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An electrochemical aptamer-based cocaine sensor has been developed by Plaxco et. al., which involves immobilization of MB functionalized aptamer on a gold electrode surface and the use of square wave voltammetry (SWV) to detect an MB reduction current change that is proportional to the cocaine concentration. This aptasensor design has demonstrated excellent sensitivity and specificity in vitro [37,44,45]. By integrating cocaine aptamers onto implantable silicon MEAs, we showed successful in vivo cocaine sensing and electrophysiology recording from rat brains [35]. However, the sensor exhibited signal degradation 1 h after implantation [35]. Histology investigation revealed a layer of biological material composed of plasma proteins and microglia cells on the electrode sites that could compromise sensor performance [35,59]. The brain tissue foreign body response to the implanted silicon MEA devices has been well characterized by previous research and determined to cause recording quality decline [33,59,60,61,62,63,64]. A rich body of research has also shown that neural recording MEAs made from flexible polymer substrate cause less damage and inflammatory brain tissue response than their stiff counterparts [64,65,66]. In addition to the mechanical factors, surface chemistry is critical in the initial interaction between device and host tissue. Zwitterionic polymers carry positive and negative charges at a 1:1 ratio in each repeating unit. The high concentration of ions along the backbone gives zwitterionic polymers exceptional hydration power. Surfaces with zwitterionic polymer coatings are super-hydrophilic. Water molecules bind strongly to the zwitterionic surface and form a hydration layer that can inhibit protein adsorption and cell attachment [67,68,69,70,71,72]. Our previous studies have demonstrated that zwitterionic polymers can prevent non-specific protein adsorption and cell adhesion in vitro and are also beneficial in reducing glia cell adhesion and tissue response in vivo [72,73]. Another potential cause of sensor signal degradation could be aptamer degradation by extracellular DNase-1. In addition to the excellent anti-fouling potential, the zwitterionic polymer coating may also act as a physical barrier that blocks large biomolecules such as DNase-1 from interacting with the electrode surface and aptamers.



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