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A chip for counting cells homing in on the most sensiSifting through cells from the tive wavelengths to get the best human body to either detect or LOD. “What we have done is monitor a disease is standard prosomething similar to whitecedure in many parts of the light spectroscopy,” says world, yet cell screening is often Llobera. “We are able to detect too expensive for routine use in which wavelength has the developing countries. An affordmaximum sensitivity.” able and disposable lab-on-a-chip Next, the researchers device that can count and differchecked whether dead cells, entiate cells, such as the one dewhich are readily stained with scribed in an article in AC (DOI strongly absorbing trypan 10.1021/ac100590z), may make blue, could be detected. Bepotentially life-saving cellular dicause the stained cells will agnostics globally accessible. scatter and absorb, the re“The idea was to try to desearchers decoupled the sigvelop something very portable A chip made from PDMS and designed for multiple internal reflecnals by subtracting a lightand not expensive at all,” says tion (MIR). Cells pass through a microchannel and are detected by scattering principle investigator Andreu spectrumOobtained from Llobera. “One of the chips costs light scattering and absorbance measurements. unlabeled cellsOfrom the almost nothing.” To create the population of cells. “This was the first dead cells’ light-scattering-plus-absorthrifty chips, Llobera and colleagues at time that something like this was done,” bance spectrum for each cellular Technische Universita¨t Braunschweig says Llobera. “Optically, it is quite adconcentration. (Germany), the Centre Nacional de Mivanced.” The resulting MIR chip has an As a final test, different ratios of croelectro`nica (Spain), and Universitat elaborate geometry comprising selfdead-to-living cells were fed through the Auto`noma de Barcelona needed to find alignment systems, microlenses, “air chip. The features of the spectra predictjust the right materials and approach to mirrors”, and fluidic ports that flank the ably changed as a function of this ratio. measure cells with a clinically relevant interrogation chamber. As the live cells increased relative to limit of detection (LOD). “This is the first time I’ve seen an dead cells, the scattering features of the For the chip’s medium, the researchers optical path incorporated into a chip, spectra dominated. Alternatively, the selected PDMS because of its affordability which makes it similar to flow cytomemore dead cells present in a sample, the and minimal bioreactivity. PDMS was try,” says Guillermo Alvarez de Toledo greater the intensity of the trypan absorpoured over a glass mold to create, in soft of the University of Seville (Spain). “It’s bance band. The demonstration showed lithography parlance, a replica, which was basically a microspectrophotometer.” that the chip could be used to distinthen bonded to a rectangular 3 ⫻ 2 cm The chip set-up makes it possible to guish cells by this property. piece of glass to make a finished chip. detect light scattering, light scattering The LOD for all of these experiments The next consideration was the deplus absorbance, and absorbance. To ranged between 53 and 105 cells, which tection method. To avoid cumbersome test the photonic chip and determine its is in the ballpark of what would be necfluorescence labeling, the researchers essary to diagnose AIDS on the basis of configured their chip to work with light- LOD for each of these detection schemes, the researchers set up a series T cell count, according to Llobera. scattering and absorbance spectroscopy. “They have created a powerful cellTypically, cells are counted individually, of experiments with monocytes. First, living cells were introduced to the counting device for quantifying events in but this can be time-consuming and exchip and, as they passed through the inter- cell biology. In this case, they are counting pensive. To overcome these obstacles, the rogation chamber, their light-scattering cells, but you could be studying someauthors selected an optical configuration properties were detected (no absorbance thing else, like metabolism,” says Raquel for their chip called multiple internal rewas observed). One of the most appealing Perez-Castillejos of the New Jersey Instiflection (MIR). Data collection with MIR aspects of MIR is its ability to collect data tute of Technology. “It would be great if allows the researchers to measure the you could take this piece of plastic, fill it properties of a group of cells in just 30 ms. from the entire spectrum, rather than just a single wavelength. This allowed the rewill blood, and make a diagnosis.” MIR requires light to travel a zig-zag —Erika Gebel path along the chip through an “interro- searchers to optimize their measurements by examining complete spectra, then gation” chamber containing a small 5398
ANALYTICAL CHEMISTRY /
JULY 1, 2010
10.1021/AC1011552 2010 AMERICAN CHEMICAL SOCIETY
Published on Web 05/14/2010
