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Putting microfluidics in other people’s hands

Press/Media: Research

02/03/2018

Putting microfluidics in other people’s hands

In microfluidics, sharing is hard. But practitioners are exploring new ways to share designs, devices and experience.

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Academic sharing

University of Groningen researcher Matthias Heinemann faces a nail-biter situation. He has only one silicon wafer with which to make microfluidic devices. It’s nine years old, which, in wafer years, is a geological time frame. With age, it has become slightly damaged, so it’s only half a wafer that five people

in his lab share. They rely on it for making devices for their daily experiments. It’s the only one that leads, via soft lithography, to well-working microfluidic devices. “My nightmare is that if this would now break, then half of my lab gets stuck,” he says. He would like to share copies of the wafer with external scientists. But he doesn’t have those.

The device works for the Heinemann lab’ single-cell experiments about yeast metabolism, to learn, for example, about factors influencing life span3,4. Some labs, using different microfluidic devices, have found that caloric restriction extends yeast life span.

“When we tried this in our microfluidic device, we couldn’t see this,” he says. Plenty of reasons, including different protocols, dissimilar device designs and builds, likely contribute to the different experimental results, he says.

When he was at ETH Zurich, Heinemann’s postdoc designed this wafer and built a microfluidic device with it. Heinemann later took the wafer to his Groningen lab. The postdoc, who now designs and fabricates microfluidics full time at the ETH’s microscopy core facility, has tried to make another such wafer, and failed. Heinemann collaborated with MicroLIQUID but the devices the company made didn’t work as well as ones made from the original wafer.

Blanco acknowledges this and says that in the company’s early years, the team was setting up internal standards and the company is still learning. He and his team work through failures, sometimes investing in new equipment to be ready for the next wave of microfluidic devices.

Perhaps the first wafer was a lucky fluke, says Heinemann. He uses it and worries. Even with simple designs, if one tiny pillar in the microfluidic device is a micron too low, too many cells get trapped and experiments can stall. Even simple microfluidics design can be hard to replicate. “If you compare it with Steve Quake’s designs, it’s not even kindergarten design,” he says, referring to the microfluidics pioneer Stanford University researcher Stephen Quake.

A “magic mold” is not uncommon, says Carr. “That story does not surprise me at all.” Sources of microfluidic device variability include batch-to-batch variability with the elastomer polydimethylsiloxane (PDMS), the length of time polymer and initiator are mixed, and uneven temperatures when the elastomer is cured onto the wafer (see Box 1, “Soft lithography at work”).

As Blanco explains, his company spent a year and a half prototyping microfluidic designs for the lab of University of Zaragoza researcher Rosa Monge, who uses microfluidics to model processes in glioblastoma. “Reproducibility was the main challenge,” he says. “Their patience was very important.” Monge has founded a company, BEOnChip, and is collaborating with MicroLIQUID to scale up manufacture of the devices and broaden the cancer types they can be used for.

For Heinemann, no wafer is as good as the ‘mother wafer’. The lab continues work with its half a wafer, enabled by devices made of PDMS, which is transparent and thus microscopy-ready5. But PDMS has its challenges.

Material matters

PDMS can interact with small molecules and wreak havoc in basic research projects. A few years ago, as part of his work on metabolism, Heinemann and his team did experiments in his device using smallmolecule inhibitors, but saw no inhibitory effect. The inhibitor was getting stuck to the PDMS. “It never reached the cells,” he says. Microfluidics certainly enables many types of experiments but in some cases, “you need to think about different materials.”

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Heinemann, who shares his designs in papers and via e-mail, likes the idea of Metafluidics. He also hopes for a “universal supplier” of validated microfluidic devices. “Having a fabrication facility coupled with Metafluidics would be a wonderful advance,” says Kong. In the Metafluidics community there are ‘microfluidic nerds’ invested in the nuances of device design and remixing, while others are users who just want the device and don’t want to have to manufacture it themselves.

The reproducibility issue Heinemann describes “is a big one for the field,” says Kong. “There are real microfluidic artisans out there, and even they may have difficulty reproducing the ‘workhorse wafer’ that makes the devices just right.” He and his team are setting up a forum for Metafluidics, where the community can interact and share. The idea, he says, is to help convert some of the artisanal aspects of fluidics into more reproducible engineering practice.

References

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