The Directorate for Biological Sciences through their Instrument Development for Biological Research program and the Division of Chemistry through Chemical Measurement and Imaging support Prof. Chad A. Mirkin, Northwestern University, and Prof. Adam B. Braunschweig, New York University, to develop a new instrument to fabricate nanoarrays of biologically active probes. This new instrument, termed the Nanosizer, will produce combinatorial arrays of oligonucleotides, oligopeptides, and many other biologically active small molecules with sub-100 nanometer feature diameters over large areas (10's of cm2); thereby achieving order of magnitude improvements in feature size, production rate, and cost over current technologies and providing access to fundamental biological experiments that could not otherwise be undertaken. This goal will be achieved by combining massively-parallel tip based nanolithography strategies with new microfluidic designs, and photochemically activated combinatorial surface syntheses. Following proof-of-concept demonstrations, the instrument will be systematically optimized with regard to chemical kinetics and reaction times and automated to facilitate instrument operation. This interdisciplinary project uniquely combines elements of chemistry, engineering, and materials science to create an instrument capable of producing arbitrary patterns of soft matter over large areas, where the chemical composition and position of every feature can be controlled precisely.
The new instrument developed in the context of this collaborative proposal will address a major problem for industrial and academic researchers by providing a facile method for preparing arbitrary nanopatterns of biologically active probes. Moreover, the Directorate of Biological Research will sustain Prof. Mirkin and Prof. Braunschweig's outreach activities, including financial support of summer students from minority-serving four year colleges to assist in this project during the summer and a range of other outreach activities that increase scientific awareness at eminent institutions including the Museum of Science and Industry in Chicago, the Metropolitan Museum of Art in New York, and the Young Women's Leadership School of East Harlem.
The desktop printer has changed the way we interact with paper documents, and modern integrated circuit factories have defined the way we use electronics. In contrast, biomolecules have not undergone this type of revolution as there remains no easy way to rapidly print arbitrary arrangements of biologically relevant materials such as DNA, proteins or sugars. If such a tool existed, it would revolutionize personalized medicine and accelerate research in all facets of biological science. The intent of this grant was to address this deficiency and develop a new approach for desktop nanofabrication of biomolecules. Doing this necessitated advances in physical equipment as well as chemical processes. Through the collaborative effort of a scanning probe lithography group and an organic chemistry group, we were able to overcome these challenges. Specifically, we developed a novel platform for performing photochemistry in a site-specific fashion with tens of thousands of nanoscopic probes simultaneously, termed the "Nanosizer". The fundamental principle here is that by using holes smaller than the wavelength of light, light can be confined to a smaller volume than would be otherwise possible. If this highly confined light is co-localized with molecules that can undergo light-activated chemical transformations, then one can use it to control chemical reactions. One critical aspect of the novelty of our approach is that we can use many thousands of independently addressable probes to direct this process at the same time. In fact, it is only through parallelization that this local photochemical approach can be transformed from a lab-scale curiosity to a production tool. Therefore, our critical innovation was the development of an instrument that allows one to control thousands of beams of light and direct them to an array of microscopic probes with nanoscopic holes at their tips. Additionally, the choice of chemistry is critical as it must be selective and robust. To that end, we developed new processes that are compatible with sensitive biomaterials. While this grant was initially focused around delivering light on a site-specific basis, these explorations led us to a powerful new paradigm: the delivery of light and materials from the same probes. This unanticipated advance allowed us to drastically increase the utility of our nanofabrication approach as well as study the fundamental processes that govern the transport of materials from a nanoscopic tip to a surface. Taken together, the progress made in pursuit of the goals of this grant have led to a new nanofabrication technique that is poised to transform the synthesis of biomaterials in a manner analogous to the way that the desktop printer has transformed printed information. We expect that these advances will set the stage for impactful studies in biology and novel diagnostic tools that together change how we understand ourselves and the world.
