Receptor Polymers for Enhanced Antibody-Mediated Electronic Neurological Protein Detection

用于增强抗体介导的电子神经蛋白检测的受体聚合物

基本信息

批准号：
1807292
负责人：
Howard Katz
金额：
$ 42.48万
依托单位：
Johns Hopkins University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807292&HistoricalAwards=false
关键词：
Receptor Polymers Enhanced Antibody Mediated

项目摘要

Non-Technical AbstractMany medical disorders, including some brain injuries, can be detected by changes in the amounts of certain proteins in the body. The amounts of proteins can be measured using simple electrical devices. However, some proteins do not give a strong enough electrical signal to be detected in the amounts that would indicate a medical problem. This project is to improve the materials used in the electrical devices so that small amounts of the proteins can be more easily detected. The proteins are recognized by the devices using "antibodies", which are substances that are naturally generated when new proteins are introduced to the bloodstream. By maximizing the number of antibodies in the device, and using more effective concentrations of water and salt to surround the antibodies, the electronic signal for the protein can be made stronger. Designing better materials to hold the antibodies in the device will accomplish these goals. The new material designs will be based on knowledge of the chemical properties of the materials and computer models of how they interact with the proteins. A fundamental understanding of these important surrounding materials will be a scientific benefit of the project. The knowledge gained about proteins used in this project will speed the development of devices that can detect the proteins faster than they can be detected now. Graduate students will make the materials and perform computer and electronic studies of devices. They will acquire a broad foundation for science and technology employment. Minority female high school students will be selected to participate in summer internships at JHU, working as part of a research team under the mentorship of a graduate student supervised by the PIs. Technical AbstractMany approaches to polymeric materials with rapid electronic responses to biomacromolecule analytes such as proteins depend on analyte-induced changes in polymer properties such as dielectric constant and ion distribution. These property changes lead to changes in electronic parameters of devices in which the polymers are incorporated. Polymer receptor material design represents an unrealized opportunity to improve the sensitivity, selectivity, and stability of electronic biosensors based on proteins being recognized by their corresponding antibodies. This proposal connects fundamental observations of biomolecule-receptor polymer interactions to the electronic responses, while designing new polymers to amplify those responses The overarching scientific hypothesis is that the electrical signal measured during protein-antibody binding is caused by simultaneous combined changes in the electrical double layer at the solid-liquid interface (surface potential contribution) and by an impedance response within the polymer (capacitive or injection barrier contribution), the fundamental understanding of which are essential to the design of new materials that give improved signaling of protein-antibody binding. The emphasis in this program is on structure-activity relationships among material components and fundamental properties, leading to design and synthesis of new biopolymer materials. The work of the proposal will include electronic signaling of proteins with different net charges, generating a model of how the newly introduced charges generate the signals, and using the model to guide the synthesis of improved polymers that support the antibodies and maximize the signaling obtainable from protein binding. Design features will include increasing the area density of antibody incorporation and decreasing the double layer screening effect of the media surrounding the antibodies. The effectiveness of field effect and complex impedance transduction will be compared on similar material platforms. The knowledge gained about biomarkers of this proposal will accelerate development of real time biosensors providing timelier indications of neurological injuries. Graduate students will synthesize materials and perform computational and electronic characterizations of devices. They will acquire a broad technical basis for diversified science and technology employment. Minority female high school students will be selected to participate in summer internships at JHU, working as part of a research team under the mentorship of a graduate student supervised by the PIs.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.

非技术摘要许多医学疾病，包括一些脑损伤，可以通过体内某些蛋白质含量的变化来检测。蛋白质的含量可以使用简单的电子设备来测量。然而，一些蛋白质不能发出足够强的电信号，无法检测到表明存在医疗问题的量。该项目旨在改进电子设备中使用的材料，以便更容易检测到少量蛋白质。这些蛋白质被使用“抗体”的设备识别，“抗体”是当新蛋白质被引入血液时自然产生的物质。通过最大限度地增加设备中的抗体数量，并使用更有效浓度的水和盐来包围抗体，可以使蛋白质的电子信号更强。设计更好的材料来将抗体固定在设备中将实现这些目标。新材料的设计将基于对材料化学性质的了解以及它们如何与蛋白质相互作用的计算机模型。对这些重要的周围材料的基本了解将是该项目的科学效益。获得的有关该项目中使用的蛋白质的知识将加速设备的开发，这些设备可以比现在更快地检测蛋白质。研究生将制作材料并对设备进行计算机和电子研究。他们将为科技就业奠定广泛的基础。少数族裔女高中生将被选拔参加约翰霍普金斯大学的暑期实习，作为研究团队的一部分，在 PI 指导下的研究生的指导下工作。技术摘要许多对生物大分子分析物（例如蛋白质）具有快速电子响应的聚合物材料的方法取决于分析物引起的聚合物特性（例如介电常数和离子分布）的变化。这些性质的变化导致掺入聚合物的器件的电子参数发生变化。聚合物受体材料设计代表了一个尚未实现的机会，可以提高基于被相应抗体识别的蛋白质的电子生物传感器的灵敏度、选择性和稳定性。该提案将生物分子-受体聚合物相互作用的基本观察与电子响应联系起来，同时设计新的聚合物来放大这些响应。总体科学假设是，蛋白质-抗体结合过程中测量到的电信号是由双电层的同时组合变化引起的固液界面（表面电位贡献）和聚合物内的阻抗响应（电容或注入势垒贡献），对此的基本理解对于设计可改善蛋白质-抗体结合信号传导的新材料至关重要。该计划的重点是材料成分和基本特性之间的结构-活性关系，从而设计和合成新的生物聚合物材料。该提案的工作将包括具有不同净电荷的蛋白质的电子信号传导，生成新引入的电荷如何产生信号的模型，并使用该模型指导改进的聚合物的合成，这些聚合物支持抗体并最大限度地提高从蛋白质结合。设计特点包括增加抗体掺入的面积密度和减少抗体周围介质的双层筛选效应。将在类似的材料平台上比较场效应和复阻抗转换的有效性。该提案中获得的有关生物标志物的知识将加速实时生物传感器的开发，提供更及时的神经损伤指示。研究生将合成材料并对设备进行计算和电子表征。他们将为多样化的科学技术就业奠定广泛的技术基础。少数族裔女高中生将被选拔参加 JHU 暑期实习，作为研究团队的一员，在 PI 指导下的研究生的指导下工作。该奖项反映了 NSF 的法定使命，经评估认为值得支持利用基金会的智力优势和更广泛的影响审查标准。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Carboxylic Acid‐Functionalized Conjugated Polymer Promoting Diminished Electronic Drift and Amplified Proton Sensitivity of Remote Gates Compared to Nonpolar Surfaces in Aqueous Media

与水介质中的非极性表面相比，羧酸-功能化共轭聚合物可减少电子漂移并增强远程门的质子灵敏度

DOI：
10.1002/aelm.201901073
发表时间：
2020-06
期刊：
Advanced Electronic Materials
影响因子：
6.2
作者：
Jang, Hyun‐June;Wagner, Justine;Song, Yunjia;Lee, Taein;Katz, Howard E.
通讯作者：
Katz, Howard E.

Material and circuit design for organic electronic vapor sensors and biosensors

有机电子蒸汽传感器和生物传感器的材料和电路设计

DOI：
10.1117/12.2530058
发表时间：
2019-08
期刊：
110960A
影响因子：
0
作者：
Dailey, Jennifer;Li, Hui;Song, Jian;Besar, Kalpana;Jang, Hyun;Chu, Yingli;Katz, Howard E.;Shinar, Ruth;Kymissis, Ioannis;List
通讯作者：
List

Enhanced and unconventional responses in chemiresistive sensing devices for nitrogen dioxide and ammonia from carboxylated alkylthiophene polymers

化学电阻传感装置对来自羧化烷基噻吩聚合物的二氧化氮和氨的增强和非常规响应