MICRODEVICES FOR MEASURING CPB SYSTEMIC INFLAMMATION

DESCRIPTION (provided by applicant): Several studies have shown that cardiac surgery induces systemic inflammatory responses, particularly when cardiopulmonary bypass (CPB) is used. CPB induces complex inflammatory responses characterized by complement, neutrophil, and platelet activation, and the release of pro-inflammatory cytokines. Considerable evidence suggests that systemic inflammation causes many postoperative complications, including vital organ dysfunction that can lead to multi-organ failure and even death. The intensity of the inflammatory response appears to be directly correlated with the severity of CPB-related morbidity. The ability to clinically intervene in inflammation, or even study the inflammatory response to CPB, is limited by the lack of timely measurements of inflammatory responses (complement, neutrophil, monocyte, platelet activation, and the release of pro-inflammatory cytokines). It is anticipated that real-time measurement of the production of cytokine and complement concentration using the devices as described herein will correlate with measurements obtained by the conventional ELISA technique. More immediate measurements will aid in understanding the mechanisms of cellular activation, and modify surgical and perfusion protocols for minimizing the adverse effects of cardiopulmonary bypass. The proposed study is designed to develop a novel approach to measuring plasma cytokine and complement concentrations in a continuous real-time fashion within a microfluidic analytical system for online monitoring of inflammatory responses during CPB procedures. The microsystem includes a plasma autoseparation device and a novel microimmunoassay for continuous measurements. The measurement methods will use microfabrication technology to create blood carrying fluidic circuits and will be evaluated in a ex-vivo simulated cardiopulmonary bypass procedure with donor human blood. The microimmunoassay is based upon controlling the movements of immunoassay beads that will be passed through a series of flow streams including the plasma sample of interest with time varying cytokine and complement concentrations, washing solutions, secondary antibody solutions and a detection zone. Two designs will be evaluated. The first design uses magnetic beads whose movement is controlled by a magnetic field to pass between flow streams, while the second design uses a specially designed flow structure to allow the beads to pass between different flow streams without mixing or dilution.