DOE OSTI2012
The project aimed to develop a standalone module for Atomic Force Microscope systems that the biological and environmental research community could use to image and quantify to a greater extent the interactions between nanoparticles and cells. If successful, it would enable the thousands of biological and environmental researchers with access to atomic force microscopes to perform scanning near field ultrasound holography to image nanoparticle interactions with cells. Over the course of this effort, grantees were able to develop a standalone module capable of performing scanning near field ultrasound holography on a variety of commercial systems. The add-on module was tested on systems from 3 of the major Atomic Force Microscope manufacturers (Veeco, JEOL and Park Systems). Furthermore, the investigators believe that the hardware developed will be capable of performing the technique on any AFM with standard signal access modules. The discrete components previously used to perform the SNFUH technique could cost upward of $\$$40,000. Beyond the cost issue, the components are bulky and cumbersome to work with because of the wiring needed between each of the components when implementing the technique. NanoSonix was able to dramatically reduce both the cost and complexity of implementing SNFUH, developing two functional versions of an add-on module (A&B) using National Instruments hardware as put forth in the proposal. More significantly, NanoSonix exceeded the aims of the proposal by developing completely custom electronics that should enable an almost order of magnitude cost reduction while improving the capability versus the discrete componentry. Because potential biological systems are so complex, biological applications of the technique are very diverse and require very distinct domain knowledge. This inhibits the utilization widespread adoption and penetration of new metrology techniques. Northwestern University and NanoSonix has made it both possible and practical for widespread adoption of the technique through the development of a standalone system with order of magnitude cost reduction and significant reduction in complexity. NanoSonix believes that it can produce the add-on modules and make them available to the academic research community at a price point below $\$$10,000, thereby enabling the biological research community to hardness the over 30,000 AFMs in existence around the world today, approximately 18,000 of which reside in the United States at a very modest incremental cost. Finally, we were able to implement a multi-frequency function generator and simultaneous multi-frequency lock-in amplifier with an internal reference frequency (which significantly simplifies the experimental setup) that it believes could lay the foundation for future non-destructive nanoscale 3-D tomography of buried and embedded sub-structures in cells and tissues. To date, we has been unable to find multiple frequency combinations which yield sufficiently strong mixing at the tip-sample interaction, but believes it is conceptually possible and doing so would enable the use of frequency dependent phase shift to better characterize the subsurface structures. Taken together, we believes that this work has materially advanced the prospects of enabling researchers to develop time-resolved cellular uptake of the nanoparticles used for drug delivery, cancer therapies, gene delivery and gene silencing and to assess cellular uptake of nanoparticles for environmental monitoring/remediation/impact.
77 NANOSCIENCE AND NANOTECHNOLOGY↗