Start-up companies and big corporate deals don’t always go smoothly, says Princeton engineering professor Robert Prud­’homme. He was speaking at the 30th anniversary symposium of Princeton University’s Princeton Institute for the Science and Technology of Materials (PRISM), a series of lectures and presentations held March 13 and 14 at the university’s Andlinger Center.

Prud’homme tells four war stories that illustrate the dilemma facing doctoral candidates in engineering — which career path to take? Continue to do basic research and teach at a university? Go to a big corporation? Or be an entrepreneur?

Those who choose the entrepreneurial path can develop and profit from their own discoveries, says Claire Gmachl, a MacArthur fellow and associate chair of the department of electrical engineering. Suggesting that PRISM attracts those with an entrepreneurial spirit, she says, it’s “a wonderful home for students starting companies. A good number of the graduate students want to be entrepreneurial and independent of academe.”

Just as each individual student and professor must ponder these priorities, so does the university as a whole. Universities are supposed to focus primarily on education and basic research, and they invest millions of dollars in high-tech labs to develop the seminal ideas that might — or might not — result in discoveries that the world can use.

How to encourage the transfer of technology to the “real world,” how to profit but not make too much profit — this is the job of John Ritter in the Office of Technology and Licensing. Ritter led a panel that included a funder, a former student who founded a start-up, and the head of the organization tasked to encourage the entrepreneurial spirit, the Keller Center.

PRISM’s laboratories and networks represent the engineering nexus of all four — education, basic research, entrepreneurial startups, and corporate research. In addition to electron microscopes, PRISM’s Imaging and Analysis Center (IAC) boasts two dozen state-of-the-art instruments and is a world-leading center for advanced materials characterization. Students train to operate equipment for research experiences that win national awards. Industrial scientists from more than 100 companies pay hourly fees to use the IAC instruments to develop new products.

At the PRISM symposium, professors and graduate students trotted out examples of exciting discoveries, and corporate keynoters showed how discoveries blossom into products. Eager collaborators, some from far away, buttonholed researchers at coffee breaks. Undergraduate and doctoral students clustered around their mentors at lunch, then stood at easels to explain their research at the poster session. Enormously expensive laboratories are where the work gets done, but the real value of PRISM is the confluence of ideas and people — networking.

James Lallo was there to represent the Princeton office of ThermoFisher Scientific. Princeton University and Rutgers own his firm’s devices that study the chemical composition of material and cost from $500,000 to $1.5 million. “We try to maintain an ongoing relationship, not only so the university gets the most use out of the instrument, but also so we can keep on the cutting edge of the technology,” says Fisher.

Andrew McCandless came from Baton Rouge, Louisiana, the home of his six-year-old firm, Bascom Hunter. Also eager for networking opportunities were Thomas Acton of Evotec on College Road; Bruce Boman, whose office for Cancer Code Research Fdn is at TigerLabs on Nassau Street; and Eric Anderson, a consultant to a couple of firms including Wardenclyffe Chemicals Inc.

Invited to help celebrate NJ STEM month was Judith Sheft from the New Jersey Institute of Technology, which has its own powerful technology transfer programs. Rutgers technology transfer and instrumentation initiatives were represented by Vincent Smeraglia, Edward J. Yurkow, and Derek Adler.

Joseph X. Montemarano, director for industrial enterprise at PRISM, coordinated the program, noting that his job there, as always, is to “let large and small companies/entrepreneurs know they are welcome and help them access people and resources at PRISM and more broadly throughout the university.”

PRISM director Craig Arnold was the maitre d’ of the two-day symposium, and he also gave the keynote speech at the Keller Center’s version of the Shark Tank on Wednesday afternoon (see sidebar, page 28). He and his cohorts, including Christian Theriault, spun the technology for a Tunable Acoustic Gradient lens into TAG Optics (U.S. 1, March 14).

After the official welcome — the talk from an encouraging politician (Assemblyman Andrew Zwicker, who also happens to be a physicist), and the first of five keynotes — came the first slew of discovery reports delivered by fast-talking professors, PhD students, and post-docs, many relying on their slides to cram 30 minutes of information into 20. Amazing stories and tales of innovation over a 30-year period came one after another, each demonstrating the need for cross-discipline thinking.

‘The problems are more interdisciplinary than before,” says Naveen Verma, associate professor of electrical engineering. “Universities have a unique ability to bring together deep-thinking interdisciplinary teams.” He does research on advanced sensing systems using algorithms that exploit new technologies using, for instance, low temperature semiconductors that can produce microphone arrays in wall paper and three-dimensional gesture sensing

Salvatore Torquato, director of the Complex Materials Theory Group, spoke about a category of materials that, 10 years ago, he named “hyperuniformity.” Even experts don’t completely understand it.

Asked for a definition, Torquato offers, “It provides a theoretical framework to unify our traditional notions of order in materials with exotic disordered forms.” As in the past, scientists now struggle to replicate what nature has already made. An example of an amazing hyperuniform structure is the pattern of color-sensing cells in the eye of a bird.

Torquato and Adam Hopkins have a start-up company, Uniformity Labs, that uses ultradense ceramic and metal powders for three-dimensional printing inks.

What revolutionary possibilities does this have? Jay Morrealle, a consultant with p-brane LLC in Summit, says, “In 1965 no one would have predicted that a battery-powered wireless computer with a high-definition display would fit in my pocket (my cell phone).”

Yuyang Fan, a postdoctoral researcher, discussed how tools used to measure turbulence — found anywhere from the plume of a volcano to the fluttering of hummingbird wings — can be extremely sensitive to very small flow rates. These sensor tools, including the Nano-Scale Thermal Anemometry Probe (NSTAP) and Elastic Filament Velocimetor (EFV), are made at PRISM.

Fan, assistant professor Marcus Hultmark, and two others, founded Tendo Technologies. It works on flow monitoring for HVAC applications, water leak detection, drones, and autonomous underwater vehicles. The most exciting applications are for healthcare — integrating this new technology into infusion pumps (to monitor real-time drug dosage and detect injection failure) and into IV tube sets (offering visual feedback of administration rate). “Think of it as bringing the drip chamber into the 21st century,” says Fan.

Tuesday afternoon presenters focused on soft materials for polymer and biological systems. Jean Schwarzbauer, associate chair of the department of molecular biology, studies the role played by the matrix that surrounds cells in regulating what the cells do. As part of long-time collaborations with researchers in many fields, particularly with chemist Jeffrey Schwartz, she focuses on how to encourage cells to orient themselves in a linear way by growing the matrix in a tube. Eventually this could lead to improved wound care.

An enthusiastic new arrival from Cal Tech, Sujit Datta, works on how drying soft materials can heal cracks. It affects everything from cracks in caulking and paint to storing nuclear waste. If he can control the geography of the material as it dries, that helps to determine whether it dries around the edges and expands to fill a space — or whether it dries from the inside out and shrinks to heal its gaps. The smaller the space it occupies, the less likely that a material will crack.

“Princeton is a fantastic place to set up a program and distill complex problems,” says Datta, a graduate of Penn (Class of 2008) with a PhD from Harvard. “What really drew me is that it is a leader for focusing on deep fundamental science, which yields results that make an impact not just after five years, but even 50 years from now. This style of research could change the face of engineering.” In six months he has attracted nine students and three postdoctoral researchers to his lab, not counting a pug/terrier mix mascot, Squid.

Daniel Cohen is a brand new assistant professor of bioengineering, here just a month, but already attracting collaborators for bioengineering research on crowd control — not of people or dogs or birds — but of cells. Almost a dozen researchers at Princeton focus on swarming and collective behaviors of diverse species, but Cohen focuses on individual cell behavior. Using a sheepdog to illustrate “outside-in” control of tissues, he tells how microfluidic and bioelectric devices can “herd” hundreds of thousands of cells to improve wound healing.

To explain the opposite “inside-out” method, he describes how a “secret agent” robot cockroach, which smells like a cockroach, might theoretically be able to lead all the real cockroaches away. Using this approach, materials and microstructures can mimic cells and be integrated into living tissues to control them. Cohen has been long been committed to working in diverse areas; as a student he convinced surgeons to invite engineers into their operating rooms to brainstorm new technologies.

James Spurlin, a post-doctoral scientist in the chemical/biological engineering lab of Celeste M. Nelson, showed how studying the development of the lungs in mice and chicks might lead to engineering materials for different cellular functions. Rick Register spoke on how to manipulate the strength and stiffness of polyethylene.

#b#Photonics & Lasers: The Science – and Business – of Light#/b#

Wednesday’s topics focused on photonics and laser technology development, commercially important in Princeton since the 1970s when optical fibers were introduced. Yet new learning about lasers won’t get to market as quickly as new software discoveries. Wednesday’s first keynote speaker, David T. Beatson, warned that it took 35 years to get from the dial phone to the smart phone. Especially for mid-range infrared imaging technology, plan on a product development cycle of at least 10 years.

Beatson is a business unit leader at Thorlabs Quantum Electronics, a subsidiary of Thorlabs in Newton. Founded by Alex Cable in the late 1980s and named after Cable’s dog, Thorlabs has grown to 1,600 employees worldwide with more than 20,000 photonics products. In high tech markets, Beatson says, engage potential beta customers early so you can develop a conservative marketing plan. Other tips: Save plans for improvements for future products. Bake the software into the hardware early. Be sure to understand the patent and IP landscape from the beginning: Go in with open eyes.

Gerard Wysocki, the first university presenter on Wednesday, is the director of MIRTHE+ Photonics Sensing Center. Princeton University partners with five universities for this National Science Foundation Engineering Research Center that advances mid-infrared photonics sensing technologies for environmental, medical, and homeland security applications.

An earlier encounter at lunch demonstrated how the “magnetic field” of Princeton’s labs and talent works. Fabulous facilities attract the best scientists, who in turn gather eager acolytes, and the cycle continues. At Wysocki’s table were a young woman from Germany, a fellow from Poland, and a postdoc from Sweden. To the question, “why are you here,” each pointed to Wysocki.

Wysocki showed how spectroscopes that use mid-infrared and terahertz (THZ) semiconductor frequencies can detect harmful substances, such as ammonia, in real-world settings.

Mark Zondlo, associate professor of civil and environmental engineering, is passionate about the role of aerosol particles in atmospheric chemistry and air quality. He showed how cleverly used spectroscopy can remotely sense such dangerous pollutants as ammonia (NH3) and nitrous oxide (N2O). “Nitrous oxide is unregulated in large part due to limited knowledge of its emissions,” Zondlo says. It has a 130-year atmospheric lifetime.

Using quantum cascade lasers (QCLs) (semi-conductor lasers in the mid-infrared spectrum), his collaborators measured emissions by driving sensor-equipped cars around fertilized cornfields and the feeding fields of cattle. They also put sensors in towers in pristine forests (such as Duke Forest in North Carolina) as well as polluted cities (Houston and Beijing). By 2019 Zondlo plans to put sensors on a NASA aircraft to monitor forest fires. Knowing the emissions in all of these areas will help to design effective policies to improve air quality and reduce greenhouse gas emissions.

Arthur Dogariu, a research scholar in the mechanical and aerospace engineering department, discussed how “Coherent Raman Spectroscopy,” used at an airport, could remotely and almost instantly detect the elements of a nerve agent in an opaque bottle. It can detect home-made explosives (such as ammonium nitrate) from more than five meters away. In the healthcare field it can save valuable time. If now surgeons have to get cells biopsied by pathologists at each stage of dissection, the hope is that in the near future spectroscopy will be able to identify cancer tissues in real time. Real-time monitoring of blood is also possible.

Lasers and laser photonics were the next focus, with Stefan Heinemann of Cranbury-based Trumpf Photonics and Jerry Meyer of the Naval Research Laboratory giving keynotes. Chemistry professor Greg Scholes explored how complex molecular systems in chemistry and biology can interact with light. Using tools based on super fast laser pulses to study “coherent” phenomena (wave-like properties that maintain a fixed relationship with each other over time), he aims to design efficient devices to harvest light and use that energy to improve manufacturing processes.

Alexandra Werth, a PhD candidate in Claire Gmachl’s electrical engineering group, made the first of two presentations that day. A couple of hours later she would vie for a prize in the Keller Center’s Innovation Forum. Her company, Alira Infrared Biosensing, didn’t win a prize but the presentation garnered praise. She and her cohorts used a quantum cascade laser to detect glucose in the dermis layer of skin — a big improvement to the finger pricks that most glucometers use. It could also be used by vineyards to detect sugar content.

The last presenter on the two-day program, James Sturm, the former director of PRISM, used the term “Galapagos Islands on a chip” to describe the first “evolution accelerator” for cancer, on which he, Bob Austin, and graduate student KC Lin collaborate. Just as different species are isolated from each other on Charles Darwin’s favorite islands, so individual cells see different environments when a drug to treat multiple myeloma, such as Doxorubicin, pulses through the blood vessels. Cells that are distant from the artery don’t get much of the drug, so a heterogeneous environment is key for studying the development of drug resistance. In such interconnected “microhabitats” with different drug concentrations on a chip, cancer can develop drug resistance 40 times faster than usual.

He also discussed how to use microfluidics (tiny plumbing) to separate the elements of blood — red blood cells from white blood cells and platelets — and how to genetically modify the harvested “T” white cells for new immunotherapy approaches to cure cancer. The conventional cell preparation process can require 35 manual steps, and the new automated approach could help reduce both variability as well as the $500,000 treatment cost.

Princeton’s engineering department has 90 faculty members, three Nobel Prize winners, two dozen members of the National Academy of Science, and a couple of MacArthur fellows, an impressive array. Some remain committed to basic research that might eventually lead to a ground-breaking discovery. Others scratch the entrepreneurial itch.

But will they stay in New Jersey? Government monies, which used to encourage the start-ups, have dwindled. In the 1980s, ’90s, and early 2000s, the New Jersey Commission on Science and Technology supported business incubators, early stage grants, entrepreneurial education, and first-year salaries to encourage post doctoral students to take jobs in the state.

When the commission was defunded, did that matter? “Look at the tech startup explosion in New York City in last decade,” says Judith Sheft, associate vice president for technology and enterprise development at the New Jersey Institute of Technology. She was on the transition team for Governor Phil Murphy. “Look at New York City’s support for the entrepreneurial ecosystem with co-working spaces. We saw companies leaving or not wanting to start here. The decline in funding for very early startups had a chilling effect.”

During the two-day PRISM symposium, two dozen senior professors and doctoral students laid out their hopes and dreams for their life’s work and heard from others outside the tunnel of their own lab space. They took inspiration from the success stories, especially Universal Display Corporation, which hatched here at PRISM and is now the poster child for how to translate technology in commercial success (see page 27).

In this rarefied atmosphere, engineers talked to engineers, using — for the most part — the necessary shorthand of technical jargon.

Robert Prud’homme, in contrast, spoke about the joys and sorrows of how basic research gets “translated,” meaning how a discovery gets from the laboratory to the real world. He ended with a real joy, a collaboration with the Gates Foundation, that illustrates his choice to stay in academe. The four war stories:

• A failed research collaboration involved Rhone Poulenc (at that time at Exit 8A) trying to scale up its new method of making complex polymers. They funded his research, but could only produce one type of polymer. Rather than giving up, he combined the polymer in a mixing process based on a BASF collaboration. This formed the basis of his group’s nanoparticle production platform that has continued over the last dozen years. Conclusion: “You can’t predict the future.”

• A corporate path that crashed and was resurrected 10 years later. How it happened: Merck funded research in Prud’homme’s lab to adopt his nanoparticle technology for a new class of drugs. The research was successful, and resulted in a joint patent and papers. The PhD student funded by Merck declined to accept Merck’s job offer after graduation; instead he went to work for Alnylam, a Boston startup. However, Merck abandoned the therapeutic area, and sold all of the patents to Alnylam. So the student had access to his patents.

In the next twist, Alnylam was sued by another biotech company, and the settlement terms prevented Alnylam from working with the type of nanoparticle developed with the Merck/Princeton patent. So the patent was stranded, and useless. The rights to the patent were returned to Princeton. The student left the research field to be a venture capitalist. Ten years later another large biotech company approached Princeton and has licensed the patent. Conclusion: “You can’t predict the future of companies.”

• A small scale collaboration that “pivoted” and became a startup. The Prudhomme lab collaborated for three years with Optimeos Life Science Inc., based around imaging nanoparticles. The lab developed the ability to encapsulate peptides and biologics at higher loadings and efficiencies than had been done previously. Optimeos “pivoted” (a startup term meaning, “Our first idea wasn’t so great, but this new idea will be terrific”) and turned to biologics, the fastest growing segment of the pharma market. It became a biologics delivery company. They have received first round funding from IP Group, and have three projects with major pharma companies. Conclusion: “Random opportunities are better than planning.”

• A new challenge and huge opportunity with the Gates Foundation, for global health. Sensitive medicines often come in blister packs and sealed packets, but that doesn’t work for sub-Saharan Africa. Liquid medicines for infants are too expensive to ship. Any powder or tablet must be able to withstand 75 percent humidity and sweltering temperatures and must cost only pennies a tablet.

The Prud’homme lab had been working on high value therapeutics for cancer, HIV, and TB. The Gates Foundation challenged them to use their formulation technology to produce low-cost medicines at high volumes. Making the nanoparticles of the drug was straightforward; the low cost additives to prevent aggregation and enable rapid delivery was the challenge. Three additives were tested. One was lecithin (the ingredient in Pam spray for frying pans), zein (a corn protein byproduct of ethanol that is sprayed on cornflakes to keep them crispy in milk), and cellulose-based polymer. All worked, but zein performed best in the first animal trials, for the first drug, for a diarrheal infection, the second leading killer of infants in sub-Saharan Africa.

Researchers and the university get no royalties, and no profit is involved. Two drugs are undergoing clinical trials and a third is in the pipeline. The World Health Organization, using Gates funds, buys the drugs made by a Chinese manufacturing company, whose head of formulation development is one of Prud’homme’s former students (it’s a small world). Conclusion: Persistence with your vision can make a difference, but you may not know that today.”

“In life sciences change does not happen quickly, not like in IT,” says Prud’homme. “But you can position yourself for success if you do the best research you can, and take advantage of random things.”

It’s heady stuff, this talk of patents and start-ups and million dollar payoffs. Prud’homme is allowed, by university policy, to have only a very small stake in any of the start-ups. Has he ever been tempted to leave the ivory tower and pursue profits with one of the many discoveries? Actually, no, he says. “I’ve always loved learning. Someone once told me he had never met anyone as curious as I am. I love putting things together, solving puzzles. And I have always loved teaching.” He pauses. “I also know I don’t have the constitution to be a gambler. The best entrepreneurs do.”

More information: www.princeton.edu/~prism

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