According to the International Union of Pure and Applied Chemistry, a chemosensor is defined as “a device that transforms chemical information, ranging from the concentration of a specific sample component to total composition analysis, into an analytically useful signal” [14]. As shown in Figure 1, a typical chemosensor consists of two main functional units: a receptor that selectively recognizes the analytes of interest with high sensitivity and transforms their concentration into a physical or chemical output signal, and a transducer that alters this output signal to a readable value. Moreover, there is a signal amplifier circuit, a microcontroller, and wireless communication modules for the signal transmission to different displayers, such as a mobile phone or smart watch.

Wearable chemosensors can be categorized based on their receptors as affinity or catalytic-based, as well as on sensing principles as electrochemical, capacitive, calorimetric, piezoelectric, optical, and piezoresistive sensors ^[16][17][18][16,17,18]. Over the past decade, due to the evolving of new technologies, many types of wearable sensors have been rapidly developed since they can provide noninvasive monitoring and real-time information of a wearer’s health status in daily life. Apart from health monitoring, they can be used to improve athlete’s fitness, the optimization of soldier’s performance ^[18][19][20][18,19,20], and a wide range of purposes like security, communications, and business ^[19][20][21][19,20,21]. More specifically, wearable electrochemical sensors have received great attention because of their flexibility, portability, and biocompatibility, offering in situ personal health monitoring. Furthermore, the growing interest in those types of wearable sensors stems from the effort of decreasing health care costs transferring the centralized diagnosis and clinical monitoring of a patient at hospitals to personalized care at home ^{[14][16][22][23]}[14,16,22,23]. Point-of-care-testing exhibit several advantages in patient’s continuous health monitoring, such as convenient application for unskilled users, following of specific biochemical biomarkers, and a significant decrease of testing duration; however, it will never replace laboratory tests.

Generally, wearable chemosensor platforms enabling remote detection and monitoring of analytes comprise three functional elements: (1) the sensing system for physiological signal’s detection and collection, (2) the communication system for data transferring to a remote receptor, and (3) the data analysis system where the collected information from the sensing system will be extracted and evaluated [24]. The great requirement for highly sensitive, portable, and easy-to-use sensing devices that can provide important physiological information forced researchers to develop various detection platforms. Lately, advances in wearable chemosensors have been achieved due to the miniaturization of sensor’s electronics, the progress in material science and engineering, the growth of wireless communication systems, and the advances in energy harvesting systems.

The miniaturization of electronic circuits and devices has contributed significantly to wearable chemosensor’s evolution since one of the major obstacles to further employment of sensing technology into wearable applications was the sensor’s size. Recent advances in the field of microelectronics enable the development of miniature electronic circuits preserving sensing capability, microcontroller operations, and data transmission. Figure 2 illustrates the configuration of a typical example of a sensor employing this technology. The electronic microcircuit system is integrated onto a flexible substrate, detecting the targeted analyte’s signals, and transmitting the corresponding data wirelessly via Bluetooth. Nowadays, miniaturized devices are widely used in many applications, taking advantage of design versatility, high analytical efficacy, and low cost due to the minimization of fabrication materials.

Another essential component for the construction of wearable chemosensors is the sensing electrodes which are mostly metal-based films. Simultaneously, great efforts have been made for the development of new materials that could be used for the fabrication of wearable biochemical biosensors to ameliorate the sensor’s functionality, such as carbon and polymeric materials, nanocomposites, and nanoparticles ^[25][26][27][25,26,27]. Furthermore, the flexibility and stretchability of biointegrated electrodes play a key role in developing wearable electronics since it is a crucial design parameter for the uninterrupted operation of the sensor’s microcircuits. The term “electrode’s stretchability” is defined as the electrode’s ability to maintain its conductivity under mechanical deformation and can be quantified as the strain at which the electrode losses its conductivity and being nonconductive [28]. Since it is reported that even a minimum stretch of 1% could provoke a detachment of the electrode from the substrate ^[29][30][29,30], it is well understood that there is a high demand for high stretchability to preserve the seamless performance of the electrodes in the sensor device. Although there is difficulty finding materials that combine high conductivity and stretchability, composites of stretchable polymers with a conductive metal or carbon are used to obtain the desired properties ^[28][31][28,31].

Moreover, an emerging area for researchers in the field of chemistry is microfluidics ^[32][33][32,33]. Recently, microfluidics technology has gained attention because of the reduction in samples and solvent quantities required, resulting in lesser amounts of residue. This technology seems to have great prominence in wearable chemosensor platforms since it can be applied in portable sensor devices of various configurations and composition of the detector ^[33][34][35][33,34,35], whilst a local anesthetic (dibucaine) was detected with success at arrays of liquid/liquid micro interfaces [36]. Additionally, 2D and 3D printing technologies are used to develop new systems or upgrade existing ones, such as inkjet printing of wireless chemosensors [37]. Herein, further development and combination of the above-mentioned technologies with electrochemical techniques for the fabrication of miniaturized devices could guide a revolution in wearable chemosensors. Moreover, the combination of microfluidics with optics could guide applications for microfluidic drug delivery and drug screening [38], avoiding toxicity effects [39], as well as for tumor-treating [40] 

While many chemosensors are designed in the microscale, in our age nanofabrication techniques are gaining acceptance since materials in the nanoscale demonstrate remarkable properties (physical, chemical, thermoelectrical, mechanical, as well as biological) that makes them attractive candidates for applications in wearable chemosensors offering amended performances. Depending on the sensor’s type, the most suitable nanomaterials, fabrication methods, and transduction principles are selected in order to develop a sensing system with satisfying functionality and compatible wearability. The nanomaterials that will be used to prepare the sensing layer play a key role in selecting the proper fabrication method, whilst several different techniques and processes may be applied for the fabrication of a wearable chemosensor. Researchers use several common fabrication technologies, including printing ^{[41][42][43][44]}[41,42,43,44], lithography ^[45][46][45,46], and coating for fabricating sensors in the microscale. As a recent example of micro-fabrication via coating, in their latest paper Koralli et al. [47] presented the fabrication of a p-type Cu_xO and Cu_xO:Au compound thin films synthesized by Pulsed Laser Deposition in order to act as a CO gas detector.

In general, surface patterning in the micro and nanoscales, has become increasingly important as it enables manufacturing of NEMS-MEMS and sensors allowing for systematic investigation of cell-biomaterial interaction. Additionally, by these technologies it is possible to manufacture rapid, high-throughput tests for disease diagnosis and drug screening ^[48][52]. Recent advances in three-dimensional patterning allow for recapitulation of the cellular microenvironment, providing valuable insights into the interplay between biomolecules, cells, and biomaterials and facilitating the generation of personalized tissues for regenerative medicine applications ^[49][53].

It must be here reported, that, the whole armory of almost all types of micro- and nanoenabled chemo/bio sensors was made available to public health systems to detect COVID-19 virus symptoms ^[50][54] and presence in human breath, fluids etc. ^[51][55]. Criticism on which sensor–development pathways are best in such pandemics, has also been recently published ^[52][56].

Two-dimensional printing is applying for the preparation of conductive thin films integrated onto inert substrate materials such as ceramics, glass or polymers, as well as for the fabrication of screen-printed electrodes ^[53][54][57,58], whilst 3D printing facilitates the production of analytical devices and custom labware showing applications in many fields (biomedical engineering, medical science, etc.) ^[55][56][57][59,60,61]. Moreover, 3D printing is a cost-effective process that exhibits several sustainability benefits, such as materials savings, free design, complex structure’s manufacturing, and extension of the product life ^[58][62], while due to significant progress in the additive manufacturing process, the fabrication of electronic components and circuits is possible. Several commonly used 3D printing techniques are inkjet printing, fused deposition modelling (FDM), selective laser sintering (SLS), powder bed fusion, stereolithography (SLA), and laminated object manufacturing (LOM), whilst the direct energy deposition (DED) is mostly used for the fabrication of large and less complex components ^[59][63].

In the past few years, several studies have presented the development of novel 3D-printed microfluidic devices with applications in chemistry and biology ^[31][60][31,64]. Gowers et al. presented a 3D-printed microfluidic analysis device that acts as a biosensor for the continuous monitoring of glucose and lactate levels in human tissue, comprising an FDA-approved clinical microdialysis probe ^[61][65]. Under this strategy, Katseli and co-workers designed a ring-shaped wearable sensor device for noninvasive perspiration glucose monitoring, which was fabricated using commercially available filaments and a dual extruder 3D printer through a single–step printing process. The ring sensor was smartphone-addressable enabling self-testing nonenzymatic measurement of glucose levels in sweat ^[62][66]. A highly innovative glucose sensor was fabricated by printing a photonic microstructure with a periodicity of 1.6 μm, on a glucose-selective hydrogel film functionalized with phenylboronic acid ^[63][67] for wearable contact lenses. Yeh et al. reported the fabrication of a novel low-cost rotation chip for the real-time determination of the antibiotic-resistant bacteria profile. More specifically, the 3D printed device successfully made a rapid antibiotic-resistant screening test of E. coli by analyzing the RGB color values via a smartphone pixel analysis app ^[64][68]. Another group presented a portable 3D printed plastic optical fiber sensor compatible with use in IoT sensor applications for respiratory monitoring. The sensor was able to detect and discriminate between normal breathing, deep breathing, and breath-holding through the signal’s amplitude change ^[65][69]. Gevaerd et al. reported the development of a low-cost, portable, and microfluidic electrochemical sensor device fabricated via 3D printing for the determination of cortisol levels in saliva samples. The lab-made point-of-care sensor device had the ability to detect cortisol in a range of 0.25 to 25.0 μmol/L with exceptional analytical performance ^[66][70]. In further development of 3D printed biosensing, a new type of flexible piezoresistive tactile sensor was fabricated via a 3D printing method that mimics the texture and sensitivity of human skin. In this design, researchers used a new type of elastomeric 3D printing ink that contains carbon nanotubes distributed on the surfaces of interconnected polydimethylsiloxane microspheres in order to fabricate an electronic skin that simulates touch behavior of human skin, exhibiting high sensitivity, large durability and short time response ^[67][71].

Three-dimensional printing of a resin-based on the composite between a poly(ethylene glycol) diacrylate (PEGDA) host matrix and a poly(3,4ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) filler, and the related cumulative volatile organic compounds’ (VOCs) adsorbent properties was recently reported ^[68][72]. In the context of an interesting approach for volatile organic compounds (VOCs) sensing, an environmentally sustainable route to produce graphene ink designed explicitly for 3D extrusion-printing technology was shown ^[69][73]. The fabricated sensor devices under this strategy and the new ink displayed high-resolution patterning (average height/thickness of ~12 μm) and a 10-fold improvement in surface area/volume (SA/V) ratio compared to a conventional method of drop-casting.