Duke BME Magazine Spring 2018

DukeBME
Duke Biomedical Engineering Magazine

Engineering Entrepreneurship

Moving Innovation from Minds to Markets

DUKE BME
STARTUP
INCUBATOR
OPENS IN THE
CHESTERFIELD
|4

FACULTY
FOUNDERS
TALK SHOP
| 10

A NEW CLASS OF
ENTREPRENEUR
| 22

Spring 2018 Issue 2

The growing focus on entrepreneurship within Duke BME

Dear Colleagues and Friends,
I’m pleased to present you with the second issue of our thematic BME magazine that highlights
the many faces of Duke Biomedical Engineering.
We believe that the goal of engineering is to serve society, and promoting entrepreneurship
is one way to achieve that goal. One of my goals as chair is to strengthen our entrepreneurial
efforts by creating an ecosystem of shared knowledge, intellectual expertise, and a physical
infrastructure that supports entrepreneurship in the department.
In this issue, we explore the growing entrepreneurial efforts within Duke BME, with stories
covering our numerous faculty-led companies, the creation of a BME incubator—housed within
the department—in downtown Durham that empowers our faculty, students and alumni to
launch startups, and profiles of entrepreneurial faculty, students and alumni who have taken
their research out of their labs and into society via startups.
These stories showcase the entrepreneurial efforts of our innovative faculty and students, and
we hope you enjoy learning more about this facet of Duke BME.
Ashutosh Chilkoti, PhD
Chair, Duke Biomedical Engineering

DukeBME A researcher works in BRiDGE
lab space in the Chesterfield building.
Duke Biomedical Engineering Magazine

Spring 2018 Issue 2

2 Letter from the Chair

The growing focus on entrepreneurship within Duke BME

4 An Old Space for New Ideas
BME entrepreneurs find a new home in the Chesterfield building

in downtown Durham

10 Innovative Scholars

An overview of faculty startups in BME

19 A Mentor for New Entrepreneurs

B ill Walker uses his own experience to guide student and faculty-led startups

20 Encouraging Engineering and Entrepreneurship

A Q&A with Barry Myers, the director of the Duke-Coulter Translational
Research Partnership

22 A New Class of Entrepreneur

S tudents and researchers tackle new challenges through their own startups

30 A History of Entrepreneurship

H ow advancements in ultrasound technology paved the way for future innovation

32 Duke BME by the Numbers

Duke BME Magazine is published twice yearly Cover rendering of the Chesterfield created by the architecture
by Duke Biomedical Engineering, Room 1427, and planning firm, Gaudreau, Inc., from Baltimore, MD.
Fitzpatrick Center (FCIEMAS), 101 Science Drive, Photography by: Les Todd: pgs. 2, 12, 25; Chris Hilldreth: pg. 4;
Campus Box 90281, Durham, NC 27708-0281 Megan Mendenhall: pgs. 5, 6, 14, 15, 27; Catherine Reyes: pg. 10;
Phone: 919-660-5131 Jared Lazarus: pg. 11, 13, 20; Shawn Rocco: pg. 16; Jason R. Maher:
bme.duke.edu pg. 17.
Additional images provided by: Adam Wax, Bill Walker, Lucinda
Editorial Director: Ashutosh Chilkoti Camras, David Ousterout, Stephen Smith and Olaf Von Ramm.
Editor: Michaela Kane, Duke BME Communications
Designed by Pam Chastain Design

Copyright 2018 Duke University

ENTREPRENEURSHIP

An Old Space for New Ideas

A view of downtown Durham from the south side.
The Chesterfield building, which houses BRiDGE,
is the largest building in this view, and it occupies
a full city block.

4 Duke BME Spring 2018

The BRiDGE initiative for faculty, alumni and
student startups opens in downtown Durham

From the outside, the imposing red-brick rooms and private offices for calls and small
Chesterfield building in downtown Durham hasn’t meetings. Mirroring the building that houses it, the
changed much since 1948, when it was built as a renovated space is a medley of the old and the new,
cigarette factory for the Liggett & Myers tobacco with vintage tiles from the building’s tobacco days
company. But inside, the building is gleaming with decorating walls lined with brand-new biomedical
bright new surfaces and endless walls of glass, lab equipment.
illuminated by the 3,500-square-foot skylight that
sits over an airy new central atrium. “To me it was clear that there needed to be a
physical space that co-located companies in
This 21st-century version of The Chesterfield was close proximity so they could work with each
designed expressly as a hub for biomedical science other to provide moral support and foster a true
in Durham, emphasizing shared, open spaces to entrepreneurial community,” says Chilkoti, himself
encourage collaborative work between the bright a serial entrepreneur. “BRiDGE provides not only
minds in the building. Re-opened in January 2017, a physical infrastructure but a hub of intellectual
The Chesterfield has filled up fast with numerous expertise for these young startups.”
startups and labs affiliated with Duke University,
which leased about 100,000 square feet in the Chilkoti began to pursue this idea shortly after
building for engineering and medical research. becoming chair of the department in 2013, and in
2017, Chilkoti partnered with Maria Iglesias de Ussel,
Now, a new initiative will find its home in The
Chesterfield: The Bioengineering Research initiative
to Develop Global Entrepreneurs, a.k.a. BRiDGE.

The brainchild of Ashutosh Chilkoti, chair of Duke
University’s Department of Biomedical Engineering,
The BRiDGE program was created to support new
bioengineering startups founded by students,
faculty, and alumni in Duke BME.

BRiDGE will help Duke researchers and inventors
tap into the entrepreneurial talent available to
them across Duke, helping them create and refine
business plans with training and guidance from
Duke’s Innovation & Entrepreneurship initiative
and Pratt’s Mattson Family Director of Engineering
Entrepreneurial Ventures.

Companies selected to participate in the initiative
will move into a 2,000-square-foot space on the
fourth floor of The Chesterfield. Modeled on
traditional startup incubators, the open space
includes a large shared lab area, and rooms with
shared equipment; companies lease lab benches
and cubicles and have shared access to conference

The atrium in the Chesterfield building in 5
downtown Durham

BRiDGE space includes multiple lab
benches for shared lab space.

a project leader at Duke’s Clinical and Translational In addition to lab space, each startup can
Science Institute, to assess the needs of the project. rent cubicles for their staff.
With a faculty and student body full of innovative
ideas, he wanted to expand the resources available
to would-be entrepreneurs and make it easier for
them to succeed.

“At the time, there was nothing like this at Duke,” says
Iglesias de Ussel, now the director of operations
at BRiDGE. “BRIDGE is more than an incubator, as
it has an educational component and we provide
entrepreneurial mentorship and expertise.”

The initiative gained steam after Alan L. Kaganov
(BSME ’60) generously donated funding towards
the effort, which also received support from
both BME and the Pratt School of Engineering. In
November of 2017, seven bioengineering startups
were selected to move into the renovated space:

6 Duke BME Spring 2018

Qatch Technologies, founded by postdoctoral director of MEDx. “It’s a tool that works especially “With this
fellow Zehra Parlak; Isolere Bio, founded by Chilkoti well as a starting point for BME entrepreneurs at new space,
and recent BME PhD graduate Kelli Luginbuhl; Duke University, because they get a good sense of researchers
Restor3D and Deep Blue Medical Advances, how their ideas can be implemented into clinical will have the
founded by mechanical engineering and materials use.” resources
science chair and secondary BME faculty member to carry out
Ken Gall; Gateway Bio, founded by Chilkoti and Faculty, graduate students and research staff
Angus Hucknall, a senior research scientist in in BME can also participate in the Duke-Coulter the early
BME; and DMC and AccuBeing, founded by BME Translational Research Partnership. Established development
faculty members Michael Lynch and Xiling Shen, in 2006, the program supports collaborative
respectively. translational research that addresses unmet clinical work that
needs and leads to improvements in healthcare and is essential
Although BRiDGE is based in Duke BME, this to commercial products. So far, the partnership has
initiative also reflects a growing focus on awarded more than $8 million in funding to more to attract
entrepreneurial work within the Pratt School of than 39 projects, and these have subsequently funding
Engineering, as evidenced by a number of new gone on to attract more than $489 million in follow- from angel
collaborative programs created to jump-start on funding from grants or angel investments. networks,
entrepreneurship. Among them is Duke MEDx, a venture
program created in 2015 with support from the This decade-spanning partnership between Duke’s capitalists,
Provost’s Office, School of Medicine and Duke medical and engineering schools has resulted in and the
Engineering to facilitate collaborative research numerous innovations, patents, and startups, and federal
and education between faculty and students in Chilkoti hopes to build on this success through government
medicine and engineering. BRiDGE. through
SBIRs and
“Our mission with MEDx is to bring together faculty “We thought it would make sense to have a pipeline STTRs.”
at the early stages of research to create these that could begin with the Coulter Translational
unique collaborations,” says Gall, the associate Partnership to develop nascent bioengineering

The shared lab space in BRiDGE will initially
house seven companies, including Restor3D,
a 3-D printing startup.

7

ENTREPRENEURSHIP

“BRiDGE was technologies that then develop into a startup Companies
created to company that is located in the physical space
lower the provided by BRiDGE. BRiDGE’s mission is to help Mike Lynch—DMC: Based on
activation these startups travel safely across the valley of a novel process that will allow
barrier death and into functional companies,” says Chilkoti. researchers to scale up and
for people “With this new space, researchers will have the streamline the production of molecules used in flavors,
who want resources to carry out the early development fragrances, agricultural chemicals and other commercial
to launch work that is essential to attract funding from angel products.
innovative networks, venture capitalists, and the federal
biomedical government through SBIRs and STTRs.” Kelli Luginbuhl and Ashutosh
companies. Chilkoti—Isolere Bio: Currently
We want One of the most recent additions to Duke’s developing IsoTag™, a technology
to empower entrepreneurial efforts is Bill Walker, a Duke that merges affinity capture
the local Engineering alumnus and entrepreneur who with liquid-liquid phase
Duke BME joined the school in 2016 as the school’s first separation to provide an innovative alternative to the
community to Mattson Family Director of Entrepreneurial current “gold” standard, protein A chromatography
pursue new Ventures. Working closely with the Duke to purify antibodies.
and exciting Innovation & Entrepreneurship Initiative and the
ideas.” Bass Connections Program, Walker helps Duke Zehra Parlak—Qatch
Engineering faculty and students assess business Technologies: Based on a new
opportunities for commercializing their ideas and technology that can be used
develop new companies. to measure blood coagulation.

With the opening of BRiDGE, Walker’s role as a Ken Gall—Restor3D and
mentor to engineering entrepreneurs will be Deep Blue Medical Advances:
expanding, as he will provide guidance to the Restor3D will 3D print materials
bioengineering companies. for biomedical implants, allowing
researchers to lower the cost
“My role is to be the go-to person in that space and and increase the complexity for
to help them find deeper resources and provide patient-centered designs. Deep
strategy,” says Walker. “My job isn’t to tell them what Blue Medical Advances is based on a new hernia mesh
to do, but to share my experiences and give them a that integrates directly into the tissue, eliminating the
clear way to move forward.” need for sutures.

Already, there are plans to expand the program GATEW        Y  BIO
Angus Hucknall and Ashutosh
to provide more educational opportunities for A  new  WAY  to  ConjuGATE
  Chilkoti—Gateway Bio:
engineering master’s and PhD students interested Developing a non-immunogenic
in entrepreneurship. “Bill and I have launched a alternative to PEGylation that eliminates PEG
summer internship program in BRiDGE for Duke antigenicity and improves drug delivery profiles relative
students,” says Chilkoti. “Ultimately we want these to traditional PEGylation strategies.
summer interns to work with these companies
and have a hands-on learning experience in Xiling Shen—­ AccuBeing:
entrepreneurship that is still relevant to their Developing technology to
bioengineering interests.” increase the precision of
personalized cancer therapies.
For Chilkoti, The Chesterfield was a prime location AccuBeing’s patient-derived
for BRiDGE, placing the startups in the center of a screening platform provides a
busy and growing downtown area. In the last five way to identify drugs that can overcome drug resistance
years alone, more than 3,500 Duke employees after standard chemotherapy fails. The platform will also
have moved into the booming entrepreneurial enable a patient drug response database for cancer drug
hubs in downtown Durham, including the American discovery and development.
Tobacco Campus, the American Underground, the

8 Duke BME Spring 2018

A researcher adjusts a 3-D printer while
working in BRiDGE.

Carmichael building and the Bullpen, the focal point Chilkoti worked to make BRiDGE a reality through
of Duke University’s innovation and entrepreneurship his role as chair of the BME Department.
efforts. Already, Duke faculty and staff work in more
than 1.3 million square feet of space in downtown New opportunities in a new space are just what
Durham, and there are plans to take on more than Chilkoti had in mind. “BRiDGE was created to lower
200,000 square feet of space in new buildings already the activation barrier for people who want to launch
under construction by 2018. innovative biomedical companies,” he says. “We want
to empower the local Duke BME community to pursue
The growth of downtown Durham can be seen in new and exciting ideas.”
real time from BRiDGE, where large windows frame
multiple cranes at work placing together the skeletons
of towering glass skyscrapers and renovating other
historic buildings nearby. For researchers who will
move into the space, its location at the center of a
growing city and the influx of entrepreneurs is one of
the many benefits of The Chesterfield.

“The space is a brilliant concept and creates a sense of
community,” says Gall. “When you interact with people
who work toward similar problems and challenges, that
gives you a sense of confidence in your work. I believe
BRiDGE in combination with Duke Angel Network will
be a major factor in the success of Duke’s bio-focused
startups.”

9

ENTREPRENEURSHIP

Innovative Scholars

An overview of faculty startups in BME

Charles Gersbach Launching a Platform

for Genomics-Based Drug Development

Prior to starting his own company, Charles Gersbach sought advice from a
number of Duke BME faculty entrepreneurs on the best way to get started. But
what he learned was surprising.

“When we asked people what process they went through to found a business,
basically everyone told us something different,” says Gersbach. “Initially our idea
was just to learn from their formula, but it was clear that there wasn’t just one
path to success.”

When he first started at Duke in 2009, Gersbach wasn’t focused on

entrepreneurial work. But as he began to win grants and publish research in the

field of genome editing and genome engineering, it drew the attention of several

pharmaceutical companies who wanted to use his technology for improved drug

development.

Charles Gersbach: Rooney Family “I was working on characterizing the non-coding genome, which is essentially
Associate Professor of Biomedical the 98 percent of our genome that we don’t fully understand, and there was
Engineering evidence that it plays a large role in drug response and disease susceptibility.
I was developing tools for perturbing that portion of the genome, and that
Companies: Element Genomics, Inc., process opened up a whole new class of drug targets for common diseases,”
Locus Biosciences

says Gersbach. “Through our discussions with several pharmaceutical companies we realized the

technology was something that could go beyond our academic lab.”

In August of 2015, Gersbach approached Barry Myers in the Duke-Coulter Translational Partnership,
which had supported Gersbach’s research at Duke, for help to form a startup. Within 48 hours,
Gersbach and his collaborators Tim Reddy and Gregory Crawford had formed Element Genomics,
Inc. The team received further support from Duke in the form of John Oxaal, who was then working
as the Entrepreneur-in-Residence at Duke BME. Oxaal, an alumnus of Duke Engineering and a serial
entrepreneur himself, worked with the team to finalize licenses and find space in an incubator in
Durham, eventually serving as CEO of the company.

The company is up and running with 12 employees and is currently located in The Chesterfield building
to take advantage of the entrepreneurial culture created by other co-located BME-based startups in
Durham. Today, the team continues to refine and develop their high-throughput platform to identify
new drug targets for common diseases while they pursue more funding opportunities. “There’s a
growing culture for entrepreneurial work in the BME department,” says Gersbach. “I’m one of many
faculty who have been influenced by that.”

10 Duke BME Spring 2018 Editor’s Note: Element Genomics was acquired by UCB, a global pharmaceuticals company with a focus on
neurology and immunology, in March 2018. To learn more about the acquisition, read the press release on the
BME website at: bme.duke.edu/about/news/element-genomics-acquired-global-biopharmaceutical-company.

FACULTY

Mike Lynch From Entrepreneurship
to Academia

Michael Lynch was a postdoctoral researcher at the University
of Colorado when he founded his first company, OPX
Biotechnologies, in 2007, but he soon threw himself into working
full-time to build the startup’s footprint in functional genomics
technology. But prior to the company’s acquisition in 2015, Lynch
decided to return to his academic roots.

“By the time the board was ready to sell the company we had
been scaling up and doing a few small improvements here
or there, but it wasn’t as exciting for me from a technology
standpoint,” Lynch says. “I knew I wanted to get back into
biomedical work and be more involved in the technology
development, and I also wanted to launch more companies, and
for me, academia is a better place to do that.”

Mike Lynch: Assistant Professor of Biomedical By November of 2014, he was working as an assistant professor
Engineering in Duke University’s Department of Biomedical Engineering,
drawing upon his expertise in genomics to engineer microbes to
Companies: OPX Biotechnologies, DMC produce useful chemicals. It wasn’t long before Lynch founded
DMC, based on a novel process that will allow researchers to
scale up and streamline the production of molecules used in
flavors, fragrances, agricultural chemicals and other commercial
products.

“If you think about it from an entrepreneurial perspective, there are lots of molecules you’d never make because
they don’t cater to a large market or you can’t commercialize them easily,” says Lynch. “For example, you can get
genetically modified E. coli to make what you want, but it traditionally takes tens of millions of dollars to get the
research and development done, so earning any return on R&D investments is difficult. With DMC, we’re trying to
democratize access to these molecules.”

Lynch’s entrepreneurial perspective extends beyond his business. In his Duke BME design classes, he encourages
students to think strategically about the needs of the marketplace and a product’s value to a customer when
developing their own technology. His lab will also become more entrepreneurial when it moves next to BRiDGE, a
space in the Chesterfield building in downtown Durham for Duke BME students and faculty to grow new startups
and ideas.

“Coming back to academia has allowed me to pursue riskier ideas, and even if it doesn’t pay off I get to learn
something new,” says Lynch.

11

ENTREPRENEURSHIP An overview of faculty startups in BME

Warren Grill Neuroengineering and
Entrepreneurship

For Warren Grill, running a small business isn’t much
different than running a research lab—and he’s had plenty
of experience doing both.

In 2002, Grill founded NDI Medical based on technology
his lab had developed to use electrical stimulation to treat
overactive bladder. Grill and his partners sold the company
to Medtronic in 2008, but by the next day they had
launched their next company, also called NDI Medical.

“We had assembled a really spectacular team, from
engineering to regulatory to clinical to legal, and we didn’t
want those people to fly to the wind,” says Grill. “We told
them that they still had a job, we just didn’t know exactly
what we’d be doing yet.”

The second generation of NDI quickly became an incubator,

where Grill and his collaborators hunted for “medium-rare

ideas” in electrical stimulation systems that they could

Warren Grill, Edmund T. Pratt, Jr. School develop into products. To further their efforts, the team
Professor of Biomedical Engineering also started the NDI Healthcare Fund, a small venture fund
that raised money to support the incubator.
Companies: NDI Medical, Checkpoint Surgical,
Deep Brain Innovations Three companies were eventually ‘hatched’ from the

incubator. The first, Checkpoint Surgical, currently sells

two FDA-approved products, including a hand-held, disposable intraoperative

stimulator that surgeons use to identify and protect nerves in the surgical field.

For Warren Grill, The second is SPR Therapeutics, which develops devices to relieve chronic pain. Its
running a small main product is the Sprint, which recently received FDA approval and includes an
business isn’t much electrode that goes through the skin and delivers electrical stimulation over the
course of several weeks to achieve durable pain relief.

different than Grill co-founded and acts as the CTO of the third company, Deep Brain Innovations,
running a research or DBI. Based on intellectual property developed in his Duke lab, the company is
lab—and he’s had improving the efficacy of deep brain stimulation by changing the temporal pattern

plenty of experience of stimulation, or the timing between pulses, so it requires less energy, provides

doing both. superior symptom relief and the implant lasts longer.

“Right now if you have one of these devices implanted for Parkinson’s, it lasts about
four years before you need to come back to the medical center to have it replaced,”
says Grill. “With the DBI technology, the device would last closer to ten years.”

12 Duke BME Spring 2018

FACULTY

Nimmi Ramanujam Developing Tools
to Improve Cancer Care

Nimmi Ramanujam founded Zenalux Biomedical to make it easier for
cancer researchers to perform real-time, non-destructive analysis of
biological tissue and tumors. Based on novel technology Ramanujam
developed while a professor at the University of Wisconsin–Madison,
and launched with support from the Duke-Coulter Translational
Partnership, Zenalux is one part of Ramanujam’s larger goal to
improve cancer therapy.

The company’s flagship tool is the Zenascope, a visible spectroscopy
device that rapidly measures biomarkers, like tissue oxygenation
levels, without the need to biopsy tissue. This technology allows
doctors and scientists providing patient care and conducting cancer
research to characterize key cancer hallmarks that differentiate
aggressive from indolent disease. Using the Zenascope, researchers
can also examine the effectiveness of therapy by monitoring changes
in the tumor microenvironment.

Nimmi Ramanujam, the Robert W. Carr, Jr., Zenalux is currently working on head and neck cancer diagnostics
Professor of Biomedical Engineering and treatment. The company successfully implemented pressure

Company: Zenalux Biomedical sensing and automated self-calibration, in addition to customization
of several probe designs for the diagnosis of clinical head and neck
Above: Nimmi Ramanujam demonstrates the tumors in collaboration with Dr. Walter Lee at Duke University Medical
Pocket Colposcope during the “Invented at Center. Further supporting the market focus on head and neck cancer,
Duke” event Zenalux has worked with Roswell Park Cancer Institute, University of

“Thinking about Minnesota and the University of Rochester on a multi-site study to guide photodynamic therapy (PDT)
opportunities for head and neck cancer.

for innovation in A newer version of the Zenascope measures additional hallmarks related to tumor metabolism—
the entire cancer specifically, glycolysis and mitochondrial metabolism such that both the vascular biology and
care continuum metabolism can all be measured with one system.

is important and Ramanujam is also introducing entrepreneurial work in global health to students at Duke on the latest
engaging students product her team has developed, the Pocket Colposcope, a low cost cervical cancer-screening device.
in that holistic Through her Bass Connections course (currently in year 2), students traveled to Lima, Peru to engage
process is highly stakeholders to identify strategies for adoption of the Pocket Colposcope in the community setting
rewarding.” to improve access to early screening. Additionally, she has created a post baccalaureate program in
which fellows work with industry partners on product development and regulatory activities. Hadleigh

Health Technologies in San Rafael, California, will commercialize the Pocket Colposcope for global

cervical cancer screening.

“My core motivation is to improve cancer care, whether it is developing a research tool to evaluate
the effectiveness of cancer therapies in the laboratory setting or to develop a clinical device for
screening,” says Ramanujam. “Thinking about opportunities for innovation in the entire cancer care
continuum is important and engaging students in that holistic process is highly rewarding.”

13

ENTREPRENEURSHIP An overview of faculty startups in BME

Ashutosh Chilkoti The Serial Entrepreneur

Since 2002, Ashutosh Chilkoti has founded five companies
based on research from his lab at Duke University, ranging
from drug delivery to diagnostics—a string of companies he
never would have anticipated at the outset of his academic
career.

“I’m an accidental entrepreneur,” Chilkoti says. “I happened to
meet a venture capitalist named Clay Thorp at a large meeting
at Duke, and we were sitting together and we started talking
about my work and that quickly led to the launch of my first
company, PhaseBio.”

Chilkoti founded PhaseBio Pharmaceuticals in 2002 after

he discovered a new way to purify and capture proteins and

deliver drugs using elastin-like polypeptides, or ELPs. Today,

the company develops ELP fusions to improve the stability,

bioavailability, activity and ease of administration of proteins

and peptides to achieve greater potency, reduce side effects,

and improve patient compliance. So far, PhaseBio has launched

Ashutosh Chilkoti, Chair and Alan L. Kaganov and completed multiple clinical trials of ELPs for use in the
Professor of Biomedical Engineering treatment of diabetes and heart disease.

Companies: PhaseBio Pharmaceuticals, Sentilus In 2012, Chilkoti and Angus Hucknall, then a graduate student
Inc., BioStealth, Gateway Bio, Isolere Bio working on his PhD with Chilkoti, founded Sentilus, based on
a unique nonfouling polymer brush developed in Chilkoti’s

lab. The polymer coating acts like Teflon to prevent non-target

protein analytes from sticking to a surface, essentially eliminating background noise in

sandwich immunoassays. In a streamlined tech-transfer deal, Sentilus was acquired by

“I’ve learned Immucor in 2014.
a lot about
entrepreneurship Shortly after, Immucor returned all fields of use of the technology outside of human
the hard way, in vitro diagnostics. Chilkoti and Hucknall then co-founded BioStealth to develop and
and now I hope to commercialize the nonfouling coating technology for other areas of interest, including
pass on what research diagnostics and tools, veterinary diagnostics, and biomaterials.
I have learned to
our students.” Now, Chilkoti has two additional startups moving into the new BRiDGE incubator in the
Chesterfield building in downtown Durham. GatewayBio, again founded with Angus
Hucknall, will focus on the next generation of polymer conjugates of protein and
peptide drugs that improve their efficacy. Isolere Bio will develop technology to purify

monoclonal antibodies for therapeutics.

Despite his serendipitous path to the entrepreneurial world, Chilkoti is pleased with
the results and the knowledge that he can impart to BME students. “It’s been an
interesting journey,” he says. “I’ve learned a lot about entrepreneurship the hard way,
and now I hope to pass on what I have learned to our students.”

14 Duke BME Spring 2018

FACULTY

Ken Gall The Forces Behind a Spinal
Implant Startup

Ken Gall, the chair of Duke University’s Department of Mechanical
Engineering and Materials Science and a secondary faculty member
in BME, founded Vertera Spine in 2013 after his team discovered
a new way to create a high strength spinal implant from a porous
polymer. When Gall moved to Duke from the Georgia Institute of
Technology in 2015, he continued to grow the company with support
from both schools, leading to a successful and highly collaborative
startup.

Vertera Spine is based on a novel process to create porous PEEK
(polyether ether ketone), a high-strength biopolymer that allows for
better bone attachment and repair following spinal surgery. Gall and
his team invented a way to form a highly porous, interconnected
network on the polymer’s surface without adding or subtracting
material and without negatively impacting the mechanical
properties of the material.

Ken Gall, Chair of Mechanical Engineering During lumbar or cervical spinal fusion procedures, physicians insert
and Materials Science and secondary faculty a spinal cage implant between vertebrae to provide stability and
member in BME support while the segments fuse. More than three-quarters of the
spinal market uses PEEK technology for implants, but porous spinal
Companies: Vertera Spine, Restor3D, Deep cages were only available in metals, which do not show up as well in
Blue Medical Advances, MedShape medical imaging.

“We are “Our porous PEEK is the first FDA-approved load-bearing porous plastic implant in the human body, and
extremely it’s the first porous implant that has the potential to be tracked for bony attachment by CT scan,” says
fortunate at Gall. “Surgeons wanted to use this plastic implant, so we happened to create the right product at the
Duke to have right time.”
this incredible
resource for In the four years since its inception, the company has already progressed through significant milestones.
faculty, students In 2015, the team published their first paper on porous PEEK and the implant was approved by the Food
and alumni and Drug Administration. The following year, the technology was clinically introduced when Vertera
entrepreneurs.” launched its COHERE implant, which has subsequently been used in more than 2,000 successful spinal
surgeries. But the most significant change for the company occurred in September of 2017, when
Vertera was acquired by NuVasive, Inc., a leading medical device company with a focus on spinal surgery.

Although Gall continued to rely on aid and technical expertise from the Georgia Research Alliance and
Bob Guldberg, the executive director of the Parker H. Petit Institute for Bioengineering and Bioscience
at Georgia Tech, he was also able to use entrepreneurial resources available at Duke after moving to
the university. Among them was the Duke Angel Network, an organization within the Duke Innovation
& Entrepreneurship Initiative (I&E) to help Duke startups grow by facilitating the flow of capital and
support from Duke-affiliated angel investors.

“The Duke I&E and the Duke Angel Network have provided us with capital investment and key guidance 15
during the last two years of Vertera’s growth into the market,” says Gall. “We are extremely fortunate at
Duke to have this incredible resource for faculty, students and alumni entrepreneurs.

ENTREPRENEURSHIP

Imaging Inventions

Two Duke BME startups bring optical imaging
technologies to patients across the spectrum of
clinical settings

Joseph Izatt

Joseph Izatt first began working with optical coherence
tomography, or OCT, in 1991 as a postdoctoral researcher
at the Massachusetts Institute of Technology. In the
intervening years, he’s become one of the leading experts
in OCT, and he has continued to advance the optical
technology through both his lab at Duke University and
his former company, Bioptigen, Inc.

Optical coherence tomography is an imaging technique
that uses coherent light waves to penetrate beneath the
surface of living tissues, allowing researchers to diagnose
and subsequently treat diseases. Today, the technique
produces both 2-D and 3-D images of tissue in much finer
detail than other techniques like ultrasound, CT or MRI
scans. OCT can provide in-depth, cross-sectional images
with a resolution of 10 micrometers—smaller than a width
of human hair—making it an ideal technique for detecting
and monitoring the treatment of serious eye diseases like
glaucoma and age-related macular degeneration (AMD).

“OCT allows you to advance from surface imaging to

cross-sectional or volumetric imaging, and with much

Dr. Cynthia Toth, the Joseph A.C. Wadsworth greater resolution,” says Izatt, the Michael J. Fitzpatrick
Professor of Opthalmology, and Joseph Izatt, the Professor of Engineering at Duke. “That’s really important

Michael J. Fitzpatrick Professor of Engineering because many diseases that cause blindness are

quite subtle to diagnose accurately with conventional

instruments, and that requires many years of training. But OCT is a major advance in the speed and ease of

diagnosing these problems, and just as importantly in monitoring their successful treatment.”

Izatt came to Duke in 2001, in part to collaborate with leading ophthalmologists at the Duke University Eye Center.
Among them was Dr. Cynthia Toth, a retinal surgeon at the Duke University School of Medicine and a professor
in BME and ophthalmology. At the time, Toth and other ophthalmologists were able to use OCT on their patients
before and after surgery, but not intraoperatively.

“My lab was able to contribute to a revolution in the technology underlying OCT, which made it many times more

16 Duke BME Spring 2018

FACULTY

sensitive and much faster at acquiring images in patients,” says Izatt. “After I started at Duke I
was approached by Eric Buckland, an optics PhD and veteran executive who was looking to start a
high-tech company in North Carolina.”

After working with Duke to find incubator space, Izatt, Buckland and optical scientist William
Brown founded Bioptigen in 2004. The team concentrated their efforts on developing technology
that could show images to physicians in real-time, eventually creating their first successful
product—a handheld OCT probe that allowed doctors to hold the tool over a patient’s eye and
simultaneously see the image in a screen.

“Dr. Toth had been asking me for OCT in the operating room since 1994, and she ended up taking
the handheld tool into surgery with her,” says Izatt. “That still wasn’t especially convenient
because she’d need to stop the surgery, move the microscope out of the way and put the probe
over the patient, but it was so useful to have that information while the patient was still on the
table that she was willing to do it.”

By 2010, the company began to build OCT “OCT allows
into a surgical microscope, resulting in their you to advance
first intra-operative OCT tool. Its success
drew the attention of Leica Microsystems, from surface
a European optical instrument brand that imaging
supplies top-quality research and surgical to cross-
microscope systems. In 2015, the company
acquired Bioptigen to incorporate its proven sectional or
real-time OCT technology into their own volumetric
surgical microscope product line. imaging, and
with much
After the success of Bioptigen, Izatt and his
team are enthusiastic about the ongoing greater
entrepreneurial framework in Duke BME, and resolution.”
they are looking ahead to see how they can
continue to advance OCT.

Adam Wax, Professor of Biomedical Engineering “I was fortunate to work with talented
surgeons at Duke, and at Bioptigen I was
very lucky to work with talented managers
and engineers,” says Izatt. “The whole
experience was terrific, and to be able to go
into an environment and see our technology
being used to benefit patients is truly
gratifying.”

Adam Wax

OCT is considered the gold standard for eye disease imaging and diagnosis, but its high cost—
ranging between $35,000 to $150,000—often puts it out of reach for people without access to a
large eye center or hospital. Adam Wax, a professor of biomedical engineering at Duke University,
aimed to change that when he founded Lumedica in 2014.

“Our goal is to democratize access to this valuable imaging tool. Say you live in a rural community

17

ENTREPRENEURSHIP and you need to be screened for retinal disease as you get older—are you going to be able
to drive to the Duke Eye Center and get an OCT every year like you’re supposed to?” asks
“With OCT, Wax. “Maybe you go the first year, maybe the second year, but it’s not easy to constantly go
you have the back. If it was at the doctor’s office in town, though, then they have an easier time getting
capability of screened.”
finding these
problems early, With 20 years of experience in the field of biomedical optics, Wax started Lumedica
so our goal is to to commercialize low-cost biomedical imaging strategies developed in his lab at Duke.
put OCT where it The poster child for his work is Lumedica’s OQ LabScope, an OCT-equipped tool that is
wasn’t before.” approximately the size of a shoebox and weighs less than 6 pounds. Rather than use metal
parts in the spectroscope, Wax and his engineering team created a design with 3-D-printed
18 Duke BME Spring 2018 parts, allowing the tool to be more flexible without affecting the spectrometer’s alignment.

In addition to bringing the device to smaller ophthalmologist offices, Wax and his team
plan to explore how their tool can also be used in the context of global health. “The most
impressive demonstration is that we put it in a box, put it on a plane, and when we took it
out of the box it immediately works without any additional calibration,” says Wax. “It’s the
perfect modality for resource-limited settings.”

While the device isn’t as precise as the high-end OCT tools used in eye centers, the OQ
LabScope matches the performance of entry-level OCT systems. According to Wax, the
tool is also three to five times less expensive than portable competitors, costing less than
$10,000 while offering a more precise reading.

“People have talked the talk, but we’re the first ones to walk the walk,” says Wax. “We’re
really the first ones to put an acceptable OCT device on the market and there aren’t any
competitors that are close to the price point.”

In addition to helping patients with eye diseases, the
lower price has piqued the interest of researchers
who never thought to use OCT in their work because
of the high cost. “While we can’t say we predicted
every market the tool would go to, this price
point makes it compatible for undergraduate and
graduate laboratories,” Wax notes.

Now, Wax and his collaborator, Nick Ulrich, an

assistant professor of ophthalmology at the

University of North Carolina in Chapel Hill,are

working with the Duke-Coulter Translational

Research Partnership to develop a device similar to

the LabScope that is optimized to work for retinal

imaging. To commercialize this idea, the team plans

Lumedica’s OQ LabScope is three to start a spin-off from Lumedica, called Lumedica
to five times less expensive than Vision, focused on bringing low cost OCT imaging to
the other portable OCT tools while the ophthalmology market.

offering a more precise reading. “With lots of eye diseases, if you can find them

you can halt their progression. The problem is

that people often don’t go to the eye doctor until part of their vision is lost, and at that

point they can’t reverse it,” says Wax. “With OCT, you have the capability of finding these

problems early, so our goal is to put OCT where it wasn’t before.”

MENTORS

Bill Walker: A Mentor
for New Entrepreneurs

Bill Walker When biomedical engineer Bill Walker launched his first company, it didn’t go well.

“I tried to start a company around my research as a graduate student at Duke, and I really struggled to
find a mentor who could show me the ropes,” says Walker. “I learned a lot, but it was through trial and
error, and I ultimately decided that my idea didn’t really make commercial sense.”

While his initial experience with entrepreneurship was challenging, Walker also recognizes that it
provided him with a valuable learning experience—one that makes it easier to advise students in
his new role as the Pratt School of Engineering’s first Mattson Family Director of Entrepreneurial
Ventures.

In the new position, made possible by a gift from Pratt Board of Visitors member George Mattson
E’87 and Holly Mattson, Walker works with faculty, staff and students to foster and develop
entrepreneurial ideas, guiding them from the lab bench into startups.

“One of the great things about Duke BME is that we are just a short walk away from a great clinical world, and
that gives students and faculty a unique opportunity to see what clinicians are doing and really understand what
challenges they can address and how they can make life better for doctors and patients,” says Walker. “My job is to
help people at Duke make an impact.”

Walker is an accomplished researcher with more than 15 years of experience in the entrepreneurial world. Since
earning both his undergraduate degree and PhD in biomedical engineering from Duke, he went on to work at the
University of Virginia (UVA) for 16 years, where he founded PocketSonics, a successful ultrasound imaging company.
He also spun HemoSonics out of his UVA lab. HemoSonics is now marketing the Quantra™ in vitro diagnostic system
to aid in the diagnosis of critical bleeding.

“As engineers, we often get really excited by technology and assume that the greatest tech will win the day. But
that’s not what happens in many cases,” he says. “It’s more important that you know what your customers’ most
urgent needs are and can build a product that solves those needs. You can never do that by just reading papers or
getting outside opinions. I always encourage those I work with to meet with people face-to-face to discover the true
needs of the market.”

In the 18 months since Walker began as Pratt’s entrepreneurship director, he has worked with faculty and students
in departments across Duke Engineering, supporting projects like Zephyr Mobility, a company founded by BME
undergraduate Samuel Fox, and Realtime Robotics, founded by electrical and computer engineering professor
Daniel Sorin. Beyond acting as a mentor for new entrepreneurs, Walker has rolled up his sleeves to help them raise
capital, develop a patent strategy, understand technology and industrial practices, and pursue corporate leadership.

In addition to working with specific startups, Walker has worked with Donna Crenshaw to create a series of Saturday
Entrepreneur’s Workshops to provide in-depth exploration of topics relating to entrepreneurship. Courses include
market assessment, patent law, intellectual property, and fundraising. “My goal is to make Duke more of an
entrepreneurial institution,” says Walker. “I want to make it easier to get our great ideas and research discoveries
out to the world.”

19

Barry MyersENTREPRENEURSHIP

Encouraging Engineering
and Entrepreneurship

Q&A with Barry Myers

Barry Myers is a man of many hats—or
helmets, depending on the project. A
professor of biomedical engineering
at Duke University, Myers studies the
biomechanics of catastrophic head and
neck injuries, such as those suffered in a
car accident or through contact sports
like football. But in the last few years, he
has built a second career as the director
of innovation at the Duke Clinical and
Translational Science Institute (CTSI),
where he helps translate research into
marketable products, and as the director
of the Duke-Coulter Translational
Research Partnership, where he helps
support collaborative research that
addresses unmet clinical needs and leads
to commercial products.

That research and entrepreneurial
experience converged in 2016, when
the National Football League and the
NFL Players Association asked Myers
to lead a new initiative to create and
develop safer football helmets and
protective equipment for players. Dubbed
“HeadHealth,” the partnership between Duke CTSI and NFL’s Football Research
Inc. encourages entrepreneurs and researchers to develop and market improved
football helmet technologies for better head and neck safety.

From his unique position at the intersection of engineering and translational
research, Myers shared his perspectives on Duke’s growing strengths across the
entrepreneurial pipeline.

20 Duke BME Spring 2018

MENTORS

H ow did the Duke branch of the Coulter suddenly having a strong resource base. From there,
Foundation Translational Partnership Program we hired skilled project managers to help the faculty
get started? with project development and walk them through the
regulatory and commercial side of development, which
We were looking for a way to help biomedical has also been a great tool for the department.
engineers become more successful in translating
university inventions into the marketplace. Initially Why is Duke BME a good place to pursue your
we were one of more than 60 schools competing for own entrepreneurial work?
the grant for the Coulter program. We were one of
nine schools to be chosen for a five-year grant, and Having the two programs at Duke that are focused
over that initial period we funded several startups on entrepreneurial and translational work, and
and licenses for industry. The foundation was excited subsequently being nationally recognized for those
by our success and we were ultimately granted a $20 two programs, really drew the attention of the NFL,
million endowment, which has been a benefit to the which was interested in creating products to improve
engineering and medical programs here. Since 2011, head protection. Duke has a long history of working
the Duke-Coulter Partnership has awarded $8 million in the field of biomechanics, especially regarding
to 29 projects, yielding $489 million in follow-on head and neck injuries, and coupled with the support
funding and 13 licenses to industry. Eight companies from BME and CTSI, there are very few places in the
have also been founded through the program, country that have those tools and skills available. So
including Oncoscope, PhaseBio, Sentilus, Zelanux Duke was really the unique and perfect place to run
Biomedical, Retroject, Biomimetix, Cernova, Cytex, this program.
Gateway Bio, Microelastic Systems, Element Genomics,
Imageon, Celldom, Editas Medicine, and Isolere Bio. What advice do you give to researchers who are
interested in entrepreneurship?

What other programs have helped foster People most often have questions about finding the
entrepreneurial work in Duke BME? right home for their technology and subsequently
working on regulatory work and raising capital. I’d
In 2005, the National Institutes of Health announced advise anyone interested in entrepreneurship to
their own Clinical and Translational Science Initiative, explore the tools that are available to them—at Duke,
and they were specifically looking for tools that could they can work with Coulter, CTSI, or the Office of
be translated out of universities. We were fortunate Licenses and Ventures. It’s always helpful to have
to get both the CTSI and Coulter grants at the same someone on your side to support your projects and
time, so we went from having limited resources help you build an infrastructure of project managers
for translational work and no project managers to who know how to make your company successful.

MicroElastic Ultrasound Systems

One of the companies to arise through the Duke-Coulter Translational Research Partnership is
MicroElastic Ultrasound Systems. Founded in 2016 by Peter Hollender, a research scientist in BME, the
company is using technology developed in collaboration with Mark Palmeri, an associate professor of the
practice in BME, to develop a handheld tool that allows clinicians to measure the elasticity of skin by using
ultrasound to locally vibrate tissue. Although the tool has multiple applications for evaluating procedures
in aesthetic dermatology, physicians can also use the tool to better evaluate and track skin manifestations
of difficult-to-manage diseases like Graft-Versus-Host disease (GVHD). So far, the MicroElastic team
has received a phase 1 STTR grant from the NIH to develop their prototype into a handheld commercial
product for GVHD.

21

ENTREPRENEURSHIP

A New Class of Entrepreneur

Students and researchers tackle new challenges
through their own startups

The Undergraduate
Entrepreneur

Samuel Fox’s Student-Project-
Turned-Startup Improves Patient
Mobility

Not many students can say they formed a successful company
before earning their undergraduate degree. But Samuel Fox, a
biomedical engineering student at Duke University, did just that
when he founded Zephyr Mobility before his senior year of college.

Fox was a junior at Duke when he was introduced to BME professor
Kevin Caves. At the time, Fox was hoping to design a tool that would
make it easier for people in wheelchairs to shower, and he thought
that Caves, who taught the “Devices for People with Disabilities”
design course at Duke, would offer him valuable feedback. They
discussed the idea before Caves put Fox in touch with Laura Juel,
an occupational therapist at Lenox Baker Hospital, to give him a
better idea about the needs of patients and caretakers.

Through their discussion, Fox learned that safely moving patients
in and out of bed was a major issue for healthcare workers, as the
current mobility devices are slow and often require two or more
caretakers to use.

Samuel Fox and the prototype of Their discussion gave Fox an idea—what if he could create a tool
Zephyr Mobility’s device that could safely move patients out of bed and place them into a
wheelchair, all without putting the caretakers under physical strain?
Fox quickly changed his initial wheelchair design, opting instead to
create a device that would safely and effectively solve this problem.
To further pursue his idea, Fox formed Zephyr Mobility, drawing on
the expertise of BME faculty to aid him in his efforts.

22 Duke BME Spring 2018

STUDENTS

“My BME advisor, Professor Robert Malkin, was the first person I went to for advice, and he
helped me plan an ambitious development strategy,” says Fox, a senior in BME. “He continually
encouraged me that I was moving in the right direction.”

Unlike current devices on the market which hoist patients into the air, Fox designed a device
that scoops an air cushion beneath the patient’s body, which then slides them laterally from
the bed to the wheelchair. According to Fox, this method is not only more comfortable for the
patient, but also less likely to malfunction—and it doesn’t physically strain the caregivers.

“I encourage After building his proof-of-concept design in the Foundry—an interdisciplinary student
other students workspace sponsored by the Pratt School of Engineering—Fox entered the Duke Startup
to experiment Challenge and received the 2017 Duke BME Prize offered through the competition. The prize
with their ideas provided Fox with $5,000 to turn his prototype into a field-testable device.
as early as
possible and Fox also began to collaborate with Bill Walker, Duke Engineering’s first Mattson Family Director
get advice from of Entrepreneurial Ventures. “Bill had a transformative impact on the project, bringing his huge
anyone they wealth of knowledge and network to help me,” says Fox. “He’s meeting with me as often as I
can, because need it to give me lots of advice on every topic.”
everyone in
BME wants to With Walker’s help, Fox has pitched his company to potential investors at the Melissa & Doug
help curious, Entrepreneurs Demo Day event in Connecticut, where he raised nearly $30,000 in funding.
energetic He also pitched his design at an Innovation Jam at the Duke University Medical Center, and is
students currently nearing an agreement for a collaboration with Duke Health, which would give him
succeed.” access to facilities and nurses to field-test his product.

While Fox recognizes that starting a company is challenging, he is Other Entrepreneurial Efforts Cassio Fontes
thankful for the support undergraduate students have to pursue
entrepreneurship. “The big barrier in healthcare startups is PhD student Cassio
getting access to the system and communicating with clinicians,” Fontes joined the
says Fox. “Duke has really made it easy to do that by encouraging Chilkoti lab after
connections between engineering and medicine. founding a successful
diagnostics company in
“This experience has made me realize how important it is to seek his native Brazil. Fontes
out problems that you think really matter,” he says. “I encourage is developing a new
other students to experiment with their ideas as early as possible method to generate and
and get advice from anyone they can, because everyone in BME pair antibodies that will
wants to help curious, energetic students succeed.” be used in a point-of-
care diagnostic test for
Ebola.

23

ENTREPRENEURSHIP Student and researcher startups in BME

“You really need Entrepreneurial
to be your own Insight
champion. No
one will care Lucinda Camras’s
as much for what Startup Aims to
you are doing Fight Glaucoma
as you. Saving
sight is certainly Lucinda Camras was 19 years old when her father
something worth asked her if she could help him design a new device
championing.” to help treat glaucoma. For some, this would be
an unusual request—but not for Camras, where
invention was part of her family lineage. Her father,
Carl, discovered what is now the first-line drug
therapy in glaucoma and her grandfather, Marvin,
invented magnetic tape recording and is in the
Inventors Hall of Fame.

Together, Camras and her father created the Camras
Shunt, a device designed to improve the success rate
of glaucoma surgery by relieving eye pressure in a
Lucinda Camras controlled and predictable manner. During her time
as a biomedical engineering PhD student at Duke
University, she co-founded Camras Vision to develop and, one day, commercialize the
Camras Shunt.

“Glaucoma causes irreversible blindness because it puts pressure on the optic nerve. The
only way to treat the disease is by reducing the pressure inside the eye via medication
and/or surgery,” says Camras. “Unfortunately, medications may not sufficiently lower
the eye pressure; and the more aggressive surgeries to achieve low pressures are
unpredictable with high complication rates and, if successful, may only last 3–5 years.”

Instead, the Camras Shunt drains to a new area of the eye to avoid the major source of
device failure over time. It also has an adjustable component that allows the eye pressure
to be predictably manipulated non-invasively in the clinic. This feature of the Camras
Shunt ensures that the eye pressure is sufficiently lowered to stop future vision loss.

“My father was a busy academic and I was still an undergrad, so I didn’t have the time
or knowledge to commercialize a device,” says Camras. “Also, we knew that this device
would require more research, so my original plan was to go to grad school and develop the
device as part of my PhD thesis. When I came to Duke, it became clear that, since Duke did
not own the intellectual property, I would have to do something else for my thesis.”

Although Camras was unable to use the Camras Shunt as her thesis, her PhD advisor,
Duke BME’s Fan Yuan, supported her interest in entrepreneurship outside of her thesis

24 Duke BME Spring 2018

STUDENTS

An early prototype of the work. Through this process, Camras met

Camras Shunt and worked with Dr. Bruce Klitzman, an

associate professor of surgery who is

himself an entrepreneur, and Drs. Sanjay Asrani and Rand Allingham, clinicians

in the Duke University Eye Center, who helped Camras apply for small business

grants and refine the design of the shunt. While taking the Program for

Entrepreneurs course at Duke, Camras met MBA student Robert Alfaro, who

was interested in commercializing her device. Together they co-founded Camras

Vision, named to honor Camras’s father, who passed away in 2009.

After graduating from Duke with her PhD in biomedical engineering in 2013, Other Entrepreneurial Efforts Encapsio
Camras went to work full-time as the Chief Scientific Officer at Camras Vision,
with Alfaro serving as the company’s President/Chief Financial Officer. They Encapsio was created
were later joined by Ray Krauss, a successful executive in the medical device by PhD Wyatt Shields, and
industry, who became their CEO. the company is developing a
system of manufacturing
Today, Camras and her team have received more than $2.5 million in small premium silicone
business grants from the National Science Foundation and National Eye Institute microscoperes for
to develop the Camras Shunt. The company has also raised millions from encapsulation, protection,
investors. With these achievements, Camras is optimistic about the impact her and controlled delivery of
decade of hard work will have. “You really need to be your own champion. No active ingredients in product
one will care as much for what you are doing as you,” says Camras. “Saving formulations. Currently, the
sight is certainly something worth championing.” team is focusing their efforts
on topical applications for
skin care.

25

ENTREPRENEURSHIP Student and researcher startups in BME

Dave Ousterout

Using CRISPR to Disrupt
the Antibiotics Industry

David Ousterout made an unusual career move after graduating from Duke
University with a PhD in biomedical engineering. Rather than pursue a job in
industry or return to academia, Ousterout got a job as a business consultant,
and instead of working with companies in the biomedical world, he opted to do
something completely out of his comfort zone.

“I purposefully didn’t do work relating to healthcare, pharma or biotech,” says
Ousterout. “I wanted to challenge myself so I would learn faster.”

This wasn’t the first time Ousterout had thrown himself into something
new. When he first arrived at Duke in 2009, he worked in the lab of Charles
Gersbach, where he developed novel gene editing technologies to correct
genetic mutations that cause Duchenne muscular dystrophy.

David Ousterout Ousterout was ready to take on another challenge in 2015 after being
introduced to Paul Garofolo, who had spent two decades as a CEO of
pharmaceutical companies. Garofolo had pitched Ousterout an idea to start a
business centered on using the CRISPR method in a new way by returning it to
its roots in bacteria.

The CRISPR system is a modified version of a bacterial defense system that allows researchers to
target specific stretches of genetic code and precisely edit DNA. Traditionally, researchers will use the
Cas9 enzyme to make the edits, but Garofolo wanted to work with the Cas3 enzyme, a larger molecule
that can only target bacteria.

“With Cas3, you aren’t making elegant changes,” says Ousterout. “Instead, you’re destroying the cells
from within and it’s different in both application and function.”

“Find a group of Ousterout, Garofolo, Gersbach and their collaborators founded Locus Biosciences in 2015 with the aim
mentors, trust of using the Cas3 enzyme to combat issues like antibiotic resistance. According to Ousterout, the Cas3
in yourself, system acts like a Pac-Man and chews up target DNA, killing the bacterium. By using this process, their
and compete, technology would allow them to specifically target disease causing bacteria, potentially limiting the
compete, need for broad-spectrum antibiotics to treat bacterial infections.
compete.”
“When we use broad-spectrum antibiotics, they hurt both the bad and good bacteria in the body,” says
Ousterout. “But this process could potentially get us back to the idea of ‘one drug for one bug’ by
turning CRISPR back on the bacteria.”

Currently, Ousterout and his co-founders are working on getting FDA approval for their technology
while they pursue additional funding sources.

“My advice to anyone who wants to pursue entrepreneurship is to compete and go after every
challenge,” says Ousterout. “Find a group of mentors, trust in yourself, and compete, compete,
compete.”

26 Duke BME Spring 2018

“Our ultimate STUDENTS
goal is to
improve global A Better Way to Make
access to Monoclonal Antibodies
these drugs
by making it Kelli Luginbuhl spent her time as a PhD student studying elastin-
easier and less like polypeptides, a biopolymer technology pioneered by her PhD
expensive to advisor, Ashutosh Chilkoti. Now, Luginbuhl and Chilkoti hope to explore
manufacture how they can use ELPs to purify monoclonal antibodies for use in
monoclonal therapeutics through their startup, Isolere Bio.
antibodies.”
Monoclonal antibodies are artificial antibodies that can be used as
drugs. When injected into the blood stream of patients, they help
the body fight off disease. They are typically made by genetically
engineering cells.

Once the cells secrete the antibody, they go through an extensive
downstream purification process. The first step of purification is a
process called affinity chromatography, where a column is packed
with beads attached to a protein that binds to the antibody. When cell
culture media is poured through the beads, the antibodies attach to the
proteins on the bead while everything else flows through. From there,
Kelli Luginbuhl researchers separate the antibodies from the column by dissociating
the antibody from the protein on the bead. While the process is
effective, it’s expensive and requires trained technicians to perform.

With Isolere Bio, the team aims to simplify and reduce the cost of the purification process
by using the unique properties of ELPs. “We fuse the capture proteins to our ELPs and
mix them with a solution of cells that make the monoclonal antibodies and secrete
them out of the cell and into the culture medium,” says Luginbuhl. “We then add a small
amount of salt, and this causes the ELP to go from soluble to insoluble, capturing the
antibodies and separating them from cellular contaminants, which stay soluble.”

From there, lab technicians simply spin the solution in a centrifuge to separate the
components, leaving the ELP and attached antibodies at the bottom while they scoop
out all other proteins and contaminants. To access the purified antibodies, researchers
then re-suspend the ELPs in a saline solution to make it soluble and lower the pH, which
causes the antibodies to separate and ELP to be recycled.

“Currently, you need someone skilled in chromatography to purify antibodies, but with
our method I could teach anyone to do it and they could be working within an hour, and
our process only requires salt and a centrifuge rather than a complex chromatography
system, which significantly lowers the cost,” says Luginbuhl. “Our ultimate goal is
to improve global access to these drugs by making it easier and less expensive to
manufacture monoclonal antibodies.”

27

ENTREPRENEURSHIP

The Pioneers of 3D Ultrasound

The Beginning of Entrepreneurship in Duke BME

Most people are familiar with ultrasound as a tool that allows pregnant couples to see their baby before
it’s born. Thirty years ago, ultrasound images typically showed vague black and gray shapes, and it could
be difficult to distinguish between a baby’s nose or foot without a doctor’s explanation. But today, these
images are so clear that new parents can even see their baby sucking on its thumb.

This difference in clarity is due to the use of 3D ultrasound, created by Olaf von Ramm, Stephen Smith and
John Oxaal through their company Volumetrics Medical Imaging, Inc.

An early Von Ramm (PhD ’73) and Smith (PhD ’75) first began working together at Duke as PhD students in the lab of
ultrasound image Frederick Thurstone, an ultrasound researcher who was recruited to work in Duke’s biomedical engineering
department as a faculty member in 1967. At the time, ultrasound was a relatively new technology, and
it wasn’t widely used in clinical applications. This changed after von Ramm and Thurstone helped
revolutionize the ultrasound scanner, a device that both transmits and receives ultrasound pulses.

By designing a phase array ultrasound scanner that could emit thousands of pulses at once, the tool could
receive more detailed images from the scanned tissue, giving physicians a better look at what was going
on inside the body. While this advancement was effective, von Ramm and Smith wanted to continue to
improve the technology to see three dimensional moving images in real-time.

“We ended up sketching out our idea on a napkin,” says Smith. “To test it out, we filled a garbage can with
water from the Eno River and dropped a wrench into it, and we were able to see the wrench through this
muddy water. That experiment really gave us the idea to pursue real time 3D ultrasound for medical use.”

To make their plan a reality, Smith and von Ramm aimed to increase the sensitivity of their device. Rather
than keep the sensors in a row like previous ultrasound probes, they arranged hundreds of sensors in a
checkerboard pattern to better analyze more complex ultrasound reflections. They also created their own
computer systems to quickly read the feedback and show the image.

“I had thought of doing 3D when we had developed 2D ultrasound in the ’70s, but we didn’t have the
technology that would allow for that,” says von Ramm. “We were only able to make our first 3D image by
1987, and even then, it wasn’t very good. But the images we made improved each year.”

The team applied for patents in 1986 and 1987, and shortly after they were joined by John Oxaal, a
biomedical engineer who had graduated from Duke in 1976 and had previously worked with von Ramm on
2D ultrasound. Together, they formed Volumetrics Medical Imaging in 1992 to develop the first real-time 3D
commercial system.

28 Duke BME Spring 2018

Renting space in downtown Durham, the team formed a collaboration between Volumetrics and Duke’s Department of
Biomedical Engineering, relying on funding from the National Science Foundation as they built their initial prototype. By
2000, the company had sold nearly 20 3D scanners, which were used for obstetrics and cardiovascular imaging. Since
then the basis of their technology has been widely used in clinics in nearly every developed country around the world.

In the intervening years, von Ramm has continuously looked for ways to improve the technology, especially for
cardiology. Today, he’s contributing to research relating to high-speed ultrasound imaging, which shows upwards of
1,000 frames a second. With this improved view, he says, physicians and researchers could visualize the depolarization of
the heart, potentially limiting the need for invasive procedures that examine heart muscle.

“We’d be able to examine areas that aren’t contracting well and potentially learn why they aren’t contracting well, or we
could examine regions that are contracting prematurely and reducing the efficiency of the heart,” says von Ramm. “Right
now, there are only very difficult ways to map the electrical excitation of the heart. You’d have to do it invasively with a
catheter, and it can take four hours. If this works out, we’d be able to do it easily and non-invasively.”

Smith has also continued to advance ultrasound probes, John Oxaal: The Entrepreneurial Alumnus
designing esophageal probes that can clearly examine a patient’s
heart by circumventing the lungs and fatty tissue. One of his After graduating from biomedical engineering at
long-term goals is to use ultrasound imaging to visualize the brain Duke with his bachelor of science in engineering
through the skull, potentially giving physicians an easier way to degree in 1976, Oxaal enrolled at the University
diagnose issues like a stroke and immediately start treatment. of Chicago, earning his business degree before
returning to Duke to help start Volumetrics
“We’re always looking for good, non-invasive ways to monitor the Medical Imaging with von Ramm and Smith. Oxaal
body, and ultrasound imaging has played a vital role,” says Smith. continued to work at the company until 1999, after
“The goal of our work has always been to change the practice of which he moved to the west coast to work as a
medicine for the better.” venture capitalist at Sevin Rosen funds. While
there, his entrepreneurial work focused on a
variety of scientific topics, including imaging and
photonics.

His experience as both an entrepreneur at
Volumetrics and as a venture capitalist led BME
Chair Ashutosh Chilkoti to invite Oxaal back
to Duke to serve as the first entrepreneur-in-
residence in the department for the 2015–2016
school year, providing support and guidance
to new entrepreneurs in the BME department.
Through this role, Oxaal helped Charles Gersbach
found Element Genomics in 2015, eventually
becoming CEO of the company.

Top: Stephen Smith (center) holds one of the ultrasound probes After years of experience in the entrepreneurial
he helped design. world, Oxaal was pleased to return to his alma
mater and help a new generation of entrepreneurs.
Above: Olaf von Ramm (left) was a co-director of Duke’s “The BME department at Duke has always been full
Center for Emerging Cardiovascular Technologies, the first of leaders in the field, and it’s given them a very
National Science Foundation Engineering Research Center clear idea of where the unmet needs are,” says
focusing on biomedical engineering research. Oxaal. “Engineers are an entrepreneurial bunch,
and they’re solving real-world problems in ways
that can have enormous benefits.”

29 29

ENTREPRENEURSHIP

Duke BME Stats

By the Numbers

15More than $600More than 127
startups created million inventions
through Duke BME in license revenue in disclosed out of
315 from all of
37the 2017 fiscal year Duke
patents
issued (85 for
all of Duke
Faculty)

Rankingsin world in ShanghaiRankings’s global ranking of in the United
States for
biomedical engineering programs (Academic Ranking of undergraduate
World Universities) BME programs in

among doctoral biomedical engineering programs by U.S. News & World

# the National Research Council Report Best

3 in the country for highest median Colleges rankings
starting salary for biomedical
engineers—$70,000 (Medical Product
#4Manufacturing News)

30 Duke BME Spring 2018

48 Tenure-track faculty Companies launched by BME Faculty,
21AIMBE fellows Students and Alumni include:

7 BMES fellows PhaseBio Pharmaceuticals
S entilus
5 members of the National Academy of Inventors: B ioStealth
Joseph Izatt, Nimmi Ramanujam, Tuan Vo-Dinh, GatewayBio
Jennifer West and Ashutosh Chilkoti I solere Bio
Deep Brain Innovations (DBI)
4 Society for Biomaterials NDI Medical
Clemson Award winners Bioptigen
(since 2010) DMC Ltd
Z enalux Biomedical
4 SPIE and OSA fellows Lumedica, Inc.
O ncoscope
2 members of the National Academy of Engineering: M 2 Photonics Innovations
Jennifer West and Blake Wilson M icroElastic
K ela Health
Research 2 E ncapsio
E lement Genomics, Inc.
$30More than NIH pre-doctoral AccuBeing
million training grants: V olumetric Medical Imaging
in new research awards Medical Imaging Cytex Therapeutics
in fiscal year 2017 (Nightingale, PI) and Camras Vision
Biomolecular and Locus Biosciences
Tissue Engineering Zephyr Mobility
(Gersbach, PI)
31

NonProfit Org
U.S. Postage Paid
Durham, N.C.
Permit No. 60

Duke University
Department of Biomedical Engineering
Room 1427, Fitzpatrick Center (FCIEMAS)
101 Science Drive
Campus Box 90281
Durham, NC 27708-0281

“We want to provide a physical infrastructure and
intellectual expertise for innovative startups in
Duke BME.” | 5

The exterior of the Fitzpatrick Center for
Interdisciplinary Engineering, Medicine and Applied
Sciences, home to Duke BME.