Monosaccharide-mediated rational synthesis of a universal plasmonic platform with broad spectral fluorescence enhancement for high-sensitivity cancer biomarker analysis.
Monosaccharide-mediated rational synthesis of a universal plasmonic platform with broad spectral fluorescence enhancement for high-sensitivity cancer biomarker analysis.
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单糖介导的通用等离子体平台的合理合成，具有广谱荧光增强功能，用于高灵敏度癌症生物标志物分析
DOI：
10.1186/s12951-022-01359-z
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发表时间：
2022-04-10
影响因子：
10.2
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Liu M;Li Y;Xing W;Zhang Y;Xie X;Pang J;Zhou F;Yang J
背景有效、准确地筛选外周血肿瘤生物标志物对肿瘤的诊断和预后起着越来越重要的作用。高灵敏度检测可以有效地帮助临床决策，并在癌症转移并变得无法控制之前在局部状态下进行干预。与此同时，通过消除不必要的治疗和重复抽血来防止对非危及生命的癌症的过度诊断也同样重要。不幸的是，目前的临床筛选方法很难同时达到足够的灵敏度和特异性，特别是在资源有限的情况下。为了规避这些限制，特别是对于早发和复发的癌症生物标志物，我们的目标是开发用于临床应用的通用等离子体平台，其宏观地放大宽光谱窗口中的多路复用荧光信号，并且容易地以低成本适应当前的测定设置，而无需复杂的附件或专业知识。通过合理筛选一组还原性单糖，并在不同的催化剂密度和前体浓度下调节氧化还原反应，来改善液体界面。用Benedict法和电化学方法研究了其氧化还原性能。我们通过扫描电子显微镜（SEM）和光谱学系统地表征了工程等离子体银结构的形态和光学性质。通过时域有限差分（FDTD）模拟和间隙分布计算模型，明确解释了结构-荧光增强的相关性。接下来，我们使用前列腺癌（PCa）的模型生物标志物建立了增强型荧光免疫测定法（eFIA），并在健康和PCa队列中进行了验证。预后进行了探讨，在患者接受手术和激素干预后，建议PCa guidelines.ResultsThe monosuride介导的氧化还原反应产生了广泛的类别的银结构，包括稀疏分散的纳米粒子（NP）的各种大小，半连续的nanoislands，和无裂纹的连续薄膜。观察到了由甘露糖介导的平衡氧化还原反应以稳定速率合成的不均匀、形状不规则的半连续Ag纳米岛基底（AgNIS）从绿色到远红色的最佳宽光谱荧光增强。此外，不同的局部电场强度分布响应于各种入射激发观察到在纳米尺度，阐明了需要不规则和不均匀的结构。AgNIS能够实现最大化的54.7倍宏观放大荧光和持久的光稳定性。使用具有良好配对光学器件的定制智能手机原型来实现护理点可用性。eFIA有效检测细胞系、异种移植肿瘤和患者血清中的PCa标志物。等离子体平台提供了86.0%的诊断灵敏度和94.7%的特异性，并且能够对临床金标准测试未能分层的高级别PCa进行分期。在有效的医疗干预后，对机器人辅助手术和激素治疗的患者预后进行了无创监测。在微波辐射下，等离子体平台上的测定时间显着缩短。结论通过研究还原单糖对种子介导的等离子体Ag结构的化学合成的影响，我们推断，有效的多重荧光增强源于足够的还原功率和稳定的还原速率。
BackgroundEffective and accurate screening of oncological biomarkers in peripheral blood circulation plays an increasingly vital role in diagnosis and prognosis. High-sensitivity assays can effectively aid clinical decision-making and intervene in cancer in a localized status before they metastasize and become unmanageable. Meanwhile, it is equally pivotal to prevent overdiagnosis of non-life-threatening cancer by eliminating unnecessary treatment and repeated blood draws. Unfortunately, current clinical screening methodologies can hardly simultaneously attain sufficient sensitivity and specificity, especially under resource-restrained circumstances. To circumvent such limitations, particularly for cancer biomarkers from early-onset and recurrence, we aim to develop a universal plasmonic platform for clinical applications, which macroscopically amplifies multiplexed fluorescence signals in a broad spectral window and readily adapts to current assay setups without sophisticated accessories or expertise at low cost.MethodsThe plasmonic substrate was chemically synthesized in situ at the solid–liquid interface by rationally screening a panel of reducing monosaccharides and tuning the redox reactions at various catalyst densities and precursor concentrations. The redox properties were studied by Benedict’s assay and electrochemistry. We systemically characterized the morphologies and optical properties of the engineered plasmonic Ag structures by scanning electron microscopy (SEM) and spectroscopy. The structure-fluorescence enhancement correlation was explicitly explained by the finite-difference time-domain (FDTD) simulation and a computational model for gap distribution. Next, we established an enhanced fluoroimmunoassay (eFIA) using a model biomarker for prostate cancer (PCa) and validated it in healthy and PCa cohorts. Prognosis was explored in patients subject to surgical and hormonal interventions following recommended PCa guidelines.ResultsThe monosaccharide-mediated redox reaction yielded a broad category of Ag structures, including sparsely dispersed nanoparticles (NPs) of various sizes, semi-continuous nanoislands, and crackless continuous films. Optimal broad-spectral fluorescence enhancement from green to far-red was observed for the inhomogeneous, irregularly-shaped semi-continuous Ag nanoisland substrate (AgNIS), synthesized from a well-balanced redox reaction at a stable rate mediated by mannose. In addition, different local electric field intensity distributions in response to various incident excitations were observed at the nanoscale, elucidating the need for irregular and inhomogeneous structures. AgNIS enabled a maximized 54.7-fold macroscopically amplified fluorescence and long-lasting photostability. Point-of-care availability was fulfilled using a customized smartphone prototype with well-paired optics. The eFIA effectively detected the PCa marker in cell lines, xenograft tumors, and patient sera. The plasmonic platform rendered a diagnostic sensitivity of 86.0% and a specificity of 94.7% and capably staged high-grade PCa that the clinical gold standard test failed to stratify. Patient prognosis of robotic-assisted surgeries and hormone therapies was non-invasively monitored following efficient medical interventions. The assay time was significantly curtailed on the plasmonic platform upon microwave irradiation.ConclusionsBy investigating the effects of reducing monosaccharides on the seed-mediated chemical synthesis of plasmonic Ag structures, we deduced that potent multiplexed fluorescence enhancement originated from both an adequate reducing power and a steady reduction rate …
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DOI：
10.1073/pnas.0701250104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Linse, Sara;Cabaleiro-Lago, Celia;Dawson, Kenneth A.
通讯作者：
Dawson, Kenneth A.
DOI：
10.1109/jstqe.2021.3060496
发表时间：
2021-09-01
影响因子：
4.9
作者：
Guo, Jiuchuan;Zhang, Jiechen;Guo, Jinhong
通讯作者：
Guo, Jinhong
影响因子：
17.1
作者：
Bharill S;Chen C;Stevens B;Kaur J;Smilansky Z;Mandecki W;Gryczynski I;Gryczynski Z;Cooperman BS;Goldman YE
通讯作者：
Goldman YE
影响因子：
8.6
作者：
Jacobsen MT;Fairhead M;Fogelstrand P;Howarth M
通讯作者：
Howarth M
等离激元金芯片上的高性能、多重肺癌生物标志物检测
影响因子：
19
作者：
Liu, Bin;Li, Yaling;Qian, Kun
通讯作者：
Qian, Kun