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Dwarfed by a penny, this tiny network of synthetic blood vessels mimics part of a lung structure. Blood flowing through the system is oxygenated by the interior air sac.

Jordan Miller, Rice University

Small wonder

“It’s about the size of a postage stamp,” Jordan Miller told me in our first conversation.

That wasn’t quite right. The intricate network of synthetic blood vessels and accompanying airway was a lot smaller than a stamp. The challenge facing Jordan, a bioengineer at Rice University in Houston, Texas, was producing a workable picture for this week’s cover of Science.

Creating the structure, Jordan explained, tests the limits of 3D printing. “We create a model on a computer,” he said, “then digitally slice that up into thousands of individual layers. Each layer becomes an image that is solidified, becoming part of the object. The smallest blood vessels are just 0.3 millimeters in diameter.”

Jordan Miller, Rice University

The initial attempt at a cover was intriguing but needed much sharper focus to display the intricate network of blood vessels and the air sac. Lighting refinements would help emphasize the structure.

Using a macro lens—a specialized optic for imaging very small objects—Jordan and his team photographed the tiny system, complete with its blood and oxygen supply tubes. After seeing their initial effort, I contacted Jordan, hoping we could make refinements to produce a more arresting cover image. The complex blood vessel network wasn’t fully sharp. There was microscopic debris obscuring the view. And lighting on the vessel system, air sac, and background could be modified to provide more impact. We talked through the desired goals and the challenges.

Jordan Miller, Rice University

Jordan and his team created an elaborate lighting setup supporting a specialized macro lens to produce images of the miniature vessel system.

“We were excited,” Jordan said. “We’d never done a cover picture before so this was a great opportunity for us to learn how to do better photography.” We needed the entire network to be in focus, not just a single region. But at this very small scale, obtaining sharp focus from the front to the back of an object is a daunting optical challenge.

Jordan and Ph.D. student Daniel Sazer worked with Rice University photographer Jeff Fitlow, who used a high-end professional camera and skillful lighting to provide more detail. “Jeff showed us a lot about lighting that made the picture more dramatic,” Jordan said. The results were much better, but still lacked the desired crisp detail.

After reviewing the images with Jordan, I suggested we consider a more complex approach called focus stacking. To my surprise, Jordan already had the equipment in hand and was familiar with the technique, which involves taking a series of front-to-back pictures of the object, each focused on a different plane.

The first focus stack attempt yielded a much sharper result, with the entire structure now clearly defined. But a few steps remained to produce a final cover-worthy image. “It was complicated,” Jordan said. “We had to keep blood and air flowing smoothly all throughout the photo session. And after shooting, the open network of vessels could fool the focus-stacking software into merging pixels in the wrong order, creating more of an impressionistic look than the accurate one we wanted for the cover.”

The solution, seen here in the second attempt, required an unusually large number of exposures, which software then combined into a single exceptionally sharp image. “The first effort involved more than 100 separate images,” Jordan said. “Each was taken 50 microns apart from the previous one.” The final result, depicting transport of blood and oxygen in an artificially created lung system, suggests tantalizing future possibilities for the creation of entire replacement organs for human patients in need.

Dan Sazer, Jeff Fitlow, and Jordan Miller, Rice University

Lighting refinements by Jeff added definition to the blood vessels and air sac, as well as produced a subdued background to emphasize the bright red network.

Bill Douthitt is the Photography Managing Editor at Science.