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ty of Washington. “Cell arrays in esearchers have developed Fabricate microwellmicrofluidic environments have an innovative soft lithopatterned substrates been demonstrated before, but graphic process for the fabricathe challenge that Langer’s tion of patterned microfluidic Align the first array group demonstrated successfully arrays that could substantially of microchannels is the ability to address many speed up the screening of new on microwells PDMS types of array units with differdrugs. The process, which was microfluidic mold ent fluids—a paramount goal in reported by Robert Langer, Ali Flow each cell high-throughput drug testing. Khademhosseini, and coltype in a specific With devices like these, using leagues at the Massachusetts channel and wait for cells to dock in these arrays in real drug testing Institute of Technology and the microwells is just around the corner.” Harvard Medical School, uses Although initially the rethe reversible sealing of PDMS Remove the searchers used 5 5 arrays, molds to create an array of mimicrofluidic mold Khademhosseini, Langer, and crowells with volume capacities colleagues anticipate creating as small as 100 µL (Lab Chip Orthogonally align arrays with as many as 2500 2005, 5, 1380–1386). and attach the wells/cm2. These arrays will “If you want to test new second array drugs, it is desirable to look at have a far greater density of of microchannels the effects of each drug on all wells than that of conventional the cell types of the body,” says Schematic diagram of reversible sealing of microfluidic arrays multiwell plates currently in Khademhosseini, the first auuse. In addition to increasing onto microwell patterned substrates. (Adapted with permission. thor on the paper. “Traditionthroughput, the microfluidic Copyright 2005 Royal Society of Chemistry.) ally, people working on drug techniques will significantly recrowells was filled with a different cell discovery with cells or tissue cultures duce the necessary volume of samples type, such as hepatocytes, embryonic have relied on expensive equipment and reagents. stem cells, or fibroblasts. As a solution and large robots for rapid screening of “This technique fills a vacancy: a wellcontaining cells flowed through the drugs. The use of microfluidics may podesigned technique for arraying cells and tentially make the process cheaper, more channels, the cells accumulated in the probing them with different reagents that wells because of decreased shear stress. efficient, and [more] sensitive.” moves the fields of cell biology and tissue The microchannel mold was then In the new process, the researchers engineering one step closer to performing peeled off and replaced with a new set of used photolithography to produce patexperiments that generate statistically sigmicrochannels, which were oriented to terns of wells on a silicon master, which nificant data,” says Douglas Weibel of allow reagents to be added in a perpenacted as a template. Two PDMS molds Harvard University. “The arrays are dicular direction. “We are working toward cleverly designed, and the approach is were then fabricated on the silicon tema system in which a technician can peel off straightforward and should make it possiplate. One mold, engineered with microchannels, was matched with a second the channels and put on new ones as well ble to probe large numbers of different as minimizing the number of inlets and mold containing microwells. The chemcells under controlled conditions,” he istry of the mated surfaces was modified outlets,” says Khademhosseini. “It is a adds. In the future, the researchers plan fairly complicated process to optimize the to make a tight, but reversible, seal. to optimize the surface chemistries of the surface chemistries and flow rates.” After the PDMS microwell and mimolds, in order to improve the reversible “This work is a good demonstration of bond between molds and the interaction crochannel molds were sealed together, how microfluidic technology can be used the system was filled under a negative of microchannel and microwell walls with to test large numbers of conditions on cell various types of samples. a pressure with solutions containing cells. arrays,” says Albert Folch of the UniversiIn a typical experiment, each row of mi—Steve Miller 642
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