? ? A field-portable instrument that can determine the blood level of specific toxic metals is vital in establishing the link between toxic exposure and genetic expression in that it aides in identification of genes whose expression is modified by exposure. Such data is critical for both laboratory and epidemiological studies. Standard assay methods require samples be sent to off-site laboratories, increasing costs and errors, and imposing a delay in identifying exposure sources. The overall goal of the proposed work will be to develop a small, easy-to-use, handheld instrument used with disposable silicon microchips to provide rapid, in field simultaneous detection of lead, cadmium, copper and zinc in blood. The microsampling and assay chip, which integrates a microneedle comparable in size to a human hair for painless blood drawing with a microcuvette containing an electrochemical detection structure, can be cost-effectively fabricated using MEMS (microelectromechanical systems) technology. The assay will employ electrochemical-stripping analysis; a proven technique for accurate and precise detection of trace amounts of toxic heavy metals. The assay permits detection of the analytes without requiring sample de-oxygenation, and uses an internal standard to avoid the need for external calibration. It is thus ideal for field use and can be used by untrained personnel. In addition, self-metering of sample volume will provide for accurate determination of levels of the four metals in blood. Phase I will demonstrate feasibility by: developing the assay and validating it with in vitro testing, designing the microchip and fabricating key components, and developing measurement and control instrumentation. In Phase II, a complete prototype system will be fabricated and evaluated via in vitro and animal testing. ? ? ? ?
