The research objective of this proposal is to develop a noninvasive imaging technique for detecting magnetically labeled biological molecules with zeptomole sensitivity, micrometer spatial resolution, and a detection range of several centimeters. The technique is based on atomic magnetometry for magnetic field sensitivity and scanning imaging for spatial resolution. The research activities focus on four related areas: new-generation atomic sensors, novel imaging schemes, improved applicability, and unique biological applications.
Intellectual Merit This proposed research represents a novel approach for molecular imaging. The unique long detection range distinguishes this new technique from existing surface techniques, making it well suited for three-dimensional molecular imaging at practical settings. Design of sensors with new engineering concepts will lead to a zeptomole detection limit. Unique scanning schemes will be developed to provide high spatial resolution for three-dimensional imaging. The applicability of the technique is enhanced by eliminating the magnetic shield which is currently required for most magnetic imaging techniques. The removal of magnetic shield is facilitated by the design of new sensors and a new compensating concept to overcome the nonlinear Zeeman effect which will otherwise degrade the sensitivity. On the application front, a novel method is proposed to provide critical details regarding bond rupture that have not been revealed with existing techniques. In addition, the new technique does not require a transparent environment since the laser beam does not interact with the molecular system, contrary to optical imaging techniques; this technique detects dc magnetic signal, avoiding the limited penetration depth of ac signal in conductors, which is a problem for magnetic resonance imaging. Therefore, the proposed research will have transformative impact on the field of molecular imaging.
Broader Impacts Broader impacts lie in both the research front and the educational aspect of this proposal. The proposed research will fill the technology gap between magnetic microscopy and long-distance magnetic field sensing. Consequently it will open up new imaging applications that are not experimentally feasible at present. The interdisciplinary research, which involves physics, engineering, chemistry, and biology, offers a wide range of training for students. Their education is central to this proposal, as their input determines both the success of the projects and the future of this new field. In addition, substantial effort will be continuously devoted to recruiting underrepresented undergraduate students into the research program. It is foreseeable these students will broadly impact the society in a positive manner by sharing their fruitful experiences with their classmates and friends. Outreach activities include hosting high school students during summer to work on specifically-tailored research tasks, interacting with local liberal arts colleges to expand the impact of cutting-edge research, and serving to guide worldwide science fairs held in the local area.
The objective of this project was to develop a scanning magnetic imaging(SMI) technique for detecting magnetically-labeled molecules with high sensitivity, spatial resolution, and molecular specificity. The technique was awarded with US patent 8570027. With the support by NSF, the outcome includes the development of SMI with a sensitivity of a few tens of molecules, a spatial resolution of 20 microns at a detection distance exceeding 1 centimeter, and two new techniques capable of revealing molecular information for the first time. The new techniques are force-induced remnant magnetization spectroscopy (FIRMS) and exchange-induced remnant magnetization (EXIRM). The FIRMS technique reveals molecular specificity by measuring the binding force with unprecedented accuracy. The EXIRM technique detects molecules in a label-free fashion. Overall, two pending US and international patents, eight publications on prestigious journals, and training for five graduate students have been accomplished. The following section provides the details of these achievements. Intellectual Merit The technological outcome of this work includes three techniques. The first is we substantially improved the sensitivity of SMI by designing and constructing a new apparatus. By improving its sensitivity and using stronger magnetic particles, we are able to detect a few tens of magnetically labeled molecules. The detection range has also been extended. The applicability of this scanning magnetic imaging technique has been improved by the unique design of a new atomic magnetometer. The second technique is the recently invented FIRMS technique, which implements molecular signatures into magnetic sensing for the first time. The third is the EXIRM technique. EXIRM offers single-nucleotide resolution in identification of DNA/RNA strands without applying an external force or labeling on the target molecules. The fundamental scientific outcome consists of eight publications and one more under review. We reported our progress on the sensitivity, resolution, and applicability of SMI. We also published a novel fundamental concept that the dissociation force of molecular bonds is well defined and can serve as a discriminator for different molecules. Recently, as a landmark experiment, we measured the mechanical force of a motor protein during its functioning in protein synthesis. Other applications of the invented techniques have also been explored. Broader Impacts The educational outcome includes training for five graduate students, one postdoctoral fellow, one undergraduate student, and one high school student. One of the graduate students obtained her PhD and became a chemist in a Houston-based company. The other four have made significant progress in their research and are on track to graduation. The postdoctoral fellow pioneered a significant portion of the research and was a co-inventor on all the patent applications. He has obtained an independent academic position at a top-tier research institute. The undergraduate student is currently pursuing his PhD at the engineering school of the University of Texas at Austin, one of the top programs in the country. The high school student was a Welch Summer Scholar, an honor that is only given to the brightest high-school students in Texas. These achievements are made possible by NSF support as well as by the students’ own efforts.
