Method for assessing the reliability of molecular diagnostics based on multiplexed SERS-coded nanoparticles.

Method for assessing the reliability of molecular diagnostics based on multiplexed SERS-coded nanoparticles.
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DOI:
10.1371/journal.pone.0062084
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Liu JT
Liu JT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Leigh SY;Som M;Liu JT

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表面增强拉曼散射(Sers)纳米粒子已被设计成产生独特的指纹光谱,并有可能作为明亮的对比剂用于分子诊断。用于生物医学诊断和成像的一种有前景的策略是使各种颗粒类型(“风味”)功能化,每种颗粒类型发射独特的光谱特征,以靶向分子生物标志物的大的多路复用面板。虽然Sers颗粒发射窄光谱特征,使它们在理想条件下容易分离,但竞争噪声源和背景信号(如检测器噪声,激光背景和自发荧光)的存在混淆了解复用算法的可靠性。在时间受限的体内成像实验期间获得的结果可能不可再现或不准确。因此,我们的目标是为实验者提供一个可以监控的指标,以在用户定义的置信度范围内强制执行所需的准确性范围。我们已经定义了一个光谱可靠性指数(SRI)的基础上,输出的直接经典最小二乘(DCLS)解复用例程,它提供了一个衡量的可靠性计算的纳米粒子的浓度和比率。我们提出了模拟和实验来证明这种策略的可行性,它可以潜在地用于一系列涉及多重Sers纳米颗粒的仪器和生物医学应用。
Surface-enhanced Raman scattering (SERS) nanoparticles have been engineered to generate unique fingerprint spectra and are potentially useful as bright contrast agents for molecular diagnostics. One promising strategy for biomedical diagnostics and imaging is to functionalize various particle types (“flavors”), each emitting a unique spectral signature, to target a large multiplexed panel of molecular biomarkers. While SERS particles emit narrow spectral features that allow them to be easily separable under ideal conditions, the presence of competing noise sources and background signals such as detector noise, laser background, and autofluorescence confounds the reliability of demultiplexing algorithms. Results obtained during time-constrained in vivo imaging experiments may not be reproducible or accurate. Therefore, our goal is to provide experimentalists with a metric that may be monitored to enforce a desired bound on accuracy within a user-defined confidence level. We have defined a spectral reliability index (SRI), based on the output of a direct classical least-squares (DCLS) demultiplexing routine, which provides a measure of the reliability of the computed nanoparticle concentrations and ratios. We present simulations and experiments to demonstrate the feasibility of this strategy, which can potentially be utilized for a range of instruments and biomedical applications involving multiplexed SERS nanoparticles.
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