The result was a simple yet versatile chip that could image C. elegans throughout all its developmental stages. To make the chips, Koushika and her postdoc Sudip Mondal poured a resin called polydimethylsiloxane into silicon wafer molds to create the device’s flexible walls. By changing the mold size and varying the amount of resin they added, they could create different-sized chambers to look at animals in various stages of growth. The resin chamber was simply glued to a coverslip and voilà: instant microfluidic imaging device.

Koushika and Mondal improved on existing devices by using water instead of gas to apply pressure to the chamber membrane. They found that gas causes bubbles to form and the light that is reflected off the bubbles decreases the resolution of the images. Water alleviates this problem.

Koushika and her team have used their microfluidic device to look at various cellular and subcellular processes in C. elegans, such as axonal transport and the migration of developing nerve cells. Because of the chamber’s ability to accommodate different-sized animals, they’ve also used it to visualize cell division in the worm’s embryos, which are as small as 0.04 mm long, and to make movies of axonal transport in a 7-mm-long fruit fly larva. Their findings were reported in the April 2011 issue of the journal Traffic. Koushika and her colleagues have also used the device to image the heartbeat of zebrafish embryos.

A Drosophila larva crawls into the microfluidic chamber where it is immobilized, visualized, and eventually released.
Video: Sudip Mondal

“In one talk I gave, someone in the audience referred to the device as a straitjacket,” says Koushika. She says it’s better than that. Straitjackets are more constricting, less versatile, and not as easily reversible.

Now, Koushika is working on a version of the chip that can track changes in a single animal from birth to death. She has used her current device to repeatedly immobilize and image animals over the course of an hour. The new chip would go further, allowing the animal to spend its entire life in the chamber where researchers can repeatedly immobilize it for long-term imaging and developmental studies.

She’s begun sharing her device with others. “My hope,” Koushika says, “is that as more and more people use C. elegans as a cell biological model to acquire real time data, they will turn to devices such as ours and consider them as a nice method to try for their system.”

As for her worms, she’s got them where she wants them.

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