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UConn spin-off gets stem cell patent for autoimmune diseases

September 13, 2017

John Stearns

ImStem Biotechnology Inc. and the University of Connecticut today announced that a joint patent was recently issued for human embryonic stem cell technology being used by ImStem to develop therapies for autoimmune diseases, with an initial focus on Multiple Sclerosis.

The company, spun out of the UConn Stem Cell Core Lab, was formed to commercialize the technologies developed by Dr. Ren He Xu, the former director of the UConn Stem Cell Core, and his then postdoc, Dr. Xiaofang Wang. Wang now leads the company as its chief technology officer with CEO Dr. Michael Men.

In 2010, Xu was one of few researchers to derive new stem cell lines when he announced that four UConn lines had been approved for use in federally funded research and added to the National Stem Cell Registry by the National Institutes of Health, according UConn. Both ImStem and its enabling research had been funded by the state of Connecticut Stem Cell Grant program.

Today, ImStem operates through private capital raised by its founders and is located at the UConn Technology Incubation Program (TIP) in Farmington.

While ImStem has proven its T-MSC cell therapy protects mice from MS, it is currently working with the FDA on necessary clearances to begin clinical trials next year and has completed FDA required experiments. ImStem believes its technology might address diseases beyond MS, including the company’s next target, Inflammatory Bowel Disease.

Teaching Robots to Think

September 13, 2017 – Colin Poitras – UConn Communications

Ashwin Dani, assistant professor of electrical and computer engineering, demonstrates how the robot can be given a simple task which can be repeated. Sept. 7, 2017. (Sean Flynn/UConn Photo)

Ashwin Dani, assistant professor of electrical and computer engineering, demonstrates how the robot can be given a simple task which can be repeated. Sept. 7, 2017. (Sean Flynn/UConn Photo)

In a research building in the heart of UConn’s Storrs campus, assistant professor Ashwin Dani is teaching a life-size industrial robot how to think.

Here, on a recent day inside the University’s Robotics and Controls Lab, Dani and a small team of graduate students are showing the humanoid bot how to assemble a simple desk drawer.

The “eyes” on the robot’s face screen look on as two students build the wooden drawer, reaching for different tools on a tabletop as they work together to complete the task.

The robot may not appear intently engaged. But it isn’t missing a thing – or at least that’s what the scientists hope. For inside the robot’s circuitry, its processors are capturing and cataloging all of the humans’ movements through an advanced camera lens and motion sensors embedded into his metallic frame.
Ashwin Dani, assistant professor of electrical and computer engineering, is developing algorithms and software for robotic manipulation, to improve robots’ interaction with humans. (Sean Flynn/UConn Photo)
Ashwin Dani, assistant professor of electrical and computer engineering, is developing algorithms and software for robotic manipulation, to improve robots’ interaction with humans. (Sean Flynn/UConn Photo)

Ultimately, the UConn scientists hope to develop software that will teach industrial robots how to use their sensory inputs to quickly “learn” the various steps for a manufacturing task – such as assembling a drawer or a circuit board – simply by watching their human counterparts do it first.

“We’re trying to move toward human intelligence,” says Dani, the lab’s director and a faculty member in the School of Engineering. “We’re still far from what we want to achieve, but we’re definitely making robots smarter.”

To further enhance robotic intelligence, the UConn team is also working on a series of complex algorithms that will serve as an artificial neural network for the machines, helping robots apply what they see and learn so they can one day assist humans at their jobs, such as assembling pieces of furniture or installing parts on a factory floor. If the process works as intended, these bots, in time, will know an assembly sequence so well, they will be able to anticipate their human partner’s needs and pick up the right tools without being asked – even if the tools are not in the same location as they were when the robots were trained.

This kind of futuristic human-robot interaction – called collaborative robotics – is transforming manufacturing. Industrial robots like the one in Dani’s lab already exist. Although currently, engineers must write intricate computer code for all of the robot’s individual movements or manually adjust the robot’s limbs at each step in a process to program it to perform. Teaching industrial robots to learn manufacturing techniques simply by observing could reduce to minutes a process that currently can take engineers days.
From left back row, Ph.D. students Iman Salehi, Harish Ravichandar, Kyle Hunte, Gang Yao, and seated, Ashwin Dani, assistant professor of electrical and computer engineering. (Sean Flynn/UConn Photo)
From left back row, Ph.D. students Iman Salehi, Harish Ravichandar, Kyle Hunte, Gang Yao, and seated, Ashwin Dani, assistant professor of electrical and computer engineering. (Sean Flynn/UConn Photo)

“Here at UConn, we’re developing algorithms that are designed to make robot programming easier and more adaptable,” says Dani. “We are essentially building software that allows a robot to watch these different steps and, through the algorithms we’ve developed, predict what will happen next. If the robot sees the first two or three steps, it can tell us what the next 10 steps are. At that point, it’s basically thinking on its own.”

In recognition of this transformative research, UConn’s Robotics and Controls Lab was recently chosen as one of 40 academic or academic-affiliated research labs supporting the U.S. government’s newly created Advanced Robotics for Manufacturing Institute or ARM. One of the collaborative’s primary goals is to advance robotics and artificial intelligence to maintain American manufacturing competitiveness in the global economy.

“There is a huge need for collaborative robotics in industry,” says Dani. “With advances in artificial intelligence, lots of major companies like United Technologies, Boeing, BMW, and many small and mid-size manufacturers, are moving in this direction.”

The United Technologies Research Center, UTC Aerospace Systems, and ABB US Corporate Research – a leading international supplier of industrial robots and robot software – are also representing Connecticut as part of the new ARM Institute. The institute is led by American Robotics Inc., a nonprofit associated with Carnegie Mellon University.

Connecticut’s and UConn’s contribution to the initiative will be targeted toward advancing robotics in the aerospace and shipbuilding industries, where intelligent, adaptable robots are more in demand because of the industries’ specialized needs.

Joining Dani on the ARM project are UConn Board of Trustees Distinguished Professor Krishna Pattipati, the University’s UTC Professor in Systems Engineering and an expert in smart manufacturing; and assistant professor Liang Zhang, an expert in production systems engineering.

“Robotics, with wide-ranging applications in manufacturing and defense, is a relatively new thrust area for the Department of Electrical and Computer Engineering,” says Rajeev Bansal, professor and head of UConn’s electrical and computer engineering department. “Interestingly, our first two faculty hires in the field received their doctorates in mechanical engineering, reflecting the interdisciplinary nature of robotics. With the establishment of the new national Advanced Robotics Manufacturing Institute, both UConn and the ECE department are poised to play a leadership role in this exciting field.”

The aerospace, automotive, and electronics industries are expected to represent 75 percent of all robots used in the country by 2025. One of the goals of the ARM initiative is to increase small manufacturers’ use of robots by 500 percent.

Industrial robots have come a long way since they were first introduced, says Dani, who has worked with some of the country’s leading researchers in learning and adoptive control, and robotics at the University of Florida (Warren Dixon) and the University of Illinois at Urbana-Champaign (Seth Hutchinson and Soon-Jo Chung). Many of the first factory robots were blind, rudimentary machines that were kept in cages and considered a potential danger to workers as their powerful hydraulic arms whipped back and forth on the assembly line.

Today’s advanced industrial robots are designed to be human-friendly. High-end cameras and elaborate motion sensors allow these robots to “see” and “sense” movement in their environment. Some manufacturers, like Boeing and BMW, already have robots and humans working side-by-side.

Of course, one of the biggest concerns within collaborative robotics is safety.

In response to those concerns, Dani’s team is developing algorithms that will allow industrial robots to quickly process what they see and adjust their movements accordingly when unexpected obstacles – like a human hand – get in their way.

“Traditional robots were very heavy, moved very fast, and were very dangerous,” says Dani. “They were made to do a very specific task, like pick up an object and move it from here to there. But with recent advances in artificial intelligence, machine learning, and improvements in cameras and sensors, working in close proximity with robots is becoming more and more possible.”

Dani acknowledges the obstacles in his field are formidable. Even with advanced optics, smart industrial robots need to be taught how to distinguish a metal rod from a flexible piece of wiring, and to understand the different physics inherent in each.

Movements that humans take for granted are huge engineering challenges in Dani’s lab. For instance: Inserting a metal rod into a pre-drilled hole is relatively easy. Knowing how to pick up a flexible cable and plug it into a receptacle is another challenge altogether. If the robot grabs the cable too far away from the plug, it will likely flex and bend. Even if the robot grabs the cable properly, it must not only bring the plug to the receptacle but also make sure the plug is oriented properly so it matches the receptacle precisely.

“Perception is always a challenging problem in robotics,” says Dani. “In artificial intelligence, we are essentially teaching the robot to process the different physical phenomena it observes, make sense out of what it sees, and then make the appropriate response.”

Research in UConn’s Robotics and Controls Lab is supported by funding from the U.S. Department of Defense and the UTC Institute of Advanced Systems Engineering. More detailed information about this research being conducted at UConn, including peer-reviewed article citations documenting the research, can be found here. Dani and graduate student Harish Ravichandar also have two patents pending on aspects of this research: “Early Prediction of an Intention of a User’s Actions,” Serial #15/659,827, and “Skill Transfer From a Person to a Robot,” Serial #15/659,881.

UConn Spin Out Issued Stem Cell Patent for Autoimmune Disease

Rita Zangari

Farmington, Conn. – September 12, 2017 – ImStem Biotechnology, Inc. and the University of Connecticut today announced that a joint patent was recently issued for human embryonic stem cells derived mesenchymal stem cells “hES-T-MSC” or “T-MSC” and the method of producing the stem cells.

The patented technology is being used by ImStem to develop therapies for autoimmune diseases with an initial focus on Multiple Sclerosis (MS).  The company, a spin out of the UConn Stem Cell Core Lab, was formed to utilize and commercialize the technologies developed by Dr. Ren He Xu, the former director of the UConn Stem Cell Core, and his then postdoc Dr. Xiaofang Wang.  Dr. Wang now leads the company as its chief technology officer with CEO Dr. Michael Men, M.D.

In 2010,  Xu was one of few researchers to derive new stem cell lines when he announced that four University of Connecticut lines had been approved for use in federally funded research and added to the National Stem Cell Registry by the National Institutes of Health. Both ImStem and its enabling research had been funded by the State of Connecticut Stem Cell Grant program.

Today, ImStem operates through private capital raised by its founders and is located at the UConn Technology Incubation Program (TIP) in Farmington.

According to Wang, ImStem aims to address the needs of the 450,000 patients in the United States and approximately 2.5 million people around the world that have MS. About 200 new cases are diagnosed each week in the United States with no cures currently available.

“Current therapies temporarily treat MS symptoms, but come with severe side effects and high costs –$60K per year,” Wang said. “ImStem’s technology can offer strong immunosuppression and tissue regeneration with no side effects. It is more robust than other adult stem cell therapies.

While ImStem has proven that their T-MSC cell therapy protects mice from MS (EAE Model), they are currently working with the FDA on necessary clearances to begin clinical trials next year and have completed FDA required experiments.

“None of this would have been possible without the vision and support of the state of Connecticut and UConn,” said CEO Michael Men.  “As a physician and business person, I am naturally pleased to be part of the ImStem team, but without visionary partners like CT Innovations, UConn and Connecticut’s elected officials, the work of our company would not have progressed.”

ImStem continues to collaborate with UConn researcher’s including Dr. Joel Pachter from the Department of Cell Biology and Dr. Liisa Kuhn from the Center for Regenerative Medicine and Skeletal Development.

“That is one of the unique benefits offered by TIP,” said UConn Vice President for Research, Dr. Radenka Maric. “Not only do our TIP startups benefit from use of the unique R&D resources that can only be found at a research institution like UConn, but they have the opportunity to collaborate with leading scientific experts, business advisors, and top student talent to help ensure their success.”

According to TIP’s Executive Director, Dr. Mostafa Analoui, the program has a proven track record of successfully accelerating the growth of high-potential technology startups.

“As the only university-based technology business incubator in the state, TIP has helped over 90 companies that have raised $54 million in grants and $135 million in equity and debt since 2004,” Analoui said. “We are committed to helping Connecticut companies grow and training the next generation of scientists and entrepreneurs for the state.”

ImStem believes that their technology might be able to address a variety of diseases beyond MS, including the company’s next target, Inflammatory Bowel Disease.

UConn, Calif. firm partner on dental bridge technology

Published by Hartford Business Journal on August 29, 2017

Patricia Daddona

UConn and California-based Preat Corp. have entered into a license agreement to commercialize improved dental bridges for tooth repair and restoration.

Terms of the deal were not disclosed.

The licensed technology developed by Dr. Avinash Bidra, a prosthodontist and associate professor at the UConn School of Dental Medicine, resolves a problem commonly related to proper fitting dental implants when a patient experiences total tooth loss, the university said.

Preat Corp. is a provider of dental implants and attachments.

Using Bidra’s invention, acrylic resin that is added during the implant fabrication process does not come in contact with other components that could be scratched or damaged or interfere with the fit of the dental bridge, said Radenka Maric, vice president for research at UConn/UConn Health.

“This is a prime example of the unique ability of academic-industry partnerships to address unmet clinical needs,” said Maric.

UConn Professor Synthesizing Pure Graphene, a ‘Miracle Material’

Published by UConn Today on August 29, 2017

Jessica McBride

Formed deep within the earth, stronger than steel, and thinner than a human hair. These comparisons aren’t describing a new super hero. They’re describing graphene, a substance that some experts have called “the most amazing and versatile” known to mankind.

UConn chemistry professor Doug Adamson, a member of the Polymer Program in UConn’s Institute of Materials Science, has patented a one-of-a-kind process for exfoliating this wonder material in its pure (unoxidized) form, as well as manufacturing innovative graphene nanocomposites that have potential uses in a variety of applications.

If you think of graphite like a deck of cards, each individual card would be a sheet of graphene. Comprised of a single layer of carbon atoms arranged in a hexagonal lattice, graphene is a two-dimensional crystal that is at least 100 times stronger than steel. Aerogels made from graphene are some of the lightest materials known to man, and the graphene sheets are one of the thinnest, at only one atom thick – that is approximately one million times thinner than a human hair. Graphene is also even more thermally and electrically conductive than copper, with minimal electrical charge.

Because of these unique qualities, graphene has been a hot topic for academic researchers and industry leaders since it was first isolated from graphite in 2004. Since then, more than 10,000 scholarly articles have been published about the material. But of these publications, only Adamson’s discusses a proprietary process for manufacturing graphene in its pristine form.

What others are calling “graphene” is often actually graphene oxide that has been chemically or thermally reduced. The oxygen in graphene oxide provides a sort of chemical handle that makes the graphene easier to work with, but adding it to pristine graphene reduces the material’s mechanical, thermal, and electrical properties in comparison to unmodified graphene like the kind Adamson produces.

It also significantly increases the cost to manufacture the material. Oxidizing graphite requires adding expensive hazardous chemicals, such as anhydrous sulfuric acid and potassium peroxide, followed by a lengthy series of manipulations to isolate and purify the products, known as a chemistry workup. Adamson’s process doesn’t require any additional steps or chemicals to produce graphene in its pristine form.

“The innovation and technology behind our material is our ability to use a thermodynamically driven approach to un-stack graphite into its constituent graphene sheets, and then arrange those sheets into a continuous, electrically conductive, three-dimensional structure” says Adamson. “The simplicity of our approach is in stark contrast to current techniques used to exfoliate graphite that rely on aggressive oxidation or high-energy mixing or sonication – the application of sound energy to separate particles – for extended periods of time. As straightforward as our process is, no one else had reported it. We proved it works.”

Soon after the initial experiments by graduate student Steve Woltornist indicated that something special was happening, Adamson was joined by longtime collaborator Andrey Dobrynin from the University of Akron, who has helped to understand the thermodynamics that drive the exfoliation. Their work has been published in the American Chemical Society’s peer-reviewed journal ACS Nano.

A distinctive feature of graphene that seems like an obstacle to many – its insolubility – is at the heart of Adamson’s discovery. Since it doesn’t dissolve in liquids, Adamson and his team place graphite at the interface of water and oil, where the graphene sheets spontaneously spread to cover the interface and lower the energy of the system. The graphene sheets are trapped at the interface as individual, overlapping sheets, and can subsequently be locked in place using a cross-linked polymer or plastic.

Adamson began exploring ways to exfoliate graphene from graphite in 2010 with a grant from the Air Force to synthesize thermally conductive composites. This was followed in 2012 with funding from a National Science Foundation (NSF) Early-concept Grants for Exploratory Research (EAGER) award. Since then he has also been awarded a $1.2 million grant from the NSF Designing Materials to Revolutionize and Engineer our Future program and $50,000 from UConn’s SPARK Technology Commercialization Fund program.

“Dr. Adamson’s work speaks not only to the preeminence of UConn’s faculty, but also to the potential real-world applications of their research,” says Radenka Maric, vice president for research at UConn and UConn Health. “The University is committed to programs like SPARK that enable faculty to think about the broader impact of their work and create products or services that will benefit society and the state’s economy.”

Graphene for Water Desalination

While stabilized graphene composite materials have countless potential uses in fields as varied as aircrafts, electronics, and biotechnology, Adamson chose to apply his technology to improving standard methods for the desalination of brackish water. With his SPARK funding, he is developing a device that uses his graphene nanocomposite materials to remove salt from water through a process called capacitive deionization, or CDI.

CDI relies on inexpensive, high surface area, porous electrodes to remove salt from water. There are two cycles in the CDI process: an adsorption phase where the dissolved salt is removed from the water, and a desorption phase where the adsorbed salts are released from the electrodes by either halting or reversing the charge on the electrodes.

Many materials have been used to create the electrodes, but none have proven to be a viable material for large-scale commercialization. Adamson and his industry partners believe that his simple, inexpensive, and robust material could be the technology that finally brings CDI to market in a major way.

“The product we are developing will be an inexpensive graphene material, with optimized performance as an electrode, that will be able to displace more expensive, less efficient materials currently used in CDI,” says Michael Reeve, one of Adamson’s partners and a veteran of various successful startups.

The team formed a startup called 2D Material Technologies, and they have applied for a Small Business Innovation Research grant to continue to commercialize Adamson’s technology. Eventually, they hope to join UConn’s Technology Incubation Program to advance their concept to market.

For more information on the UConn SPARK Technology Commercialization Fund, visit the Office of the Vice President for Research website. The deadline to submit a brief letter of intents to the 2017 UConn SPARK Technology Commercialization Fund competition is Sept. 1.

Adamson, together with collaborators Andrey Dobrynin of the University of Akron and Hannes Schniepp of the College of William and Mary, previously conducted research that sparked the idea for this invention through support from the National Science Foundation as part of the Designing Materials to Revolutionize and Engineer our Future initiative: DMR1535412. This NSF program supports the federal government’s Materials Genome Initiative for Global Competitiveness. However, no resources from this previous award were used to fund product development or testing of the current prototype device.  

 

UConn Researchers: Dyes Detect Disease Through Heartbeat Signals

Published on phys.org on August 22, 2017

Jessica McBride

Vibrant tones of yellow, orange, and red move in waves across the screen. Although the display looks like psychedelic art, it’s actually providing highly technical medical information – the electrical activity of a beating heart stained with voltage-sensitive dyes to test for injury or disease.

These voltage-sensitive dyes were developed and patented by UConn Health researchers, who have now embarked on commercializing their product for industry as well as academic use.

Electrical signals or voltages are fundamental in the natural function of brain and heart tissue, and disrupted electrical signaling can be a cause or consequence of injury or disease. Directly measuring electrical activity of the membranes with electrodes isn’t possible for drug screening or diagnostic imaging because of their tiny size. In order to make the electrical potential visible, researchers use fluorescent voltage sensors, also known as voltage-sensitive dyes or VSDs, that make cells, tissues, or whole organs light up and allows them to be measured with microscopes.

Not all dyes respond to voltage changes in the same way, and there is a common trade-off between their sensitivity and speed. Slower dyes can be used for drug screening with high sensitivity, but they can’t measure the characteristics of rapid action potentials in some tissues, like cardiac cells. Fast dyes can be used to image action potentials, but they require expensive, customized instrumentation, and are not sensitive enough for crystal clear results on individual cells.

Professor of cell biology and director of UConn’s Center for Cell Analysis & Modeling, Leslie Loew and his team have developed new fast dyes that are also highly sensitive, eliminating the speed/sensitivity trade-off.

Moving Ideas Beyond the Lab

Loew and research associates Corey Acker and Ping Yan have devoted much of their careers to developing and characterizing fluorescent probes of membrane potential like voltage-sensitive dyes. The team has even been providing their patented fast dyes to fellow researchers for the past 30 years, but they only recently became interested in commercializing their work.

To learn more about the science of entrepreneurship, they took advantage of several of UConn’s homegrown programs. Loew and Acker’s first step into entrepreneurship began in the fall of 2016, when they were accepted into UConn’s National Science Foundation (NSF) I-Corps site, Accelerate UConn. They credit the program with giving them a solid foundation to evaluate their technology and business strategy.

Launched in 2015, Accelerate UConn aims to successfully advance more university technologies along the commercialization continuum. Under the auspices of the Office of the Vice President for Research and the Connecticut Center for Entrepreneurship and Innovation (CCEI), Accelerate UConn provides participants with small seed grants and comprehensive entrepreneurial training.

“Dr. Loew’s experience is a prime example of how UConn can transform high-potential academic discoveries into viable products and services with the right training,” says Radenka Maric, UConn’s vice president for research. “Accelerate UConn helps our preeminent faculty move their ideas beyond the lab so they can join the ranks of other successful Connecticut entrepreneurs and industry leaders, and have an impact in our communities and on the state economy.”

Dyes detect disease through heartbeat signals
Research associate Corey Acker, left, and cell biology professor Les Loew in the lab at the Cell and Genome Sciences Building at UConn Health in Farmington. Credit: Peter Morenus/UConn Photo

Acker says the program also helped them identify an exciting new market opportunity targeting pharmaceutical companies. These companies need dyes that are both fast and sensitive for high-throughput screening of potential therapeutic targets. In high-throughput drug screening, scientists create special cell lines, and then use advanced equipment to robotically apply different drugs to rotating dishes of cells. The cells are stained with a voltage-sensitive dye that displays any change in membrane potential or voltage after drug application with changes in fluorescence. Acker estimates that pharmaceutical companies and contract research organizations (CROs) spend over $10,000 on these dyes for each week-long study.

The dyes that Loew, Acker, and Yan develop will also allow drug companies to respond to new cardiac safety screening regulations from the Food and Drug Administration called CiPA (the Comprehensive in vitro Proarrythmia Assay).

CiPA regulations aim to establish better ways to detect side effects of new drugs that could cause a cardiac arrhythmia. In a key component of CiPA, screening is completed in cardiac cells with a realistic electrical heartbeat. The Loew team’s fast-sensitive dyes could offer drug companies more effective options than are currently available. Since CiPA applies to any new therapies from weight-loss drugs to allergy medications, Loew and Acker anticipate high demand for their technology.

“We initially joined the Accelerate UConn program to learn how to build a business so we could sell our existing fast dyes to other scientists like us. Instead, we ended up discovering an entirely new customer segment with greater potential and more urgent need,” says Acker. “We feel lucky to have had the opportunity to participate in this elite program based right here at UConn.”

Gaining Outside Input

By following one of Accelerate UConn’s most important tenets to “get out of the building,” Acker conducted dozens of interviews with experts from industry who use VSDs for drug screening. They all expressed a need for dyes with improved sensitivity, faster speed, and fewer unwanted interactions or toxicity with the cells being tested.

Loew and his team were confident they could deliver.

Loew, Acker, and Yan’s new dyes improve on the current sensors used for , which involve a two-component system and energy transfer between the components. The researchers produce dyes that use a novel VSD system where energy transfer is more efficient, resulting in faster, more sensitive, and less toxic dyes.

Loew says that support from UConn’s entrepreneurship programs was pivotal in transforming their initial discovery from project to product.

Dyes detect disease through heartbeat signals
Research associate Ping Yan prepares voltage-sensitive dyes, that cause cells, tissues, or whole organs to light up as a result of electrical impulses and allow this activity to be measured. Credit: Peter Morenus/UConn Photo

“We learned so much from these programs, and we’re still reaping the benefits,” says Loew. “Targeting the right customer helped us gain additional research funding through UConn’s SPARK Technology Commercialization Fund, and encouraged us to form a startup, Potentiometric Probes, to advance our product towards the market.

“We’ve been supplying VSDs to hundreds of cardiac and neuroscience research labs for over 30 years,” he adds. “We’re hopeful that Potentiometric Probes will assure that this continues, especially now that the demand is high and new commercial sector applications are emerging.”

The team is currently developing a new website that will be a resource for researchers using these voltage imaging techniques. Once launched it will be accessible at www.potentiometricprobes.com.

Looking to the Future

Through their UConn SPARK Technology Commercialization funding, the team has been able to develop and test two new dyes, and they have conceptualized a few additional possibilities. One of their current prototypes is extremely promising, Loew says.

Loew and Acker are continuing to optimize their dyes and pursue follow-on funding to commercialize their products through the NSF’s Small Business Innovation Research (SBIR) program and BiopipelineCT, which is administered by Connecticut Innovations.

They have also continued to grow as entrepreneurs by participating in the CCEI Summer Fellowship. Potentiometric Probes was named a finalist in this program, and will compete for an additional $15,000 prize in the Wolff New Venture Competition, also administered by CCEI.

The team members hope that one day their dyes will have a major impact for both the pharmaceutical industry and fellow university researchers.

“As academics,” says Loew, “we don’t really think about money. We’re just happy to do our science and hope that it helps people one day. But considering the needs of an end user beyond other scientists will potentially lead to greater adoption of our discoveries, more funding for our projects, and ultimately more scientific breakthroughs. That’s a culture change worth considering.”

UConn Researchers: Dyes Detect Disease through Heartbeat Signals

Published by UConn Today on August 21, 2017

Jessica McBride

Vibrant tones of yellow, orange, and red move in waves across the screen. Although the display looks like psychedelic art, it’s actually providing highly technical medical information – the electrical activity of a beating heart stained with voltage-sensitive dyes to test for injury or disease.

These voltage-sensitive dyes were developed and patented by UConn Health researchers, who have now embarked on commercializing their product for industry as well as academic use.

Corey Acker, left, and Les Loew in the lab at the Cell and Genome Sciences Building at UConn Health in Farmington on Aug. 4, 2017. (Peter Morenus/UConn Photo)
Research associate Corey Acker, left, and cell biology professor Les Loew in the lab at the Cell and Genome Sciences Building at UConn Health in Farmington. (Peter Morenus/UConn Photo)

Electrical signals or voltages are fundamental in the natural function of brain and heart tissue, and disrupted electrical signaling can be a cause or consequence of injury or disease. Directly measuring electrical activity of the membranes with electrodes isn’t possible for drug screening or diagnostic imaging because of their tiny size. In order to make the electrical potential visible, researchers use fluorescent voltage sensors, also known as voltage-sensitive dyes or VSDs, that make cells, tissues, or whole organs light up and allows them to be measured with microscopes.

Not all dyes respond to voltage changes in the same way, and there is a common trade-off between their sensitivity and speed. Slower dyes can be used for drug screening with high sensitivity, but they can’t measure the characteristics of rapid action potentials in some tissues, like cardiac cells. Fast dyes can be used to image action potentials, but they require expensive, customized instrumentation, and are not sensitive enough for crystal clear results on individual cells.

Professor of cell biology and director of UConn’s Center for Cell Analysis & Modeling, Leslie Loew and his team have developed new fast dyes that are also highly sensitive, eliminating the speed/sensitivity trade-off.

Moving Ideas Beyond the Lab

Loew and research associates Corey Acker and Ping Yan have devoted much of their careers to developing and characterizing fluorescent probes of membrane potential like voltage-sensitive dyes. The team has even been providing their patented fast dyes to fellow researchers for the past 30 years, but they only recently became interested in commercializing their work.

To learn more about the science of entrepreneurship, they took advantage of several of UConn’s homegrown programs. Loew and Acker’s first step into entrepreneurship began in the fall of 2016, when they were accepted into UConn’s National Science Foundation (NSF) I-Corps site, Accelerate UConn. They credit the program with giving them a solid foundation to evaluate their technology and business strategy.

Launched in 2015, Accelerate UConn aims to successfully advance more university technologies along the commercialization continuum. Under the auspices of the Office of the Vice President for Research and the Connecticut Center for Entrepreneurship and Innovation (CCEI), Accelerate UConn provides participants with small seed grants and comprehensive entrepreneurial training.

“Dr. Loew’s experience is a prime example of how UConn can transform high-potential academic discoveries into viable products and services with the right training,” says Radenka Maric, UConn’s vice president for research. “Accelerate UConn helps our preeminent faculty move their ideas beyond the lab so they can join the ranks of other successful Connecticut entrepreneurs and industry leaders, and have an impact in our communities and on the state economy.”

Ping Yan prepares voltage-sensitive dyes in the lab at the Cell and Genome Sciences Building at UConn Health in Farmington on Aug. 4, 2017. (Peter Morenus/UConn Photo)
Research associate Ping Yan prepares voltage-sensitive dyes, that cause cells, tissues, or whole organs to light up as a result of electrical impulses and allow this activity to be measured. (Peter Morenus/UConn Photo)

Acker says the program also helped them identify an exciting new market opportunity targeting pharmaceutical companies. These companies need dyes that are both fast and sensitive for high-throughput screening of potential therapeutic targets. In high-throughput drug screening, scientists create special cell lines, and then use advanced equipment to robotically apply different drugs to rotating dishes of cells. The cells are stained with a voltage-sensitive dye that displays any change in membrane potential or voltage after drug application with changes in fluorescence. Acker estimates that pharmaceutical companies and contract research organizations (CROs) spend over $10,000 on these dyes for each week-long study.

The dyes that Loew, Acker, and Yan develop will also allow drug companies to respond to new cardiac safety screening regulations from the Food and Drug Administration called CiPA (the Comprehensive in vitro Proarrythmia Assay).

CiPA regulations aim to establish better ways to detect side effects of new drugs that could cause a cardiac arrhythmia. In a key component of CiPA, screening is completed in cardiac cells with a realistic electrical heartbeat. The Loew team’s fast-sensitive dyes could offer drug companies more effective options than are currently available. Since CiPA applies to any new therapies from weight-loss drugs to allergy medications, Loew and Acker anticipate high demand for their technology.

“We initially joined the Accelerate UConn program to learn how to build a business so we could sell our existing fast dyes to other scientists like us. Instead, we ended up discovering an entirely new customer segment with greater potential and more urgent need,” says Acker. “We feel lucky to have had the opportunity to participate in this elite program based right here at UConn.”

Gaining Outside Input

By following one of Accelerate UConn’s most important tenets to “get out of the building,” Acker conducted dozens of interviews with experts from industry who use VSDs for drug screening. They all expressed a need for dyes with improved sensitivity, faster speed, and fewer unwanted interactions or toxicity with the cells being tested.

Loew and his team were confident they could deliver.

Loew, Acker, and Yan’s new dyes improve on the current sensors used for drug screening, which involve a two-component system and energy transfer between the components. The researchers produce dyes that use a novel VSD system where energy transfer is more efficient, resulting in faster, more sensitive, and less toxic dyes.

Loew says that support from UConn’s entrepreneurship programs was pivotal in transforming their initial discovery from project to product.

“We learned so much from these programs, and we’re still reaping the benefits,” says Loew. “Targeting the right customer helped us gain additional research funding through UConn’s SPARK Technology Commercialization Fund, and encouraged us to form a startup, Potentiometric Probes, to advance our product towards the market.

“We’ve been supplying VSDs to hundreds of cardiac and neuroscience research labs for over 30 years,” he adds. “We’re hopeful that Potentiometric Probes will assure that this continues, especially now that the demand is high and new commercial sector applications are emerging.”

The team is currently developing a new website that will be a resource for researchers using these voltage imaging techniques. Once launched it will be accessible at www.potentiometrics.com.

Looking to the Future

Through their UConn SPARK Technology Commercialization funding, the team has been able to develop and test two new dyes, and they have conceptualized a few additional possibilities. One of their current prototypes is extremely promising, Loew says.

Loew and Acker are continuing to optimize their dyes and pursue follow-on funding to commercialize their products through the NSF’s Small Business Innovation Research (SBIR) program and BiopipelineCT, which is administered by Connecticut Innovations.

They have also continued to grow as entrepreneurs by participating in the CCEI Summer Fellowship. Potentiometric Probes was named a finalist in this program, and will compete for an additional $15,000 prize in the Wolff New Venture Competition, also administered by CCEI.

The team members hope that one day their dyes will have a major impact for both the pharmaceutical industry and fellow university researchers.

“As academics,” says Loew, “we don’t really think about money. We’re just happy to do our science and hope that it helps people one day. But considering the needs of an end user beyond other scientists will potentially lead to greater adoption of our discoveries, more funding for our projects, and ultimately more scientific breakthroughs. That’s a culture change worth considering.”

Loew previously conducted research through an award from the National Institutes of Health (R01 EB001963-32), which was in continuous operation for more than 30 years and provided all prior funding for the development of voltage-sensitive dyes. However, no resources from this previous award were used to fund product development or testing of the current technology.

UConn Program Gives College Students Real-World Experience

Published by the New Britain Herald on August 6, 2017

Charles Paullin

NEW BRITAIN – Two students from Central Connecticut are getting real-world experience while pursuing careers in their fields of interest.

Ethan Cope of Kensington and George Andrews of Terryville recently participated in the University of Connecticut Technology Incubation Program (TIP), a summer immersion fellowship program.

“It’s not your usual experience; there’s a lot more put onto you,” said Cope, who earned his master’s degree in microsystems analysis in June before beginning dental school at UConn.

“Because it was with a small startup, you were exposed to so many different fields” said Andrews, who is entering his junior year, majoring in biomedical engineering.

The 10-week program, consisting of 18 students sponsored by their respective academic departments and based at the Cell and Genome Sciences Building of the UConn health facility in Farmington, pairs Connecticut startup companies with UConn undergraduates, graduate and recent graduates.

“When you’re in kind of a startup environment and there’s less people in the company, you might be doing a lot more than what you initially expected,” said Cope. “You kind of open your mind and explore opportunities more openly.”

Cope worked with Oral Fluid Dynamics and tested how sterilization affected a membrane flux and salt rejection for a medical device that he wasn’t allowed to go into specifics on because the product is still in early stages of development.

This meant coordinating the effort to procure membranes from Yale University, testing them on the variable sterilization methods and then returning them to Yale for study on the findings.

“I never thought I might go into sales, but now I may,” said Andrews.

Andrews worked with Avitus Orthopedics in the sales department, coordinating its marketing effort and scheduling meetings with doctors to discuss the distribution of a unique bone harvesting device.

This involved taking a trip to Johns Hopkins University in Maryland to test the product and learning the technique of cold-calling doctors to sell the product.

Throughout the program, seminars were held.

The program culminated with a Research Day at the headquarters, where MaryJane Rafii, a leader in the biotech industry, gave a keynote speech.

Latest UConn Research Innovation Newsletter

Check out the latest in UConn Research Innovation News in the August edition of our UConn Research Newsletter.

UConn Professor: Light Show Dances To The Beat Of The Music

Published by the Hartford Courant

Rebecca Lurye

EAST HARTFORD — LED strips and twinkle lights flash constantly in the office of University of Connecticut professor Ed Large, just waiting for a beat to latch onto.

They’re controlled by a brain, an intelligent listening system designed by Large, who himself is partial to jazz and funk. He thinks his invention, Synchrony LED, which listens to music and creates real-time light shows, is too.

“If you play a rhythmically boring song. it’ll just go with the beat and it becomes boring really fast,” Large said of Synchrony’s lighting effects. “But if you listen to music that has an interesting rhythm, that’s when it does super interesting things.”

Large teaches psychological science and physics and directs UConn’s music dynamics laboratory. Synchrony, his first commercial product after 25 years of research, will be available for sale to the public this winter.

Synchrony works in the same way that people bounce their knees to a tune; the same way that mangroves full of fireflies in Southeast Asia blink their lights in unison; the same way that pacemaker cells all fire at once to make our hearts beat.

People, organisms and even cells have a natural rate of internal vibrations, or oscillations. This back-and-forth activity tends to sync up with surrounding vibrations. In humans, this is particularly effective with music, which explains how a snappy tune can set people tapping their toes, nodding their heads and harmonizing to the beat.

Synchrony does the same, just with patterns of light.

And the more Large learns about the way the brain perceives sound, the more intricate Synchrony’s effects will become, he said.

“At this stage of programming, we’re not going to compete with a light show that somebody spent two months programming,” he said. “But we will.”

Large began the project in October from the office he rents at the Connecticut Center for Advanced Technology, a nonproft manufacturing innovation hub on Pitkin Street. He launched a Kickstarter campaign in June and, by July 12, raised more than $60,000 to move into final engineering and production.

Large says he’s already seen interest from other companies interested in using his technology in their own sound-capturing products and apps, which is exactly what he was hoping for.

“One goal of this was to show off to them,” Large said.

Unlike other sound-activated light shows on the market — some of which sell for about $25 — Large’s nearly $200 version does not need to be programmed and its visuals go beyond flashing in time with every note.

Using a built-in microphone and an advanced neural network, it synchronizes its rhythms like the human brain does, intelligently translating songs into patterns that mimic the way we process music.

“We’re taking a flashing light and making it feel really good to watch,” said Dylan Reilly, chief technology officer for Large’s company, Oscilloscape.

A starter kit, including a controller box and one LED strip or two LED strings, will sell for $189.

Large says it all started with the desire to understand how the brain predicts and hears the beat of a song.

“It seems like it’s so easy and it’s so obvious. You listen to music, and there it is,” Large said. “But no one knew how it was done.”

In the early 1990s, he decided to go to graduate school to study in the then-novel field of music cognition.

Since then, his experiments have ranged far and wide, including finding a bonobo at the Jacksonville Zoo that was amenable to banging on a drum to a steady beat.

Large wanted to prove that apes could sense oscillations in music the same as humans, and the same as Snowball the dancing cockatoo, whose head-banging and high-kicking moves gained Youtube fame in the mid-2000s. The parrot was deemed the first animal capable of “beat induction,” or perceiving music and synchronizing body movements to it.

Large has moved on to another group of bonobos in Iowa, but his auditory research has also attracted the attention of the U.S. Air Force, which issued him contracts worth $2.5 million.

The technology behind Synchrony was developed with significant grants from the National Science Foundation and National Institutes of Health, Large said.

He went through several iterations of the product itself. The first concept, wearable pins, were bad business — too costly to manufacture for the price people would be willing to pay. A second idea, rave gloves, was a bit too complicated.

Then he hit on LED strips.

“It was really captivating. When you see it happen, you just can’t take your eyes off it,” Large said. “So we decided that’s got to be the thing.” Large says he plans to send the first round of products to his backers in time for them to string up their Christmas trees.

And though holiday lighting was Large’s original concept, and it remains one of his favorites, he says Synchrony works best with songs that have some funk. The more complex the music, the more interesting the visuals.

When he was developing the system, Large played Stevie Wonder’s “Superstition” on repeat.

And no, he’s used to saying: That didn’t ruin the music.

“You could play that song for me every moment of the day.”