Silicon photonic microring resonators for quantitative cytokine detection and T-cell secretion analysis.
Silicon photonic microring resonators for quantitative cytokine detection and T-cell secretion analysis.
复制标题
用于定量细胞因子检测和 T 细胞分泌分析的硅光子微环谐振器。
DOI：
10.1021/ac902725q
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发表时间：
2010-03-01
影响因子：
7.4
通讯作者：
Bailey, Ryan C.
中科院分区：
文献类型：
--
作者：
Luchansky, Matthew S.;Bailey, Ryan C.
在具有皮摩尔灵敏度的复杂介质中同时进行多个蛋白质生物标志物测量的能力对疾病诊断和基础生物学研究提出了很大的挑战。硅光子微环谐振器代表了一个有前途的平台，用于实时检测生物分子，因为它们对目标和抗体修饰的微环之间的表面结合事件具有光谱灵敏度。对于所有基于折射率的感测方案，结合的分析物的质量与其他因素（例如抗体亲和力和表面密度）组合，有助于观察到的信号和测量灵敏度。因此，同时具有低丰度和较低分子量的蛋白质通常难以检测。通过采用更大质量的二抗来放大由初始结合事件产生的信号，可以提高蛋白质测定的灵敏度和特异性，从而允许在复杂样品基质中进行定量感测。本文中，夹心测定用于检测浓度低至100 pg/mL（6.5 pM）的15.5 kDa人细胞因子白细胞介素-2（IL-2），并在跨越2.5个数量级的动态范围内定量未知溶液浓度。然后使用该相同的夹心测定来监测在整个Jurkat分泌组存在下，在含血清的细胞培养基中来自Jurkat T淋巴细胞的IL-2的时间分泌谱。使用商业ELISA平行进行相同的时间分泌分析，揭示了类似的IL-2浓度曲线，但对于微共振器感测平台具有上级精度。此外，我们证明了夹心测定方法的一般性的microbe谐振器平台上的任何生物分子的目标，其中两个高亲和力抗体存在通过检测~8 kDa的细胞因子白细胞介素-8（IL-8）的检测限和动态范围相似的IL-2的分析。这项工作展示了硅光子微谐振器用于检测细胞因子分泌的首次应用，并代表了在新兴分析平台上检测蛋白质生物标志物的重要进展。
The ability to perform multiple simultaneous protein biomarker measurements in complex media with picomolar sensitivity presents a large challenge to disease diagnostics and fundamental biological studies. Silicon photonic microring resonators represent a promising platform for real-time detection of biomolecules on account of their spectral sensitivity towards surface binding events between a target and antibody-modified microrings. For all refractive index-based sensing schemes the mass of bound analytes, in combination with other factors such as antibody affinity and surface density, contributes to the observed signal and measurement sensitivity. Therefore, proteins that are simultaneously low in abundance and have a lower molecular weight are often challenging to detect. By employing a more massive secondary antibody to amplify the signal arising from the initial binding event, it is possible to improve both the sensitivity and the specificity of protein assays, allowing for quantitative sensing in complex sample matrices. Herein, a sandwich assay is used to detect the 15.5 kDa human cytokine interleukin-2 (IL-2) at concentrations down to 100 pg/mL (6.5 pM) and to quantitate unknown solution concentrations over a dynamic range spanning 2.5 orders of magnitude. This same sandwich assay is then used to monitor the temporal secretion profile of IL-2 from Jurkat T lymphocytes in serum-containing cell culture media in the presence of the entire Jurkat secretome. The same temporal secretion analysis is performed in parallel using a commercial ELISA, revealing similar IL-2 concentration profiles but superior precision for the microring resonator sensing platform. Furthermore, we demonstrate the generality of the sandwich assay methodology on the microring resonator platform for the analysis of any biomolecular target for which two high affinity antibodies exist by detecting the ~8 kDa cytokine interleukin-8 (IL-8) with a limit of detection and dynamic range similar to that of IL-2. This work demonstrates the first application of silicon photonic microring resonators for detecting cellular secretion of cytokines and represents an important advance for the detection of protein biomarkers on an emerging analytical platform.
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影响因子：
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作者：
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通讯作者：
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DOI：
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