Scientists at the Janelia Farm Research Campus are not the type to take "it can't be done" for an answer. Fortunately, when equipment is not quite strong enough, small enough, or otherwise up to the task, several resident tinkerers are ready to step in to design and fabricate a tool that allows researchers to overcome the limits of existing technologies.

When Janelia scientists want a microscope designed and built to their specifications, they'll likely find the expert they need at a desk, maneuvering virtual mirrors, lasers, and lenses across a computer monitor. Engineer Dan Flickinger has taken things apart and put them together all his life. These days, he relies on three-dimensional modeling software to ensure that the parts he chooses fit together optimally to direct and capture light. Recently, he has been modifying the custom-made, two-photon microscopes that Karel Svoboda's lab uses to look deep inside brain tissue—work he began in Svoboda's lab at Cold Spring Harbor Laboratory before that group moved to Janelia Farm.

Flickinger is redesigning components to capitalize on the latest advances in commercially available parts so microscope users can capture as much information as possible from a sample. Meanwhile, he's helping other group leaders re-create microscopes they've worked with in the past, with an emphasis on making it easier for nonengineers to assemble and use them.

Sometimes an existing microscope simply needs a tweak—for example, an edge sanded to alter its height or a hole drilled to accommodate the shape of a new sample type. Steve Bassin and Jason Osborne, who both came to Janelia Farm after years producing parts for the aerospace industry, say that modifications like these account for much of the machining they do in the instrument design and fabrication facility. But they produce plenty of original parts, too. Harald Hess, director of the applied physics and instrumentation group and a frequent customer, is now awaiting dozens of carefully designed metal components he will use to build a new type of light microscope he hopes will achieve exceptionally high resolution in three dimensions.

Bassin and Osborne design and construct gadgets and contraptions from scratch too. Working with visiting scientist David Anderson, for example, they created an acrylic box—about the size of a small microwave oven—with hand pockets that allow a researcher to manipulate objects inside without letting anything in or out. Anderson, an HHMI investigator at the California Institute of Technology, will use this "fly arena" to study behavioral choices in fruit flies. He expects its spacious interior may help him discover behaviors that cannot be observed in standard arenas, where flies have less room to move.

Several Janelia scientists have expressed interest in learning just how these fabricators ply their skills. To help make the design piece of the process more tangible, Flickinger hosts periodic demonstrations of the modeling software. And Bassin is teaching a series of courses for scientists at Janelia who want to learn how to measure, drill, mill, and lathe. Those who complete the basic safety course gain access to a satellite machine shop where they can indulge their own inner tinkerer.

—J.M.