Receptor Polymers for Enhanced Antibody-Mediated Electronic Neurological Protein Detection

许多医学疾病，包括一些脑损伤，可以通过体内某些蛋白质数量的变化来检测。蛋白质的数量可以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，以至于无法检测到表明医学问题的数量。这个项目是为了改进电子设备中使用的材料，以便更容易检测到少量的蛋白质。这些蛋白质是由使用“抗体”的设备识别的，“抗体”是当新蛋白质被引入血液时自然产生的物质。通过最大化设备中的抗体数量，并使用更有效的水和盐浓度来包围抗体，可以使蛋白质的电子信号变得更强。设计更好的材料来将抗体保存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。从根本上理解这些重要的周围物质将是该项目的科学收益。在这个项目中获得的关于蛋白质的知识将加快设备的开发，这种设备可以比现在更快地检测到蛋白质。研究生将制作材料，并对设备进行计算机和电子研究。他们将获得广泛的科技就业基础。少数民族女高中生将被选中参加JHU的暑期实习，作为研究小组的一部分，在私人投资机构指导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(如蛋白质)具有快速电子响应的聚合物材料的方法依赖于分析物引起的聚合物性质的变化，如介电常数和离子分布。这些性质的改变会导致包含聚合物的器件的电子参数发生变化。聚合物受体材料的设计为提高电子生物传感器的灵敏度、选择性和稳定性提供了一个尚未实现的机会，该传感器基于蛋白质被其相应的抗体识别。这一建议将生物分子-受体聚合物相互作用的基本观察与电子反应联系起来，同时设计新的聚合物来放大这些反应。最主要的科学假设是，在蛋白质-抗体结合过程中测量的电信号是由固-液界面双电层的同时变化(表面电位贡献)和聚合物内部的阻抗响应(电容或注入屏障贡献)引起的，对这两方面的基本理解对于设计新材料提供更好的蛋白质抗体结合信号是必不可少的。该计划的重点是材料组成和基本性质之间的结构-活性关系，从而导致设计和合成新的生物聚合物材料。该提案的工作将包括为具有不同净电荷的蛋白质发出电子信号，生成一个新引入的电荷如何产生信号的模型，并使用该模型来指导支持抗体的改进聚合物的合成，并最大限度地利用从蛋白质结合获得的信号。设计特点包括增加抗体掺入的面密度，减少抗体周围介质的双层筛选效应。在类似的材料平台上对场效应和复阻抗转换的有效性进行了比较。这项提议所获得的关于生物标记物的知识将加速实时生物传感器的发展，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。他们将获得广泛的科技就业多元化的技术基础。少数族裔女高中生将被选中参加JHU的暑期实习，作为研究团队的一部分，在PIS监督的研究生的指导下工作。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。

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.