Non-Invasive Biosensors for Real-Time Health Monitoring: Recent Engineering Advances

The need for an ongoing, decentralized, and patient-focused approach to healthcare has resulted in increased development of non-penetrating biosensor technology that can provide clinically meaningful data through the extraction of data without blood sampling and/or penetration of the skin. Advances in both the field of functional materials as well as micro/nano-fabrication techniques, and flexible electronic devices with embedded intelligence have allowed for a new class of wearables/portable biosensors to be developed that will extract data from biofluids (e.g., sweat, saliva, tears, breath, etc.) and physiologic signals from the skin's surface. These types of platforms allow for the real time collection of biochemical/biophysical data and are increasingly being integrated into digital health networks.This paper is intended to provide a critical analysis of recent advancements in engineering that contribute to the development of non-penetrating biosensors, including: sensing mechanisms; transducer architectures; strategies for integrating devices; and frameworks for analyzing data. In addition to providing a summary of current technologies, this paper proposes a paradigmatic shift toward developing multimodal, adaptive and self-calibration biosensing systems that utilize heterogeneous sensors along with intelligent algorithms to compensate for variations in biology and environmental noise. Examples of healthcare applications and challenges associated with these applications are discussed along with future directions for research that could potentially lead to clinical-deployment of large scale, clinically-robust non-penetrating biosensors. Ultimately, non-penetrating biosensors are considered to be foundational elements in the development of future generations of precision and preventative healthcare. Key Words:Non-invasive biosensors; wearable sensing; real-time monitoring; multimodal biosensing; digital health; point-of-care diagnostics. .