This article introduces distance-based paper analytical devices (dPADs) integrated with molecularly imprinted polymers (MIPs) and carbon dots (CDs) for simultaneous quantification of cytokine biomarkers, namely C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in human biological samples for diagnosis of cytokine syndrome. Using fluorescent CDs and MIP technology, the dPAD exhibits high selectivity and sensitivity. Detection is based on fluorescence quenching of CDs achieved through the interaction of the target analytes with the MIP layer on the paper substrate. Quantitative analysis is easily accomplished by measuring the distance length of quenched fluorescence with a traditional ruler and naked eye readout enabling rapid diagnosis of cytokine syndrome and the underlying infection. Our sensor demonstrated linear ranges of 2.50–24.0 pg mL⁻¹ (R² = 0.9974), 0.25–3.20 pg mL⁻¹ (R² = 0.9985), and 1.50–16.0 pg mL⁻¹ (R² = 0.9966) with detection limits (LODs) of 2.50, 0.25, and 1.50 pg mL⁻¹ for CRP, TNF-α, and IL-6, respectively. This sensor also demonstrated remarkable selectivity compared to a sensor employing a non-imprinted polymer (NIP), and precision with the highest relative standard deviation (RSD) of 5.14%. The sensor is more accessible compared to prior methods relying on expensive reagents and instruments and complex fabrication methods. Furthermore, the assay provided notable accuracy for monitoring these biomarkers in various human samples with recovery percentages ranging between 99.22% and 103.58%. By integrating microfluidic systems, nanosensing, and MIPs technology, our developed dPADs hold significant potential as a cost-effective and user-friendly analytical method for point-of-care diagnostics (POC) of cytokine-related disorders. This concept can be further extended to developing diagnostic devices for other biomarkers.

中文翻译：

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基于距离的纸质分析装置，使用与分子印迹聚合物集成的碳点对细胞因子生物标志物进行多重定量

本文介绍了与分子印迹聚合物 (MIP) 和碳点 (CD) 集成的基于距离的纸质分析装置 (dPAD)，用于同时定量细胞因子生物标志物，即 C 反应蛋白 (CRP)、肿瘤坏死因子-α (TNF- α) 和白细胞介素 6 (IL-6) 在人类生物样本中用于细胞因子综合征的诊断。dPAD 采用荧光 CD 和 MIP 技术，具有高选择性和灵敏度。检测基于通过目标分析物与纸质基材上的 MIP 层相互作用实现的 CD 荧光猝灭。通过使用传统的尺子和肉眼读数测量猝灭荧光的距离长度，可以轻松完成定量分析，从而能够快速诊断细胞因子综合征和潜在的感染。我们的传感器在检测时表现出 2.50–24.0 pg mL ⁻¹ ( R ² = 0.9974)、0.25–3.20 pg mL ⁻¹ ( R ² = 0.9985) 和 1.50–16.0 pg mL ⁻¹ ( R ² = 0.9966) 的线性范围CRP、TNF-α 和 IL-6的限值 (LOD) 分别为 2.50、0.25 和 1.50 pg mL ^-1。与采用非印迹聚合物 (NIP) 的传感器相比，该传感器还表现出卓越的选择性，以及最高相对标准偏差 (RSD) 为 5.14% 的精度。与依赖昂贵试剂和仪器以及复杂制造方法的现有方法相比，该传感器更容易使用。此外，该测定为监测各种人类样本中的这些生物标志物提供了显着的准确性，回收率在 99.22% 至 103.58% 之间。通过集成微流体系统、纳米传感和 MIP 技术，我们开发的 dPAD 作为细胞因子相关疾病的即时诊断 (POC) 的经济高效且用户友好的分析方法具有巨大的潜力。这一概念可以进一步扩展到开发其他生物标志物的诊断设备。