Porous Silicon-Based Aptasensors: Toward Cancer Protein Biomarker Detection.
Porous Silicon-Based Aptasensors: Toward Cancer Protein Biomarker Detection.
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DOI：
10.1021/acsmeasuresciau.1c00019
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发表时间：
2021-10-20
期刊：
影响因子：
--
通讯作者：
Segal E
中科院分区：
文献类型：
--
作者：
Arshavsky-Graham S;Ward SJ;Massad-Ivanir N;Scheper T;Weiss SM;Segal E
前梯度同源蛋白-2(AGR2)是一种有吸引力的多种癌症的生物标志物。在胰腺癌中，它是由癌前病变分泌到胰液中的，这将是诊断的理想阶段。因此，设计灵敏的AGR2检测方法对胰腺癌和其他类型癌症的早期诊断具有重要价值。在这里，我们提出了一种用于无标记AGR2检测的生物传感器，并研究了通过加速靶传质速率和降低系统噪声来提高适体传感器灵敏度的方法。该生物传感器是基于修饰了抗AGR2适配子的纳米结构多孔硅薄膜，通过实时监测反射率的变化，可以检测和定量AGR2，以及研究扩散和靶-适配子结合动力学。该适配子传感器对AGR2具有高度的选择性，可以在模拟胰液中检测到这种蛋白质，在模拟胰液中，其浓度比许多蛋白质多出几个数量级。该传感器的线性检测范围为0.0 5~2 mg m L-1，表观解离常数为2 1±1μM，检测下限为9.2μg m L-1(0.2μM)，这归因于传质限制。为了改善后者，我们采用了不同的策略来增加进入纳米结构和在纳米结构内的扩散通量，例如应用等速电泳法在适配子传感器上预浓缩AGR2、混合或与微通道整合。通过将这些方法与采用Morlet小波滤波和相位分析的新的信号处理技术相结合，我们在不影响生物传感器的选择性和特异性的情况下实现了15 nm的检测极限。
The anterior gradient homologue-2 (AGR2) protein is an attractive biomarker for various types of cancer. In pancreatic cancer, it is secreted to the pancreatic juice by premalignant lesions, which would be an ideal stage for diagnosis. Thus, designing assays for the sensitive detection of AGR2 would be highly valuable for the potential early diagnosis of pancreatic and other types of cancer. Herein, we present a biosensor for label-free AGR2 detection and investigate approaches for enhancing the aptasensor sensitivity by accelerating the target mass transfer rate and reducing the system noise. The biosensor is based on a nanostructured porous silicon thin film that is decorated with anti-AGR2 aptamers, where real-time monitoring of the reflectance changes enables the detection and quantification of AGR2, as well as the study of the diffusion and target-aptamer binding kinetics. The aptasensor is highly selective for AGR2 and can detect the protein in simulated pancreatic juice, where its concentration is outnumbered by orders of magnitude by numerous proteins. The aptasensor’s analytical performance is characterized with a linear detection range of 0.05–2 mg mL–1, an apparent dissociation constant of 21 ± 1 μM, and a limit of detection of 9.2 μg mL–1 (0.2 μM), which is attributed to mass transfer limitations. To improve the latter, we applied different strategies to increase the diffusion flux to and within the nanostructure, such as the application of isotachophoresis for the preconcentration of AGR2 on the aptasensor, mixing, or integration with microchannels. By combining these approaches with a new signal processing technique that employs Morlet wavelet filtering and phase analysis, we achieve a limit of detection of 15 nM without compromising the biosensor’s selectivity and specificity.
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影响因子：
6.1
作者：
Bottenus D;Hossan MR;Ouyang Y;Dong WJ;Dutta P;Ivory CF
通讯作者：
Ivory CF
影响因子：
8
作者：
Dumartin L;Alrawashdeh W;Trabulo SM;Radon TP;Steiger K;Feakins RM;di Magliano MP;Heeschen C;Esposito I;Lemoine NR;Crnogorac-Jurcevic T
通讯作者：
Crnogorac-Jurcevic T
影响因子：
8.4
作者：
Chhasatia, Rinku;Sweetman, Martin J.;Voelcker, Nicolas H.
通讯作者：
Voelcker, Nicolas H.
影响因子：
2.9
作者：
Guo, Shuang;Jacroux, Thomas;Dong, Wen-Ji
通讯作者：
Dong, Wen-Ji
基于多孔硅的生物传感器的传质限制用于蛋白质检测。
影响因子：
8.9
作者：
Arshavsky Graham S;Boyko E;Salama R;Segal E
通讯作者：
Segal E