Toward the Development of a Lab-on-a-Chip Dual-Function Leukocyte and C-Reactive Protein Analysis Method for the Assessment of Inflammation and Cardiac Risk

Abstract

Inflammation has been identified as the underlying cause of atherosclerosis, a condition associated with the deposition of lipids in the lining of arteries, which progressively leads to acute myocardial infraction (AMI) or heart attack. Serum concentrations of markers of inflammation, including C-reactive protein (CRP), and the leukocyte count are powerful predictors for the development of coronary heart disease (1)(2)(3)(4)(5)(6)(7). In addition, AMI patients with increased CRP concentrations or leukocyte counts are at higher risk of mortality and recurrent AMI (8)(9)(10)(11)(12). The combination of these 2 biomarkers provides additive and powerful diagnostic information. In fact, people with both high leukocyte counts and high CRP concentrations exhibit a 7-fold higher risk for heart disease (7). Although tests targeting CRP concentrations and leukocyte counts are widely available in clinical settings, they are performed separately on different instruments. Consequently, these tests require large sample volumes, additional sample preparation steps, and longer assay times. In addition, the clinical instruments and methodologies currently used to perform these tests are not suitable for point-of-care testing, such as in a doctor’s office and in the (more relevant to a heart attack setting) emergency room or ambulance. Clearly, the diagnostic and prognostic value of these biomarkers would be increased if these 2 tests could be performed concurrently on the same instrument, in a convenient, accurate, and highly accessible manner. Previously we described studies of the design, fabrication, and testing of lab-on-a-chip (LOC) structures composed of chemically sensitized beads that are populated into etched silicon wafers with integrated fluid-handling and optical detection capabilities (13)(14)(15)(16)(17)(18)(19). These miniaturized systems have been used for the identification and quantification of electrolytes, …