Stars, diamonds, circles.

Rather than your average bowl of Lucky Charms, these are three-dimensional cell cultures that can be generated by a new digital microfluidics platform from researchers at U of T’s Institute for Biomaterials and Biomedical Engineering (IBBME).

Published this week in Nature Communications, the tool can be used to study cells in cost-efficient, three-dimensional microgels. This may hold the key to personalized medicine applications in the future.

“We already know that the microenvironment can greatly influence cell fate,” said Irwin A. Eydelnant (IBBME PhD 1T3), recent doctoral graduate from IBBME and first author of the publication. “The important part of this study is that we’ve developed a tool that will allow us to investigate the sensitivity of cells to their 3D environment.”

“Everyone wants to do three-dimensional (3D) cell culture,” explained co-author Aaron Wheeler (IBBME), Professor and Canada Research Chair in Bioanalytical Chemistry at IBBME, the Department of Chemistry, and the Donnelly Centre for Cellular and Biomolecular Research (DCCBR) at the University of Toronto.

“Cells grown in this manner share much more in common with living systems than the standard two-dimensional (2D) cell culture format.” But more naturalistic, 3D cell cultures are a challenge to grow.

“The reagents are expensive, the materials are inconvenient for automation, and 3D matrices break down upon repeated handling,” said Wheeler, who was named an Inventor of the Year by the University of Toronto in 2012.

Eydelnant was able to address these difficulties by adapting a digital microfluidics platform first created in the Wheeler lab. Cells, caught up in a hydrogel material, are gently flowed across a small field that, on a screen, looks much like a tiny chessboard.

The cells are strategically manipulated by a small electric field across a cutout shape on the top plate of the system, made from indium in oxide, and they become fixed.

The tool allows for a greater level of flexibility in both the many number and types of cells, and the shape and size of the microenvironments. Some are whimsical, like the stars; diamonds and circles like those in Lucky Charms, or those designed to mimic living 3D niches. These diverse offerings give researchers a glimpse into how these many factors can affect cell fate decisions.

What’s more, according to Eydelnant, the platform permits researchers to run, “32 experiments at the same time, automatically, and all on something the size of a credit card.”

“[This new] system allows for hands-free assembly of sub-microlitre, three-dimensional microgels,” said Wheeler. “Each gel is individually addressable, fluid exchange is gentler than macro-scale alternatives, and reagent use is reduced more than 100-fold.”

“We believe that this new tool will make 3D cell culture a more attractive and accessible format for cell biology research.”

Although the researchers can foresee numerous possible applications for this platform, the team is “particularly excited” about its potential for personalized medicine.

“We may be able to collect small tissue samples from patients, distribute them into 3D gels on digital microfluidic devices, and screen for conditions to identify individually tailored therapies. This is in the ‘dream’ stages for now,” Wheeler argued, “but we think the methods described here will be useful for these types of applications in the future.”

They howl, they chew, and sometimes they leave you unpleasant surprises on the carpet. When dogs are left alone at home, it’s easy for them to get up to no good. But what if you could visit and play with them from a thousand miles away through your smartphone?

Enter Pawly, a durable digital toy that lets owners interact remotely with their pets via smartphone. Pawly was first developed by U of T Engineering student Gordon Dri (CivE 1T5), alumnus and Master of Engineering student Yunan Zhao (CompE 1T2, MEng 1T4), and their team of engineers, designers and strategists during an intense 54-hour contest called Startup Weekend: Maker Edition in Toronto.

Startup Weekend events are held across the world in cities ranging from Cape Town and Islamabad to Melbourne and beyond. Finalists from each weekend move on to a championship round called the Global Startup Battle − dominated most recently by teams with members from U of T.

Pawly had only placed second at its Startup Weekend behind Griflens, a team developing a set of interactive story beads for children. Griflens, whose roster included Helen Kula, librarian at University of Toronto Mississauga’s Institute of Management and Innovation, went on to take third place overall in the Global Startup Battle.

Pawly took the top prize.

“The Pawly team is perhaps the best example of what can be accomplished at a Startup Weekend when you combine great skill, motivation and impressive teamwork,” said Chris Eben, founding organizer of Startup Weekend Toronto.

“Their success in this significant annual competition demonstrates that Toronto’s startup community is an international powerhouse. The rest of the world should take note – Toronto is where you want to build your startup!”

Inventor Dri spoke with U of T News about the Pawly team’s experience in the global competition.

Tell us about why and how you got involved with the Global Startup Battle.

My journey began at the beginning of third year when I was provided with the choice to work for a year through the Professional Experience Year (PEY) program at U of T. I realized not one job seemed like the “perfect fit” and it was then I decided I would create my own job and work for myself. Coupled with the inspiration that past entrepreneurs (e.g., Andrew Mason, Reid Hoffman, Steve Jobs) provided me, I began my journey as an entrepreneur.

I realized that all great entrepreneurs in the past surrounded themselves with like-minded individuals and fed off their innovation and creativity. Therefore, I wanted to join a community of budding innovators and thus registered for Startup Weekend. I collaborated with a 10-person team for 54 hours to launch our startup, Pawly. We placed second in the competition for our concept and execution and qualified for the Global Startup Battle. We competed in this national competition against other teams across the globe and came out on top.

What was your experience like at Startup Weekend?

Startup Weekend was a no sleep, high stress, yet exciting marathon. I had the opportunity to work with inspirational, creative, and budding entrepreneurs whom I had never met before.

The event was held at OCADU and the theme was ‘Maker Edition,’ stressing that startups launch a hardware-related product. We were given the support of all the resources at the university including woodworking labs, laser cutting as well as the donation of 10 3-D printers by General Electric.
The weekend focused not only on building a product but also market validation, customer development and practicing LEAN Startup Methodologies. We managed to receive over 100 responses to our Google Survey and received our first sources of revenue in just 54 hours.

What’s the most important thing you learned from being part of Startup Weekend?

The most important thing that I learned from the weekend is the power that entrepreneurs have to drive the world forward. All the great innovations in the past have derived from creative entrepreneurs with a common mission to change the world. Our future is in our hands as innovators and entrepreneurs.

What did winning the Global Startup Battle mean for you and your team?

Once my team and I won the Global Startup Battle we were both surprised and excited. The success in this competition validated our concept and we immediately knew Pawly was the start of something big.
As a team we have committed ourselves to an official startup with the goal of developing Pawly and bringing it to market. The success of this competition provided us visibility which is crucial in the beginning stages of any startup. We have the luxury of approaching media, investors and potential partners with the news that our concept won the largest startup competition in the world powered by Google for Entrepreneurs.

We are currently preparing for the LAUNCH Conference in San Francisco, California held from February 24th to 26th where we will demo our prototype and hopefully attract the interests of investors and partners.

How have you found the ‘entrepreneurship’ environment at U of T?

The University of Toronto has an exceptional community for entrepreneurship from incubators like The Hatchery and Creative Destruction Labs to conferences such as Young Entrepreneurs Challenge. Although we have not engaged in the resources to date we hope to get involved and take advantage of them in the future.

What’s next for you as an entrepreneur?

I will continue working with my team to revolutionize the next generation of pet technology while completing my engineering degree. I hope to join the team full time through the Professional Experience Year program and again post-graduation. I enjoy learning about new startups and hearing about both successful and unsuccessful experiences of other entrepreneurs.

A study co-published in Nature Medicine this week by University of Toronto researcher Penney Gilbert (IBBME) has determined a stem cell based method for restoring strength to damaged skeletal muscles of the elderly.

Skeletal muscles are some of the most important in the body, supporting functions such as sitting, standing, blinking and swallowing. In aging individuals, the function of these muscles significantly decreases.

“You lose fifteen per cent of muscle mass every single year after the age of 75, a trend that is irreversible,” said Gilbert, Assistant Professor at the Institute of Biomaterials & Biomedical Engineering and the Donnelly Centre for Cellular & Biomolecular Research (CCBR). The study originates from Gilbert’s postdoctoral research at Stanford University’s Baxter Laboratory for Stem Cell Biology.

Through tracing the signaling pathways of the cells, the researchers – including lead author, Professor Helen Blau, and postdoctoral researcher Ben Cosgrove – determined that during aging, a subpopulation of stem cells begin to express a modification of a protein that inhibits their ability to grow and make new stem cells.

“But if we instead treated those cells outside the body with a drug that prevented that protein modification from occurring, in combination with culturing the cells on something soft that is reminiscent of soft skeletal tissue, like a hydrogel biomaterial, the combination allowed the aged cells to grow and make more copies of themselves,” said Glibert.

The rejuvenated cell cultures were then transplanted into injured and aged tissues, with remarkable results: the transplanted cells returned strength to the damaged and aged tissues to levels matching a young, healthy state.

“An important thing to stress here is that this is not a panacea for aging in general,” warned Dr. Blau. The stem cell treatment would only be used to repair localized defects in relatively small muscles found in the hip area, the throat, or the muscles in the eye.

One of the significant challenges to elderly individuals who receive hip transplants, for instance, is the repairing of skeletal muscles around the joint that have been injured during surgery. The study points to the potential for future post-surgery therapies that could leave elderly hip replacement patients spry in a fraction of the time.

“Even a small, localized transplantation could have a huge impact on quality of life,” said Blau. “One big advantage is that because the cells would come from the person’s own muscles there would be no problem with an immune response.”

“It’s a really new, exciting field,” said Gilbert, who noted that the muscle stem cell field, which only began to isolate muscle stem cells for study within the last five years, is especially “wide open” in Toronto where “there are really impassioned clinician researchers who are interested in restoring strength in aging and disease.”

Fourth-year pharmacy student Michael Zhang was so enriched by his experience in developing his start-up company CrowdQuarter at the U of T Engineering’s Entrepreneurship Hatchery that he contributed his $10,000 prize from the national Walmart Green Student Challenge right back to the Hatchery.

Last summer, Zhang partnered with Satyam Merja (EngSci 1T5) at the Hatchery to develop a social media customer rewards app for retailers called DealsHype. They were recognized for their great idea with an Orozco Prize, named after the Hatchery’s executive director, Joseph Orozco, and sponsored by ECE Professors Jonathan Rose and Vaughn Betz. DealsHype allows users to earn rewards for sharing photos of their favourite brands or venues via social media, which, in turn, provides retailers with valuable analytics and enables them to offer more targeted loyalty programs.

“Our experience at the Hatchery was absolutely amazing and we were able to gain great advice from our advisors, Professor Betz and Rotman student Elton Law,” says Zhang. “Their insights in software development and business strategy have truly helped us develop a successful technology start-up.”

Since then, Zhang and a team of marketers and engineers formed CrowdQuarter at U of T to further develop analytics tools and mobile apps. They took one of their ideas to the Walmart Green Student Challenge: an app that helps people make healthy and sustainable shopping choices by leveraging personalized analytics and their network of friends. It was awarded the $10,000 first-place prize by a panel of executives from Walmart Canada, Google Canada, Ford, S.C. Johnson and Son, Bullfrog Power and Canadian National Railway. CrowdQuarter promptly contributed the prize money to the Hatchery.

“I hope that this donation will help to support and expand the amazing work that is being done at the Hatchery,” says Zhang. “From our personal experience in the program, we knew exactly the kinds of challenges that would be faced by future entrepreneurs. We felt that the donation would greatly help to fund summer fellowships and awards for future start-ups, which are crucial in helping others scale their businesses at the Hatchery.”

A new study from the Institute of Biomaterials & Biomedical Engineering (IBBME) is challenging some of science’s fundamental understandings of cellular behaviour.

The foundational study, published in this month’s Proceedings of the National Academy of Sciences (PNAS), suggests that unlike what was previously understood, cells do not communicate movements by being joined, but instead move along pathways determined by physical space and ‘crowd’ flow.

“Since the 30s we’ve known that cells will follow features on their substrate. If you scratch a slide, cells with move along the scratch,” said Camila Londono (IBBME), first author of the study and PhD candidate.

Playing with this theory, the researchers had a special plate created that had striations or grooves on the surface of one side of the well, and remained flat on the other side. Cells were treated so that they would not be able to connect with one another, and then were formed into a sheet on the surface of the dual-topography wells.

In keeping with previous knowledge, the researchers found that cells moved along the grooves in groups. But what surprised the team were the cells on the flat surface in the same well.

“We found that a small fringe of cells moved as if they were on a line, as well,” states Londono.

[youtube https://www.youtube.com/watch?v=QWVW11Gq1ig]

“The best way to describe it is to say that the cells move like a school of fish,” explains Assistant Professor Alison McGuigan (ChemE/IBBME), corresponding author of the study.

The results of the study, Londono argues, point to something about cellular communication that was previously unknown.

“Researchers have always thought that signals are transferred to cells through connections to one another. But even when we prevented those connections from forming we didn’t see any difference in the signal propagation,” she said, citing that the results suggest that the cells move where they have space to move – a purely physical communication.

While the results of the study are “really new and unexpected,” according to Londono, “it’s only recently that we’ve been able to do data collection on group cell migration” due to the sheer amount of data to be collected, and the need for specific tools. In fact, the researchers collaborated with Professor Stewart Aitchison (ECE) to make the special well plate for the group.

U of T Engineering alumni behind a wearable device that eliminates the need for passwords, PIN codes and more, are making news around the world again as they prepare to launch a new Bitcoin wallet feature for their Nymi wristband.

Bionym was recently featured in a video as part of U of T’s Spotlight on Startups series, in which CEO Karl Martin (EngSci 0T1, ECE MASc 0T3, PhD 1T0) explained how U of T’s entrepreneurship climate and supports helped set he and co-founder Foteini Agrafioti (ECE MASc 2T7, PhD 1T1) on their path to a thriving business.

Watch Bionym’s Spotlight on Startup video (1:47)

The Spotlight on Startups series profiles the many entrepreneurial efforts growing from the hundreds of companies spun out from research and connections sparking every day at the University of Toronto:

U of T hosts more than 50 enterprise-fostering courses, programs, labs, clubs, contests and speaker series across its faculties, departments and campuses — and then there are all the innovations developing in informal settings. U of T ranks No. 1 in North America for number of startups launched. And its roster of spin-off companies driving innovation in Toronto and around the world continues to grow.

U of T Engineering’s own Entrepreneurship Hatchery offers undergraduate students access to mentoring, space and equipment to help them turn their ideas into viable businesses. They can engage directly with experienced entrepreneurs, like Bionym’s Karl Martin, to learn the ins and outs of start-up life.

For Bionym, the newest feature of the Nymi wristband has caught the attention of The Wall Street Journal, Slate, Mashable and more, as the company prepares to launch a feature capitalizing on an emerging digital currency, called Bitcoin.

Martin gave U of T an update on the Bitcoin connection and what’s next for the growing company.

The Nymi has been in the media lately for a new feature relating to Bitcoin. What is it?

Bitcoin is an emerging digital currency that is not controlled by any country or central bank. It’s still in the early days for this technology, and it is not well understood or accessible to the general public. Bionym announced that the Nymi will launch with a Bitcoin wallet that will make it easier for people to make payments and securely manage the Bitcoins they own. Essentially, the Nymi will help make Bitcoins accessible and not require a deep understanding of the underlying Bitcoin technology to make it useful. As more merchants start accepting Bitcoin payments, the Nymi will enable users to pay in a seamless and secure manner.

Why does the Bitcoin connection seem to be exciting the public so much? The Nymi was cool from the start, and has lots of potential uses, but people seem to be talking about it a lot more since the Bitcoin wallet came into play…

Bitcoin has been gaining a lot of attention lately as it is on the cusp of transitioning from an early adopter “curiosity,” to being a mainstream disruptor. This is a natural place for the Nymi to be, and I think people are very excited to see that the Nymi will be at the forefront of digital commerce.

What are you most excited about in the near future for Bionym?

We’re about to start releasing our developer units [ed: testing units for potential users, independent software developers and entrepreneurs]. We have such an eager community of developers and early customers, so we’re extremely excited to start putting things in their hands.