The Impedance-Transduced BioResistor (ITBR): A Biosensor Architecture for Rapid, Sensitive, Label-Free Quantitation of Proteins.

该项目的目标是以电学方式检测蛋白质分子与病毒颗粒的结合，作为在非常低的浓度（低至1皮摩尔）下检测这些蛋白质的手段。 这种检测过程涉及一种新的生物传感器结构，称为阻抗转换生物电阻器，由一层导电的非常薄的塑料薄膜组成，其中嵌入了病毒颗粒。 这些病毒颗粒负责识别和结合作者正在检测的蛋白质。 然后使用两个金属电极监测该病毒塑料膜的电阻，并且当检测到感兴趣的蛋白质时，电阻增加。 该项目的目标是提高阻抗传感生物电阻器的性能，扩大可以检测的分子范围，并发现传感器操作的详细机制和原理。 还提出设计一种多通道传感器，其提供同时且快速测量十种不同蛋白质的能力。 与这项研究计划相协调，研究人员将开展一项名为NEXTech 2018：纳米电化学扩展到技术的暑期推广计划，面向高中生，重点关注电化学和纳米科学应用。 这些学生还将在该补助金资助的研究生的监督下进行实验室实验，以证明关键原理。 如何才能设计出能够在纳米级生物结构和电路之间进行通信的电接口？在这项提案中，作者试图通过电学检测蛋白质分子与病毒颗粒的结合，作为检测浓度低至1 pM的这些蛋白质的手段。 这是使用一种非常简单的传感器架构来实现的，该架构称为阻抗转换生物电阻器，由导电PEDOT（或聚（3，4-乙撑二氧噻吩）薄膜组成，该薄膜含有高体积密度的M13病毒颗粒，这些病毒颗粒被设计用于识别和结合特定的靶蛋白。 作为一个例子，阻抗转导的生物电阻检测蛋白质人血清白蛋白（66 kDa）在10 nM的浓度和更高的浓度高达800 nM。 这些传感器的响应时间在5秒范围内。 与基于场效应晶体管的蛋白质传感器相比，这种传感器设计的一个主要优点是，即使在1 M的高浓度下，其性能也不会因溶液中盐的存在而降低。 即使在这种情况下，对这些蛋白质分子的存在的大振幅、高精度的电响应也被测量。 该项目的目标是进一步提高阻抗传感生物电阻器的性能，扩大可检测分子的范围，并发现传感器工作的详细机制和原理。 还提出设计多通道版本的传感器，其提供同时并行测量十种不同蛋白质的能力。 将寻求对阻抗传感生物电阻器工作机制的更深入理解。 研究的这一部分将涉及测试一系列假设，这些假设将几个候选机制隔离开来。 为了配合这项研究计划，作者将开展一项名为NEXTech 2018：纳米电化学扩展到技术的暑期推广计划，面向高中生，重点关注电化学和纳米科学应用。 这些学生还将在该基金资助的研究生的监督下进行实验室实验，以证明关键原理。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The goal of this project is to electrically detect the binding of protein molecules to virus particles as a means for detecting these proteins at very low concentrations, down to one picomolar. This detection process involves a new biosensor architecture called the Impedance-Transduced BioResistor consisting of an electrically conductive and very thin plastic film in which are embedded virus particles. These virus particles are responsible for recognizing and binding to the proteins the authors are detecting. The electrical resistance of this virus-plastic film is then monitored using two metal electrodes, and the resistance increases when the protein of interest is detected. The goals for this project are to improve the performance of the Impedance-Transduced BioResistor, to broaden the range of molecules that can be detected, and to discover the detailed mechanism and principle of sensor operation. It is also proposed to design a multi-channel sensor that provides the capability to simultaneously and rapidly measure ten different proteins. In coordination with this research program, the investigators will operate a summer outreach program, called NEXTech 2018: Nano Electrochemistry eXtensions to Technology for high school students focusing on electrochemistry and applications to nanoscience. Laboratory experiments that demonstrate key principles will also be carried out by these students under the supervision of the graduate students funded by this grant. How can one design electrical interfaces that enable communication between nanoscopic biological structures and an electrical circuit? In this proposal, the authors seek to electrically detect the binding of protein molecules to virus particles as a means for detecting these proteins at concentrations down to 1 pM. This is accomplished using an extremely simple sensor architecture called the Impedance-Transduced BioResistor that consists of a conductive PEDOT (or poly(3,4-ethylenedioxythiophene) film that contains a high volume density of M13 virus particles engineered to recognize and bind a particular target protein. As one example, the Impedance-Transduced BioResistor detect the protein human serum albumin (66 kDa) at a concentration of 10 nM and at higher concentrations up to 800 nM. The response time of these sensors is in the 5 second range. A major advantage of this sensor design compared with field-effect transistor-based protein sensors - is that its performance is not degraded by the presence of salt in the solution, even at high concentrations of 1M. Even in this case, large amplitude, high precision electrical responses to the presence of these protein molecules are measured. The goals for this project are to further improve the performance of the Impedance-Transduced BioResistor, to broaden the range of molecules that can be detected, and to discover the detailed mechanism and principle of sensor operation. It is also proposed to design multi-channel versions of the sensor that provide the capability of measuring ten different proteins in parallel, at the same time. A deeper understanding of the mechanism by which the Impedance-Transduced BioResistor operates will be sought. This component of the research will involve testing a series of hypotheses that isolate several candidate mechanisms. In coordination with this research program, the authors will operate a summer outreach program, called NEXTech 2018: Nano Electrochemistry eXtensions to Technology for high school students focusing on electrochemistry and applications to nanoscience. Laboratory experiments that demonstrate key principles will also be carried out by these students under the supervision of the graduate students funded by this grant.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.