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A completely automated, microfluidic cell-culture chip It’s a postdoc’s dream: be hardwired, in that each running a hundred difcompartment with cells is Input manifold & mixer ferent cell-culture experipermanently connected to Chambers ments at the same time, a particular reservoir with Multiplexers all with different media, just one particular type of Control channels without having to pipette a medium. And if they want Flush channel drop. Oh, and not having to change it, they have to Peristaltic pump to come to the lab to feed connect and disconnect your cells during the weekthe tubes by hand,” says end might be really nice, Gómez-Sjöberg. “With our Flow too. The dream becomes a valve system, we can decide Input sieve reality in the November 15 on the fly which comissue of Analytical Chempounds go to which cells.” 1 mm Output sieve istry (pp 8557–8563), Another big advantage Mixer because Stephen Quake, is that the researchers Cell input flush visiting professor Anne can precisely control the 1 mm output Leyrat, and postdoc Ranumber of cells seeded in fael Gómez-Sjöberg at each chamber. With the Stanford University report A photograph of the microfluidic cell-culture chip. The channels are filled integrated imaging system, a new microfluidic cellwith colored water to indicate different parts of the device. The left inset they can even follow indiculture system that allows gives a closer view of two culture chambers, and the right inset shows vidual cells throughout the researchers to program the root of the input multiplexer. experiment. “For certain conditions in up to 96 inexperiments, [seeding dendividual culture chambers. The device surface-area ratio,” says Leyrat. “The sity] is crucial—especially for the mesenautomatically monitors cells and modiexchange is more like what’s going on chymal stem cells. Their differentiation fies their culture conditions over time. in the tissues.” depends on how crowded the cells are,” The system was born through a colBesides designing the microfluidic explains Gómez-Sjöberg. “So we can play laboration with Christopher Chen at hardware, the team wrote software to with that parameter, too, which is somethe University of Pennsylvania, who fully automate their system. The media thing that other people have not done.” had been studying the differentiaformulations are input by the user, and Leyrat adds that “if you start at a low tion of mesenchymal stem cells. Chen the computer takes over from there. “It’s enough density, you can tell which cell had been stamping adhesion-protein totally automated—that’s the beauty of is which from one picture to another.” islands of different sizes onto PDMS it,” says Gómez-Sjöberg. “In principle, The researchers say that their system substrates, and he found that differenyou can do some of these things in traalready is generating interest outside tiation was affected by the cells’ degree ditional ways, but then you have to have of their research group and that it of spreading on those islands. But once somebody there pipetting all the differshould transfer smoothly to other labs; the experiments were under way, Chen ent compounds by hand into 100 differthe Chen lab already has a version up had no way to easily vary the growth ent chambers. The labor and all the time and running. “When we created [the conditions, such as the composition of it takes is enormous.” He also points out software], we tried to make it as userthe culture medium, that also could afthat the potential for human error is refriendly as possible,” says Gómez-Sjöfect the way the stem cells behaved over moved with the automated system. berg. “People in other places could eastime. “That’s where we came in,” says Once the growth conditions are inily duplicate the system and use it.” Gómez-Sjöberg. “We had the expertise put into the software, the media formuThe researchers continue to work on the microfluidics side of it.” lations in each chamber are controlled on and with the system. “This is not The microfluidic cell-culture system precisely by a mixer that has 16 inputs something that we just made and pubconsists of a PDMS chip with 96 60and by a multiplexer. The formulations lished and then forgot about,” says GónL chambers. “We believed that the can be changed over time by simply inmez-Sjöberg. “We’re actually using this environment offered by microfluidics putting new values into the computer— system at this moment for two other would be, in a way, more physiological an advantage of this setup compared projects, and we’re going to keep using than whatever you can do in wells and with other microfluidic cell-culture it for a long time and improving it.” a flasks, because of the low volume-todevices. “All the other systems tend to —Jennifer Griffiths D EC e m b e r 1 , 2 0 0 7 / A n a l y t i c a l C h e m i s t r y
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