Translational Biophotonics Laboratory, Institute of Bioengineering and Bioimaging, Agency for Science Technology and Research (ASTAR), Singapore.
Skin Research Institute of Singapore, Agency for Science, Technology and Research (ASTAR), Singapore.
Int J Nanomedicine. 2021 Aug 27;16:5869-5878. doi: 10.2147/IJN.S303130. eCollection 2021.
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.
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.
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.
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.
伤口管理正在全球范围内挑战卫生系统的极限，临床医生需要评估治疗效果并为患者提供适当的护理。肉眼观察和手动测量伤口大小具有主观性，且往往不够准确和一致。促炎细胞因子和蛋白酶等生长因子在皮肤伤口愈合中起着重要作用。然而，人们对这些愈合标志物在愈合过程中的即时监测知之甚少。在此，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，以监测慢性伤口愈合过程中这些愈合状态替代标志物的变化。
我们使用纤维素纤维（CF）开发了一种具有生物功能化、成本效益高、可扩展且易于制造的等离子体 SERS 基底，该基底可基于改良的免疫测定法用于检测伤口标志物。
我们评估并选择了可靠的银纳米岛厚度，将其溅射在 CF 基底上，以实现最高的 SERS 增强。使用这种生物功能化的 SERS 基底，我们检测了不同浓度的 MMP-9（10-5000 ng/mL）和 TNF-α（5-100 ng/mL）蛋白，以模拟伤口渗出物。这种 SERS 检测方法在生物相关浓度范围内表现出线性响应，MMP-9 的浓度范围为 10 至 500 ng/mL，TNF-α 的浓度范围为 5 至 25 ng/mL，适用于这些替代标志物。
我们的 SERS 传感平台实现了µM 至亚纳摩尔范围的检测限，并表现出高灵敏度和选择性。这可能导致一种廉价的即时护理设备，能够实时提供皮肤伤口愈合的非侵入性测量。我们设想，这些经激活的柔性基底未来可能会被整合到伤口敷料中，以常规监测伤口愈合状态。
