Implantable biosensors have evolved to the cutting-edge technology of personalized health care and provide promise for future directions in precision medicine. This is the reason why these devices stand to revolutionize our approach to health and disease management and offer insights into our bodily functions in ways that have never been possible before. This review article tries to delve into the important developments, new materials, and multifarious applications of these biosensors, along with a frank discussion on the challenges that the devices will face in their clinical deployment. In addition, techniques that have been employed for the improvement of the sensitivity and specificity of the biosensors alike are focused on in this article, like new biomarkers and advanced computational and data communicational models. A significant challenge of miniaturized in situ implants is that they need to be removed after serving their purpose. Surgical expulsion provokes discomfort to patients, potentially leading to post-operative complications. Therefore, the biodegradability of implants is an alternative method for removal through natural biological processes. This includes biocompatible materials to develop sensors that remain in the body over longer periods with a much-reduced immune response and better device longevity. However, the biodegradability of implantable sensors is still in its infancy compared to conventional non-biodegradable ones. Sensor design, morphology, fabrication, power, electronics, and data transmission all play a pivotal role in developing medically approved implantable biodegradable biosensors. Advanced material science and nanotechnology extended the capacity of different research groups to implement novel courses of action to design implantable and biodegradable sensor components. But the actualization of such potential for the transformative nature of the health sector, in the first place, will have to surmount the challenges related to biofouling, managing power, guaranteeing data security, and meeting today’s rules and regulations. Solving these problems will, therefore, not only enhance the performance and reliability of implantable biodegradable biosensors but also facilitate the translation of laboratory development into clinics, serving patients worldwide in their better disease management and personalized therapeutic interventions.

In this research, an interdigitated gear-shaped working electrode is presented for cortisol sensing. Overall, the sensor was designed in a three-electrode system and was fabricated using direct laser scribing. A synthesized conductive ink based on graphene and polyaniline was further employed to enhance the electrochemical performance of the sensor. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were employed for physicochemical characterization of the laser-induced graphene (LIG) sensor. Cortisol, a biomarker essential in detecting stress, was detected both in phosphate-buffered saline (PBS, pH = 7.4) and human serum within a linear range of 100 ng/mL to 100 µg/mL. Ferri/ferrocyanide was employed as the redox probe to detect cortisol in PBS. The electrochemical performance of the developed sensor was assessed via differential pulse voltammetry (DPV), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and chronoamperometry. The electrochemical performance demonstrates high sensitivity and selectivity alongside strong repeatability (relative standard deviation (RSD) = 3.8%, n = 4) and reproducibility (RSD = 5.85%, n = 5). Overall, these results highlight the sensor’s reliability, high sensitivity, and repeatability and reproducibility in the detection of cortisol. The sensor successfully detected cortisol in the complex medium of human serum and effectively distinguished it in a ternary mixture containing cortisol and dopamine. Also, the use of direct laser writing on Kapton film makes the approach cost-effective and thus disposable, making it suitable for chronic stress diagnostics and neurological research applications.

Wearable alcohol monitoring devices demand noninvasive, real-time measurement of blood alcohol content (BAC) reliably and continuously. A few commercial devices are available to determine BAC noninvasively by detecting transcutaneous diffused alcohol. However, they suffer from a lack of accuracy and reliability in the determination of BAC in real time due to the complex scenario of the human skin for transcutaneous alcohol diffusion and numerous factors (e.g., skin thickness, kinetics of alcohol, body weight, age, sex, metabolism rate, etc.). In this work, a transcutaneous alcohol diffusion model has been developed from real-time captured data from human wrists to better understand the kinetics of diffused alcohol from blood to different skin epidermis layers. Such a model will be a footprint to determine a base computational model in larger studies. Eight anonymous volunteers participated in this pilot study. A laboratory-built wearable blood alcohol content (BAC) monitoring device collected all the data to develop this diffusion model. The proton exchange membrane fuel cell (PEMFC) sensor was fabricated and integrated with an nRF51822 microcontroller, LMP91000 miniaturized potentiostat, 2.4 GHz transceiver supporting Bluetooth low energy (BLE), and all the necessary electronic components to build this wearable BAC monitoring device. The %BAC data in real time were collected using this device from these volunteers’ wrists and stored in the end device (e.g., smartphone). From the captured data, we demonstrate how the volatile alcohol concentration on the skin varies over time by comparing the alcohol concentration in the initial stage (= 10 min) and later time (= 100 min). We also compare the experimental results with the outputs of three different input profiles: piecewise linear, exponential linear, and Hoerl, to optimize the developed diffusion model. Our results demonstrate that the exponential linear function best fits the experimental data compared to the piecewise linear and Hoerl functions. Moreover, we have studied the impact of skin epidermis thickness within ±20% and demonstrate that a 20% decrease in this thickness results in faster dynamics compared to thicker skin. The model clearly shows how the diffusion front changes within a skin epidermis layer with time. We further verified that 60 min was roughly the time to reach the maximum concentration, C_max, in the stratum corneum from the transient analysis. Lastly, we found that a more significant time difference between BAC_max and C_max was due to greater alcohol consumption for a fixed absorption time.

Zinc oxide Nanowires (ZnO-NWs) are promising biosensor materials and hold the key to overcoming challenges in the field. This chapter provides an introductory overview of biosensing technology, focusing on the fundamental principles and comparing ZnO-NWs with other nanostructures regarding the surface area, reactivity, electrical properties, charge transport behavior, optical, magnetic, and piezoelectric properties, and mechanical flexibility. Providing the synthesis and characterization methods, ZnO-NWs’ biosensing processes are also elaborated on surface modification for selectivity, integration with microfluidic systems, enhancing signal transduction, and connecting with biological elements like enzymes, antibodies, and DNA. The chapter also discusses the applications of ZnO-NWs-based biosensors in clinical diagnostics, environment monitoring, and agricultural and food safety. It investigates some case studies and challenges in practical deployments. It emphasizes how ZnO-NWs can address these challenges, such as stability, reproducibility, scalability, and integration with electronic devices. Adequate emerging trends that include the utilization of machine learning (ML) and artificial intelligence (AI) for the further enhancement of sensing performance and the prospects of ZnO-NWs in multifunctional sensor platforms are also presented, with an overview of how ZnO-NWs have been the focus for significant impacts on biosensing. Also presented in this chapter are potential breakthroughs and future research directions.

This study presents a high-performance piezoelectric nanogenerator (PENG) based on aluminum-doped zinc oxide (Al:ZnO) nanorods synthesized via a novel sonochemical method. This rapid, cost-effective, and reproducible approach enables the synthesis of ZnO nanorods (ZnO NRs) under ambient conditions. The PENG, fabricated on a 177 µm flexible Indium Tin Oxide (ITO) coated polyethylene terephthalate (PET) substrate, benefits from optimized aluminum doping, enhancing the output voltage. Structural analyses conducted using atomic force microscopy (AFM), scanning electron microscopy (SEM), and X-ray diffraction (XRD) demonstrated that the synthesized ZnO nanorods possessed a high degree of crystallinity. The synthesis process was carefully fine-tuned to avoid thermal damage, keeping the substrates intact and fully functional. Electrical performance evaluations revealed a maximum peak-to-peak open-circuit voltage of around 6 V with a mean of 3.96 V and a standard deviation(S) of 1.27 V generated under mechanical stimulation, achieved through a finger-tapping method at a frequency of 2 Hz. Graphical abstract