The marriage of biochemistry and nanotechnology for non-invasive real-time health monitoring

Abstract

Wearable biochemical sensors have received substantial attention in recent years due to their great potential to provide insights into the physical condition of individuals. Based on the innovative biochemical sensing mechanisms and the recent advances in material science, the integrated biosensors are moving toward soft and small on-body electronic systems that can smartly and persistently monitor tiny changes in biochemical markers. They are beginning to transform almost every aspect of healthcare. This review looks into the state-of-the-art advances in this rising field by connecting the noninvasive biochemical sensing principles, materials science, advanced integration methods and the most representative cases of health monitoring wearable biosensors. Specifically, starting with a brief overview of the trends in wearable healthcare devices, we introduce the fundamental of chemistry for bio-sensing. The subsequent content highlights the contributions of nanomaterials and nanotechnologies in integrating and achieving on-body bio-sensing systems. We also discuss the key issues emerging in this area from a biocompatibility and material perspective. In the end, the review concludes with a summary of opportunities where advances in biochemistry and nanotechnology will be significant for future progress.

Introduction

The biophysical and biochemical signals generated by natural physiological activities reveal critical information on the health status of individuals. More than 60% of the disease-associated deaths are caused by non-infectious diseases [1]. The data analysis based on physiological signals is an essential means of diagnosing and treating non-infectious conditions, extending people's lives [2]. In the future, the collected physiological data will be more valuable when combined with artificial intelligence (AI) technology, allowing doctors or individuals to spot abnormalities and track treatments in a timely manner. Generally, these signals can be detected by body-integrated sensors, while the available state-of-the-art measuring technologies still rely on rigid sensors with multiple wires and complex hardware/software that only professional personnel can operate and interpret. The currently emerging wearable devices, in the form of portable electronics that can be coupled to the wrist or integrated with clothing, have provided the possibility for real-time health monitoring. However, most of them can only record basic vital signs and are not suitable for long-term wearing, which still has the limitations for continuous data collection and deep analysis of physiological processes [3], [4].

Soft, thin wearable bio-sensors, that can be stacked onto skin and are able to noninvasively collect and transmit bio-signals in real-time, have demonstrated the potential to address the above limitations as a paradigm shift for healthcare monitoring [5], [6]. The first generation of wearable bio-integrated sensors have been achieved to record various biophysical signals (such as heartbeat [7], [8], [9], blood pressure [10], and body temperature [11]). Recent innovations in bio-chemical sensing technologies, material science and device integration technology have greatly improved the measuring accuracy, measuring types (chemical biomarkers [12]), function (waterproof [13], [14] and degradation [15]), durability (self-powered [16], [17] and self-healing [18]), and the affinity (to fit skin/tissue) of wearable bio-sensors. For a big step toward actual application, challenges still have to be overcome to make wearable bio-sensors even thinner, smaller, cheaper, more reliable, more lasting, and more biologically friendly. In this regard, the design of nanomaterials and the innovation of bio-nanotechnology, which will address problems from the basic principles at the atomic level, are still at the core for boosting the device’s overall performance toward clinical applications (Fig. 1).

In this review, we highlight the most relevant and recent advances in bio-integrated wearable technologies by particularly focusing on the representative examples and the chemistry concepts that hold the potential to mold the development directions of the field. The attractive capabilities of wearable bio-sensors as well as the related research advances (fabrication [19], [20], [21], [22], [23], [24], energy systems [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], designs [36], [37], [38], [39], sensing methods [40], [41], [42], [43], materials [44], [45], [46], [47], [48], [49], [50], [51], and application [52], [53], [54], [55], [56], [57]) have been examined in several recent reviews. Differently, this review provides an overview of the vital contribution of bio-nanotechnology and nanomaterial in wearable biosensors for advanced “on-body” healthcare monitoring. In particular, we start with a comprehensive introduction to the fundamental of bio-chemical sensing. The subsequent part summarized the classic nanomaterials used in wearable health monitoring sensors, highlighting their subversive influence on developing “on-body” bio-sensor systems. Furthermore, we overview the approach to achieve the wearable bio-integrated sensors in the aspects from large-scale preparation to newly emerging nanoscale integration technologies. Meantime, we discuss the applications of these integration methods in the most advanced biosensors, classified according to their ability to collect signals from the eye, mouth and skin. At last, the review discusses the key issues emerging in this area from the perspective of biochemistry and nanomaterials, highlighting the opportunities that the progress in biochemistry and nanotechnology will play critical roles for future progress.