Fiber-shaped organic electrochemical transistors for biochemical detections with high sensitivity and stability

Precise and continuous monitoring of biochemicals by biosensors assists to understand physiological functions for various diagnostics and therapeutic applications.For implanted biosensors,small size and flexibility are essential for minimizing tissue damage and achieving accurate detection.However,the active surface area of sensor decreases as the sensor becomes smaller,which will increase the impedance and decrease the signal to noise ratio,resulting in a poor detection limit.Taking advantages of local amplification effect,organic electrochemical transistors(OECTs)constitute promising candidates for high-sensitive monitoring.However,their detections in deep tissues are rarely reported.Herein,we report a family of implantable,fiber-shaped all-in-one OECTs based on carbon nanotube fibers for versatile biochemical detection including H2O2,glucose,dopamine and glutamate.These fiber-shaped OECTs demonstrated high sensitivity,dynamical stability in physiological environment and antiinterference capability.After implantation in mouse brain,7-day dopamine monitoring in vivo was realized for the first time.These fiber-shaped OECTs could be great additions to the"life science"tool box and represent promising avenue for biomedical monitoring.

Implantable Fiber Biosensors Based on Carbon Nanotubes

CONSPECTUS:Implantable 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 longterm 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.

Flexible dopamine-sensing fiber based on potentiometric method for long-term detection in vivo

Achieving real-time,continuous and long-term monitoring of dopamine(DA)in vivo is essential for revealing brain functions and preventing and treating neurogenic diseases.However,it remains challenging to achieve a low limit of detection(LOD)and high neuron-compatibility at the same time for the current microsensors,resulting in the failure of long-term and accurate detection of DA in vivo.A DA-sensing fiber was achieved by the potentiometric method to possess a low LOD of 5 nM,1-3 orders of magnitude lower than amperometry and differential-pulse voltammetry.The sensing fiber showed a wide linear range from 5 to 185 nM that well matched the DA concentration(26-40 nM)in vivo.After implantation,the sensing fiber showed no influence on the firing rates of neurons with the potentiometric test,indicating high neuron-compatibility.It was then integrated with electrophysiology to simultaneously monitor DA variation and electrical signal in the brain,with stable monitoring of DA change in vivo for 8 weeks.The sensing fiber was flexible and stably worked after hundreds of bending,and it showed high sensitivity even after protein adsorption,thus offering a reliable tool for neuroscience.

Injectable Fiber Electronics for Tumor Treatment

Electrochemical therapy emerged as a low-cost and efective method for tumor ablation.However,it has challenges such as the production of toxic byproducts and the use of rigid electrodes that damage soft tissues.Here,we report a new injectable and tissue-compatible fber therapeutic electronics for safe and efcient tumor treatment.The design of aligned carbon nanotube(CNT)fber as electrodes endowed the device with high softness and enabled mini-invasive implantation through injection.Under a mild voltage(1.2 V),the fber device released hydroxyl ions to alter the local chemical environment of the tissues without additional toxic products/gases,leading to immediate death of tumor cells.The fexible fber device could form stable interface with tissues and showed good biocompatibility after implantation for 30 days.The in vitro experimental results showed the fber device could efciently kill 90.9%of QGY-7703 cancer cells after a single treatment in a few minutes.The tumor-bearing animal models proved that the fber therapeutic device could efectively inhibit the growth of tumor tissues,indicating it is a safe,efective,controllable and low-cost method for tumor therapy.