Developing a Magnetic-Based Force Spectroscopy with High Molecular Resolution

Magnetic materials are widely used in chemistry, biology, and medicine. Consequently, many magnetic-based techniques have been developed to facilitate these applications by providing quantity, spatial information, and molecular specificity for the targeted molecules. However, each of the three aspects represents a challenge for the techniques, namely, sensitivity, resolution, and specificity, respectively. Recently, our group has reported several new techniques for quantitative and molecule-specific detection of magnetic signals. Using an atomic magnetometer coupled with a scanning detection method, as low as 103 magnetically labeled molecules can be detected; using the force-induced remnant magnetization spectroscopy (FIRMS) technique, specific molecular bonds can be distinguished from nonspecific absorption. These progresses have paved the way for the research reported here. In this dissertation, I will present two major achievements in resolving molecular information using the FIRMS technique. The first is obtaining high resolution in measuring the noncovalent binding forces between molecules using the FIRMS technique. The force resolution of 1.8 pN is nearly an order of magnitude better than the current state-of-the-art technique—atomic force microscopy (AFM). This high resolution enables precise determination of the targeted noncovalent bonds hence the molecules of interest. DNA duplexes with a single basepair difference can be completely resolved in the same sample, which cannot be accomplished by AFM or any other force spectroscopic techniques. The other accomplishment is using acoustic radiation force to distinguish molecular interactions for the first time. Antibodies of different subclasses and DNAs with different binding forces can be clearly identified. The small size of the ultrasound transducer allows for potential integration with the atomic magnetometer. The resulting instrument will be uniquely suitable for noninvasive manipulation of molecular interactions. This dissertation is organized as follows. In Chapter 1, I will provide an overview of magnetic materials and the related detection techniques. The principle of FIRMS will be introduced. Chapter 2 will be the principle of atomic magnetometry. This is the basis of the detection method for FIRMS and its derived techniques. Chapters 3 and 4 will describe in details the research progresses, both of which have been published. In Chapter 5, I will present an ongoing project that concerns building an apparatus that integrates an ultrasound probe and an atomic magnetometer. The goal is to ultimately achieve detection and manipulation of molecule-specific noncovalent bonds. Preliminary results have demonstrated feasibility of such an apparatus.