As chief technology officer and president of Optofluidics Inc., Dr. Robert Hart has helped the Cornell-born startup develop microfluidic and biophotonic nanomanipulation technologies for biological, materials science and pharmaceutical applications. With CEO Dr. Bernardo Cordovez, Hart and Optofluidics have garnered industrywide attention culminating in a 2014 Prism Award nomination for the NanoTweezer, a system that captures, manipulates and analyzes large numbers of individual nanoparticles. Q: What are you working on right now? Hart: Since the launch of our advanced nanoparticle analyzer, the NanoTweezer, this past December, we’ve been splitting our time between driving sales and pushing the frontiers of particle-measurement science. Typically, people are amazed when they find out we’re making actual tractor beams and that we can “suck” nanoparticles down onto a waveguide. But this is only half the story. We’re not just manipulating nanoparticles; we’re measuring them, too. Each particle that lands on our waveguide scatters light as if it were a defect. Imagine taking a fiber optic and nicking it in dozens of places, allowing you to see the light that was previously coursing through unseen. In our system, each spot of light we see represents a tiny nanoparticle that’s been trapped. The best part is that we can do this all in the native liquid where they normally live and function. We still have some serious technical work ahead, though. Our technical team is measuring nanoparticle shape and coating properties – something no other system can do outside of electron microscopes. Once we establish the technique and nail down the theory, we intend to apply these techniques to some big problems in health care, specifically nanomedicine, nanotoxicology and biotherapeutics. Q: What are the implications of that work? Hart: As a developer of analytical equipment, our mission is to make products containing nanoparticles better and safer. Our world is awash with nanoparticles – tiny objects around one-thousandth the width of a human hair. They have found their way into a wide variety of products, from dishwashing detergent to batteries to medicine. Yet measuring them is still extremely difficult, mainly because they are just so small. We’ve had nearly a thousand conversations with researchers and engineers around the world who work with nanoparticles, and the consensus is clear: New methods of measuring nanoparticles are desperately needed. With our new measurement system, we hope to shed light on nanoparticle behavior enabling scientists and engineers to unlock their true potential. One great example is in pharmaceutical R&D. For many years, scientists have been working on targeted drug delivery. The idea is to use specially coated nanoparticles that latch onto tumors, allowing them to deliver the chemotherapy directly to the tumors like a laser- guided missile, as opposed to traditional chemotherapy, which is more like carpet bombing. This method worked in the lab but usually failed in animals due to a poor understanding of what happened to the coating once the nanoparticles entered the biological tissue. It took years to uncover the truth, which is that the coating was fouled by a layer of proteins from the blood, masking the tumor-targeting coating. There simply were no systems capable of doing these kinds of measurements, which is why it took so long to find out. With the launch of our Nano-Tweezer system, we hope to shore up this measurement gap and help make better pharmaceuticals, including tumor-targeted therapies. Q: What’s the next step? Hart: Once we establish ourselves in the market with the early adopters, we will launch a second version of our instrument that is more integrated and user-friendly. The plan is for this system to be dedicated specifically to one of the big applications. Right now, our best bets are in nanomedicine, where a large number of drugs are being developed with huge potential but limited ways of analysis; in biopharmaceuticals, where patient safety and drug efficacy are at stake; or in nanoparticle toxicity, which is already starting to be regulated in Europe. After receiving his doctorate in biomedical engineering from Drexel University, Hart completed a postdoctoral fellowship at the University of Pennsylvania. He currently oversees product development, corporate partnerships and internal R&D for Optofluidics, and has played a central role in landing more than $3.3 million in federal and private funding. In 2012, Optofluidics was chosen as Life Sciences Startup of the Year by the Greater Philadelphia Alliance for Capital and Technologies. BioPhotonics recently asked Hart three questions about his work with nanomanipulation, including its relation to behavior analysis and its potential applications in cancer treatment.