Novel Cellulose Fibre-Based Flexible Plasmonic Membrane for Point-of-Care SERS Biomarker Detection in Chronic Wound Healing

Abstract

Background: Wound management is stretching the limits of health systems globally, challenging clinicians to evaluate the effectiveness of their treatments and deliver appropriate care to their patients. Visual inspection and manual measurement of wound size are subjective, often inaccurate and inconsistent. Growth factors, such as pro-inflammatory cytokines and proteases, play important roles in cutaneous wound healing. However, little is known about the point-of-care monitoring of the changes in such markers during the healing process. Here, we explore the capability of surface-enhanced Raman spectroscopy (SERS) as a viable point-of-care platform to monitor the changes of these surrogate indicators of healing status in chronic wounds.

Methods: We developed a biofunctionalized flexible, cost-effective, scalable and easy-to-fabricate plasmonic SERS substrate using cellulose fibre (CF), which is used for sensing of wound markers based on a modified immunoassay method.

Results: We evaluated and selected the reliable silver nano-island thickness that will be sputtered onto the CF-based substrate for the highest SERS enhancement. Using this biofunctionalized SERS substrate, we detected varying concentrations of MMP-9 (10-5000 ng/mL) and TNF-α (5-100 ng/mL) proteins to model the wound exudates. This SERS detection method demonstrates a linear response within biologically relevant concentrations, ranging from 10 to 500 ng/mL for MMP-9 and 5 to 25 ng/mL for TNF-α for these surrogate indicators.

Conclusion: Our SERS sensing platform achieved detection limits in the µM to sub-nM range and displayed high sensitivity and selectivity. This could result in a cheap, point-of-care device that provides a non-invasive measure of cutaneous wound healing in real time. We envision that these flexible substrates after activation may be incorporated into wound dressings in future for routine monitoring of wound healing status.

Keywords: SERS; cellulose fibres; flexible biosensor; membrane SERS; paper devices; point-of-care; wound biomarkers.