## 4 Wearable-Based Biosensors as Cross-Cutting Devices  
As reported by the World Economic Forum, by 2030, the very nature of diseases will be further disrupted by technology. The fourth industrial revolution will ensure that humans live longer and healthier lives, so that the hospitals of the future will become more like NASCAR pit-stops rather than inescapable black holes. You will go to the hospital to be patched up and put back on track, revolutionizing healthcare from hospital to \"home-spital\" [35]. Currently, commercially available wearable sensors are aimed at physical sensing to monitor physiological parameters, but they do not provide any information at the molecular level (chemical sensing), which is also a key issue in the defence field. Harnessing the principle of the choline oxidase based-bioassay, we developed a wearable and reagent-free biosensor, suitable for the on-site detection of both liquid and airborne mustard agents, exploiting filter paper to design a 3D structured origami-ePAD (Figure 4A). In detail, an electrochemical cell was developed onto the first layer of the origami by printing the conductive inks to realize the electrodes as well as to load the choline oxidase enzyme, and in the second layer, the electrolyte salts as well as the choline substrate were pre-loaded by exploiting the adsorptive properties of filter paper. Then, the measurements were carried out by assembling the origami layers, allowing for reaction within the pre-loaded reagents. The monitoring of choline oxidase enzyme was carried out using a filter paper-based sensor to detect sulphur mustard in the liquid phase, as well as in the gas phase, obtained by aerosolising sulphur mustard with a nebulizer. In detail, the origami-like biosensor was successfully tested for the rapid and real-time detection of sulphur mustard with detection limit equal to 1 mM and 0.019 g \(\times\cdot\)min/m\({}^{3}\) for the liquid and gas phase, respectively. The results achieved demonstrated the applicability of paper-based origami-inspired ePAD for ready-to-use wearable sensors for the monitoring of substances into the liquid as well as the gas phases [36]. [PERSON]'s group developed the first wearable skin and textile-worn biosensors for the continuous monitoring of nerve agents in the vapour-phase using organophosphate hydrolase (Figure 4B). This electrochemical biosensor was fabricated with elastomeric inks to deliver a flexible device integrated with an electronic interface able to maintain the functionality under mechanical stress and to send the data to a mobile device by wireless data transmission. By detecting the enzymatic by-product nitrogenhol product in square wave voltammetry, the epidermal tattoo and textile sensors allowed for linearity over the 90-300 mg/L range and detection limit of 12 mg/L, demonstrating the suitability as a rapid warning device for personal exposure to nerve-agent vapours [37]. The same group developed a potentiometric tattoo biosensor for real-time on-body quantification of G-type nerve agent simulant by using a pH-sensitive polyaniline sensor combined with organophosphate hydrolase as a biocomponent. This biosensor demonstrated a linearity between 20-120 mM using a nebulizer solution of nerve agent simulant diisopropyl fluorophosphates, with a limit of quantification of around 10 mM [38]. Figure 4: _Cont._  
The novel approach using a wearable microneedle sensor array to distinguish between opioid overdose and nerve agent poisoning was reported in the Journal of American Chemical Society in 2020 by the same group [39]. The microneedle array was fabricated by using a hollow microneedle working electrodes allowing (i) for direct voltammetric detection of fentanyl-based on oxidative dealkylation of the piperidine tertiary amine and nonfentanyl production with a peak at +0.7 V, and (ii) for square wave voltammetry of the organophosphate hydrolase-by product, i.e., p-nitrophenol using methyl paraoxon as a nerve agent simulant, with a peak at ca. +0.72 V (Figure 4C).