John T. McDevitt, Pierre N. Florianoa, and Nicolaos Christodoulides
Rice University, Houston, TX
The programmable bio-nano-chip (PBNC), synergizes components and achievements from nanotechnology, clinical chemistry, bioinformatics, microfluidics, optics, image analysis, and pattern recognition to create a powerful new integrated measurement approach in a small device footprint. The PBNC ensemble employs a size-tunable network of nanometer-scale fibers (“nano-net”) within agarose microspheres or a polymer membrane and a fluorescent signal arising from nanoparticles (nano) to isolate and quantify biologically important analytes (bio) from complex matrices within a closed, miniaturized system (chip). The PBNC features a flexible assay design and has a diverse collection of validated analyte subtypes. The PBNC’s modular design elements allow for rapid inclusion of tests for new biomarker signatures; assays for nucleic acids, proteins, and cells are arranged in the PBNC to create analytical test modalities specific to different disease types. Collectively, the modularity, flexibility, and ability to process and learn new biomarker signatures is here referred to as “programmability”. This presenation will highlight the development of an integrated lab-on-a-chip system, suitable for enumeration of CD4 T-helper lymphocytes from HIV-infected adult and pediatric patients and amenable for use in resource-poor settings. The miniaturized system consists of a self-contained, inexpensive, disposable biochip and an analyzer that includes optical, mechanical and software elements, designed to work in settings where trained personnel and-or basic lab equipment and supplies may not be available. Injection-molded integrated test units feature lab-on-a-chip microfluidic components with self-metering volume capabilities leading to an analysis chamber which serves to entrap, isolate and immuno-label white blood cells on the surface of a track-etched polycarbonate membrane, with reagents stored in solid-state matrices within the biochip. Only fingerstick quantities of whole blood are required through the deposition of variable volume whole blood samples into the biochip’s introduction port. Fluorescently-labeled cells are excited by light emitting diodes and microphotographs of captured lymphocytes are acquired with a charged-couple device camera then analyzed with custom image analysis macros. Blood samples from 63 HIV-infected patients were tested and correlated well to flow cytometry for %CD4 (r=0.96), absolute CD4 (r=0.93), and total lymphocyte counts (range 0-2700 cells/µL). These powerful devices have secured the Popular Science Best of What’s New in the Medical device category as well as the Science Coallition’s Discovery of the Year.
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