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.



中文翻译：

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用于慢性伤口愈合中即时 SERS 生物标志物检测的新型纤维素纤维基柔性等离子膜

背景：伤口管理正在扩大全球卫生系统的极限，挑战临床医生评估其治疗的有效性并为患者提供适当的护理。目视检查和手动测量伤口大小是主观的，通常不准确且不一致。生长因子，如促炎细胞因子和蛋白酶，在皮肤伤口愈合中起重要作用。然而，关于在愈合过程中对此类标志物变化的即时监测知之甚少。在这里，我们探索了表面增强拉曼光谱 (SERS) 作为一种可行的即时护理平台来监测这些慢性伤口愈合状态替代指标的变化的能力。
方法：我们使用纤维素纤维 (CF) 开发了一种生物功能化的柔性、经济高效、可扩展且易于制造的等离子体 SERS 基板，该基板用于基于改进的免疫测定方法检测伤口标志物。
结果：我们评估并选择了可靠的银纳米岛厚度，将其溅射到基于 CF 的基板上，以获得最高的 SERS 增强。使用这种生物功能化的 SERS 底物，我们检测到不同浓度的 MMP-9 (10–5000 ng/mL) 和 TNF-α (5–100 ng/mL) 蛋白来模拟伤口渗出液。这种 SERS 检测方法在生物学相关浓度范围内表现出线性响应，对于这些替代指标，MMP-9 的范围为 10 至 500 ng/mL，TNF-α 的范围为 5 至 25 ng/mL。
结论：我们的 SERS 传感平台实现了 μM 至亚 nM 范围内的检测限，并显示出高灵敏度和选择性。这可能会产生一种廉价的即时护理设备，可以实时提供皮肤伤口愈合的非侵入性测量。我们设想这些激活后的柔性基材将来可能会被纳入伤口敷料中，用于常规监测伤口愈合状态。