Groundbreaking chemistry research at record speeds

Penn’s High-Throughput Experimentation Laboratory reduces the time and resources required for chemistry experiments while allowing students and faculty to push the boundaries of their research.

a man working on a computer inside a chemistry lab with equipment in the background — From research on energy-efficient reactions to making new pharmaceutical chemicals, the High-Throughput Experimentation Laboratory is an integral part of the science done by students, researchers, and faculty across the Department of Chemistry.

Say that someone wants to make a better chocolate chip cookie. They decide to try a different type of flour but, after an entire afternoon of baking, discover that the cookies came out worse than before. The baker soon realizes that flour is just one of many factors that can influence the quality of their cookies. What about a different brand of milk, sugar, or butter, or where the cookies are placed in the oven? Suddenly, there’s a seemingly endless number of factors that comprise this recipe but not enough time, or appetite, to test them all.

Chemistry researchers face a similar sort of challenge in their work. When looking for a new “recipe” for an existing chemical reaction, they are faced with a large number of factors that can be adjusted. Developing new approaches to reactions in a systematic way can quickly become a laborious and time-consuming process.

Thanks to Penn’s High-Throughput Experimentation (HTE) Laboratory, researchers in the Department of Chemistry can test new approaches to chemical reactions in a fundamentally different way. Instead of running one reaction at a time, waiting for results, and then running a second reaction, the HTE allows researchers to run hundreds of reactions at the same time.

“It’s hands down the best academic facility anywhere in the world for doing this type of work and probably better than most places in industry,” says Gary Molander. “There’s no other academic setting that has a facility like this, and it’s a model for every other facility that’s been established ever since.”

The HTE was initially funded by a $1 million NSF grant and was modeled after the facilities used at the pharmaceutical giant Merck. The HTE was set up in 2009 as an initiative led by Molander, Marisa Kozlowski, and Patrick Walsh in collaboration with Merck chemist Spencer Dreher.

Since it was established 10 years ago, the HTE has tripled its capabilities and is a crucial resource that students, postdocs, faculty, and even external industries use on a regular basis. Because the HTE is a low-barrier facility that doesn’t rely on automated systems or complicated robotics, students can use the facility whenever they need it after taking a short training session.

One example of research made possible by the HTE is a recent study from the Molander group that describes a way to break extremely strong chemical bonds using energy from visible light. This new method, published in Chem earlier this year, requires far less energy than standard approaches that rely on extreme temperatures or rare metals as catalysts and can be used to create the precursors for a number of chemicals that are used across medicine and agriculture.

Graduate student Shuai Zheng says that the HTE was instrumental in figuring out how to control this chemical reaction. “This reaction can go through multiple pathways, so we looked at the mechanism and tried almost all of the possibilities to get to the product we wanted. With the HTE, we were able to find the optimal conditions in three months,” says Zheng. Without the HTE, Zheng says this work would have taken more than six months or even a year to complete.

a man putting his hand into a large glove that is sticking out from a glass box inside a chemistry lab — Zheng’s recent project involves looking for new methods to create complex organic molecules from more simple chemical building blocks. The biggest challenge was finding a way to control how chemical bonds formed so they could create new molecules using as few reactions as possible. Using the HTE, Zheng was able to screen a large number of reactions and found the ideal conditions for controlling bond formation. “I would not have been able to do this work without the HTE,” says Zheng.

Not only does the HTE enable groundbreaking chemistry, it also provides a way for students to gain key technical and transferrable skills that they will use throughout their careers. “Collaborations are now a fundamental part of research,” says Walsh. “Having students engage in collaborative efforts, gain skills in communication, and work together, along with the technical skills of doing high-throughput experimentation, makes them very marketable.”

With as many as half the papers published by the labs of Kozlowski, Molander, and Walsh relying on the HTE facility in some way, many of the discoveries made by chemists at Penn would not have been possible without this facility. “Nobody does it like our facility, nor at the technological level that we can,” says Kozlowski. “We can do extraordinary things with our HTE. Our facility is quite special.”

The research was supported by the National Institute of General Medical Sciences Award R01 GM 113878. The High-Throughput Experimentation Laboratory was initially funded by National Science Foundation Grant Opportunities for Academic Liaison with Industry (GOALI) Award 0848460 and is supported by the National Institutes of Health Award S10 OD011980.