Wearable devices are becoming widespread in a wide range of applications, from healthcare to biomedical monitoring systems, which enable continuous measurement of critical biomarkers for medical diagnostics, physiological health monitoring and evaluation. Especially as the elderly population grows globally, various chronic and acute diseases become increasingly important, and the medical industry is changing dramatically due to the need for point-of-care (POC) diagnosis and real-time monitoring of long-term health conditions. Wearable devices have evolved gradually in the form of accessories, integrated clothing, body attachments and body inserts. Over the past few decades, the tremendous development of electronics, biocompatible materials and nanomaterials has resulted in the development of implantable devices that enable the diagnosis and prognosis through small sensors and biomedical devices, and greatly improve the quality and efficacy of medical services. This article summarizes the wearable devices that have been developed to date, and provides a review of their clinical applications. We will also discuss the technical barriers and challenges in the development of wearable devices, and discuss future prospects on wearable biosensors for prevention, personalized medicine and real-time health monitoring.

SummaryThe enzyme triosephosphate isomerase (TIM) is a model of catalytic efficiency. The 11-residue loop 6 at the TIM active site plays a major role in this enzymatic prowess. The loop moves between open and closed states, which facilitate substrate access and catalysis, respectively. The N-and C-terminal hinges of loop 6 control this motion. Here, we detail flexibility requirements for hinges in a comparative solution NMR study of wild-type (WT) TIM and a quintuple mutant (PGG/GGG). The latter contained glycine substitutions in the N-terminal hinge at Val167 and Trp168, which follow the essential Pro166, and in the C-terminal hinge at Lys174, Thr175, and Ala176. Previous work demonstrated that PGG/GGG has a 10-fold higher K m value and 10 3 -fold reduced k cat relative to WT with either [D]-glyceraldehyde 3-phosphate or dihyrdroxyacetone phosphate as substrate. Our NMR results explain this in terms of altered loop-6 dynamics in PGG/GGG. In the mutant, loop 6 exhibits conformational heterogeneity with corresponding motional rates < 750 s −1 that are an order of magnitude slower than the natural WT loop-6 motion. At the same time, ns-timescale motions of loop 6 are greatly enhanced in the mutant relative to WT. These differences from WT behavior occur in both apo PGG/GGG and in the form bound to the reaction-intermediate analog, 2-phosphoglycolate (2-PGA). In addition, as indicated by 1 H, 15 N and 13 CO chemical-shifts, the glycine substitutions (a) diminished the enzyme's response to ligand, and (b) induced structural perturbations in apo and 2-PGA-bound forms of TIM that are atypical of those observed in WT. Altogether, these data show that PGG/GGG exists in multiple conformations that are not fully competent for ligand binding or catalysis. These experiments elucidate an important principle of catalytic hinge design in proteins: structural rigidity is essential for focused motional freedom of active-site loops.

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