In a move that slashes 90 percent of the cost of mass-producing metastatic microtumors and therapeutic microtissues for screening and research, Rice University bioengineers have adapted techniques from the “maker” movement to reprogram a commercial laser cutter to etch up to 50,000 tiny “microwells” per hour into sheets of silicone.
The fabrication technique, which was developed with open-source software and hardware, is described in a new study published in the journal RSC Advances.
To study micrometastases in the lab, researchers grow multicellular aggregates of tumor cells. Traditionally, scientists have formed these by manually placing individual droplets of cells onto a plate using a pipette. But Miller said this method is labor-intensive, highly variable and typically produces small numbers of usable samples, which makes it impractical for studies that may require thousands of aggregates.
“Recent studies have revealed that cancer patients can have microtumors throughout their bodies,” Miller said. “Most of these remain dormant, but some will actually grow into a full-blown tumor that can threaten the patient. We don’t know exactly how the environmental conditions around a microtumor can promote or suppress this dangerous transition, but one way to investigate this process is with screening studies that involve large numbers of aggregates placed into defined environments.”
One method for making many multicellular aggregates at once is to place cells onto a test plate containing several thousand microscopic wells, or microwells. Although commercial microwell products are on the market, Miller said they can be expensive, and the wells also come in a limited selection of shapes and sizes, which can make it difficult to produce small aggregates.
Miller and graduate student Jacob Albritton, the lead author of the new study, found they could produce up to 50,000 microwells per hour by developing hardware and software modifications for a commercial CO2 laser cutter — the same kind of machine used to make trophies, jewelry, toys, acrylic figurines and other commercial products.
“We found we could create a conical well with a millisecond laser pulse in a sheet of poly(dimethylsiloxane), or PDMS,” Albritton said. The material is a silicone-based organic polymer that’s commonly used in industrial fabrication. This polymer is also nontoxic to living cells and is used often in biological experiments.
“When the laser flashes across the surface, it’s like a Gatling gun, and you can see little spouts of flame from each strike,” Albritton said. “Our laser-based fabrication method can achieve something that standard lithography cannot: sharp, conical depressions that help guide the cells into a single aggregate.
Regarding production costs, Miller said, “Using our technique, it costs around $30 to fabricate 100,000 microwells. This is less than one-tenth the cost of commercial sources.”
The Latest on: Open-source laser fabrication
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