Non-Invasive Wearables in Inflammation Monitoring: From Biomarkers to Biosensors

Abstract

Quantifying inflammation plays a critical role in understanding the progression and development of various diseases. Non-invasive or minimally invasive wearable biosensors have garnered significant attention in recent years due to their convenience, comfort, and ability to provide continuous monitoring of biomarkers, particularly in infectious diseases and chronic diseases. However, there are still areas for improvement in developing reliable biosensing devices to detect key inflammatory biomarkers in clinically relevant biofluids. This review first introduces common biofluids with a focus on the most clinically significant inflammatory biomarkers. Specifically, it discusses the challenges encountered in extracting and detecting analytes in these biofluids. Subsequently, we review three popular types of non-invasive wearable biosensors for inflammation monitoring (microneedle patches, flexible electronic skins, and textile-based sensors). The design and operational considerations of these devices are analyzed, followed by an exploration of the information processing approaches employed during data processing. Finally, we envision future opportunities by guiding the development and refinement of non-invasive or minimally invasive wearable biosensors for continuous inflammation monitoring in chronic diseases.

Keywords: biological fluids; biomarkers; inflammation; non-invasive diagnostics; wearable sensors.

Figure 1

Overview of the review contents.

Figure 2

Several common representatives of non-invasive or minimally invasive biosensing devices for inflammation monitoring: Microneedle patch: (a) A hollow microneedle-lateral flow assay device for CRP monitoring in skin ISF [98]; (b) an encoded solid Microneedle Arrays for TNF-α, IL-1β and IL-6 detection in skin ISF [99]; (c) an antigen-modified porous microneedles for protein detection in skin ISF [100]. Flexible electronics: (d) A regenerative aptameric graphene-Nafion biosensor for IFN-γ monitoring in sweat [101];, (e) a laser-engraved graphene on fabrics for TNF-α monitoring in sweat [102]. Textile-Based sensors: (f) A TMB stained cotton swab for CRP detection in biofluids [103]; (g) antigen-modified electrospun nanofibers for CRP detection in biofluids [103].

Figure 3

Workflow of GNFET for CRP detection [136]: (a) Illustration of the fabrication, detection, and regenerative process of the GNFET biosensor; (b) photograph of the GNFET biosensor for biomarker detection; (c) photograph of the highly flexible biosensor conformably mounted on the human hand; (d) transfer characteristic curves measured when the biosensor was exposed to various IFN-γ concentrations in undiluted sweat; (e) and detection of various IFN-γ concentrations in artificial human hand sweat.

Figure 4

Main challenges faced by wearable biosensors for inflammation quantification.