Receptor Polymers for Enhanced Antibody-Mediated Electronic Neurological Protein Detection

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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.