CAREER: Single Molecule AFM Tips

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AbstractCTS-0349228C. Cai, University of HoustonThis CAREER proposal outlines the development of a practical and reliable method to modify silicon AFM tips with single functional molecules for biological research at thenanoscale, including the specific study of Taq DNA polymerase. Additional educational efforts will focus on the development of a special topics course on Organic Thin Films, and the introduction of Supramolecular Chemistry to the undergraduate Organic Chemistry curriculum.The fabrication of satisfactory AFM tips remains a major obstacle to realizing the full potential of AFM as an ultra-sensitive analytical instrument for studying biological systems. Although previous work has demonstrated that AFM tips can be modified with probe molecules to detect their interaction with target molecules, most of these tips interact non-specifically with biomaterials, hindering the reliable measurement of specific interactions. Moreover, the number, location, and activity of probe molecules at the tip apex often confound the measurements, since these parameters are usually unknown and cannot be precisely controlled. To resolve these longstanding formidable issues, a rational approach to the reliable preparation of well-defined, highly specific AFM tips is proposed herein. The novel strategy involves coating silicon AFM tips with a robust monolayer of oligo(ethylene glycol) (OEG) to resist non-specific interactions, selectively activating the apex of the OEG-coated tips by electrochemical reactions, and introducing a single functional group via a dendron molecule to the activated area to form a single-molecule AFM tip (SMAT). The judicious confluence of these steps is entirely unique.Relevant surface chemistry will be explored using a series of silicon substrates designed to mimic silicon AFM tips. These model systems include flat silicon (111) and (100), porous silicon, and silicon nanoparticles. The deposition and properties, especially the protein resistivity, of a series of OEG films on these model systems will be studied using a variety of analytical techniques.These studies will be followed by the examination of nanoscale electrochemical reactions on the OEG films and subsequent derivatization. The insights gained from these studies will provide valuable insight for achieving the targeted objective. Furthermore, the results will likely benefit several fields that utilize biocompatible silicon devices, such as silicon-based biosensors and implantable microdevices.An additional goal of the proposed research is to showcase SMATs in the study of the mechanical properties of Taq DNA polymerase, even during DNA synthesis. The results from this study should provide new insight toward understanding the fidelity of DNA replication. Using single-molecule tips and genetically engineered polymerases, well-defined systems will be generated for reliable pulling experiments.In addition to the educational benefits that will undoubtedly arise from the proposed research, this proposal seeks also to develop a special topics course on Organic Thin Films, which will provide students with an in-depth introduction to this ever-expanding interdisciplinary field of research. The material covered will familiarize the students with the types of molecular building blocks and principles needed to design functional thin films for a variety of applications. A script will be written for this course, since existing related texts have limited focus. To facilitate learning among students with diverse backgrounds and expertise, the "group learning" technique will be adopted. An additional effort to promote interdisciplinary education is the incorporation of Supramolecular Chemistry into Introductory Organic Chemistry.