UF Explore Magazine | Fall 2015

FALL 2015

Science Takes Shape Dawn of the Soft Matter Age

Fall 2015, Vol. 20, No. 3

Extracts Research Briefs

4 Soft Matter Solutions

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UF ushers in a new age of engineering with a novel technology for 3-D printing the softest objects.

Discovering the Deep

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UF geologist Michael Perfit shares his experiences at the bottom of the ocean in a new book.

About the cover: 3-D printed polymer jellyfish float in an aquarium at a UF engineering lab.

Photo by John Jernigan

Dr. Kent Fuchs President Dr. David Norton Vice President for Research

Infinite Creativity

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Fab Lab technology allows makers of all sorts to turn their visions into reality.

Incubating Innovation

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The Sid Martin Biotechnology Incubator celebrates two decades of nurturing young companies.

Explore is published by the UF Office of Research. Opinions expressed do not reflect the official views of the university. Use of trade names implies no endorsement by the University of Florida. Š 2015 University of Florida. explore.research.ufl.edu Editor: Joseph M. Kays joekays@ufl.edu

The Conversation

Art Director: Katherine Kinsley-Momberger

Mathematics goes viral.

Design and Illustration: Katherine Kinsley-Momberger Nancy Schreck

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Writer: Cindy Spence Copy Editor: Bruce Mastron

Explore Magazine Turns 20

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Board of Trustees Steven M. Scott – Chair David L. Brandon Susan M. Cameron Christopher T. Corr Paul Davenport Charles B. Edwards James W. Heavener Joselin Padron-Rasines Rahul Patel Jason J. Rosenberg Robert G. Stern David M. Thomas Anita G. Zucker

Printing: StorterChilds Printing, Gainesville Member of the University Research Magazine Association www.urma.org

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Tracking Parkinson’s with MRI UF breakthrough measures Parkinson’s progression in the brain

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Substantia Nigra

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niversity of Florida researchers have identified a biomarker that shows the progression of Parkinson’s disease in the brain, opening the door to better diagnosis and treatment of the degenerative disease.

By comparing brain images of Parkinson’s patients to those of a control group over a year, an interdisciplinary team found that an area of the brain called the substantia nigra changes as the disease advances. The findings provide the first MRI-based method to measure the disease’s progression, which can inform treatment decisions and aid in identifying new therapies, said UF applied physiology and kinesiology professor David Vaillancourt, one of the study’s authors.

“The Parkinson’s drugs available today help reduce symptoms. They don’t slow the progression of the disease, which is the major unmet medical need,” Vaillancourt said. “We’ve provided a tool to test promising new therapies that could address progression.”

The substantia nigra of a Parkinson’s patient has more “free water” — fluid unconstrained by brain tissue, likely because of

disease-related degeneration.

The new study uses diffusion imaging, a type of MRI, to show that free-water levels increase as the disease progresses. The free-water level was also a good predictor of how bradykinesia — the slowness of movement common to Parkinson’s — advanced over the course of the subsequent year.

Because doctors typically diagnose the disease by evaluating patients’ symptoms and how they respond to medication, the indicator could also be useful to distinguish Parkinson’s from similar disorders. That could lead to better clinical trials, Vaillancourt said.

Lead researcher Edward Ofori, a postdoctoral fellow in UF’s College of Health and Human Performance, was joined in the study by UF neurology professor Michael Okun, M.D., medical director of the National Parkinson Foundation; postdoctoral students Peggy Planetta and Roxana Burciu; study coordinator Amy Snyder; Song Lai, Ph.D., human imaging director for UF’s Clinical and Translational Science Institute; and collaborators from Harvard Medical School and Rush University Medical Centre.

David Vaillancourt, vcourt@ufl.edu

Alisson Clark

MICROARRAY

makes Chemo Personal

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wo University of Florida researchers have invented a device that makes chemotherapy treatments more personalized, efficient and affordable.

The miniaturized platform, known as a microarray, uses patients’ cancer cells to test various doses and combinations of chemotherapy drugs. The device’s breakthrough capability — its ability to work with a smaller number of cancer stem cells — is especially crucial because such cells are particularly rare.

Cancer stem cells comprise about 1 percent of a typical tumor, and other drug-testing methods require larger amounts of cells.

The device was developed by Benjamin G. Keselowsky, an associate professor in the J. Crayton Pruitt Family Department of Biomedical Engineering, and Matthew R. Carstens, a postdoctoral associate in Keselowsky’s laboratory. Researchers from the Cleveland Clinic and University of California collaborated on the research, which was published in the Proceedings of the National Academy of Sciences.

The microarray is a piece of square glass the size of a quarter that can hold a tiny grid of several hundred polymer “islands.”

The “islands” are first loaded with various combinations and doses of chemotherapy drugs. Cancer cells are then added, and the cells’ interaction with the drugs is observed to determine which combinations work best, Carstens said.

The new array uses less than 6 percent of the cancer stem cells that are typically needed for such testing. Extracting elusive and rare cancer stem cells from patients is time consuming and expensive, and the new technique makes the process more efficient and cost-effective, Carstens said. The process has been granted a patent, although clinical trials may likely be required

before it could be put to widespread use in clinics and laboratories, according to Keselowsky.

It also represents an advance in personalized medicine: A patient’s cancer stem cells can be extracted and tested with various combinations of chemotherapy drugs. Currently, physicians try various drug combinations directly on patients — a process that the new microarray may someday replace.

“The potential for treatment is that we can do a lot of testing and know what will work in the patient. The ability to test multiple chemotherapy treatments with fewer cancer cells is a big advancement,” said Emina H. Huang, M.D., a colorectal surgeon at the Cleveland Clinic, professor of surgery at the clinic’s Lerner College of Medicine at Case Western Reserve University and vice chair of the clinic’s department of stem cell biology and regenerative medicine.

Some of the research was done in Huang’s lab at UF Health, where she was a colorectal surgeon and professor of surgery. She also supplied the cells for the research and taught Carstens how to culture them.

While the microarray was tested on colorectal stem cells, Keselowsky said the approach could be used to test the efficacy of chemotherapy drugs on virtually any kind of cancer that involves a solid tumor.

Chemotherapy for colorectal cancer is often a combination of two drugs, and researchers tested the interaction of the

drugs nutlin-3a and camptothecin on cancer stem cells.

The cells were taken from a 70-year-old, stage IV cancer patient and a 60-year-old patient with stage III colorectal cancer. The microarrays were seeded with approximately 200 cells per “island” — 16 times fewer cells than other chemotherapy testing methods use.

The new array’s efficient use of rare cells means that a patient could undergo a biopsy and the cancer stem cells could be tested with combinations of chemotherapy drugs sooner.

“Because it requires far fewer cells, there would be a quicker turnover time. That makes it possible to personalize the chemotherapy regimen much sooner,” Keselowsky said.

In addition to potentially needing clinical trials, bringing the new microarray into widespread use would likely require a company to invest in further research and possibly production, Keselowsky said. Still, the invention is a significant advance in personalized medicine for cancer patients, he said.

“It’s a combination of having a novel device that works on colon cancer stem cells, which is an important cancer biology topic right now,” he said.

The research was started with a grant from the UF Research Opportunity Seed Fund and then supported by grants from the National Science Foundation and the National Institutes of Health.

Benjamin Keselowsky, bgk@ufl.edu

Doug Bennett

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Prosthetics Feel Real

UF neuroprosthetics research awarded up to $5.4 million

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group of U.S. military veteran and civilian volunteers with upper limb amputations will soon have the chance to test neural implants designed to offer more intuitive control of their prosthetics, thanks to a research collaboration between the University of Florida and the Defense Advanced Research Projects Agency.

The aim of the Hand Proprioception & Touch Interfaces, or HAPTIX, program is to develop an implantable neural interface that can restore closed-loop sensory motor control of dexterous mechatronic prostheses, ultimately offering amputees a prosthetic limb system that feels and functions like a natural limb.

UF’s proposal for the HAPTIX project, named the Implantable Multimodal Peripheral Recording and Stimulation System, or IMPRESS, has been awarded $2.7 million for the next 18 months, with a potential for a total award of $5.4 million over 30 months.

“IMPRESS aims to create new peripheral nerve interfaces with far greater channel count, electrode density, and information stability than exist today, enabling effective bidirectional control of dexterous hand prosthesis in real time,” said Rizwan Bashirullah, a professor of electrical engineering at UF and project lead of IMPRESS. “In other words, we hope to develop new neural interface technology so that patients can experience a prosthetic limb as close to natural as a real limb.”

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Bashirullah has assembled a multidisciplinary team composed of an international leader in upper-extremity rehabilitation from Germany, one of the top research organizations in advanced microfabrication (IMEC, Belgium) and a team of UF neuroengineers — including electrical engineering professors Jose Principe and Jack Judy and biomedical engineering professor Aysegul Gunduz. The UF team works on the cutting edge of neural-interface algorithm development and system design.

“This research will directly impact the quality of life for a number of our veterans,” said Cammy Abernathy, dean of the UF College of Engineering, “and in doing so, we will further develop our faculty’s already outstanding work in

neuroprosthetics. This kind of research exemplifies how UF works for the ‘Gator Good.’”

While U.S. soldier fatalities have dropped in recent years, the prevalence of powerful explosives on the battlefield has resulted in a large number of veterans suffering from upper-limb amputations. Advances have been made in the development of dexterous mechatronic prostheses, yet without the type of naturalistic controls that are being developed by the HAPTIX program, the learning curve for these prostheses is lengthy, unintuitive, has a high cognitive load and offers limited performance, responsiveness and sense of embodiment.

“The University of Florida has tremendous resources

in the areas of neuroscience and neuroengineering,” said David Norton, vice president for research at UF, “in part because our interdisciplinary departments ­— including the College of Engineering, the College of Medicine and the McKnight Brain Institute — all work so seamlessly together. This is a wonderful opportunity to use our strengths to help those who have served our country.”

Rizwan Bashirullah rizwan@tec.ufl.edu

Lateral Line

Solving a fish mystery, with human implications

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Leif Ristroph / New York University

ow do you find out what a fish feels?

For University of Florida researcher James Liao, the answer involves lasers, taxidermy and more than a few mathematicians.

In the late winter of 2013, Liao packed up his equipment from UF’s Whitney Laboratory in St. Augustine to visit New York University’s Courant Institute of Mathematics.

The trip was part of a 10-year journey that started when Liao was a graduate student at Harvard. Liao was intrigued by the arrangement of the lateral line organ, a “sixth sense” used by fishes to detect water flow and pressure, which remains consistent across more than 33,000 species. Was this sensor organization related to function, or a developmental constraint that occurs commonly in biology? In order to

answer this, Liao knew that he needed to directly measure what a fish feels when it is swimming.

That’s where it got tricky.

“Putting sensors on a live fish makes it behave unnaturally,” he said.

Liao, whose expertise is in biomechanics and neuroscience, brought together a team of mathematicians and roboticists to answer the question, question, which resulted in a recent paper published in Physical Review Letters and featured in The New Yorker.

Liao, an aspiring professional angler, recreated the shape of a fish with the help of an accomplished taxidermist from Missouri. They created a model based on a fish for which his lab had collected extensive swimming data.

“This way we could drill holes into the model and place pressure sensors where the

actual biological sensors would be on the lateral line,” he said, directly measuring what a fish feels for the first time.

To measure the flow of water, Liao used transducers intended to detect subtle pressure changes in rat arteries and veins. The transducer proved to be ideally designed, but cost $1,000 each. Fortunately, Liao was able to secure several of them — along with amplifiers and analysis software — with grant support from the National Institutes of Health. It turns out that the Center for Hearing and Deafness Disorders is very interested in how hair cell systems, like the lateral line, can tell us more about human inner ear function.

Since his collaboration in the math lab, Liao’s work on lateral line continues to evolve, employing new technologies along the way.

His lab now scans real trout and 3-D prints the shape, equipped with an even more accurate placement of lateral line holes. Liao is advancing a new line of research using a robotic controller, and, with colleagues at Harvard University, is investigating how the pressure signal across a fish’s head changes while it is actively swimming.

“The fish at NYU didn’t wiggle, so while the PRL paper made great advances in understanding what fish feel when they glide, the reality is that fish move their bodies back and forth when they swim,” he said. Liao feels this new line of research, using robotics to ask better questions about biology, will allow him to ask — and answer — more questions that impact human health.

James Liao, jliao@whitney.ufl.edu

Jessica Long

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Rhyme Time Research provides evidence of learning and memory six weeks prior to birth

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f you’ve ever been pregnant, did you have a saying you’d repeat to yourself — something about taking things one day at a time, or maybe even wishing that men could know what it’s like to carry a child? Or did you have a favorite song you’d listen to obsessively? Well, if you said or heard something like that over and over again during pregnancy, your newborn may remember it too.

A study funded by the National Science Foundation’s Social Behavioral and Economic Sciences Directorate suggests babies begin to acquire knowledge in the womb earlier than previously thought.

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Research led by Charlene Krueger, an associate professor at UF’s College of Nursing, and published in the journal Infant Behavior and Development, provides evidence that what fetuses hear by their 34th week in utero can inspire learning. That’s three weeks earlier than the evidence of learning detected by previous research.

By the 38th week of pregnancy, memory is evident; births normally occur around 40 weeks.

Krueger conducts research on early developmental exposure to sound, specifically maternal voice. She and co-investigator Cynthia Garvan, UF’s statistics director in the Office of Educational Research, asked

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32 women to repeat aloud the same 15-second nursery rhyme twice a day for six weeks from their 28th week of pregnancy through their 34th week.

After the 34th week, the mothers stopped reciting the nursery rhyme. All along, they visited a lab at 28, 32, 33 and 34 weeks’ gestation to determine whether the unborn babies had familiarized themselves with the nursery rhyme. They also came in for testing at 36 and 38 weeks.

Lab testing involved measuring the fetuses’ heart rates while the unborn babies listened to a recorded female voice repeat the same nursery rhyme that was spoken at home by the mothers.

If the heart rate accelerated, the researchers surmised the fetuses hadn’t totally grasped the new sounds. If the heart rate decelerated, it meant the fetuses found the nursery rhyme familiar.

Krueger and Garvan found that by the 34th week, the heart rates of the fetuses began to decline while listening to the recording. By 38 weeks, four weeks after their mothers stopped repeating the rhyme, testing found statistically evident heart rate deceleration,

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meaning the fetuses remembered the rhyme.

Meanwhile, a control group of fetuses heard a different rhyme also spoken by a stranger. Since a mother’s voice is the main source of sensory stimulation for an unborn baby, the researchers wanted to determine if the fetuses simply were responding to their mothers’ voices rather than to a familiar pattern of speech. When this group listened to a recording of a new nursery rhyme, their heart rates slightly accelerated.

Krueger and Garvan concluded that the fetuses in the experimental group were responding to the nursery rhyme; that they begin to show evidence of learning by 34 weeks gestational age; and that they are capable of remembering what they hear inside the womb.

The study’s goal was to increase basic knowledge of not only when, but ultimately how, humans learn and remember. This is important to a baby’s experience in neonatal intensive care units, as new technologies give preterm infants a greater chance of survival and alter patterns of stimulation for developing fetuses in and out of the womb.

Further study is needed to more fully understand how ongoing experience, in the context of ongoing development in the last trimester of pregnancy, affects learning and memory.

Charlene Krueger, ckrueger@ufl.edu

Bobbie Mixon National Science Foundation

Fjords: Carbon-Sequestration

SUPERSTARS

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n the effort to remove excess carbon dioxide from our atmosphere, humans have an unlikely ally: fjords.

The dramatic, glaciercarved inlets found from Alaska to Antarctica capture and store carbon better than other open-water marine systems, removing it from the atmosphere, says University of Florida geochemist Thomas Bianchi, a member of the team that made the discovery.

“Carbon sequestration is the big buzzword, but we’re still getting a handle on how it works,” Bianchi said.

In order to make informed land-use decisions and accurate climate predictions, “finding and understanding these hot spots is critical,” he said.

Bianchi’s former doctoral student Richard Smith — now a postdoctoral fellow at

the University of Connecticut — led the team, which included researchers from New Zealand, South Africa, Tulane University in New Orleans and the Woods Hole Oceanographic Institution in Massachusetts.

Although fjords represent a tiny fraction of the seas, they store 11 percent of the carbon buried in the oceans — an estimated 18 million metric tons a year, the study showed. Locking that carbon away prevents it from converting to carbon dioxide, one of the greenhouse gases that contribute to a warming atmosphere. Fjords’ efficiency at storing carbon comes from their deep, narrow V shape, which allows carbon to sink into low-oxygen zones where it is less likely to be consumed by aerobic bacteria and re-enter the atmosphere as a greenhouse gas.

Scientists had known for years that fjords were coastal environments with high carbon storage, but because they make up just a tenth of a percent of the world’s oceans, no one realized just how important they were, Bianchi says.

“Most of the focus has been on the big river deltas, because they drain so much more surface area in their large watersheds,” he said.

The team studied samples of core and surface sediment from fjords in New Zealand, then compared their results with previous data from the Arctic, sub-Arctic Canada, Norway, Sweden, Scotland, Greenland, Alaska, Chile and Antarctica. Their results revealed fjords to be five times more efficient at sequestration than continental shelves, another key area for carbon burial. Averaged by

area, fjords buried carbon at a rate double that of the oceans overall.

Bianchi hopes the findings will draw attention to fjords’ importance for better-informed conservation decisions.

“It’s amazing that systems that are so small can have such a huge global impact,” he said. “It sends the message that fjords are not only beautiful, they’re providing a very important service.”

Thomas Bianchi, tbianchi@ufl.edu

Alisson Clark

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Tooth Tales

Dental enamel reveals surprising migration patterns in ancient Indus civilizations

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niversity of Florida researchers have discovered that ancient peoples in the Indus Valley apparently did not stay put, as was previously thought. Equally surprising is how they found out: by examining 4,000-year-old teeth.

When tooth enamel forms, it incorporates elements from the local environment — the food one eats, the water one drinks, the dust one breathes. When the researchers looked at remains from the ancient city of Harappa, located in what is known today as the Punjab Province of Pakistan, individuals’ early molars told a very different story than their later ones, meaning they hadn’t been born in the city where they were found.

Much of what modern researchers have gleaned about our common ancestors, particularly those from Egypt and Mesopotamia, comes from well-studied tombs and burial sites.

Discovering the narrative of peoples from the Greater Indus Valley — which comprises much of modern-day Pakistan and northwest India — is more challenging. The text of the Indus Valley Civilization remains undeciphered, and known and excavated burial sites are rare.

The new study illuminates the lives of individuals buried more than 4,000 years ago in those rare grave sites by providing a novel comparison of the dental enamel and chemical analyses of the water, fauna and rocks of the time, using isotope ratios of lead and strontium.

In its heyday, Harappa held a population of 50,000, although the number of individuals represented by skeletal

remains across the entire culture area totals in the hundreds.

The UF research team was led by Benjamin Valentine, now a postdoc at Dartmouth; biological anthropologist John Krigbaum, his dissertation adviser; and geological sciences professor George Kamenov, an isotope geologist.

“The idea of isotope analysis to determine the origin of individual migrants has been around for decades. But what people haven’t been doing is looking at the different tooth types, essentially, snapshots of residents during different times of individuals’ lives,” said Valentine. “We didn’t invent the method, but we threw the kitchen sink at it.”

The researchers discovered that the people in the Harappa grave sites weren’t born there, but migrated there from the hinterlands.

Said Krigbaum, “Previous work had thought the burial sites represented local, middle-class people. There was no notion that outsiders were welcomed and integrated by locals within the city. It’s not clear why certain young hinterland people were sent to the city.

“All told, these novel methods provide windows into the life history of past people and underscore the role of interdisciplinary approaches to illuminate dynamics of human migration.”

John Krigbaum, krigbaum@ufl.edu George Kamenov, kamenov@ufl.edu

Gigi Marino

reactions “toOverall the notion that Spanish should be a required subject in public schools was far less polarized and more popular than we imagined.

”

Chris McCarty, Director UF Survey Research Center, Bureau of Economic and Business Research

The magnitude of support for requiring Spanish (67 percent) is important because a constitutional amendment requiring Spanish instruction would need 60 percent of voters.

As we know from “ research, bilingualism has many advantages — cognitive, educational, sociocultural and economic. It is increasingly recognized that intercultural competence and multilingualism has the future competitive edge.

”

Ester de Jong, Director UF School of Teaching and Learning

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Kristin Grace

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Floridians supporting required Spanish language instruction in Florida public schools

100 95% 75%

SPANISH

67%

Geometry

0

77%

Florida History

20

2nd language of choice

40

Basic computer skills

60

81%

UF researchers reveal first Tree of Life for all 2.3 million named species

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Tree of Life

Floridians support of REQUIRED courses in Florida public schools

66%

Floridians support for required Spanish language class in Florida public schools by region

63%

62% 72%

To read the full survey visit: http://bit.ly/1WMIUQR

n the mid-90s, many of Doug Soltis’ colleagues told him that creating a tree of life — a map of Earth’s 2.3 million named species and the connections between them — couldn’t be done.

Two decades later, the University of Florida plant biologist and colleagues have proved their detractors wrong, publishing the first draft of a Tree of Life that covers every named organism on the planet.

Just as the sequencing of the human genome led to advances in medicine and healthcare, the Tree of Life will help researchers studying diverse disciplines related to biodiversity as they develop new drugs, study climate change and trace the origins of infectious diseases, said Soltis, a distinguished professor with appointments in the Florida Museum of Natural History and UF’s biology department and a member of the UF Genetics Institute.

“There is nothing more foundational or important than knowing how organisms are related,” Soltis said. “For example, organisms respond in similar ways to climate change based on how they are related. So there is predictive power in the Tree of Life.”

Three years ago, the National Science Foundation awarded Soltis, UF biology department and Genetics Institute faculty member Gordon Burleigh and a team of colleagues from across the country the opportunity to build the first Tree of Life, which includes animals, plants, fungi and microbes. Recent advances in algorithm development, computer technology and DNA sequencing made the project possible.

The study was published online in the Proceedings of the National Academy of Sciences.

Study researchers pieced together nearly 500 smaller trees previously created for groups like birds and mammals that scientists have been working on for several decades.

In the end, Soltis said, the biggest discovery in the tree’s development was not only finding out what scientists know about biodiversity, but also the immense amount that is still unknown.

“This tree is just a starting point,” Soltis said. “Most trees of species relationships are based on DNA data, but less than 5 percent of all species on Earth actually have DNA data available. Plus there’s still so much diversity out there that we know nothing about.”

Soltis said the tree is far from perfect, with many organisms whose relationships are not well understood scientifically. But study researchers are hopeful the tree will be a stimulus that helps direct future efforts. To help fill in the gaps, the team is also developing software that will enable researchers to log on, update and revise the tree as new species are named or discovered.

“At a time when we’re facing a biodiversity crisis and many forms of life are disappearing, I think it is good for the public to be reminded that there is so much we don’t know about life on our planet,” Soltis said. “With tens of millions of species out there still undiscovered, I hope this first draft inspires more interest in biodiversity, because with that interest and further research, the tree will continue to grow.”

To browse the current Tree of Life online, visit www.etreeoflife.com or www.opentreeoflife.org.

Doug Soltis, dsoltis@fl.edu

Stephenie Livingston

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SOFT UF ushers in a new age of engineering with a novel technology for 3-D printing the softest objects story by Cindy Spence photos by John Jernigan

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dozen or so polymer jellyfish float in an aquarium in Tommy Angelini’s engineering lab, not alive but freaks of nature nonetheless, about to rock the world.

Just months ago, these jellyfish could not have existed; there was no way to make something so soft. That changed in 2014.

Angelini was exploring ways to create fragile arrays of cells when he realized the contraption he had cobbled together not only did what he wanted it to do, but much, much, much more. As experiments piled up — let’s try this, what if we try that — the contraption met every challenge, and doors long closed to scientific inquiry sprang open. A new age of engineering, the Age of Soft Matter, had arrived.

As Angelini worked, he updated colleague and mentor Greg Sawyer on the eerily soft objects coming out of his lab. Sawyer issued a challenge.

“As engineers, you look at a jellyfish, and you say, that’s utterly impossible, how on earth could we manufacture that thing,” says Sawyer. “You want to make something? Make a jellyfish.”

Angelini did, and Sawyer says, “Now, let’s cross that off the impossible list, and get started.”

As a symbol of a new age and an engineering revolution that will change medicine and manufacturing, the no-longer-impossible jellyfish is perfect. If you can make a jellyfish, think what else you can make: cells, tissues, organs, tumors.

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The

Beginning Before the jellyfish, there was a grant. Angelini had won a National Science Foundation Early Career Development Award, NSF’s most prestigious award for promising junior faculty, with a proposal to use the $500,000 to explore cell mechanics. To do that, he needed arrays of cells not confined to a petri dish. He needed cells in three dimensions.

“I wanted to study the basic physics of collective cell behavior,” Angelini says. “What do cells do spontaneously when driven by their own internal machinery?”

Angelini hired doctoral student Tapomoy Bhattacharjee and drew on assistance that ranged from a high school student working on a science fair project to Sawyer, a world-renowned tribologist and the Ebaugh professor in the Department of Mechanical and Aerospace Engineering. Angelini bought a see-through laminar cabinet commonly used by geneticists because it had a way to filter air. He procured a fine-tipped nozzle like those used in 3-D printers. All he needed was a way to hold the printed cells in place; in other words, something that did not exist.

In traditional 3-D printing, the nozzle deposits liquid on a platform, and it hardens layer by layer until an object takes shape. That method would not work with something as squishy as a cell, which could not harden and would not be supported in air.

Angelini needed a specialized material, one soft enough to allow the most fragile object to take shape, but strong enough to hold it in place, so it could be studied and manipulated. The substance had to be neutral, neither contaminating nor augmenting the object it cradled, and

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it had to be soluble so it would rinse off, leaving no trace. It was a tall order, but Angelini figured a granular gel medium might work.

You know it as hand sanitizer.

The granular gel medium is the same as hand sanitizer without fragrance or alcohol. It straddles the solid-fluid states that Angelini needed to both hold a fragile object and later release it because the substance is 99.8 percent water. The other 0.2 percent is a polymer. As the nozzle passes through, the gel heals in its wake, leaving no sign of disturbance other than the soft, printed object, visible through the clear gel.

The intended goal — studying cells in 3-D — had an unintended, but groundbreaking, consequence — the invention of 3-D printing of soft matter.

As word spread across campus, the kneejerk reaction was, “No, that isn’t possible.” As chemists, biologists, neurologists, doctors and engineers trooped through Angelini’s laboratory, Bhattacharjee demonstrated, printing jellyfish after jellyfish, filling an aquarium with polymer creatures.

“We showed them, ‘This is the science, this is how it works,’” Bhattacharjee says. “It’s fun for a physicist, it’s fun for a biologist.”

Disbelief, Sawyer says, quickly turned to, “Wow, this is really cool!”

Seconds later, wheels turning, that became, “What can I do with it?”

Sawyer and Angelini had suggestions.

The intended goal — studying cells in 3-D — —had had anan unintended, unintended, but groundbreaking, but groundconsequence —g , b r e a k i n consequence — the invention of 3-D printing of soft matter.

The intended goal — studying cells in 3-D the invention of 3-D printing of soft matter.

Tommy Angelini uses the refrigerator in his lab as a white board for quick calculations.

Early examples of polymer jellyfish and nested dolls, neither of which could be printed using traditional methods.

Tapomoy Bhattacharjee monitors the printing of a jellyfish.

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A Grand Challenge

In 2015, the American Cancer Society estimates 1,658,370 cases of cancer will be diagnosed in the United States; 589,430 cancer patients will die. By 2020, treating cancer will cost the U.S. over $200 billion a year.

Perhaps more staggering than the statistics is cancer’s reach. Every family has a cancer story, and that makes cancer a grand challenge for medicine.

For Sawyer, it’s a personal challenge as well.

In 2013, Sawyer was diagnosed with stage IV metastatic melanoma. At first he felt helpless but, being an engineer, he did his homework. He joined a new immune therapy clinical trial, had a trio of painful operations and months of intense radiation to fight the disease.

When Angelini printed the jellyfish a year later, the intersection with cancer was clear.

When the College of Medicine’s Celebration of Research rolled around, they browsed the posters at the O’Connell Center to see if they could find a collaborator. They ran into cancer researcher Steve Ghivizzani.

“I listened to them talk about this new technology, and I thought, ‘That’s just crazy.’ Greg says, ‘Just think about it: If you had the ability to position cellular things in space without restrictions, what could you use it for?’”

Ghivizzani did think about it and emailed Sawyer that night. He was in.

Cancer has been a thorny research subject because it is a chameleon. A cancer cell in one person doesn’t behave like a cancer cell in another, even if the cancers are the same. Even more confounding, each tumor is heterogeneous. On its exterior, it might be gorging on nutrients and replicating rapidly.

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Deep inside, it may be almost starving, but still alive, waiting for nutrients before growing. With thousands of cancer cells in each tumor, figuring out how the cells interact will be a key to future cancer treatment.

Ghivizzani says a tool that could allow cancer research to take not one step, but possibly many giant steps, got him excited.

“Innovations in science can sometimes be subtle,” Ghivizzani says. “This rocks.”

Cancer researchers have been stuck for years with two models, the petri dish and the mouse.

Cancer cells are easy to grow in a petri dish. But the biology of a cell growing in a dish is different from the biology of a cell growing in a body. In the body, cancer cells compete with other cells for nutrients, exhibiting aggression, or malignancy. In a petri dish, without competition, they adapt to their environment and often lose the malignancy a researcher wants to study. Ghivizzani says about two-thirds of the genes expressed in a tumor in the body are expressed in opposite ways in a petri dish.

The other model is the mouse, but that, too, has limits. Many cancers don’t grow in mice, prostate cancer, for

Greg Sawyer examines a small-scale, soft matter model of a brain.

3-D spheres are printed with cancerous cells for use developing personalized cancer therapies.

A model of a bioreactor the lab is designing to house arrays of cells on which drugs and other therapies can be tested.

instance. Most mice used for cancer research also have been genetically engineered to suppress their immune system, so immune therapies cannot be studied.

Cancer grows slowly in mice, if at all, and sometimes the patients succumb before the mice can be tested. To see inside the mouse, you have to sacrifice the animal and further study of the tumor.

What is needed is a three-dimensional model between a petri dish and a mouse: 3-D soft matter printing of cancer cells.

The goal is to harvest a patient’s cancer cells, print them into the

granular gel, and allow them to grow.

In theory, unlimited samples could be grown and an unlimited number of therapies tried. Researchers couldn’t use 10,000 mice at once, but they could grow 10,000 samples and try different approaches. From immune therapies to various drugs, all the tests could take place at once, saving critical time for the patient.

“We can use this system to learn a lot more a lot faster than we have been able to do,” Ghivizzani says. “Can you take each patient, print replicas of their tumor and then try different therapies?

That’s where we want to go.”

Ghivizzani says the ability to collaborate with engineers on cancer research is key to reaching that goal. Working with Sawyer and Angelini one afternoon during a test, it looked like they would not be able to print fast enough to continue working the next day.

“Greg sat down and did the math, and they built another machine. By the next morning, they had it reconfigured to work the way we needed it to function,” Ghivizzani says. “Their ability to solve those kinds of technical problems that are not biologic . . . without that, we won’t get where we want to go.”

Sawyer, who feels the urgency of his fellow cancer patients every 100 days when he visits his doctors, says engineers are perfect partners for cancer research. By January, he says, UF engineers will equip a lab at the College of Medicine with engineering tools for new research.

“At first, cancer seemed far from engineering. But look at it; it’s a dynamic system, far from equilibrium, and maybe that’s not so strange to engineers. This is tumor engineering. Give us six months, and we can really help from an engineering standpoint.

“Ten years from now, I think this will be the way researchers work with patients’ cancers,” Sawyer says.

Sharing the

Science A new age of engineering creates a lot of work, and Sawyer and Angelini were eager to share the cool, new science. Department Chair David Hahn agreed to a Soft Matter Engineering Research Group, and the scientists who witnessed the first jellyfish demonstrations signed on. Today, there are 28 collaborators, including two Sawyer protégés at the University of Illinois Urbana-Champaign and Florida International University.

“Tommy made that breakthrough, printing in the granular gel, that was the quantum step forward,” Hahn says.

“Now there’s a thousand things to do on top of that with the subtleties of the materials, applications, the science behind it, understanding how these materials function. It’s huge.”

Teams of engineers and doctors will tackle four areas: mechanics and failure theories of soft matter; soft matter manufacturing; transport of materials through soft matter; and soft matter for medicine.

The objects printed in the lab are orders of magnitude softer than any man-made object. Angelini says he doesn’t know of a lower limit to the mechanical integrity of the objects the lab can make, and Hahn says new mechanics and failure theories will be needed; what works for titanium will not work for cells and polymers a million times softer.

“In simple terms, a hundred-plus years that we’ve built a foundation on in traditional mechanics is largely off the table with soft matter,” Hahn says.

“It really is a whole new frontier of engineering.”

Angelini’s lab did informal tests.

One early jellyfish was placed in a jar

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and examined weekly. It held up just fine until, at the seven-month mark, it was knocked off a shelf. On impulse, Angelini tossed a container of polymer jellyfish in his backpack to travel to a conference in Germany. They survived, so he sent them by FedEx to a colleague in Cleveland and had them shipped back. The jellyfish were no worse for wear.

Now it’s time for science to back up — or disprove — the anecdotes.

Sawyer, the go-to guy for expertise on friction and wear in mechanics and materials, says what engineering has lacked from the Stone Age to the Plastics Age and beyond is softness; soft materials have always confounded engineers.

“What is soft matter? Actually, it’s everything; it’s most of the human body. The hard matter is the weird stuff. We’ve worked with it since the Stone Age because we knew the rules,” Sawyer says. “Now, we’ve entered the Soft Matter Age.” Engineering Professor Kevin Jones, who views materials science through a broad lens that includes anthropology,

18 Fall 2015

“What is soft matter?

Actually, it’s every“What is soft matter? Actually, thing; it’s most of the it’s everything; human body.

The hard it’s most of the human body. The matter is the weird hard matter is the stuff. worked weird stuff. We’ve We’ve worked withit it with since the since the Stone Stone because Age becauseAge we knew the rules. Now, we’ve entered the rules. we knew the Soft Matter Age.” entered Now, we’ve the Soft Matter Age.” — Greg Sawyer

the classics, humanities and history, is creating a soft matter module for an interdisciplinary course he coordinates, “The Impact of Materials on Society.”

When he wrote the course flyer, one of the teasers was, “What future materials innovations will revolutionize your world?”

“I didn’t realize that at that very moment, one of those revolutions was taking place across campus,” Jones says.

That there is no textbook for this field that didn’t exist six months ago is an opportunity, not a problem, Jones and Hahn agree.

“This has a huge wow factor.

Students who thought of engineering as cars and gears, can see that mechanical engineering can be about tissue scaffolds and artificial organs and other cool stuff,” Hahn says. “The jellyfish, it’s a vehicle for excitement.”

Bhattacharjee prepares a syringe with a polymer.

A prototype of a hollow, flexible tube that represents on-demand, patient-specific medical devices.

An acrylic manifold that makes it possible to print with three different materials.

Making Things No one is waiting for theories.

Across campus, scientists are making soft materials at such a pace that six patents are pending on a technology not yet a year old.

“We had no way to make materials so soft in the past and no reason to study it. Why study something so soft and gooey you couldn’t use it for anything?” Jones says. “The minute you can engineer something out of it, that changes everything.”

The lead in manufacturing is Curtis Taylor, assistant professor of mechanical and aerospace engineering. Already, Taylor is close to solving one of the first questions raised by the new technology: Is it possible to print efficiently with more than one material? Early experiments involved printing with a single material, in most cases polymers or cells. What if you wanted to print an object with different textures at different layers — a phantom brain, for instance, with a tumor under the surface?

Taylor and a team of students tackled that problem. They came up with an acrylic tube with four ports, one for the granular gel medium and three for other materials. To avoid the need for a valve to shut off one port so another can open, they came up with an ingenious solution: use the granular gel, which easily transitions from fluid to solid, as a plug.

The device is the size of a piece of bubblegum and would cost just $2.

To make cellular or sterile materials implanted in humans the device is disposable, and although the prototype is acrylic, biodegradable materials work, too. As a manufacturing innovation, it looks simple, but it’s a workhorse.

“This little device replaces four nozzles, four pumps, four different needles, four different mechanisms for putting the needles into the gel,” Taylor says.

Also in the works are larger machines for larger objects and automation with robotic arms that can build from any angle. Questions remain, including the sequence of printing — inside out or outside in — and how fast it is possible to print with precision. To answer them, Taylor is actively recruiting. “I need a student,” he says, “I need a band of students.”

The printed soft materials can mimic the softness of human body parts, like the brain, and that opens new avenues for medical education, says neurosurgery professor Frank Bova.

By manufacturing artificial brains and other phantom organs that students can practice on, medical education could take a leap forward, Bova says.

Models of bones and cartilage have been readily available for practice, but not soft organs.

One problem with teaching medical students is having the right case at the right time. Often, complicated cases come in when a student is learning more basic methods. Bova envisions a library

of phantoms, easily printed as needed, giving students cases appropriate for their skill level as their skills grow.

Other phantoms could benefit personalized medicine. A patient’s brain could be scanned and printed with its own personal architecture — tumors, blood vessels, neurons — allowing the surgeon to rehearse before operating on the patient.

Angelini says, “Can you imagine, hearing your surgeon say, ‘Good morning, I’ve practiced this surgery on your brain five times already. You’re in good hands.’”

Some colleagues are stunned by the simplicity of his idea and how easily it adapts to different uses. But that’s engineering, Angelini says, the best solutions are simple and elegant.

“Every time we thought of a new thing to do with this technology, it turned out to be really amazing. Every time we thought of a new task or a new test, the material we were using turned out to have a fantastic solution,” Angelini says.

The jellyfish — the impossible jellyfish — was almost too easy, but the road ahead holds challenges.

“I think we will help people,” Sawyer says. “This may not help me, but it will help somebody.

“We’re engineers, and engineers, regardless of what it is, feel there’s got to be something we can do to effect change. There’s a certain amount of pleasure you get from just being in the fight. I like that.”

Thomas Angelini Assistant Professor of Mechanical and Aerospace Engineering t.e.angelini@ufl.edu W. Gregory Sawyer Professor of Mechanical and Aerospace Engineering wgsawyer@ufl.edu Related websites http://plaza.ufl.edu/t.e.angelini/ https://youtu.be/EuoFEmrSpNU

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University of Florida geologist Mike Perfit and four colleagues have sifted through thousands of photos from hundreds of dives over three decades to share with readers the hidden world at the bottom of the sea in

D. Fornari WHOI

“Discovering the Deep: A Photographic Atlas of the Seafloor and Ocean Crust.�

Mike Perfit and W. Bruce Strickrott, the chief Alvin pilot, prepare for a dive on the East Pacific Rise.

A photo illustration combined photos of submersibles and the Nature Tower at the Lost City Hydrothermal Field.

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21

This 13-meter carbonate chimney in the Lost City Hydrothermal Field in the mid-Atlantic is called Ryan.

This hydrothermal field supports dense aggregations of shrimp without eyestalks.

The cirrate, or Dumbo octopus, swims a few meters above the seafloor, searching for food.

Tubeworms, anemones and mussels congregate along the cracks of a flow vent.

Live tubeworms form a dense thicket, while vacant tubes become covered in iron oxide.

This white smoker complex, called Cathedral, was discovered in 2000, and hosted actively venting chimneys.

Dense colonies of microbes cover a three-month-old lava flow in the Axial Seamount in 2011.

THE FLOOR OF THE OCEANS This 1977 map by the American Geographical Society and the Office of Naval Research — based on the work of geologist Bruce Heezen and oceanographic cartographer Marie Tharp — illustrated the mid-ocean ridges for the first time and helped confirm the theory of plate tectonics.

White triangles indicate locations Perfit has explored.

Evidence suggests chyrostild crabs spend their entire lives on a single coral colony.

The Choo Choo Train site hosts mussels, crabs and tubeworms.

Ventfish, crabs and tubeworms form communities in nutrient-rich water near vents.

Clams and mussels along the Galapagos Rift.

Near-freezing seawater quenches molten lava to form structures like these frozen lava columns.

The three-story IMAX flange protrudes from the Poseidon edifice in the Lost City Hydrothermal Field.

A pillow tube flows in folds during an eruption on the West Mata Seamount near Samoa.

D. Fornari WHOI

LAVA TYPES

Pillow lavas bulge into a telltale bread crust texture.

Lobate lavas can coalesce into an interconnected flow.

The folds in a sheet flow can be almost entirely glass.

This hackly flow is part of an eruption on Axial Seamount.

Mike Perfit on the deck of the Research Vessel Atlantis after a dive on Alvin.

N

ot every scientist is cut out to spend eight hours crammed in with two other people in a 6-foot diameter sphere for a trip to the ocean floor and back. So when a rookie is set to go down, veterans put him through his paces. In 1985, off the Galapagos Islands, that rookie was Mike Perfit, just two years into his career at the University of Florida.

The veterans placed Perfit in Alvin, the submersible, and plied him with horror stories of what could go wrong. Dives cannot be rescheduled, so panic at 8,000 feet is costly, and they wanted to see if he would freak out. He did not.

As Alvin began the one- to two-hour descent, light faded, and at about 600 feet, the world outside his window turned black except for the twinkling of bioluminescent creatures, reminding him of stars in space. Their rendezvous with the bottom approaching, the pilot turned on the lights. Perfit remembers pillow lavas coming into view out of a “gray blueness,” then the realization that he was at the bottom of the ocean.

“Here was this silent world that just went on and on, lavas all over the place. This is the seafloor, this is where spreading takes place. We were definitely in a rift zone,” Perfit says. “Things I had studied for years, now I was actually seeing them.”

More than 35 dives later, Perfit says seeing sights few others ever see still inspires wonder.

“I love the fact that I’m in this environment where nobody’s ever been,” Perfit says. “I get to see things people might never see again.”

Mike Perfit Professor and Chair of Geological Sciences mperfit@ufl.edu

Submarine volcanoes often exhibit smooth and ropy textures like this active Hawaiian lava flow from Kilauea.

Related website: discoveringthedeep.com/

DISCOVERING THE DEEP A Photographic Atlas of the Seafloor and Ocean Crust AUTHORS Jeffrey A. Karson, Syracuse University Deborah S. Kelley, University of Washington Daniel J. Fornari, Woods Hole Oceanographic Institution Michael R. Perfit, University of Florida Timothy M. Shank, Woods Hole Oceanographic Institution CAMBRIDGE UNIVERSITY PRESS www.cambridge.org/9780521857185

A cross section of a lava pillar shows where two columns of water cooled the lava during an eruption like the one at right.

Research for “Discovering the Deep” was funded by the National Science Foundation, the National Oceanographic and Atmospheric Administration, Woods Hole Oceanographic Institution and the University of Washington. All images are from Discovering the Deep, where specific credits for each one can be found.

M. Tivey, Oceanus, (2004)

CROSS SECTION OF A MID-OCEAN RIDGE

Illustration of a mid-ocean ridge shows areas where volcanism and hydrothermal activity are concentrated. Lava flows can extend thousands of feet away from their eruptive fissures. Ridge eruptions are not explosive because of the low gas content in the magmas and great pressure from the overlying water.

J. Delaney and M. Stoermer, U.W. Center for Environmental Visualization

LIFE CYCLE OF OCEANIC LITHOSPHERE

Determining the processes that occur at mid-ocean ridges is critical to our understanding of seafloor spreading and plate tectonics.

Spreading at ridges controls the shape of the ocean basins, the geology of the seafloor, the ecology of the deep marine environment, and the formation of volcanic arcs that ring the oceans.

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U N I V E R S I T Y

O F F L O R I D A

I N F I N I T Y

INFINITE

CREATIVITY Fab Lab technology allows makers of all sorts to turn their visions into reality story by

Cindy Spence

photos by John Jernigan

Mat Chandler doesn’t have a magic wand or a vial of pixie dust, but at the intersection of art, science and technology that is the University of Florida Infinity Fab Lab, he conjures up magic all the same.

Chandler is the guiding force behind the Fab Lab, likely the most rampantly creative spot at UF. It’s a place where that idea rolling around in your head takes shape, literally, with a 3-D printer, a laser cutter or the latest addition, a water jet.

The Fab Lab started the fall semester with a new name and a new location in Infinity Hall at Innovation Square. Chandler hopes the vibe from the UF residence hall above, which will house the nation’s first entrepreneurial academic residential community, will also bring added energy.

“There are 308 beds above us filled with innovation, engineering, entrepreneurship; creative-minded kids just ready to do something,” says Chandler. “That’s awesome energy, awesome synergy.”

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Architecture junior Nicolas DelCastillo, a resident assistant for Infinity Hall, works on a project in an open space outside the Fab Lab.

“The space in Infinity Hall opens up

The 3-D printed skullcaps solved one of the challenges of his study: how to use a larger number of fiber bundles and still keep the rats comfortable during the experiments.

— Tao Zhang

Tao Zhang’s skullcap for rats, used in his epilepsy research, was printed at the Fab Lab.

30 Fall 2015

Even though the Fab Lab is only six years old, it had outgrown its original space in the College of Design, Construction and Planning, a victim of its own success. The lab started as a collaboration between the College of the Arts and the College of Design, Construction and Planning and initially was open only to art and architecture students — hence the old name A 2 Fab Lab — when it opened in 2009.

But makers and innovators from other colleges kept finding their way there and asking for advice on projects or to use the 3-D printer or laser cutter or CNC router. To meet that need, the Fab Lab opened in 2012 to all faculty and students and became one of the first university makerspaces in the country to open to the community at large. Last year, Chandler estimates, the lab served more than 2,000 clients.

When approached about a move to Infinity Hall, Chandler jumped at the opportunity because it meant he could add more and newer 3-D printers, including those that print carbon fiber, as well as a water jet that can cut such extreme materials as metal, glass and

a ton of possibilities for us, and for people who want to create.” — Mat Chandler granite up to six inches thick. The lab also houses a 3-D scanner and a threeaxis CNC router.

“The space in Infinity Hall opens up a ton of possibilities for us, and for people who want to create,” says Chandler, noting that it still operates under the auspices of the College of Design, Construction and Planning and the College of the Arts.

Just about anything that can be imagined in digital form can be rendered in physical form. With the help of 2-D and 3-D modeling software, the idea in your head becomes something you can hold in your hand.

The ideas that land on his doorstep often surprise even Chandler, who well understands the creativity the maker machinery unleashes. For example, as an architecture and entrepreneurship graduate himself, Chandler had not given much thought to applying his skills to epilepsy research.

Then doctoral researcher Tao Zhang pinged him with an intriguing idea: Could Chandler help him figure out how to fabricate a skullcap that would allow lab rats to be awake while their

brains were imaged to detect the onset of an epileptic seizure?

Chandler didn’t know, but figured it was worth a try. He walked down the hill to Zhang’s biomedical engineering lab to check out the project and decided he could use a 3-D scanner to scan the heads of rats and turn the scan into a model that could be used to print a cap.

Zhang said the 3-D printed skullcaps solved one of the challenges of his study: how to use a larger number of fiber bundles and still keep the rats comfortable during the experiments.

Previously, researchers had to surgically implant fibers for imaging the rats’ skulls, but that limited them to 10 fibers and required anesthesia that left the rats groggy.

“With the 3-D printed interface, we were able to place 30 fiber bundles onto the rats’ skulls while they were awake, and the more fiber bundles we use, the more information we can collect from the rats’ brains,” says Zhang, whose article on the research was printed in The Journal of Neuroscience Methods earlier this year.

Zhang says he knows of other locations on campus to access 3-D printers, but he knows of nowhere else that he could have tapped into 3-D modeling and printing expertise.

“When I started I had no idea how to do 3-D modeling or printing,” Zhang says. “They were the experts, they provided training, and they were there if I had questions.”

Chandler acknowledges that 3-D printers are common across campus, but some are proprietary — part of a particular lab — and some are set up for use by people who already know how to use the machines. The other labs send would-be inventors to the Fab Lab if they need help or need a high-end $120,000 3-D printer that uses multiple materials. And no place on campus has the collective machinery of invention amassed at the Infinity Fab Lab. Another huge benefit of the Fab Lab is its 24-7 laser-cutting schedule, and that is a key to keeping it accessible to the students whose work it was originally intended to support. Creativity is not a 9-to-5 endeavor, and the art and architecture students, Chandler says, are Explore 31

more likely to show up in the wee hours, especially 4 a.m., which Chandler calls “the special hour.”

Art student Hilary White said the Fab Lab was the first thing she wanted to learn about when she arrived at UF in 2013. White creates 3-D multimedia installations full of color and movement and has exhibited nationally and internationally. The Fab Lab — especially the laser cutter — expedites her vision, she says.

“With the Fab Lab, it’s a quicker way to realize an idea,” White says.

White says when she cuts by hand it can take two or three months to finish a piece. That takes time and money, and if the end product is not satisfactory, it’s time and money wasted.

“This allows me to build smarter and better. I can visualize something virtually before creating it,” White says.

The off hours at the lab offer quiet and the ability to concentrate, and she says she has run into architecture students, too, at those hours.

“The fact that it’s 24 hours is incredible,” White says. “It’s such a gift to have accessibility to these tools 24 hours a day. I’m excited that it’s growing, and I think it will become more and more of a hub.”

Chandler says some of the architecture models produced today at the Fab Lab would not have been possible at all without it. Architecture students can build small pavilions at 1-to-1 scale rather than just models, venture into furniture making and even cast new shapes and test materials in CNC (computer numerical control) created formwork.

The lab keeps a shelf of prototypes on display, and they tell a story that ranges from whimsical — a 3-D printed mask of Chandler’s face, for instance — to conventional — a valve prototype that turns ordinary Ziploc bags into vacuum bags. A local resident

32 Fall 2015

once asked if he could replicate antique croquet balls, hundreds of years old. He could. A kid came in to fabricate a gift for his dad. Professors of all disciplines have walked in.

For researchers on limited funding, bringing down the cost of prototyping is a huge benefit, and even a key to landing future grants.

UF physiology Professor Paul Davenport, who studies the science of respiration, says he is one of the Fab Lab’s biggest fans. He used the Fab Lab to prototype an idea that had been nagging him since 1982, when he worked on his first grant at the University of Florida.

The tools of creation available at the Fab Lab unlock the potential inside people who think they can’t draw or can’t cut a straight line. Making the machinery accessible puts art and science into motion.

— Mat Chandler Davenport’s goal was a device that does two things. First, it uses sound waves to break up pulmonary congestion, such as the mucus buildup experienced by a cystic fibrosis patient.

Second, it collects molecules from deep airways to help with diagnosis of lung ailments.

For 30 years, the project sat to the side. Then he had the idea to try to use sound waves to vibrate airways internally and returned to his original idea. He went to Best Buy to get a guitar amplifier, then to Lowe’s for PVC pipe. He connected them to a wave form generator and experimented to see which kind of sound waves broke up mucus and produced exhaled air full of molecules.

“So it worked,” Davenport says, but the contraption was clunky, and he knew a manufacturer would be skeptical.

“It quickly became very clear that a company was not going to buy a guitar amplifier connected to a piece of PVC pipe,” Davenport said.

He began sketching the device he imagined, but hesitated to invest $1,500 to get it produced, knowing he would want to adjust it many times— at thousands and thousands of dollars more — before arriving at a final design.

That’s when a colleague mentioned the Fab Lab. Davenport says Chandler was able to translate his amateur drawing into something that could be modeled and printed, and he did it with Davenport by his side.

They printed a device, and modified each successive design until they arrived at a final product. At a machine shop, that process would take weeks or months — perhaps longer — and cost tens of thousands of dollars. The Fab Lab was a fraction of that cost, and faster, and resulted in a better device.

Davenport says the low cost is a key for advancing science. Prototypes, he says, often are necessary to show proof of concept in winning a grant, and most researchers use money they have scrimped and saved to produce prototypes. An inexpensive prototype is the key to getting from idea to grant.

Today, a patent is pending on the device Davenport developed at the Fab Lab. “In the old days, I actually learned how to work lathes and drill presses and that sort of thing to make my own devices,” Davenport says. “The Fab Lab is like a gadget guy’s heaven, because now all I have to do is draw it. I still have gadgets I was making back in the late 1970s, more designs to try.”

The lab operates on a membership model, with students charged the lowest fees and faculty a little more.

Community members pay a higher fee because an intern or a member of the Student Design Team is assigned to help them with their projects. That helps students because they get a chance to flex their skills and learn how to interface with a customer, and it helps the customers because they are paying a quarter to half what they’d pay anywhere else.

“We’re the intermediary between manufacturing and the garage setup,” Chandler says. “We love projects that help people.”

Chandler says the tools of creation available at the Fab Lab unlock the potential inside people who think they can’t draw or can’t cut a straight line.

Making the machinery accessible puts art and science into motion, Chandler says.

“This allows people to create who never thought they could,” Chandler says. “That’s what makes me love this place the most, the creativity that comes out of here. Every day somebody surprises me with something.”

A three-dimensional piece in “The Twelve Gates” series by art student Hilary White, a big fan of the Fab lab. More pieces for which White used the Fab Lab can be found at hilarywhiteart.com.

Art technology student Madeline Morales used the laser cutter at right to construct a constellation map.

Students in the Fab Lab constructed pedestals to display artwork for an art show by Southeastern Conference schools in the fall.

The laser cutter can be programmed to cut complex shapes, like this one made out of balsa wood.

Mat Chandler mpchandler@ufl.edu Related website: fablab.arts.ufl.edu

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Bernard Brzezinski

20TH ANNIVERSARY 1995 — 2015

34 34 Fall Fall 2015 2015

The Sid Martin Biotechnology Incubator celebrates two decades of nurturing young companies story by Cindy Spence

W

photos by John Jernigan

hen Merrie Shaw was working on her science fair project on nematodes in sixth grade, the topic resonated with her because the pests were a problem for her family’s Alachua farm. Spraying pesticides meant leaving the land fallow for six months to let the toxic pesticides wear off before replanting.

Shaw grew up and left home, but when she returned 30 years later she found someone else working on her sixth-grade science fair project: Pasteuria Bioscience.

“I remember that jar of nematodes, and now all of sudden, someone can actually treat nematodes, and it’s a green formula, and it’s safe, and it doesn’t harm crops,” says Shaw, who Merrie Shaw has a front-row seat for bioscience success stories as manager of the University of Florida’s Sid Martin Biotechnology Incubator. “When I left, this was all a cow pasture. I got back, and wow, it’s a biotech center.”

When the incubator opened in Progress Park in 1995, it was a risky venture. The incubator idea was still new and bioscience incubators were rare. This year, the incubator celebrates its 20th anniversary ranked among the world’s best. But like its fledgling businesses, incubator leaders had to work hard to build a foundation for success.

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Director Patti Breedlove has watched 17 years of development and, much as the incubator shepherds its start-ups, Breedlove has shepherded the incubator, making it one of the most sought-after sites for a biotech start-up, with more applications than it can accept.

“In very recent years, I think we can say our ambitions have been realized,” says Breedlove. “Just in the last four years, we’ve had some significant events with our companies.”

That may be an understatement.

• Pasteuria Bioscience and its environmentally safe nematode control was acquired by global agricultural giant Syngenta for $113 million.

• Nanotherapeutics, a pioneer in drug bioavailability, landed a $358 million Department of Defense contract and is building a 180,000-square-foot building next to Progress Park.

• AGTC, a gene therapy developer, has products in phase II clinical trials and attracted $88 million in venture funding before a $52 million IPO last year, when it joined the NASDAQ. It also is moving into a new headquarters and has announced a collaboration with biotechnology pioneer Biogen that could become the first billion-dollar deal for a UF spinoff, if all options are triggered.

(For more, see timeline) The excitement didn’t end there.

The incubator has won four international and national first place awards or rankings in that time frame, including world’s best incubator in 2013.

“It does seem to have blossomed recently,” Breedlove says.

Although Breedlove is quick to brag on the companies, she could as easily brag on the incubator’s impact: Sid Martin companies have attracted more than $1.3 billion in funding and created more than 2,000 high-wage jobs.

The success seems sudden to outsiders, but Breedlove says it springs from a lot of activity under the radar and a lot

36 Fall 2015

Patti Breedlove

of early lessons. Along the way, incubator leaders have learned how to create an intimate environment within a huge research university to foster the business of science.

Lessons Learned Randy Scott remembers the early days, when Progress Park had the incubator and one other building, where his company, NovaMin, was located. Scott jokes that “back in the day when we were all starving” more money changed hands at the standing poker game between incubator and Progress Park tenants than in business conducted. As an incubator neighbor, he says he benefitted from the collegial atmosphere, and he says the first venture capital investment for NovaMin came through an introduction Breedlove made.

The stakes at that poker game likely would be higher today. NovaMin was bought by an international conglomerate and Scott is now a partner in

HealthQuest, a venture capital firm, as well as a mentor to a new generation of entrepreneurs.

Weaver Gaines, the incubator’s first tenant as a founder of Ixion Biotechnology, says the incubator environment created a brain trust to tap into.

“When you gather people facing the same problems you are, there is always somebody around the corner who can help,” says Gaines, who is applying his business acumen to a new company, OBMedical, in Newberry. “The very existence of a node connecting people doing the same things operationally is irreplaceable.”

Gaines was a member of the founding group that set up the guidelines for the incubator, including the critical question, “When do you hatch?”

Ixion was one of the first two graduates, and although it succeeded, Gaines says it probably was not quite ready to “hatch.” Breedlove says that is one of the early lessons incubator managers learned.

Sid Martin

September 1995

MILESTONES

UF Biotechnology Program opens Sid Martin Biotechology Incubator in Alachua.

October 2011

September 2012

November 1998

June 2003

July 2005

July 2010

Oragenics goes Oxthera lands Banyan Biomarkers public. $20 million awarded $26.2 million

investment and Department of Defense

spins out of Ixion (DOD) contract for traumatic Biotechnology. brain injury diagnostics.

AxoGen Inc. Syngenta acquires Incubator ranked AGTC completes Incubator wins SSTI’s

Nanotherapeutics completes $12.5 Pasteuria Bioscience wins $358 million top biotech successful $52 national commercialization

million merger with for $113 million. DOD medical incubator in the million IPO. award for tech-based

LecTec Corp.

countermeasures world by UBI Index. economic development.

contract.

is 5.5 years, but sometimes circumstances Initially, companies could only stay Today, the incubator has a policy of

create longer stays. Pasteuria, for examthree years before they were “force one-year renewable terms for clients,

ple, is still in-house, waiting on its new graduated,” Breedlove says. That was a with a formal review each year to see if

made enough progress

space. When it leaves, Shaw says, that typical incubation period for traditional a company has Incubator graduates first two companies: Ixion and Entomos.

companies, but she and her colleagues realized that biotech companies are different. Because of clinical trials and the approval process mandated by the U.S. Food and Drug Administration, among other hurdles, biobusinesses can take more than 10 years on average to get a product to market.

Forcing a company out too soon can lead it into a “valley of death,” after earlystage investments have been spent and before real sales revenues start flowing, where the company can wither and die.

March 2013

June 2013

to stay another year. The process is open-ended, case-by-case, because each company has a different time frame for maturity.

“We can’t be naïve, they’re not all going to be stars, some of them have to fail,” Breedlove says. “Our willingness to make those hard calls is one of the reasons we’ve been successful.”

Incubator manager Shaw says about 86 percent of the incubator’s clients are viable five years after graduating. Of the 53 companies admitted, the average stay

April 2014

September 2014

could relieve the logjam on the waiting list, creating space for more start-ups.

Interestingly, Breedlove says, the most successful companies are those which have stayed the longest.

“Unlike apps and software companies, biotech companies take years and years to get to market,” Breedlove says.

“They have long childhoods.”

Parting ways with a company that is not making it is tough, especially when Breedlove and the staff are rooting so hard for them.

Explore 37

I

n 1995, a group of fifthgrade students worked with Miami artist Carlos Alves to design mosaics and other artwork in the University of Florida’s Sid Martin Biotechnology Incubator.

Twenty-nine Alachua County Elementary students worked with Alves, who remembers the students being taken on a field trip to learn about biotechnology.

When the students came into class the next day, they were full of ideas.

“I saw light bulbs going off,” Alves says.

The mosaics featured animals, people and plants from the students’ designs, and are displayed in the lobby and main hallway of the Sid Martin Biotechnology Incubator.

Two decades later, Sid Martin Biotech and the Alachua Business League honored the 29 students who worked on the piece.

“We thought it would be wonderful to acknowledge to them how important their artwork has been to these facilities,” says Patti Breedlove, the incubator’s director.

An event in September recognized the students, whose work has left many impressions, says Breedlove.

“I can’t tell you how many compliments we’ve had over the years from the biotech companies that are in our program in this facility as well as the many, many visitors we get from around the world,” she says.

Stacy Bingham Joyner, a student who helped create the mosaic and stayed in the area, now works as a senior manager at James Moore. She doesn’t remember a lot about creating the mosaic, but does remember that it was no ordinary art project.

Silvia Rueda

Republished courtesy WUFT News Related Website: sidmartinbio.org/beta/for-journalists/

38 Fall 2015

Photos by Hannah Pietrick

Students Who Created Mosaics Recognized 20 Years Later

“This goes beyond business success,” Breedlove says. “These companies are working on things that can really make a big difference in the world, whether it’s for patients or for the planet.”

Breedlove had one of those hard conversations recently with a company, whose CEO told her, “I hope I get good enough to come back.”

In addition to like-minded individuals with whom to share ideas, the incubator offers more than $1 million of shared scientific equipment, wet labs, ultra-low-temperature freezers, greenhouses and animal facilities. Without this common equipment, Shaw says, many start-ups would not be viable.

“An autoclave can be $80,000, and if you’re surviving on a grant, that goes fast,” Shaw says. “Here, the monthly fee covers everything but phones, and they know what to expect.”

From Tenants to Neighbors Companies that graduate need something that is in short supply in Gainesville: biotech lab space.

For some, that’s not a problem; with success comes resources. Gaines, who is still active in Nanotherapeutics, points out that the company had taken over all of one building at Progress Park and quickly needed space again. It decided to build a 180,000-square-foot complex next to Progress Park, staying close to its roots.

AGTC, too, can afford space, and will become the anchor tenant in the first, 42,000-square-foot building going up across U.S. 441 in Foundation Park. Developer Brian Crawford, of Concept Companies, says the park will fill a critical need in Alachua County for space specifically

configured for biotech companies, who can’t just leave the incubator and move to a typical office park. The need for wet labs and accommodations for scientific equipment makes biotech space about twice as costly as typical office space.

In addition to wet lab space, Gaines says the biotech community needs better access to capital and better management, and “the incubator helps us attract those things.”

Success also seems to beget success: Coqui RadioPharmaceuticals recently announced it will build a $250 million medical isotope manufacturing plant next to Progress Park, in part to capitalize on the spirit of innovation in the area.

“This is a highly educated community that attracts the creative class,” Breedlove says. “In the past, we’ve grown our own businesses, almost exclusively. In the future, I think we’ll start attracting companies from the outside that like what they see here. Our cluster here in Alachua is already large enough to attract people and retain companies. We’ve created ‘stickiness.’

“It’s beneficial to keep our companies here for the synergy,” Breedlove says.

In addition to Foundation Park, UF still has land for expansion, so the burgeoning biotechnology community seems likely to keep growing. Breedlove says UF’s science is a common thread, with many companies depending on UF’s Office of Technology Licensing to get from the point of discovery to the marketplace.

“For the incubator to be successful, that process has to work well, and it does at the University of Florida,” Breedlove says.

David Day, assistant vice president and director of the Office of Technology Licensing, assumed responsibility

“We wouldn’t be here without the visionary thinkers at the University of Florida in the mid-1990s who created this program when really there was no role model for biotechnology incubation.”

— Patti Breedlove for the incubator in 2003 and instituted some changes aimed at making it more attractive to venture capitalists.

“We courted experienced entrepreneurs and investors,” Day says. “We rebuilt the incubator’s advisory committee with investors not academics, and listened to them.”

Breedlove sees a bright future and ways to get even better. In the years ahead, she’d like to see a building for phase-two companies.

“Even after six or seven or eight — even 10 — years, a biotech company that is going through the FDA is still quite young, quite vulnerable,” Breedlove says. “They may not need all the resources of the incubation program, but it’s difficult for them to find the right lab space, so a building for those companies would be valuable. Otherwise, we could lose them.”

Breedlove looks back as she prepares to hand over the reins after her December retirement.

“We wouldn’t be here without the visionary thinkers at the University of Florida in the mid-1990s who created this program when really there was no role model for biotechnology incubation,” Breedlove says. “They gave us everything we needed to be a successful program.”

Related website www.sidmartinbio.org

Explore 39

BY KEVIN KNUDSON

I

t’s been quite a year for mathematics problems on the internet. In the last few months, three questions have been online everywhere, causing consternation and head-scratching and blowing the minds of adults worldwide as examples of what kids are expected to know these days.

As a mathematician, I suppose I should subscribe to the “no such thing as bad publicity” theory, except that problems of this ilk a) usually aren’t that difficult once you get the trick, b) sometimes aren’t even math problems and c) fuel the defeatist “I’m not good at math” fire that pervades American culture. The inability to solve such a problem quickly is certainly not indicative of a person’s overall math skill, nor should it prompt a crisis of confidence about the state of American math aptitude.

Bernard Brzezinski

Mathematics Gone Viral

Except that it wasn’t for elementary school students at all; rather it appeared on an Asian Olympiad exam designed for mathematically talented high school students. What’s more, this isn’t even a math problem, but a logic problem. It’s true that students tend to learn formal logic via mathematics (plane geometry in particular), so it is common to see problems of this type in mathematics competitions. When I was in junior high, we spent a good deal of time on these puzzles in my language arts class, and I met them again when taking the GRE prior to entering graduate school (the test contains a whole section of them).

If you’re stumped, check out a solution to the problem at http://ind.pn/1b2xvMk

VIETNAMESE 8-YEAR-OLDS DO ARITHMETIC A month later, we heard about a third-grade teacher in Vietnam who set the following puzzle for his students.

Place the digits from 1 to 9 in this grid, using each only once (the : represents division).

WHEN IS CHERYL’S BIRTHDAY? In April, the internet erupted with shock that 10-year-olds in Singapore were asked to answer the following question on an exam.

This reminds me of the (probably apocraphyl) story of one of the greatest mathematicians in history, Carl

40 Fall 2015

Friedrich Gauss. Legend has it that when Gauss was seven or eight, his teacher, wanting to occupy his students for a while, told the class to add up the numbers from 1 to 100. Gauss thought about it for 30 seconds or so and wrote the correct answer, 5,050, on his slate and turned it in.

The puzzle above has a similar feel.

It’s really a question about knowing the order of arithmetic operations (multiplication/division, addition/ subtraction, in that order). Beyond that, it just takes trial and error; that is, it’s kind of just busy work. Someone who knows some algebra might be able to generate some equations to gain insight into how you might find a solution see http://bit.ly/1cOFJrI Another approach would be to open up a spreadsheet program and just try all the possibilities. Since there are nine choices for the first box, then eight choices for the second, and so on, there are only (9)(8)(7)(6)(5)(4)(3)(2)(1) = 362,880 possible configurations, of which only a few will give a valid equation. This can be programmed with very little effort.

HANNAH'S SWEETS In June, students in the UK vented their frustration via social media about a problem on the Edexcel GCSE (General Certificates of Secondary Education) mathematics exam. It is a probability question: Hannah has a bag containing n candies, six of which are orange and the rest of which are yellow.

She takes two candies out of the bag and eats them. The probability that she ate two orange candies is 1/3. Given this, show that n² - n - 90 = 0. The students' complaint? It’s too difficult.

I’ve taught math long enough to recognize the pitfalls of setting this problem.

The students actually have the knowledge to do it, if they know basic probability, but it is unlike problems they would have practiced. A typical question would indicate the total number of candies in the bag and ask students to compute the probability of a certain outcome. This question gives the probability and asks for a condition on the number of candies. It’s just algebra. You may read the solution (and some humorous memes about the question) at http://bit.ly/1ARvqOK

A NATION AT RISK? Mathematicians dread cocktail parties because we inevitably have to endure the response we receive when asked what we do: “Oh, I hated (or am terrible at) math.”

No other subject in school receives such scorn, nor would we find it acceptable for an adult to admit they are terrible at reading or writing. So when these “unsolvable” problems pop up, they simply reinforce our culture’s math anxiety.

And that’s a real shame, because everyone likes math when they’re young. We all like to count. We like playing with blocks and shapes. We all use math daily whether we realize it or not – reading maps, planning routes, calculating tips. I once had a flooring installer tell me he was bad at math while I watched him lay tile. It’s a myth that all these people can’t do math. When people say they are “bad at math,” they usually mean that they had trouble with algebra, although if you corner them and ask the right questions you can usually make them realize that they use algebra all the time without noticing it. This leads to valid criticisms of how we teach math, but it doesn’t mean we’re a nation of math idiots.

So, the next time one of these outrageous problems comes along, instead of giving in to anxiety, why not think about it for a few minutes and try to find a solution?

You might be surprised how satisfying it can be.

Kevin Knudson Professor of Mathematics kknudson@ufl.edu

The column originally appeared in The Conversation, an online service that provides a vehicle for academics to address news and share their research. To read more columns by UF faculty, visit https://theconversation.com/institutions/university-of-florida

Explore 41

I

n one of the first issues of Explore, then UF Vice President for Research Karen Holbrook wrote that this magazine’s mission is “to inform the public about how research funding benefits the citizens of Florida, the United States and the world by producing new knowledge, new ideas and new products that improve the health and welfare of people everywhere and create an informed public and a highquality workforce.”

This issue celebrates the completion of Explore’s 20th year of fulfilling that mission by publishing compelling articles about science and scholarship at the University of Florida. Explore has featured almost 400 faculty and students over the years in stories on topics as diverse as personalized medicine and comic books.

During those 20 years UF’s research enterprise has grown dramatically. In 1996, the university received $205 million in research awards. By 2015 that total had reached a record $706.8 million. More grants have resulted in more research results and a steady supply of compelling Explore stories about those results.

A novelty when it first appeared in campus mailboxes, Explore today is a part of the fabric of the university.

Faculty, students and staff regularly comment about it.

Copies can be found in offices across campus and around Florida. One issue each year even appears as a supplement to Florida Trend magazine, extending its reach to a whole new audience.

Technology has changed dramatically since that first Explore appeared online as plain text on a white background. Today, people can access words, pictures and even video at their desks or on their phones. We post stories on Facebook and tweet them on Twitter, all to fulfill that mission of sharing UF’s research successes with the world.

Next spring, Volume 21, Number 1 of Explore will come off the press. We invite you to continue to share in the University of Florida’s extraordinary research mission through the pages of UF’s research magazine.

Joseph Kays Editor and Director of Research Communications

Research Funding UF receives record $706.8 million in research funding in 2015

T

he University of Florida received $706.8 million in research awards last year, surpassing the previous record set in fiscal year 2014 by $5.1 million.

Among the highlights of the 2015 fiscal year, which ended June 30, was a record $102 million in funding from industry, a 41 percent increase over 2014.

“The success of our relationships with industry last year are a testament to our researchers’ ability to move new discoveries from conceptualization to commercialization,” said David Norton, UF’s vice president for research. “Leading engineering, health and agricultural companies know UF can help them advance the science of their industries more effectively.”

Funding from the federal government topped $432 million in 2015, led by the National Institutes of Health, with $152 million, up 7 percent over 2014, and the National Science Foundation, also up 7 percent to $47 million. State of Florida and local government agencies provided another $46.9 million. Foundations and non-profits awarded $90.4 million.

The College of Medicine in Gainesville and Jacksonville brought in $268.3 million; the Institute of Food and Agricultural Sciences, or IFAS, received $125.8 million; the College of Engineering was at $79.7 million; and the College of Liberal Arts and Sciences received $34.8 million. The remaining colleges had a combined $198.2 million.

The new total marks a 32 percent increase in UF research awards since 2005-06.

Joseph Kays

Explore 43

Explore Magazine Box 115500 Gainesville, FL 32611-5500

Non-Profit Organization U.S. Postage PAID Gainesville, FL Permit No. 94

Conversations: A 25th Anniversary Exhibition, September 25, 2015 – January 3, 2016 This exhibition marking the 25th anniversary of the Harn Museum features 125 works chosen by the Harn’s six curators and including such renowned artists as Georgia O’Keeffe, Pablo Picasso, Robert Rauschenberg, Frank Stella and Jerry Uelsmann. http://harn.ufl.edu/conversations

Frank Stella, American, born 1936, Zandvoort, 1981, mixed media on etched magnesium, gift of Martin Z. Margulies