Real-Time Monitoring of Critical Care Analytes in the Bloodstream with Chemical Sensors: Progress and Challenges

Abstract

We review approaches and challenges in developing chemical sensor-based methods to accurately and continuously monitor levels of key analytes in blood related directly to the status of critically ill hospitalized patients. Electrochemical and optical sensor-based technologies have been pursued to measure important critical care species in blood [i.e., oxygen, carbon dioxide, pH, electrolytes (K(+), Na(+), Cl(-), etc.), glucose, and lactate] in real-time or near real-time. The two main configurations examined to date for achieving this goal have been intravascular catheter sensors and patient attached ex vivo sensors with intermittent blood sampling via an attached indwelling catheter. We discuss the status of these configurations and the main issues affecting the accuracy of the measurements, including cell adhesion and thrombus formation on the surface of the sensors, sensor drift, sensor selectivity, etc. Recent approaches to mitigate these nagging performance issues that have prevented these technologies from clinical use are also discussed.

Rapid assessment of shock in a nonhuman primate model of uncontrolled hemorrhage

“…19,21,22,40 Increased circulating lactate has been used in patient risk stratification, and levels greater than 4 mM have been associated with poor outcomes. [16][17][18]41 Within the literature, there is considerable support for the use Figure 2. Blood loss analysis between survivors and nonsurvivors.…”

“…7 For this reason, focus is shifting to technologies capable of detecting impaired microvascular function or tissue perfusion either regionally (i.e., tissue oxygen saturation [StO 2 ]) and/or globally (i.e., end-tidal carbon dioxide [ETCO 2 ] and circulating lactate) in a quest to find earlier and more confident indicators of shock severity. [14][15][16][17][18][19][20][21][22][23][24][25][26][27] Despite several lines of supportive evidence, clinical application of such technologies to monitor the severity of shock and guide resuscitation has been limited.…”

Optical Sensor for Real‐Time pH Monitoring in Human Tissue

“…Blood pH analysis is one of the most common and frequently performed tests on critically ill patients in the operating room and in the Intensive Care Unit . These pH test results guide the management and diagnosis of many life‐threatening illnesses as they indicate a patient's acid‐base balance .…”

“…Ratiometric‐based detection methods give rise to a stable referenced signal and account for environmental variability at the implantation site, thereby ensuring that the sensor is immune to instabilities such as light source drift, detector variations, and photobleaching effects. In addition, fiber‐based sensors can be directly placed in human arteries, veins, or tissue and deliver real‐time and continuous monitoring of key blood analytes . These sensors can be integrated with existing catheters which can lower the barrier for adoption, as it requires little modification to existing clinician behavior.…”

Electrochemical DNA-Based Immunoassay That Employs Steric Hindrance To Detect Small Molecules Directly in Whole Blood

“…7−9 The ability to readily detect other small molecules at home, such as amino acids, lipids, sugars, or various therapeutic drugs, would open key avenues in diagnostics and treatment for various diseases and disorders, 10,11 including heart disease, 12 cancers, 13,14 and neurodegenerative diseases, 15 such as multiple sclerosis, 16 amyotrophic lateral sclerosis, 17,18 Alzheimer's, and Parkinson's. 11 However, the main challenges that have slowed down the commercialization of new quantitative home meters are that enzyme-based sensing mechanisms are hardly adaptable for the detection of most small molecules 19 while other assays based on electrocatalysis 20−24 or biorecognition 25−28 typically fail when performed directly in whole blood (e.g., sensor drift due to biofouling 27,28 ), or remain too cumbersome to be employed at home.…”