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基于溶液的超灵敏表面增强拉曼散射检测生物流体中毒素细菌生物标志物绿脓菌素的方法:利用锋利分支金纳米星。

Solution-Based Ultra-Sensitive Surface-Enhanced Raman Scattering Detection of the Toxin Bacterial Biomarker Pyocyanin in Biological Fluids Using Sharp-Branched Gold Nanostars.

机构信息

Fitzpatrick Institute for Photonics, Duke University, Durham, North Carolina 27708, United States.

Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States.

出版信息

Anal Chem. 2023 Feb 7;95(5):2690-2697. doi: 10.1021/acs.analchem.2c03210. Epub 2023 Jan 24.


DOI:10.1021/acs.analchem.2c03210
PMID:36693215
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9909734/
Abstract

There is a critical need for sensitive rapid point-of-care detection of bacterial infection biomarkers in complex biological fluids with minimal sample preparation, which can improve early-stage diagnosis and prevent several bacterial infections and fatal diseases. A solution-based surface-enhanced Raman scattering (SERS) detection platform has long been sought after for low cost, rapid, and on-site detection of analyte molecules, but current methods still exhibit poor sensitivity. In this study, we have tuned the morphology of the surfactant-free gold nanostars (GNSs) to achieve sharp protruding spikes for maximum SERS enhancement. We have controlled the GNS spike morphologies and optimized SERS performance in the solution phase using para-mercaptobenzoic acid as an SERS probe. To illustrate the potential for point-of-care applications, we have utilized a portable Raman instrument for measurements. For pathogenic agent sensing applications, we demonstrated rapid and sensitive detection of the toxin biomarker pyocyanin (PYO) used as the bacterial biomarker model system. Pyocyanin is a toxic compound produced and secreted by the common water-borne Gram-negative bacterium , a pathogen known for advanced antibiotic resistance and association with serious diseases such as ventilator-associated pneumonia and cystic fibrosis. The limit of detection (LOD) achieved for PYO was 0.05 nM using sharp branched GNSs. Furthermore, as a proof of strategy, this SERS detection of PYO was performed directly in drinking water, human saliva, and human urine without any sample treatment pre-purification, achieving an LOD of 0.05 nM for drinking water and 0.4 nM for human saliva and urine. This work provides a proof-of-principle demonstration for the high sensitivity detection of the bacterial toxin biomarker with minimal sample preparation: the "mix and detect" detection of the GNS platform is simple, robust, and rapid, taking only 1-2 min for each measurement. Overall, our SERS detection platform shows great potential for point-of-need sensing and point-of-care diagnostics in biological fluids.

摘要

迫切需要在复杂的生物流体中进行敏感的快速床边检测,以最小的样本制备量检测细菌感染生物标志物,这可以改善早期诊断,预防多种细菌感染和致命疾病。基于溶液的表面增强拉曼散射(SERS)检测平台因其低成本、快速和现场检测分析物分子而备受关注,但目前的方法仍然表现出较差的灵敏度。在本研究中,我们调整了无表面活性剂的金纳米星(GNS)的形态,以实现最大 SERS 增强的尖锐突出刺。我们控制了 GNS 刺的形态,并使用对巯基苯甲酸作为 SERS 探针在溶液相中优化了 SERS 性能。为了说明在床边应用的潜力,我们使用便携式拉曼仪进行了测量。对于病原体检测应用,我们展示了快速和敏感检测用作细菌生物标志物模型系统的毒素生物标志物绿脓菌素(PYO)。绿脓菌素是一种由常见的水生革兰氏阴性菌产生和分泌的有毒化合物,该病原体具有先进的抗生素耐药性,并与呼吸机相关性肺炎和囊性纤维化等严重疾病有关。使用尖锐分支的 GNS 实现了对 PYO 的检测限(LOD)为 0.05 nM。此外,作为策略的证明,我们直接在饮用水、人唾液和人尿中进行了 PYO 的 SERS 检测,无需任何样品预处理,在饮用水中实现了 0.05 nM 的 LOD,在人唾液和尿液中实现了 0.4 nM 的 LOD。这项工作提供了一个用于最小化样本制备的细菌毒素生物标志物高灵敏度检测的原理证明:GNS 平台的“混合和检测”检测简单、稳健、快速,每次测量仅需 1-2 分钟。总的来说,我们的 SERS 检测平台在生物流体中的即时传感和床边诊断方面具有很大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/05858747bb7c/ac2c03210_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/f8443e228cd9/ac2c03210_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/af266bc77b03/ac2c03210_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/659125355cde/ac2c03210_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/1214c13355e3/ac2c03210_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/05858747bb7c/ac2c03210_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/f8443e228cd9/ac2c03210_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/af266bc77b03/ac2c03210_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/659125355cde/ac2c03210_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/1214c13355e3/ac2c03210_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec41/9909734/05858747bb7c/ac2c03210_0006.jpg

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本文引用的文献

[1]
Ultra-high SERS detection of consumable coloring agents using plasmonic gold nanostars with high aspect-ratio spikes.

Analyst. 2022-7-12

[2]
Diagnosis and Stratification of Infected Patients by Immunochemical Quantitative Determination of Pyocyanin From Clinical Bacterial Isolates.

Front Cell Infect Microbiol. 2021

[3]
A portable SERS sensor for pyocyanin detection in simulated wound fluid and through swab sampling.

Analyst. 2021-11-8

[4]
DNA-Origami-Based Assembly of Au@Ag Nanostar Dimer Nanoantennas for Label-Free Sensing of Pyocyanin.

Chemphyschem. 2021-1-18

[5]
Plasmonic Microgels for Raman-Based Molecular Detection Created by Simultaneous Photoreduction and Photocross-linking.

ACS Appl Mater Interfaces. 2020-10-21

[6]
Electrochemical Detection of Pyocyanin as a Biomarker for : A Focused Review.

Sensors (Basel). 2020-9-13

[7]
Nanograss sensor for selective detection of Pseudomonas aeruginosa by pyocyanin identification in airway samples.

Anal Biochem. 2020-3-15

[8]
Multimodal Multiplexed Immunoimaging with Nanostars to Detect Multiple Immunomarkers and Monitor Response to Immunotherapies.

ACS Nano. 2020-1-2

[9]
Colloidal plasmonic nanostar antennas with wide range resonance tunability.

Nanoscale. 2019-10-4

[10]
Present and Future of Surface-Enhanced Raman Scattering.

ACS Nano. 2019-10-8

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