Cai Chenlei, Liu Yujie, Zhang Zheng, Tian Tongtong, Wang Yuning, Wang Lei, Zhang Kun, Liu Baohong
Department of Medical Oncology, Department of Radiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Shanghai Institute for Pediatric Research, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
ACS Appl Mater Interfaces. 2023 Feb 1;15(4):4895-4902. doi: 10.1021/acsami.2c18261. Epub 2023 Jan 23.
The monitoring of metabolites in biofluids provides critical clues for disease diagnosis and evaluation. Yet, the quantitative detection of metabolites remains challenging for surface-enhanced Raman spectroscopy (SERS) due to poor reproducibility in preparation and manipulation of SERS nanoprobes. Herein, we develop an activity-based, slippery liquid-infused porous surface SERS (abSLIPSERS) sensor for facile quantification of metabolites with unmodified naked metal nanoparticles (NPs) by integrating biocatalysis-boronate oxidation cascades with SLIPS-driven self-concentration and delivering. Upon mixing the target metabolite with a specific oxidase, a HO-sensitive phenylboronate probe, and the naked Au NPs, HO produced from the biocatalytic reaction oxidizes the phenylboronate probe to phenol, resulting in a ratiometric SERS response. Meanwhile, the SLIPS enables the complete enrichment of molecules and NPs within an evaporating liquid droplet, delivering the probes to the SERS-active sites for Raman amplification. Compared with conventional SERS biosensors, abSLIPSERS avoids multistep synthesis and biofunctionalization of nanoprobes, which significantly simplifies the detection workflow and improves the reproducibility. The abSLIPSERS sensor also shows tunable dynamic range beyond 4 orders of magnitude and allows quantifying any other metabolites with specific enzymes. We demonstrate abSLIPSERS sensing of lactate, glucose, and choline in human serum for exploring energy metabolism in lung cancer. This study opens up a new opportunity for future point-of-care testing of circulating metabolites by SERS and will help to facilitate the translation of SERS bioanalysis to clinical settings.
生物流体中代谢物的监测为疾病诊断和评估提供了关键线索。然而，由于表面增强拉曼光谱（SERS）纳米探针在制备和操作过程中重现性较差，代谢物的定量检测仍然具有挑战性。在此，我们开发了一种基于活性的、注入滑液的多孔表面SERS（abSLIPSERS）传感器，通过将生物催化-硼酸氧化级联反应与滑液驱动的自浓缩和递送相结合，利用未修饰的裸金属纳米颗粒（NPs）对代谢物进行简便定量。将目标代谢物与特定氧化酶、对HO敏感的苯基硼酸探针和裸金纳米颗粒混合后，生物催化反应产生的HO将苯基硼酸探针氧化为苯酚，从而产生比率SERS响应。同时，滑液能够使蒸发液滴中的分子和纳米颗粒完全富集，将探针递送至SERS活性位点进行拉曼放大。与传统的SERS生物传感器相比，abSLIPSERS避免了纳米探针的多步合成和生物功能化，显著简化了检测流程并提高了重现性。abSLIPSERS传感器还显示出超过4个数量级的可调动态范围，并允许使用特定酶对任何其他代谢物进行定量。我们展示了abSLIPSERS对人血清中乳酸、葡萄糖和胆碱的传感，以探索肺癌中的能量代谢。这项研究为未来通过SERS进行循环代谢物的即时检测开辟了新机会，并将有助于促进SERS生物分析向临床应用的转化。
