We propose to study and develop a new method for in vivo cardiac output (CO) monitoring that has the potential to be significantly more reliable compared to current standard. CO monitoring is important in critically ill patients and for those undergoing cardiac procedures. Accuracy and precision in measurement will mean the difference between life and death for these patients. The thermodilution method, the current standard of practice, has been shown to have poor reliability and repeatability mainly attributed to the need to measure small changes in temperature that is affected by many confounding factors. The method we propose leverages time transient electrochemical behavior of an injectate or redox active tracer molecule that is injected or generated on-demand directly into the blood stream. The principle is that a small voltage applied to specific liquids injected into blood can cause charge transfer or charge redistribution that release a measurable current. That electrochemical signature will be diluted by flowing blood. But how quickly the dilution occurs would depend on blood flow rate. Thus, the dilution response may be used to recover blood flow rate by calibration. This electrodilution method avoids the use of temperature and its associated sources of error and hence holds the potential to be significantly more reliable. Our overall aim is to test our hypothesis that the accuracy and precision in recovering the flow rate of physiological fluid will be better using our novel electrodilution method compared to the traditional thermodilution method. Specific aim #1 is to develop an electrodilution method using saline injectate which is operationally identical to the current thermodilution technique. We will build a prototype catheter, optimize design characteristics and test our hypothesis. In specific aim #2, we will explore a novel transformative idea that is even more operator independent by eliminating the need for injection. Here, a biocompatible redox active tracer molecule will be generated on-demand directly into the blood stream whose dilution may be tracked for recovering blood flow rate. We seek to study its proof of concept. If shown to work, this second method of electrodilution has the potential to be significantly more reliable and may be performed using a much smaller catheter, making these measurements less invasive and hence feasible even in pediatric patients. This small grant R03 level 2-year effort is by an investigative team of bioengineers and anesthesiologists.