**3.4. Miniaturization: implantable devices**

for drug screening applications [69]. To enhance the electrocatalytic effect of the sensing electrode, the PEDOT:PSS gate can also be supplied with electrodeposited Pt nanoparticles [70]. Owing to the high surface area of the nanoparticles and the high specificity of the biocatalyst, the authors obtained very sensitive detection of the crucial metabolites such as glucose and lactate from live cells. Lactate production in tumor cell cultures derived from real patients was also studied using an OECT circuit. Lactate production could be measured from a few cells, underlining the sensitivity of the tool in a highly complex milieu, thus shown its potential for utilization in *in vivo* applications for cancer diagnostics [71]. Also, recently, Curto et al. presented a multiparametric on-chip platform integrated with microfluidics for cell cultures, using among other in-line methods the OECT-based detection of glucose produced by the cells as a measure to validate their improved differentiation under stimuli conditions [72].

An indisputable trend in biosensor technology is on-body continuous monitoring of metabolites using wearable devices (**Figure 4**) [1]. Wearable biosensor applications aim to transform centralized hospital-based care systems to home-based personal medicine, reducing healthcare cost and time for diagnosis. Electrochemical transducers offer many benefits as wearable sensors for physiological monitoring, and can be easily integrated onto textile materials or directly on the skin. Sweat-based wearable sensors, although mostly focused on a small number of physical or electrophysiological parameters, can yield crucial information about the health status of a patient based on levels of vital metabolites [73]. Wearable biosensors can be either textile/plastic-based or epidermal (tattoo)-based systems [74]. Epidermal biosensors supply better contact with skin but commonly exhibit shorter lifetimes than the textile-based tools. Such biosensors were first developed in 2009 by Kim et al. for continuous monitoring of physical parameters [75] and, shortly thereafter, Jia et al. combined this route with biorecognition elements to generate the first printed tattoo-based biosensor [76]. A screen-printed electrode on no permanent tattoo paper was investigated with carbon and silver (Ag)/AgCl serving as the working and reference electrodes, respectively. The working electrode was also modified with carbon nanotubes carrying a mediator together with lactate oxidase for endlessly monitoring lactate in sweat during exercise [76].

CPs are specially beneficial for wearable sensor technology owing to their compatibility with production on flexible solids [77]. In a very interesting way, Pal et al. investigated PEDOT:PSS

**3.3. Wearable metabolite biosensors**

62 Green Electronics

**Figure 4.** Overview of the swiftly increasing field of wearable biosensors.

The perspectives of implantable instruments and especially home-based metabolic monitoring can only be reached if they can be simply implanted and explanted (i.e. needle-assisted) without the necessity of complicated surgery [81]. Due to that, the implantable tool should be small, which calls for novel miniaturization of different functional elements such as electrodes, power sources, signal processing systems and sensory components. In addition, miniaturized biosensors implanted by ultrafine needles induce less tissue damage and then less inflammation and foreign body response [82]. Miniaturization of implantable instruments and particularly biosensors can be listed under: (1) miniaturization of sensing electrodes and elements and (2) miniaturization of driving electronics for power, communication and their subsequent integration/packaging. Referring to the production of miniaturized electrodes for analyte sensing, immobilization of biocatalyst onto an ultra-thin Pt wire (diameters less than 50 μm) or carbon nanofibres has been substantial [83]. The latter is convenient for generating nerve stimulating microelectrodes because of the possibility of ultra-fine dimensions and flexibility [84]. Due to subsequent improvement of the electrocatalytic feature of carbon nanofibres, these were modified with different metal nanoparticles without compromising their flexibility [85]. Recently, the advent of sub-micron lithography and its further use to produce miniaturized transistors has encouraged investigators to develop solid state electrochemical sensing systems in a transistor order [86]. Biosensors based on classic Si-based transistors as well as the incipient organic thin film transistors are being investigated for a scope of analytes. The unique electrical character of 1-D nanomaterials (CPs) [86] has led researchers to use them as channel materials and investigates sensors based on modifications induced in either gate conductance, modulation, transconduction, hysteresis or threshold voltage.

The flexible nature of polymers together with their low-temperature processing and demonstrated biocompatibility with enzymes renders them beneficial over classic Si- and glass-based materials [81]. Additionally, the soft and flexible character of polymers could reduce the possibility of tissue damage to the body during implantation and can be beneficial for applications where the instrument has to be able to adjust itself to the shape of the human body.
