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Dino Di Carlo: Connecting Science Fiction, Science Fact and Science Future

Lured into science by fiction stories filled with ingenious feats of genetic engineering, SLAS2016 Co-Chair and JALA Reviews Editor Dino Di Carlo, Ph.D., later pursued bioengineering because of its opportunity to touch the future with today's research.

 

"I think science fiction impacts a lot of scientists," Di Carlo says. "It's about imagining what is possible. There's a lot of power in how we could engineer life. I wanted to be part of the positive aspects of what that could mean."

He turned to automation, microfabrication and microfluidics "when I realized that we weren't at the stage in science where we could engineer biology," he comments. "These tools help us understand biology better so that we can engineer it later. That's why I got into the more specific field that I am in now. Once you understand what is needed, you can move toward a long-term goal."

In his lab at the University of California, Los Angeles (UCLA) Henry Samueli School of Engineering and Applied Science, Di Carlo has an eye on end results and is excited about the potential for using microfluidics to make new types of materials. Most recently his team created an injectable microporous annealed particle (MAP) gel that expedites wound healing. The MAP gel does this by creating an instant scaffold that allows new tissue to latch on and grow within the cavities formed between linked spheres of gel.

"Under normal circumstances, you would think about filling a wound with a mixture of material to help heal it. You would think of a hydrogel," Di Carlo explains. "Using microfluidics, we fabricated a soft, hydrogel microbead that is about the diameter of a human hair. We then created a slurry using millions of these beads and injected that into the wound. Instead of polymerizing a whole gel, we anneal those beads together and link them to the surrounding tissue." The beads become an instant scaffolding with space for tissue to grow into without degrading the gel. This allows for the faster healing Di Carlo's team has seen in animal models where it has been tested.

"Before this, we hadn't seen many successes in tissue engineering," he observes. "In the past, you had to engineer these scaffolds outside the body and implant them, but that's not great because it doesn't fit the shape of the wound. Here you inject the gel, anneal it in the wound bed and now you have all the properties you want for enhancing regeneration. I am excited about where this is going because of the many applications there are for this process including enhancing drug discovery through the use of in vitro tissues."

Another project with a lot of potential in Di Carlo's lab is the fabrication of other, more complex 3D particles that could play unique roles in biotechnology, structural mechanics and self-assembly.

"3D printing has problems making objects quickly and at a small scale," Di Carlo says. "We succeeded in creating 3D microparticles very rapidly – one every five seconds – using a new process, called optofluidic fabrication." The novel procedure couples two processes: inertial flow shaping and ultraviolet (UV) light polymerization. Pillars within fluidic platforms are used to shape photosensitive precursor fluid streams. The channels are then illuminated with patterned UV light to polymerize the photosensitive fluid to generate complex 3D-shaped polymer particles.

"We make a complex 3D shape that's an extrusion of an extrusion," Di Carlo states. "We think this will open up a whole new realm of making 3D shaped microparticles for a number of uses across a variety of fields – from biotechnology to oil recovery – that are not available now."

Start Simple, Think Robust

Watching big things transform from small beginnings has been a part of Di Carlo's life since his father, an avid gardener, first shared his love of cultivation with his son. "It's a great experience for a child to see a seed, which looks dead, and use soil, water and sunlight to watch it blossom into a complicated, living organism. It is fascinating and awe inspiring," he comments.

Around this time, Di Carlo's mother was training to be a nurse. Discussions from the study groups she organized in their home fascinated the youngster. "I would overhear the different aspects of human health and anatomy, how our bodies work, how its systems work – it all had an impact on me," he says.

Then there was that great influence from the world of science fiction. In middle school, the illustrated book by Dougal Dixon, Man After Man: An Anthropology of the Future, captivated Di Carlo's imagination. In this compendium of hypothetical species evolution that begins 200 years in the future, Scottish geologist Dixon and illustrator Philip Hood showed how man might evolve using genetic engineering. The tome then moves millions of years further into the future, after civilization collapses, genetic engineering ceases and natural evolution of the engineered life begins. While the ideas grabbed the young student, understanding where science was in reality better helped Di Carlo determine a course of study and refine the skills he needed to have impact on bioengineering for the future.

A mentor who helped him enhance his ideas as his education unfolded was Luke Lee, Ph.D., at University of California, Berkeley (UC Berkeley), where Di Carlo earned his undergraduate degree. "He talked about how we could build more using miniaturization and automation to address problems and understand biology better," Di Carlo explains.

"Luke was helpful in allowing us to develop the logic behind the course of action we were taking, to come up with reasons on our own," he continues. "It was about asking questions and understanding why we were doing what we were doing. That pervades everything I do now. I have to think through not just the local details of why we are doing something this certain way, but also the broader framework of where it all fits in with everything else that we've done and why we are doing this at all. Thinking through all the ways you can have practical impact allows you to journey on the right path at an early stage. It saves you from dead ends."

Another technique Di Carlo learned is to keep his work simple. "As engineers, we have a tendency to overcomplicate or over engineer things. What has been most successful are the simple things we've done," he says.

He offers as an example part of a paper he wrote that has been cited more than 500 times in the past seven years. "The paper basically discusses flowing particles through a simple channel. There's obviously more complexity than that to it, but the system itself is extremely simple," Di Carlo notes. "I have come to the realization that you have to start with simple things that are robust – such as the MAP gel. This robustness will help you achieve success when you integrate them into more complex systems that are going to achieve some function."

Defending Research and Expanding Influence

Another complicated aspect of research science is defending your work, says Di Carlo. As a professor at UCLA, he uses his own experiences and some of Lee's advice to show students how to support their ideas.

For example, when he began developing inertial microfluidic systems, the literature at the time said it wasn't possible. "In fact, I remember in my thesis defense that someone asked the question 'what happens if you increase the amount of inertia in your system?' I answered that you couldn't do it because that was what was being taught in the classes at the time. But I knew that I had to be on the right track because I saw some crazy experimental things at the time that could only be explained by the importance of inertia. I had to go against the common wisdom of the time," Di Carlo explains.

"My paper on the topic was rejected for publication the first time because it didn't make sense to the editor," he continues. Even a grant application that showed a lot of data supporting the idea was returned stating that inertia wasn't important in microfluidic systems. "It was difficult to break out. I had to talk to a lot of people and maintain my persistence. I guess I thought that they were wrong," he says with a laugh, adding that he didn't do very well in his fluidic mechanics class.

"It was one of my lowest grades, and that was a good thing! I didn't know enough about the field to know that what I was doing wasn't accepted. You need conviction that arises from seeing it personally," he continues. The end result was that his research was accepted, companies went on to license the intellectual property and Di Carlo himself helped launch a few companies that used these systems in commercial applications.

He uses this experience to advise his students today. "We are always rejected. It's a daily occurrence," Di Carlo comments. "I bring them around by asking 'Are you proud of what you've done? Do you have an argument for why this is important?' If that argument makes sense to them, then they should keep pushing for it. It's not an uncommon thing. In the lab, we push for our ideas, and we persevere."

The reward? Recognition, awards and funding. Di Carlo, who has received the Defense Advanced Research Projects Agency (DARPA) Young Faculty Award, the National Science Foundation (NSF) Career Award, the National Institutes of Health (NIH) Director's New Innovator Award, the Office of Naval Research (ONR) Young Investigator Award, and most recently the Pioneers in Miniaturization Prize, has had opportunities to expand his influence in the field.

"People will more likely want to work with you after you receive recognition," Di Carlo comments. "Your network of potential collaboration goes up with the increase in awards for your work. There are opportunities that wouldn't ordinarily arise because people who want to work with you are people who have a higher level of achievement, as well. Foundations will approach us without going through the grant writing process because they know what we have done."

Connecting Through SLAS

Understanding how important funding is, particularly to students, Di Carlo is a strong supporter of the new SLAS Graduate Education Fellowship Grant Program, and has applied for the 2016 award on behalf of graduate students in his lab. The program offers a $50,000 annual award for graduate students enrolled in educational organizations and academic institutions that offer graduate degree programs related to quantitative biosciences and/or life sciences research.

Di Carlo works to make students aware of SLAS on many levels. He cites the wealth of educational, networking and collaborative opportunities available through the Society and encourages their involvement. He speaks with experience. Di Carlo has contributed hours of volunteer leadership, rising through the ranks as an associate track chair and track chair for annual SLAS International Conferences and Exhibitions, and also through publishing articles and serving as a reviews editor for the Journal of Laboratory Automation (JALA), one of two SLAS MEDLINE-indexed scientific journals. As co-chair of SLAS2016, the Fifth SLAS International Conference and Exhibition, to be held January 23-27 at the San Diego Convention Center in San Diego, CA, USA, and as a member of the SLAS Scientific Program Advisory Committee, Di Carlo joins other committee members in ensuring that the educational program presented at the SLAS meeting advances the Society's mission and goals.

"What I want to accomplish through this year's event is to be better than the sum of all our parts," he comments. "We strive for a good mix of industry, academic and government folks, as well as that fresh perspective provided by the student population. SLAS offers a different viewpoint than an academic conference. It shows the end products of research."

He is excited about the SLAS2016 program. "This year we will offer a session in the Automation and High-Throughput Technologies Track, 'Extreme Automation,' that relates to automation on Mars, Antarctica and all the different extremes that you can imagine," says Di Carlo. "I think it will be well attended not just because of the fun factor, but also in that it will give a sense of what is possible. It's just one snapshot of what is shaping up to be a great meeting."

Tasting and Touring the World

With so little time left in his schedule for relaxation, Di Carlo multitasks to make every moment (and meal) count. He combines all his favorite pastimes into one adventure, which usually also incorporates work travel. He plans his trip to include taking in the sites and local delicacies of the required destinations.

"One part of my job that is exciting and fun is learning about new cultures when I travel," Di Carlo says. "While abroad you not only go into a new culture, you also meet business associates from that cultural background."

The entire Di Carlo family visited Tokyo earlier this year. "I am always traveling to Japan for work, and usually have an opportunity to enjoy some down time while there. I love the Japanese culture. There is an incredible attention to natural details mixed with an industrial tone," Di Carlo says.

When not on the road the father of two – a 10-year-old son and a newborn daughter – also spends time in family pursuits. He even enjoys some father-and-son bonding while playing the video game Civilization when they are not traveling the world and seeing the real thing.

"My son has been very lucky. In the past year he has had the opportunity to visit not only Tokyo, but also Berlin and Hawaii, which is my second favorite destination. When he was little it was challenging to travel. Now that he's 10, it's so fun. When we were in Italy, he got to see the Leaning Tower of Pisa and some other landmarks – places he had only heard about before. It's great to see these things through young eyes. And we ate gelato twice a day; who wouldn't enjoy taking the time for that?"

November 2, 2015