Project Summary/Abstract Blood gas analysis is a cornerstone of modern critical care medicine, providing essential insights into a patient's respiratory and metabolic status. Measurements of blood pH as well as oxygen and carbon dioxide levels enable diagnosis and management of a wide range of life-threatening medical conditions, including respiratory failure and acid-base imbalances due to circulatory shock or metabolic derangement. The accurate and timely assessment of blood gases is essential for effective treatment in the intensive care unit (ICU), particularly for mechanically ventilated patients where adjustment of ventilator settings depends upon these measurements. Blood gas mea- surements are typically made by drawing blood from an indwelling arterial or venous catheter and sending this blood to a central core laboratory, where the analysis is run on calibrated machines and results then reported back to the point of care. This process leads to delays in interpretation and clinical action and limits the availability of blood gas analysis in many healthcare settings, including critical care patient transport and disaster medicine scenarios involving field hospitals. Existing point of care blood gas analyzers suffer from limitations in accuracy and cost and do not allow for high-frequency of measurements. The proposed program leverages novel physiologic sensors developed at the Wellman Center for Photo- medicine to create and validate new technology for accurate, rapid, point-of-care, and high-frequency blood gas analysis. Aim 1 will create a miniaturized and automated device that attaches externally to a standard arterial catheter setup and allows direct sampling and immediate blood gas analysis from a small volume of blood at the bedside. This device will be first tested in a preclinical swine model and subsequently validated using human sam- ples from the intensive care unit, with results benchmarked against gold-standard hospital laboratory blood gas analyzers. Aim 2 will develop next-generation continuous blood gas sensing technology leveraging miniaturized fiber optic devices incorporated into an insert compatible with existing arterial catheters. This simple-to-operate, continuous sensor will be similarly tested in a swine model system against current point-of-care devices. Together, these Aims will significantly expand the accuracy, efficiency and accessibility of blood gas analysis and augment the clinical utility of these measurements for many high-stakes scenarios in modern medicine.