The cantilever based optical interfacial force microscope (COIFM) is a new tool to be developed, through this project, for the study bio-molecular metastable energy states. A bio-molecular system passes through several metastable states before it reaches a stable state with the lowest energy. Probing the metastable states and their shape, or conformation, is crucial for understanding bio-molecular function. However, metastable states are difficult to observe because of their relatively short lifetime and their non-equilibrium nature in a solution phase. The COIFM?s sensitive distance and force control capability will allow for investigating the metastable states along the reaction coordinates. By combining a conventional interfacial force microscope (IFM) and an atomic force microscope (AFM) type cantilever and its optical detection scheme, the COIFM will substantive improve measurement accuracy .. A force feedback technique for the IFM will be adopted to remove the rapid snap-off process, an intrinsic mechanical instability associated with conventional devices, which prevents probing metastable states during bio-molecular activations. The smaller probe size of the cantilever will enable inproving the force resolution, over conventional techniques, by at least an order of magnitude. The improved COIFM capability will be demonstrated by probing metastable states during bio-molecular activations of a biological system at the single molecule level. These COIFM modifications have the potential to quantitatively measure biological interactions at various molecular levels, not only for single molecules, but also for viral, bacterial, and cellular systems. To make this development as widely available to other laboratories as possible, all details, including electronic circuits and specifications of the COIFM mechanical head, will be well-documented and openly accessible. For wide applications to biological systems, manufacturers will be encouraged to incorporate COIFM capability into their existing systems. Results of the research activities will be disseminated through, and evaluated by, (i) presentations at national/international scientific conferences; (ii) publications in peer-reviewed journals; (iii) creation of an interactive physics lab website; and (iv) demonstrations to lab visitors. This project will engage one undergraduate student and one graduate student in research and training activities each year, thus providing unprecedented research opportunities for as many as six physics, chemistry, biology, and engineering students over a three-year period. This research will be an important addition to the strong and growing multi-disciplinary undergraduate research program at Boise State University, and to its planned Biomolecular Sciences PhD program.
Normal 0 false false false EN-US X-NONE X-NONE The title of the project is "IDBR: Development of a Cantilever-Based Optical Interfacial Force Microscope." The results of this work have been published in thirteen refereed journal articles [1-13] and five patents pending [14, 15]. The research activities in this proposal included opportunities for twenty-six undergraduate students to participate in a multidisciplinary research team consisting of physicist (Byung Kim), chemist (Ken Cornell), and molecular dynamics theoretician (Dong Xu). Seven of the undergraduates are associated with underrepresented groups. This NSF project has led to a number of peer-reviewed journal articles being coauthored by undergraduates (R.D. Boehm, J.R. Bonander, L. Smith, T. Tran, S. Rossland, J.O. Holmes, S. Kim, J. Hanson, M. Turner, J.A. Rasmussen, and E.J. Kim). Each of the undergraduate research assistants disseminated their results at professional undergraduate research conferences held by Boise State University (BSU), AVS International Symposiums & Exhibitions, Annual INBRE Research Conferences, NCUR at Weber State University, AAAS Pacific Division Annual Meetings, and the BSU Biomolecular Sciences PhD. Program Open House. This project also included fifteen high-school students who were involved in individual research project as summer interns. Five high-school interns were from underrepresented groups. The research resulted in four publications [2, 5, 8, 12] in peer-reviewed journals, which were coauthored by several high-school interns (E. Parkinson, M.S. Ryu, L. Reeder, R. Clark, and T. Clark). The PI also visited a local high school (Rocky Mountain High School) and made a colloquium presentation to the high-school students to attract them to the areas of math and science. The integration of research and education has been made through the entire NSF project. Eleven undergraduate research assistants joined the research group immediately after taking the PI’s courses of PHYS307 (Introduction to Biophysics) and/or PHYS301 (Analog Electronics). The research opportunity allowed them to apply what was being learned in class to the hands-on research project. The inclusion of COIFM has contributed to the more in-depth and comprehensive development of BMOL603 (Biophysical Instrumentation and Techniques), a required course to be taught by the PI in the fall of 2013 for the newly-introduced biomolecule Ph.D. program. The cantilever-based optical interfacial force microscope (COIFM) that was developed [2, 9, 11] in this program is now available in the Science Building room 414 at Boise State University (http://physics.boisestate.edu/kimresearch/). The COIFM measures normal and frictional forces as a function of distance to probe intermediate states utilizing a newly developed force-feedback mechanism to avoid tip instabilities associated with atomic-force microscopy. It has been used to measure confined interfacial water at variable distances [1, 10, 11] and biomolecular unbinding events [16]. During the project period, the COIFM has been further applied to high-speed imaging [3, 9] and non-contact imaging [4]. The COIFM directly revealed that water exists in the form of chain-like water structures in a nanoscopic water meniscus between two oxidized silicon surfaces in air (Fig. 1). This result demonstrates the capability of the COIFM in measuring metastable states at the single molecular level. B.I. Kim, R.D. Boehm, and J.R. Bonander, J. Chem. Phys. 139, 054701 (2013). B.I. Kim, L. Smith; T. Tran, S. Rossland, E. Parkinson, AIP Adv. 3, 032126 (2013). B.I. Kim and R.D Boehm, Ultramicroscopy 125, 29-34 (2013). B.I. Kim and R. D. Boehm, Scanning 35, 59–67 (2013). B.I. Kim, J.O. Holmes, M.S. Ryu, and P. Deschateletes, International Journal of Bioscience, Biochemistry and Bioinformatics 2, 168 (2012). B.I. Kim, J. Appl. Phys. 111, 104313 (2012). B.I. Kim and S. Kim, Langmuir 28, 8010−8016 (2012). B.I. Kim, J. Hanson, M. Turner, and L. Reeder, Surf. Sci. 606, 1340–1344 (2012). B.I. Kim and R.D. Boehm, Micron 43, 1372-1379 (2012). B I. Kim, J.A. Rasmussen, and E.J. Kim, Appl. Phys. Lett. 99, 201902 (2011). B.I. Kim, J. R. Bonander, and J. A. Rasmussen, Rev. Sci. Instrum. 82, 053711 (2011). B.I. Kim, R. Clark and T. Clark, Scanning 33, 408-412 (2011). B.I. Kim, Scanning 32, v-vi. (2010). B.I. Kim, "Cantilever-Based Optical Interface Force Microscope," U.S. Patent 2011/0252512, April 9, 2010.U.S. Patent 2012/0047610, October 31, 2011. B.I. Kim, "A Single Molecule AFM-FET Biosensor for Proteomic Screening," on April 9, 2013; "System and Method for High-Speed Atomic Force Microscopy," on May 1, 2013; "Invention of Imaging Capability of Mechanical Property of Materials by Cantilever-Based Optical Interfacial Force Microscopy on July 5, 2013," filed to the U.S. Patent and Trademark Office. B.I. Kim J. Walsh, J. Rice; H. Joo, J. Holmes, K. Cornell, Dong Xu Nikolai Smolin, under preparation (2013).
