Digital microfluidic device extracts estrogen from clinical samples

Clinicians would love to be able to identify women who are at risk of developing breast cancer or to monitor anti-estrogen breast cancer therapies by measuring estrogen levels in breast tissue. But there isn’t a way to measure local hormone concentrations without removing hundreds to thousands of milligrams of breast tissue and risking scarring and deformity. So Aaron Wheeler, Robert Casper, and colleagues at the University of Toronto, Mount Sinai Hospital, and the Donnelly Centre for Cellular and Biomolecular Research (all in Canada) have developed a digital microfluidic device that quickly extracts estrogen from 1-μL raw aliquots of whole blood, serum, or breast tissue homogenate.

Courtesy of Aaron Wheeler

(Top) Schematic of the device. (Bottom) Eight movie frames demonstrate estrogen extraction from blood. The sample is lysed, the hormone is extracted into methanol, and the unwanted constituents are removed into isooctane. The extract goes to a collection reservoir. (Copyright 2009. Adapted with permission from the American Association for the Advancement of Science.)
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The droplet-based device has three input reservoir electrodes for the raw sample, a lysing solvent, and a polar extraction solvent to carry the estrogen. A fourth reservoir electrode collects the processed sample. Actuation electrodes form a path linking the reservoirs. The path passes through a fifth reservoir with a nonpolar extraction solvent that captures unwanted components. The polar phase readily circulates within the nonpolar phase and the two easily separate after liquid–liquid extraction so that the polar extract of estrogen can be delivered to the collection reservoir for quantification by ELISA or MS.

The sample size needed for the device is 1000–4000× smaller than that required for conventional methods, such as immunoassays or MS. Automation of the microfluidic method makes it less time- and labor-intensive: The conventional approaches take 5–6 hours and demand extensive pipetting, centrifugation, and drying, but the microfluidic assay takes 10–20 minutes for sample preparation. (Sci. Transl. Med. 2009, DOI 10.1126/scitranslmed.3000105)