Diabetes mellitus is a physiological and metabolic disorder affecting millions of people worldwide, associated with global morbidity, mortality, and financial expenses. Long-term complications can be avoided by frequent, continuous self-monitoring of blood glucose. Therefore, this review summarizes the current state-of-art glycemic control regimes involving measurement approaches and basic concepts. Following an introduction to the significance of continuous glucose sensing, we have tracked the evolution of glucose monitoring devices from minimally invasive to non-invasive methods to present an overview of the spectrum of continuous glucose monitoring (CGM) technologies. The conveniences, accuracy, and cost-effectiveness of the real-time CGM systems (rt-CGMs) are the factors considered for discussion. Transdermal biosensing and drug delivery routes have recently emerged as an innovative approach to substitute hypodermal needles. This work reviews skin-patchable glucose monitoring sensors for the first time, providing specifics of all the major findings in the past 6 years. Skin patch sensors and their progressive form, i.e., microneedle (MN) array sensory and delivery systems, are elaborated, covering self-powered, enzymatic, and non-enzymatic devices. The critical aspects reviewed are material design and assembly techniques focusing on flexibility, sensitivity, selectivity, biocompatibility, and user-end comfort. The review highlights the advantages of patchable MNs' multi-sensor technology designed to maintain precise blood glucose levels and administer diabetes drugs or insulin through a "sense and act" feedback loop. Subsequently, the limitations and potential challenges encountered from the MN array as rt-CGMs are listed. Furthermore, the current statuses of working prototype glucose-responsive "closed-loop" insulin delivery systems are discussed. Finally, the expected future developments and outlooks in clinical applications are discussed.
Keywords: continuous glucose monitoring; diabetes mellitus; microneedle; skin patch sensors; tattoo sensors.