Advances in the Translation of Electrochemical Hydrogel‐Based Sensors

Abstract

Novel biomaterials for bio‐ and chemical sensing applications have gained considerable traction in the diagnostic community with rising trends of using biocompatible and lowly cytotoxic material. Hydrogel‐based electrochemical sensors have become a promising candidate for their swellable, nano‐/microporous, and aqueous 3D structures capable of immobilizing catalytic enzymes, electroactive species, whole cells, and complex tissue models, while maintaining tunable mechanical properties in wearable and implantable applications. With advances in highly controllable fabrication and processability of these novel biomaterials, the possibility of bio‐nanocomposite hydrogel‐based electrochemical sensing presents a paradigm shift in the development of biocompatible, “smart,” and sensitive health monitoring point‐of‐care devices. Here, recent advances in electrochemical hydrogels for the detection of biomarkers in vitro, in situ, and in vivo are briefly reviewed to demonstrate their applicability in ideal conditions, in complex cellular environments, and in live animal models, respectively, to provide a comprehensive assessment of whether these biomaterials are ready for point‐of‐care translation and biointegration. Sensors based on conductive and nonconductive polymers are presented, with highlights of nano‐/microstructured electrodes that provide enhanced sensitivity and selectivity in biocompatible matrices. An outlook on current challenges that shall be addressed for the realization of truly continuous real‐time sensing platforms is also presented.

Wireless Battery-free and Fully Implantable Organ Interfaces

“…206−209 Common measures of cytotoxicity define a substance to be biocompatible at above 80−90% localized cell survival. 208 Even if a material is classified as bioinert, there are always surface interactions with local tissue, fluids, proteins, and ions to consider. 210 This is critically important for implantable electrodes, which often have metal contacts exposed to the local tissue environment and are susceptible to oxidation-driven impedance increases, lowering sensitivity or stimulation efficiency.…”

“…Cytotoxicity, measured qualitatively through fluorescent imaging or quantitatively with cell counting kits, is a standard metric for qualifying biocompatibility. − Common measures of cytotoxicity define a substance to be biocompatible at above 80–90% localized cell survival . Even if a material is classified as bioinert, there are always surface interactions with local tissue, fluids, proteins, and ions to consider .…”

A Review of Functional Hydrogels for Flexible Chemical Sensors

“…[ 29 ] PVA is also a water‐soluble polymer that can be physically or chemically cross‐linked, and then becomes suitable for special circumstances, such as in water or biological fluid environments. [ 11a ] Due to their unique mechanical properties, biocompatibility, and biodegradability, PVA‐based hydrogels have emerged as promising materials to manufacture wearable chemical sensors in recent years. [ 50 ] For instance, a bendable/wearable ethanol sensor had been successfully fabricated with a limit of detection (LOD) of 9.17 ppm by using PVA as coating material.…”

“…Tremendous efforts have been made to improve the performance of flexible chemical sensors by developing innovative materials and device structures. Advanced materials including carbon‐based materials (e.g., carbon nanotubes, graphene, and carbon dots), [ 1a,9 ] transition metal compounds (e.g., MnO 2 , MoS 2 , and Ti 3 C 2 T x MXene), [ 10 ] and hydrogels [ 11 ] have been developed to manufacture flexible chemical sensors because of their great mechanical, electrical, and chemical properties. Among them, hydrogels have emerged as one of the most ideal building blocks of flexible chemical sensors, especially in wearable applications due to their excellent biocompatibility as well as tissue‐like chemical, mechanical, and biological properties.…”

Challenges and Advances of Hydrogel-Based Wearable Electrochemical Biosensors for Real-Time Monitoring of Biofluids: From Lab to Market. A Review

“…Recent advances are the development of hydrogel-based wearable biosensors, which have the advantages of biocompatibility and flexibility. Besides, they mimic the properties of hydrated biological tissues, thus making them suitable for in vivo applications . Moreover, their synthetic versatility enables precise control over the chemistry of gels, offering high specificity to different stimuli …”