Tau protein in cerebrospinal fluid (CSF) is a central and relevant biomarker of Alzheimer's disease (AD) that correlates with the severity of dementia. Unfortunately, so far, direct label-free detection of tau remains a challenge. Here, we present a transistor-based biosensor that detects the net charge of tau protein directly under physiological conditions. To achieve this, readily available whole anti-tau IgG antibodies are co-immobilized on the sensor surface with polyethylene glycol (PEG) molecules of different molecular weight. We show that by increasing the PEG size from 10 kDa to 20 kDa, the electrical response upon binding of tau improves significantly. These results support recent theoretical work that predicted larger PEGs to form a thicker surface layer with a higher detectable analyte charge. With 20 kDa PEG, we demonstrate label-free tau detection in a wide concentration range with detection limits <1 pM in 150 mM buffer and cell culture media, as well as < 10 pM in artificial CSF. This purely electrical method allows fast and simple tau detection within 30 min without sample processing, washing steps, or labeled detection antibodies. By exchanging the capture antibody, the platform is also amenable to different biomarkers and may enable future diagnostic tools for AD and other diseases.

中文翻译：

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基于晶体管的无标记免疫传感器，用于快速检测tau蛋白。

脑脊液（CSF）中的Tau蛋白是阿尔茨海默氏病（AD）的重要且相关的生物标志物，与痴呆症的严重程度相关。不幸的是，到目前为止，直接无标签检测tau仍然是一个挑战。在这里，我们提出了一种基于晶体管的生物传感器，可以直接在生理条件下检测tau蛋白的净电荷。为实现此目的，将易于获得的完整抗tau IgG抗体与不同分子量的聚乙二醇（PEG）分子共固定在传感器表面。我们表明，通过将PEG大小从10 kDa增加到20 kDa，tau结合后的电响应显着改善。这些结果支持了最近的理论工作，该工作预测较大的PEG将形成具有较高可检测分析物电荷的较厚表面层。使用20 kDa PEG，我们证明了在宽浓度范围内的无标记tau检测，在150 mM缓冲液和细胞培养基中检测限<1 pM，在人工CSF中检测限<10 pM。这种纯电气方法可在30分钟内快速简便地检测tau蛋白，而无需样品处理，洗涤步骤或标记的检测抗体。通过交换捕获抗体，该平台还适用于不同的生物标志物，并可能启用针对AD和其他疾病的未来诊断工具。