record electrophysiological signals at different tissue depths simultaneously. This novel flexible MEA with integrated cocaine sensors can serve as a valuable tool for understanding the mechanisms of cocaine addiction, while the PSB coating technology can be generalized to improve all implantable devices suffering from biofouling and inflammatory host responses.

PEDOT/CNT Flexible MEAs Reveal New Insights into the Clock Gene's Role in Dopamine Dynamics

“…[ 18 , 19 , 20 , 21 , 22 , 23 , 24 ] On top of the electrical recording capability, MEAs can also be used as a versatile platform for incorporating additional functionalities (electrochemical sensing, light or drug delivery) and have achieved a considerable level of success for acute applications. [ 19 , 20 , 22 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ] The idea of using MEAs for in vivo electrochemical DA sensing and electrophysiology recording has been shown to be possible under acute conditions. [ 28 , 29 , 33 ] However, conventional MEAs have metal sites that have low specificity and sensitivity toward DA.…”

In vitro biocompatibility evaluation of functional electrically stimulating microelectrodes on primary glia

“…Other reports document the conjugation of biomolecules onto the surfaces of the electrodes to mask its foreign signature (Eles et al, 2017;Sridar et al, 2017). Antifouling compounds (e.g., zwitterionic polymers, polyethylene glycol) have also been reported in the literature to attenuate acute inflammatory responses elicited against invasive implants (Golabchi et al, 2019;Yang et al, 2020;Gori et al, 2021;Cho et al, 2023;Wu et al, 2023).…”