Zooming in on the smallest machines inside a cell

Matthew Lew earns 2017 NSF CAREER Award

Microscopes have allowed researchers to look inside of cells since the late 17th century, but the technology limits what can be seen. An engineer at Washington University in St. Louis plans to develop a new technology combining chemical probes, optics and imaging software to see inside cells at the smallest level – the nanoscale.

Top: conventional fluorescence microscopy; bottom: single-molecule nanoscopy

Matthew Lew, assistant professor in the Preston M. Green Department of Electrical & Systems Engineering in the School of Engineering & Applied Science, will develop this technology with a five-year, $500,000 CAREER Award from the National Science Foundation. The CAREER awards support junior faculty who model the role of teacher-scholar through outstanding research, excellent education and the integration of education and research within the context of the mission of their organization.

Lew is the 27th current faculty member in the School of Engineering & Applied Science to receive the award.

Lew's research intersects optics and biology to see molecules inside cells and study their behavior and activity. Cells are about 20 microns in size, or about one-fifth of the width of a human hair, so looking inside the cells to study the molecules — the small machinery that drives life — requires highly sensitive equipment.

"If we can't see the activities of individual molecules, we can't understand why cells become sick or build new devices based on biomolecules instead of electronic integrated circuits," Lew said. "One of the key challenges is to develop the imaging technology, and that's what our lab is trying to do."

Lew uses fluorescent molecules, or special molecules that absorb light and then emit light of a different color, to sense the environment inside cells. Whether or not the molecules emit light tells scientists what is happening around them.

"These molecules give our imaging technology a really unique capability," he said. "We can combine the sensing capabilities of those molecules with innovations in the imaging system, and then combine with new image processing algorithms to consider the whole thing as a full imaging system that can push the boundaries of what we're able to measure inside cells."

When developed, Lew's technology could be applied to nanomedicine: Researchers could use it to determine if a drug gets delivered to the correct therapeutic place within a cell.

"Just because a drug gets to the cell doesn't mean it's useful or effective," he said. "Our technology will be key in understanding the intracellular, versus the intercellular work that is being done now."

Lew joined the faculty at WashU in July 2015. Previously, he was a postdoctoral fellow in structural biology at the Stanford University School of Medicine. He earned a doctorate in electrical engineering working in the laboratory of W.E. Moerner, a WashU alumnus and co-recipient of the Nobel Prize in Chemistry 2014 for "the development of super-resolved fluorescence microscopy," on which Lew's work now builds.

In 2016, Lew received the Hiruma/Wagner Award at the 16th Conference of Peace through Mind/Brain Science. He also has received a second-place poster award at the Gordon Research Conference and a PicoQuant Young Investigator Award at SPIE Photonics West. At Stanford, he was a National Science Foundation Graduate Research Fellow, a 3Com Corp. Stanford Graduate Fellow and a Tau Beta Pi Fellow. He is a member the Optical Society, the American Chemical Society and Tau Beta Pi. He was co-president of the Stanford Optical Society, a student chapter of OSA and SPIE, in 2013-14 and chair of the Stanford University Photonics Retreat in 2013.

The School of Engineering & Applied Science at Washington University in St. Louis focuses intellectual efforts through a new convergence paradigm and builds on strengths, particularly as applied to medicine and health, energy and environment, entrepreneurship and security. With 90 tenured/tenure-track and 40 additional full-time faculty, 1,200 undergraduate students, 1,200 graduate students and 21,000 alumni, we are working to leverage our partnerships with academic and industry partners — across disciplines and across the world — to contribute to solving the greatest global challenges of the 21st century.

Matthew Lew

  • 2017 NSF CAREER Award: “Nanoscale sensing and imaging using computational single-molecule nanoscopy”
  • Postdoctoral fellow in the de la Zerda Group in Structural Biology at the Stanford University School of Medicine
  • PhD in the lab of Nobel Laureate and WashU Engineering alumnus W. E. Moerner, Stanford University
  • 22 published papers
  • Research areas: Microscopy, biophotonics, computational imaging, and nano-optics, especially when directed toward biological or biomedical applications.