NSF Funds First U.S-based 4Pi-Confocal Laser Scanning Microscope

New technology will open doors in biophysical research and education

The 4Pi-Confocal Laser Scanning Microscope is world’s most advanced light-based microscope-capable of revealing the structure of genetic material within a cell in three dimensions. The first such instrument is now coming to the United States, thanks to a National Science Foundation (NSF) grant to a Maine interdisciplinary biophysical research program.

The Institute for Molecular Biophysics (IMB) brings together expertise in biophysics and engineering at the University of Maine in Orono, molecular and cell biology at the Maine Medical Center Research Institute in Scarborough, and genetics and genomics at The Jackson Laboratory in Bar Harbor. The program’s goal: to explore the structure and function of genes and chromosomes within cells in order to understand precisely how genes control both normal development and disease.

“It’s been exciting to bring this enabling technology to the talented and diverse group of researchers at the IMB,” said Angela Kraus, program director in NSF’s division of biological infrastructure, which funded the grant. “High-resolution analysis is a critical next step in genetics and genomics research. Fascinating results should emerge from this research.”

The 4Pi microscope will enable the IMB researchers to examine specific structures within a cell-such as a single gene on a chromosome-at a resolution four to seven times greater than conventional confocal microscopy provides.

“Astronomers have space-based telescopes like the Hubble Space Telescope to understand the history and structure of the universe,” said IMB co-director Barbara Knowles of The Jackson Laboratory. “Physicists have giant particle accelerators to isolate the fundamental elements of energy and matter. Now researchers in genetics and biology have an advanced tool to examine the very structure of the mouse, human and other genomes.”

The 4Pi microscope is manufactured by Leica (Mannheim, Germany), based on technology developed by Stefen Hell of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany. The S4Pi” designation refers to the unique way in which light is emitted.

“Imagine looking at a satellite image of your state of such high resolution that you can spot the local college football field,” said IMB co-director Michael Grunze of the University of Heidelberg in Germany. “Now, imagine being able to see the football, in 3-D. The 4Pi represents a comparable increase in resolution, only on a nanoscale.”

The NSF grant for the acquisition of the 4Pi also includes funding for a specialized microscopist, most likely a physicist, to analyze samples on the 4Pi. Grunze foresees that researchers will be able to send or bring biological samples to the IMB for analysis. “I see biology moving towards specialized high-tech centers like the IMB, bringing in investigators from all over the world,” he said.