Misclassification of an acute disease condition as chronic and vice versa by electrochemical sweat biomarker sensors can cause significant psychological, emotional, and financial stress among patients. To achieve higher accuracy in distinguishing between a chronic condition and an acute condition, there is a need to establish a reference biomarker to index the actual chronic disease biomarker of interest by combinatorial sensing. This work provides the first technological proof of leveraging the chloride ion content in sweat for a combinatorial sweat biomarker benchmarking scheme. In this scheme, the sweat chloride ion has been demonstrated as the reference/indexing biomarker, while sweat cortisol has been studied as the disease biomarker of interest. Label-free affinity biosensing is achieved by using a two-electrode electrochemical system on a flexible substrate suitable for wearable applications. The electrochemical stability of the fabricated electrodes for biosensing applications was studied by open-circuit potential measurements. Attenuated total reflectance-Fourier transform infrared spectroscopy spectra validate the crosslinker-antibody binding chemistry. Concentration-dependent analyte-capture probe binding induces a modulation in the electrical properties (charge transfer resistance and double-layer capacitance) at the electrode-sweat buffer interface, which are transduced by nonfaradaic electrochemical impedance spectroscopy (EIS). Calibration dose responses for the sensor for cortisol (5-200 ng/mL) and chloride (10-100 mM) detection were evaluated in synthetic (pH 6) and pooled human sweat (R2 > 0.95). The variation in the cortisol sensor response due to fluctuations in sweat chloride levels and the significance of reporting normalized biomarker levels were demonstrated to further emphasize the need for biomarker benchmarking in electrochemical sensors.

中文翻译：

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用于汗液生物标志物基准分析的组合电化学生物传感器。

电化学汗液生物标志物传感器将急性疾病状况错误分类为慢性病，反之亦然，这会在患者中引起重大的心理，情感和财务压力。为了在区分慢性病和急性病方面获得更高的准确性，需要建立一种参考生物标志物，以通过组合感测对实际的感兴趣的慢性疾病生物标志物进行索引。这项工作提供了利用汗液中氯离子含量进行组合汗液生物标志物基准测试计划的首个技术证据。在该方案中，汗液中的氯离子已被证明是参考/索引生物标志物，汗液中的皮质醇已被研究为目标疾病的生物标志物。通过在适用于可穿戴应用的柔性基板上使用两电极电化学系统，实现无标记的亲和力生物传感。通过开路电势测量研究了用于生物传感应用的人造电极的电化学稳定性。衰减的全反射-傅立叶变换红外光谱证实了交联剂-抗体的结合化学。浓度依赖性分析物-捕获探针的结合在电极-汗液缓冲液界面上引起电特性（电荷转移电阻和双层电容）的调制，该调制通过非法拉第电化学阻抗谱（EIS）进行转导。在合成（pH 6）和合并的人类汗液中（R2> 0.95）评估了皮质醇（5-20​​0 ng / mL）和氯化物（10-100 mM）检测传感器的校准剂量响应。已证明由于汗液氯化物水平的波动而引起的皮质醇传感器响应的变化以及报告归一化生物标志物水平的重要性，进一步强调了电化学传感器中生物标志物标定的必要性。