July 5, 2016
Meet the first SLAS Graduate Education Fellowship Grant recipient: A keen collaborator who wants practical, yet complicated, science – such as microfluidics – to be more user-friendly. An engaging educator who helps high school students find the joy of discovery. A tireless innovator whose pursuits in high-throughput screening will benefit from the generous funding of the SLAS grant.
Selected from 24 excellent proposals and candidates, SLAS named Erik M. Werner, a graduate student and Ph.D. candidate from the University of California, Irvine (UC Irvine), as the inaugural recipient of the SLAS Graduate Education Fellowship Grant. Werner will use the $100,000 grant, to be awarded over two years, to maximize university resources to pursue the realization of his high-throughput screening (HTS) concept.
Werner’s project is to develop an indexed droplet array with a microscale valve system to enable addressable release of individual droplets. The device will consist of an array of traps connected serially, each with a bypass channel. At the entrance to each trap, an imbalance of hydrodynamic forces will either cause a droplet to enter the trap if it is empty or to bypass the trap and continue downstream if it is full. Trapped droplets can be ejected by opening the gate valve for a specific trap and reversing the direction of flow. This design can be scaled to allow large numbers of droplets to be stored and individually addressed without the need for labeling.
Using this device, reaction volumes in a typical screening assay can be shrunk more than 100 fold, greatly decreasing the cost of each library screen. Werner hopes to reach a density high enough to allow entire libraries to be screened on a single chip, greatly increasing throughput by eliminating the need for fluid handling robots to transfer samples. Finally, with addressable control of each reaction chamber, validation screening reactions can be performed rapidly and specifically by cherry-picking potential drug candidates.
Werner is excited about the SLAS grant’s support of this research. "As a student starting my career, getting a fellowship like this is very encouraging,” he says. “It is also a great opportunity for me to connect with other people and ideas in my field."
In addition, the grant will give the busy graduate student more time to focus on his research. “Right now I am working as a teaching assistant to fund my graduate education which cuts back on the amount of time that I can spend in the lab. The SLAS grant will help me have an opportunity to use the specialized microfabrication equipment that we have at UC Irvine, much of which has an hourly fee attached to its use. I will be able to get better results and make better, more complicated devices,” says Werner, who collaborated on the grant application with his faculty mentor, Elliot Hui, Ph.D.
“Erik is very qualified as a researcher,” states Hui, an associate professor of biomedical engineering at UC Irvine’s Henry Samueli School of Engineering. “As an undergrad at Vanderbilt University (Nashville, TN), he worked in a great environment and received diverse training. He arrived here quite capable – a lot more so than your average beginning graduate student.”
Werner feels his research is a good fit with SLAS’ mission to further life sciences discovery and technology education. Hui agrees, adding that “the SLAS grant supports the student. It specifically gives an opportunity to research questions in which the student may have a personal interest as opposed to being driven entirely by the resources for which the lab is directly funded. The SLAS grant also gives students more access to the life sciences discovery and technology industry and to people who are conducting drug screening and automation of biological assays.”
The first step Werner will take in his research is to demonstrate a 10 x 10 array of addressable reaction vessels that will be fabricated using a precision micromachining process developed by the UC Irvine lab. The finished device will be tested using droplets of food coloring in light mineral oil to ensure the fluidic portions of Werner's design function, and then demonstrated by screening 100 samples from an NIH compound library against a kinase reaction using a commercially available kinase assay (ADP-Glo, Promega).
Once the 10x10 array has been demonstrated, the team will begin scaling this design toward larger arrays. The greatest challenge in scaling this device will be managing the control of so many valves. While high-density integrated microfluidic valves are well established, scaling to thousands or more by conventional means is difficult because individually actuated valves typically each require a separate pneumatic control line connected to an off-chip solenoid valve. Werner's solution is to drastically reduce the number of connections from the chip to external computers by employing on-chip embedded pneumatic logic circuits.
“What I like about microfluidic pneumatic logic circuits is the power held by these simple mechanical computers. If you can perform some basic logic using these tiny mechanisms, you can greatly reduce the need for external computers to operate the chip,” says Werner.
Since his undergraduate days at Vanderbilt, Werner’s work has been an evolution of making microfluidic technology more user friendly. While there, he designed software to automate his microfluidic experiments and drive Vanderbilt’s organ-on-a-chip research.
“Ultimately when engineers like me hand over finished prototypes to biologists and doctors, the device needs to do exactly what they want with the push of a button,” Werner says. “Because software drives the mechanical and electronic parts required by the microfluidic chip, if anything goes wrong the end users blame the software engineer! It's an enormously complicated thing to deliver. It has to perform perfectly each and every time."
He isn’t daunted by this responsibility. "If you make a complicated system with automated processes that can do cool things that are really useful, it has to be user-friendly," says Werner. “It’s the job of the engineer to hide all that complicated stuff. Microfluidic logic is a great way to achieve this."
Werner anticipates employing tools available from the Integrated Nanosystems Research Facility at UC Irvine for micro- and nanoscale fabrication, including a new deep reactive-ion etching tool that can create high aspect ratio sub-micron features in glass wafers. As the device is scaled, success will be measured by the size of droplets used for screening, and the time saved to screen an entire compound library.
Hui mentions that large drug companies run only 10 to 20 screens per year of their entire library against a target. “They are limited in what they can run. They have to be selective and think through carefully where they are going to invest that resource,” he says. “If we could find technology to enable these companies to run 100 times as much, it would free them to take more risks, to run screens with more controls and maybe with different concentrations of the potential drug compounds. I think if it works out, this project could have an impact on drug discovery.”
Hui doesn’t anticipate overnight success, noting that the drug screening robots in industry today have been developed over decades. “It would be asking a lot of a graduate student to dramatically improve the current technology and get it to the point of emerging into a commercially viable product over the course of a couple of years,” he explains. “What we are hoping to demonstrate is the real potential here to dramatically improve the current technology. My hope is to get to a point where we feel like it’s worth making a larger, commercially viable product. If anyone can make this project succeed, it’s going to be Erik.”
Werner’s natural inclination toward computers and electronic gadgets led him to focus on engineering and specifically biomedical technology during his undergraduate years at Vanderbilt. A turning point for him was acceptance into a paid summer research position with Vanderbilt’s Searle Systems Biology and Bioengineering Undergraduate Research (SyBBURE) program. He laughs as he remembers that he didn’t have a firm idea about what research might entail.
“At the beginning of the summer, I attended a symposium in which all the students who had been in the program gave presentations of their work,” Werner explains. “I didn’t understand half the things the people were presenting – even those presentations of my classmates!”
Fortunately, SyBURRE offered a personal, challenging and honest exposure to academic research. “The graduate students in SyBURRE were supportive and encouraging,” says Werner, who from the beginning of the program managed all his own research. “They were open, gave me options on things I could do and showed me how I might accomplish it. It allowed me to inspire myself and find what I wanted to do rather than have someone tell me how to do just one thing.”
Werner chose to work with computer-aided design and modeling (CAD/CAM), as well as photolithography to fabricate novel, lab-on-a-chip devices. Werner, whose grandfather was a lithographer in the printing business, was excited by his prospects and looked forward to heading home to the Chicago suburbs to share his news. His spirits dampened, however, after his first several attempts at photolithography failed.
“All of the SyBBURE students get extensive training, so after that I thought I understood the process. I would execute the protocol, but time and time again after a full day of work I came out with nothing. I didn’t even know what my mistakes were,” he says. “I eventually grew to understand and scrutinize every step of the process. I was able to adjust a few parameters and I came out with this great chip because I had a thorough understanding of everything that went into the finished product. That experience helped me understand the level of detail I needed to achieve in the research process, and it will help me in the future.”
With his own hurdle cleared, Werner began to notice one that hindered others: using the microfluidic chips. "When I would collaborate with others or train new students to use this technology, I realized that many researchers in other fields have neither the time nor the desire to learn the technical skills required to benefit from these devices,” he comments. He thought that this slowed the adoption of the useful technology and decided to find a way to improve the functionality of microfluidic tools.
He had an opportunity to do this when he joined an international collaboration between Vanderbilt and the Karolinska Institutet in Stockholm, Sweden, to design a microbioreactor. During this work he developed his own software to automate his experiments, after teaching himself to use the general purpose programming language C++. The results were so successful that other researchers asked to use it, and Vanderbilt hired Werner as a software engineer and adopted the software for multiple projects. It is currently in use at several universities across the country and internationally for their organ-on-a-chip projects for drug development. Werner continued to improve the design by working with multidisciplinary teams to create a technology simple enough to be applied to basic science.
This process of carefully exploring options and experimenting to get the best results built a platform of experience for Werner in every stage of the device development pipeline. It will be part of the work he will do as he develops the new droplet microfluidic tool at UC Irvine.
As exciting and promising as all of this research is, Werner knows about the power of stepping away from work. He learned early on during his days developing software at Vanderbilt that taking a break can increase productivity.
An avid distance runner, Werner likes to unwind with a long, refreshing run and participates in any kind from marathons, half marathons and simple road races, to zipping down bike trails in European cities and trotting through the forests of Tennessee and California.
“In Nashville, because it’s a small city, a five-minute drive in any direction will take you to a park. There are a lot of trails, so I did trail running every day during my junior and senior years in college. When I studied abroad at the Karolinska Institutet, I ran Sweden’s bike trails that connect all the towns. I would come back and realize that I had just run 20 miles. It’s so beautiful, and running is so relaxing. It helps you avoid mental burnout.”
What’s new in his exercise regimen is the UC Irvine rowing crew, where early morning workouts in Southern California’s pristine Newport Back Bay are like a religious experience. “It’s one of the best places in the country for rowing,” Werner explains. “We head out on the water at 5 a.m. Rowing is a strenuous activity, but it’s totally silent, the water is perfectly flat and the sun is rising. Its effect is like meditation!”
Another outlet for his creative energy is tutoring high school students – something he did as an undergraduate and now continues at UC Irvine as a volunteer for Rocket Science Tutors at the Samueli Academy. Werner recently taught a month-long course in how to build cool stuff using microcontrollers, Arduinos and electronics. “At the school where I volunteer now, students had to develop an original invention using a 3D printer and fabrication supplies from their classroom,” he says. “The hardest thing for these kids was coming up with a new idea; they didn’t really know what is needed, what’s possible or what’s already been done. This process gives them a lot of exposure to new ideas,” Werner explains.
He likes to ask students what they do in their free time, what their hobbies are and what interests them. When he finds students who like cars, he pitches ideas to them such as hybrid vehicles, as well as renewable and regenerative energy and tries to simplify those concepts for the students to understand. He then works with the students to develop solutions. The students’ final ideas were developed and entered in the Orange County Maker Challenge – “a sort of advanced science fair,” Werner explains. One of the teams beat out dozens of other schools, including college teams, to win a first place award.
He finds this type of work rewarding as it offers an opportunity to give back and also to stay in touch with the basics of life sciences discovery and technology. “I tell the students to try as many new things as they can. If you don’t know what’s out there, how will you know what’s really important to you?”
The top five finalists for the SLAS fellowship grant also are eligible to be awarded a scholarship to attend SLAS2017 under the SLAS Tony B. Academic Travel Award. Tony B. Award winners receive complimentary airfare, lodging and registration to attend the flagship annual SLAS international conference and exhibition. In addition to Werner, finalists for this grant include Mike Garcia, University of California, Santa Barbara; Kent Gordon, University of North Carolina, Chapel Hill; Marie Malone, The Scripps Research Institute; and Kevin Yamauchi, University of California, Berkeley.
The application process for the 2017 grant award will open in fall 2016. Visit SLAS Graduate Education Fellowship Grant Program for more information.
SLAS Education Fund Supports Next-Gen Scientists
From JALA: On the Quantification of Mixing in Microfluidics
More from JALA: Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture
From JBS: Droplet-Based Microfluidics Enabling Impact on Drug Discovery