Programmable Bio-Nano-Chip Systems for Serum CA125 Quantification: Towards Ovarian Cancer Diagnostics at the Point-of-Care

• Published in: Cancer prevention research (Philadelphia, Pa.) Pa.), 2012-04, Vol.5 (5), p.706-716
• Main Authors: Raamanathan, Archana, Simmons, Glennon W., Christodoulides, Nicolaos, Floriano, Pierre N., Furmaga, Wieslaw B., Redding, Spencer W., Lu, Karen H., Bast, Robert C., McDevitt, John T.
• Format: Article
• Language: English
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.CAPR-11-0508

Point-of-care (POC) implementation of early detection and screening methodologies for ovarian cancer may enable improved survival rates through early intervention. Current laboratory-confined immunoanalyzers have long turnaround times and are often incompatible with multiplexing and POC implementation. Rapid, sensitive and multiplexable POC diagnostic platforms compatible with promising early detection approaches for ovarian cancer are needed. To this end, we report the adaptation of the programmable bio-nano-chip (p-BNC), an integrated, microfluidic, modular ( Programmable ) platform for CA125 serum quantitation, a biomarker prominently implicated in multi-modal and multi-marker screening approaches. In the p-BNC, CA125 from diseased sera ( Bio ) is sequestered and assessed with a fluorescence-based sandwich immunoassay, completed in the nano-nets ( Nano ) of sensitized agarose microbeads localized in individually addressable wells ( Chip ), housed in a microfluidic module, capable of integrating multiple sample, reagent and biowaste processing and handling steps. Antibody pairs that bind to distinct epitopes on CA125 were screened. To permit efficient biomarker sequestration in a 3-D microfluidic environment, the p-BNC operating variables (incubation times, flow rates and reagent concentrations) were tuned to deliver optimal analytical performance under 45 minutes. With short analysis times, competitive analytical performance (Inter- and intra-assay precision of 1.2% and 1.9% and LODs of 1.0 U/mL ) was achieved on this mini-sensor ensemble. Further validation with sera of ovarian cancer patients ( n=20 ) demonstrated excellent correlation ( R 2 = 0.97 ) with gold-standard ELISA. Building on the integration capabilities of novel microfluidic systems programmed for ovarian cancer, the rapid, precise and sensitive miniaturized p-BNC system shows strong promise for ovarian cancer diagnostics.