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Herschel Marchman, Senior Scientist, Janelia Farm Research Campus
For a devoted tinkerer like Bertozzi, life can imitate art: "In one of my favorite movies, Fantastic Voyage , a group of scientists and physicians miniaturize a ship, and themselves, to navigate inside the human body in order to diagnose and treat disease. This fantasy may now essentially come true as nanoscale probes and manipulators revolutionize medicine. What was fiction a few decades ago may ultimately be realized in the hands of scientists, engineers, and physicians working together."
When Herschel Marchman says "we need to look at things in different ways," he's not just talking about the view through a microscope. Marchman is intent on expanding researchers' options through creative variations on existing technology, and his unique perspective provides a wellspring of ideas for vexed scientists who think they have hit a wall in their research because of technological limitations.
Marchman, a senior scientist working in Harald Hess's applied physics and instrumentation group at HHMI's Janelia Farm Research Campus, approaches such issues as an engineer, often seeing parallels to problems the semiconductor industry—in which he spent some 15 years—has already solved. He readily borrows tools from that field, adapting them in ways he anticipates will dramatically affect biological discovery.
High on his priority list is reducing the need to stain biological samples, which enhances their contrast but also imposes constraints. In the case of scanning electron microscopy, for example, users are limited to imaging only those cellular structures that can be labeled with metal stains during sample preparation. "I'm sure there's more information there that we're missing," Marchman says.
To begin with, he'd like to harness the power of deep-ultraviolet illumination (DUV), a favorite of computer-chip lithographers because its ultra-short wavelength allows them to print exceedingly tiny patterns. Though DUV has not been applied to biological samples for high-resolution imaging, Marchman thinks that, with some experimenting, it might allow researchers to detect contrast patterns in cells more naturally, without using stains.
Meanwhile, he's working with Hess to design a detector for a scanning electron microscope that will break from the current paradigm, in which electrons bounce off a sample's surface. The modification should bring the instrument closer to the far superior resolution of transmission electron microscopy. It's an example of Marchman's way of improving on the status quo.
"When we tinker," he says, "we don't want to build something completely from scratch. We want to add value to what you can buy by modifying it."
Photo: Paul Fetters