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

该项目的目标是通过电学检测蛋白质分子与病毒颗粒的结合，作为一种在非常低的浓度下检测这些蛋白质的手段，精确度可达1皮摩尔。这一检测过程涉及一种名为阻抗传感生物电阻的新生物传感器结构，该结构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。然后用两个金属电极监测这种病毒-塑料薄膜的电阻，当检测到目标蛋白质时，电阻会增加。该项目的目标是改进阻抗感应式生物电阻的性能，扩大可检测的分子范围，并发现传感器工作的详细机制和原理。还建议设计一种多通道传感器，提供同时快速测量10种不同蛋白质的能力。与这项研究计划相协调，研究人员将开展一个名为NeXTech 2018的暑期推广计划：面向高中生的纳米电化学技术扩展，重点是电化学和纳米科学应用。这些学生还将在这笔助学金资助的研究生的监督下进行演示关键原理的实验室实验。如何设计能够在纳米生物结构和电路之间进行通信的电气接口？在这项提议中，作者试图通过电学检测蛋白质分子与病毒颗粒的结合，作为一种检测浓度低至下午1点的蛋白质的手段。这是使用一种名为阻抗传感生物电阻器的极其简单的传感器架构来实现的，该架构由一层导电的PEDOT(或聚(3，4-乙二氧基噻吩基)膜组成，其中包含高体积密度的M13病毒颗粒，其设计用于识别和结合特定的目标蛋白。作为一个例子，阻抗感应式生物电阻器在浓度为10 nM和较高浓度达800 nM时检测人血清白蛋白(66 KDa)。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势是，即使在1M的高浓度下，其性能也不会因溶液中存在盐而降级。即使在这种情况下，也可以测量到对这些蛋白质分子存在的大幅度、高精度的电响应。该项目的目标是进一步改进阻抗感应式生物电阻的性能，扩大可检测的分子范围，并发现传感器工作的详细机制和原理。还建议设计多通道版本的传感器，提供同时并行测量10种不同蛋白质的能力。我们将寻求对阻抗感应式生物电阻运行机制的更深层次的理解。这项研究的这一部分将涉及测试一系列假设，这些假设分离出几个候选机制。与这项研究计划相协调，作者将开展一个名为NeXTech 2018的暑期推广计划：面向高中生的纳米电化学技术扩展，重点是电化学和纳米科学的应用。这些学生还将在由该基金资助的研究生的监督下进行展示关键原理的实验室实验。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.