Virus Bioresistor (VBR) for Detection of Bladder Cancer Marker DJ-1 in Urine at 10 pM in One Minute
Virus Bioresistor (VBR) for Detection of Bladder Cancer Marker DJ-1 in Urine at 10 pM in One Minute
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DOI：
10.1021/acs.analchem.0c00534
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发表时间：
2020-05-05
影响因子：
7.4
通讯作者：
Penner, Reginald M.
中科院分区：
文献类型：
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作者：
Bhasin, Apurva;Sanders, Emily C.;Penner, Reginald M.
DJ-1是一种20.7 kDa的蛋白质，在膀胱癌（BC）患者中过表达。它在尿液中的浓度升高，使其能够作为BC的标志物。然而，没有生物传感器检测DJ-1已被证明。在这里，我们描述了一种病毒生物电阻器（VBR）能够在1分钟内检测尿液中浓度为10 pM的DJ-1。该VBR由一对毫米级的金电极组成，用于测量一个双层聚合物通道的电阻抗（约150-200 nm）。该通道的顶层（厚度为90-105 nm）由电沉积的病毒-PEDOT（PEDOT是聚（3，4-亚乙基二氧噻吩））复合物组成，所述复合物含有嵌入的M13病毒颗粒，所述M13病毒颗粒被工程化以识别并结合感兴趣的靶蛋白DJ-1。底层由旋涂的PEDOT-PSS（聚（苯乙烯磺酸盐））组成。这两层共同构成了一个分流器。我们在这里证明，降低底部PEDOT-PSS层的厚度增加了其电阻，并将通道的电阻降集中在顶部病毒-PEDOT层中，从而增加了VBR的灵敏度，并使DJ-1的检测成为可能。大的信号幅度加上VBR传感器设计的固有简单性导致高信噪比（S/N > 100）和优异的传感器间再现性，其特征在于在整个DJ-1结合曲线上的3-7%范围内的变异系数下降到30 pM的浓度，接近10 pM的检测限（LOD），涵盖浓度的四个数量级。
DJ-1, a 20.7 kDa protein, is overexpressed in people who have bladder cancer (BC). Its elevated concentration in urine allows it to serve as a marker for BC. However, no biosensor for the detection of DJ-1 has been demonstrated. Here, we describe a virus bioresistor (VBR) capable of detecting DJ-1 in urine at a concentration of 10 pM in 1 min. The VBR consists of a pair of millimeter-scale gold electrodes that measure the electrical impedance of an ultrathin (approximate to 150-200 nm), two-layer polymeric channel. The top layer of this channel (90-105 nm in thickness) consists of an electrodeposited virus-PEDOT (PEDOT is poly(3,4-ethylenedioxythiophene)) composite containing embedded M13 virus particles that are engineered to recognize and bind to the target protein of interest, DJ-1. The bottom layer consists of spincoated PEDOT-PSS (poly(styrenesulfonate)). Together, these two layers constitute a current divider. We demonstrate here that reducing the thickness of the bottom PEDOT-PSS layer increases its resistance and concentrates the resistance drop of the channel in the top virus-PEDOT layer, thereby increasing the sensitivity of the VBR and enabling the detection of DJ-1. Large signal amplitudes coupled with the inherent simplicity of the VBR sensor design result in high signal-to-noise (S/N > 100) and excellent sensor-to-sensor reproducibility characterized by coefficients of variation in the range of 3-7% across the DJ-1 binding curve down to a concentration of 30 pM, near the 10 pM limit of detection (LOD), encompassing four orders of magnitude in concentration.