The Lattice Light-Sheet Microscope May Soon Offer 3-D Movies From Inside Living Cells to a Website Near You

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Researchers at the South Dakota School of Mines & Technology are building a web portal for sharing 3-D images generated by the Lattice Light-Sheet Microscope (LLSM). The powerful microscope is breakthrough technology that provides high-speed real-time 3-D moving images from inside living cells without damaging them; it has the potential to push the boundaries of cellular biology and advance breakthroughs in medical science and biotechnology.

"This grant will aid us in making the best possible use of the microscope with the broadest possible impact for researchers throughout the region."

For most of human history, the existence of living cells was a complete mystery. Anton van Leeuwenhoek is credited with being the first person to view single-celled organisms. In 1674, he peered through a handmade microscope and described the algae Spirogyra. The subsequent publication of his work helped form the foundation of microbiology.

The science continued to advance alongside the microscope, but for hundreds of years much of the inner-workings of living cells have remained elusive and unknown. Cells exist in three dimensions, microscopes only produce images in two.

Today, that's changing thanks to new techniques in optical microscopy, such as the 2014 invention of Lattice Light-Sheet Microscope (LLSM) by Nobel Laureate Eric Betzig, Ph.D. This breakthrough technique provides high-speed real-time 3-D moving images from inside living cells without damaging them. This tool has the potential to push the boundaries of cellular biology and advance breakthroughs in medical science and biotechnology. The LLSM allows researchers to view cellular processes in a way they could not before.

Currently there are only a handful of these microscopes in the world, and one of them is at the South Dakota School of Mines & Technology.

“SD Mines is very proud of many successes of our faculty and students who are working on the frontiers of science and engineering,” says SD Mines Interim President Jan Puszynski.

The LLSM uses a rapid succession of lasers formed into a 2D plane to excite various fluorescent proteins that are infused into the cells. The microscope captures images plane by plane, and then a computer stacks those images to build a three-dimensional picture.

“The lattice light-sheet microscope constructed at Mines with the help of Dr. Betzig will provide unique capabilities for researching cellular dynamics and biophysics,” says Robert Anderson, Ph.D.

Anderson, a professor in the nanoscience and nanoengineering graduate program, helped solicit a $300,000 development grant from the National Science Foundation to create new computer hardware and software so the moving images generated by this powerful tool can be properly studied. The effort includes a new web portal so scientists in different parts of the world can use the internet to share images.

“This grant will aid us in making the best possible use of the microscope with the broadest possible impact for researchers throughout the region,” says Anderson.

One challenge is the huge amounts of data generated by the LLSM push the limits of modern computer hardware. For example, a single smartphone photo averages about one megabyte in size; the Lattice Light-Sheet Microscope produces enough data to equal about 500 smartphone photos every second.

Processing this imagery requires the expertise of fellow researcher John Weiss, Ph.D., a computer science professor in the Department of Mathematics and Computer Science. Weiss is an expert in the use of computer graphic cards. “Modern graphic cards are like little computer subsystems, with hundreds of graphics processing units (GPUs) that can be harnessed to perform massively parallel computational tasks in far less time than a single CPU. We call this approach GPGPU: General Purpose Computing on Graphics Processing Units,” says Weiss. With specialized hardware, the graphic cards can be stacked together, in a similar way that multiple computers can be networked to form a supercomputer, and used to process large amounts of data. “The field has just exploded in the use of these cards to process images, including the medical imaging field,” says Weiss.

The NSF grant not only includes the Mines team but also researchers from the University of South Dakota and South Dakota State University. These institutions are working together through the statewide BioSystems Networks & Translational Research Center.

The team’s work on this three-year project is already underway. Researchers are taking imagery and working to program software and build hardware.

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