Perumal, J., Lim, H. Q., Attia, A. B. E., Raziq, R., Leavesley, D. I., Upton, Z., … Olivo, M. (2021). Novel Cellulose Fibre-Based Flexible Plasmonic Membrane for Point-of-Care SERS Biomarker Detection in Chronic Wound Healing. International Journal of Nanomedicine, Volume 16, 5869–5878. doi:10.2147/ijn.s303130
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-ofcare
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-tofabricate
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-ofcare
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.
Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
This research / project is supported by the A*STAR - IAF-PP
Grant Reference no. : H1701a00H9
This research is supported by core funding from: A*STAR, Bio-Medical Research Council
Grant Reference no. :