Implantable Fiber Biosensors Based on Carbon Nanotubes

ConspectusImplantable biosensors represent a rapidly developing direction with a wide range of applications in biotechnology and life science. For example, the detection of neurotransmitters in the brain has attracted a lot of attention because of their essential effects for neural activity. The in vivo acute detection of chemicals has been developed for decades, but there are few reports about in vivo chronic monitoring of chemicals probably due to two reasons. First, it is difficult to form stable interfaces between biosensors and tissues. Specifically, most of implantable biosensors are based on stiff electrode materials such as carbon fibers, whose moduli are several orders of magnitude higher than these of soft biological tissues. The mechanical mismatch between them will cause severe inflammatory response during chronic applications. Although some flexible neural probes with mesh geometry consisting of polymer and metal and polymer composite fibers have been employed in chronic electrophysiological recording, they are rarely employed for chronic monitoring of chemicals. Second, electrode deteriorations associated with degradation and fouling of functional materials make chemical recognitions difficult in dynamic environment. Generally, biosensors usually need to be modified with several functional materials including a recognition layer in order to identify specific chemicals from various untargeted chemicals. Although nanomaterials with high surface areas are reported to enhance the loading and immobilization of recognition layers so as to improve the sensitivity of biosensors, nanostructured and soft microelectrodes with high specific surface areas are rarely employed for long-term monitoring of chemicals in vivo.In this Account, we highlight our efforts toward flexible and miniaturized implantable fiber biosensors based on carbon nanotube (CNT) fibers for stable interfaces in vivo. We first summarize the assembly structure of CNT fiber electrodes and their mechanical, electrical, electrochemical, and biocompatible properties. Then we present a family of fiber biosensors by modifying CNT fibers with different recognition materials to detect multiple chemicals in vivo. After that, all-in-one fiber organic electrochemical transistors are described with higher sensitivity and lower detection limit, aiming to detect chemicals with low concentrations and trace changes in the deep brain. Finally, considering that soft implantable biosensors are difficult to be implanted without assistance, we introduce a neural probe with alterable moduli for direct implantation into the mouse brain and forming a stable interface with brain tissues. All three kinds of fiber biosensors are soft with mechanical properties matching biological tissues, remaining stable under deformation and showing high biocompatibility for long-term in vivo applications. Finally, a brief summary of challenges and outlooks in this field is presented.