PROJECT SUMMARY/ABSTRACT Sepsis, a life-threatening organ dysfunction accounts for over 50 million cases globally and is the leading cause of death. Early intervention via antibiotic therapy, ventilator management, blood glucose maintenance, red blood cell transfusions, and fluid resuscitative strategies reduce mortality from sepsis when supported by appropriate diagnostics and ongoing monitoring. Notably, the latest Surviving Sepsis Campaign guidelines (Sepsis-3) has established blood lactate levels as a key vital sign for septic shock and acknowledged that early management of infection can reverse lactic acidosis and shock status. Every hour of delay in treatment from the time of diagnosis to antibiotic therapy increases mortality of septic shock by 7.6%. Thus, there has been great interest in culture- independent analysis at the point of care for early sepsis diagnosis, management, and prevention of antibiotic overuse. Current clinical literature has highlighted lactate, glucose, hematocrit, and oxygen saturation as early biomarkers of sepsis diagnosis and ongoing monitoring of therapy, be it fluid resuscitations to deal with hypoperfusion; insulin infusion to deal with hyperglycemia; packed blood cell transfusions to deal with anemia; or oxygenation therapies to deal with shock. However, compliance with the Sepsis-3 mandated timely lactate and other analytical measurements is poor due to various pre-analytical and analytical challenges. Notably, capillary blood glucose monitoring devices based on strips are labor intensive and erroneous, while blood gas analyzers have long turnaround times and waste substantial blood volume in patients who may already be anemic. Timely knowledge of the big 4 critical analytes (glucose, lactate, hematocrit and ScvO2) can allow prompt and appropriate administration of antibiotic therapy and supporting interventions thereby significantly reducing morbidity and mortality. This forms the basis of the patient-attached automated 4-plex measurement system proposed by Cascade Metrix (CMX). The CMX Automated Multiplex Analyzer (AutoPlexer) is a patient-attached system that enables timely, accurate, and cost-efficient delivery of automated lactate, glucose, hematocrit and oxygen saturation measurements in whole blood using proven electrochemistry and spectrophotometry without the need for any caregiver sample handling of infectious blood or any blood loss to the patient. The AutoPlexer system performs measurements at user-defined intervals or on-demand by pulling micro-volumes of blood across the sensors for measurement followed by a safe return of the blood using saline in a completely closed-loop, heparin-free, sterilized and biocompatible tubing-based blood pathway. Prior to each measurement, the system performs an automatic calibration to ensure high accuracy. A pilot pre-clinical study in rat and swine models has been performed which helped validate the preliminary design of the prototype for automated glucose meas...