Physiological monitoring of tissue pH: In vitro characterisation and in vivo validation of a quinone-modified carbon paste electrode

Abstract

The fluctuation of physiological pH from homeostatic levels has the potential to cause life threatening complications unless counteracted in a timely manner. Therefore, the development of reliable and accurate sensors for the continuous monitoring of pH is of vital importance for clinical monitoring. Herein, we describe the extensive in vitro characterisation of a quinone-modified carbon paste electrode (CPE) and its subsequent in vivo validation in the peripheral tissue of anaesthetised rats. Sensocompatibility investigations identified stable and accurate measurements in lipid (phosphatidylethanolamine; PEA) and protein (bovine serum albumin; BSA) solutions when the pH sensor was continuously cycled for nine hours in the physiological contaminants. The influence of endogenous electroactive molecules e.g., ascorbic acid and uric acid and pharmacological interferents e.g., acetaminophen and acetylsalicylic acid was deemed negligible on the pH sensitive peak. Furthermore, there was no impact of ionic strength and the quinone oxidation peak remained selective for H þ over other endogenous cations. The effect of temperature and a pseudo reference electrode (PRE) on the sensor performance have also been elucidated. The efficacy of the modified-CPE to respond to in vivo tissue pH dynamics was demonstrated using a model of peripheral ischaemia and sodium bicarbonate injections. Collectively, this body of evidence clearly support the ability of the quinone-modified CPE to continuously measure pH fluctuations under physiological conditions.

Non-Invasive Monitoring of pH and Oxygen Using Miniaturized Electrochemical Sensors in an Animal Model of Acute Hypoxia

“…Although different sensors have been already tested in vivo to detect hypoxia and acidosis [11,20,22], most of them are invasive or not compatible to be inserted for long periods of time in fetal tissue without compromising fetal wellbeing.…”

“…Going in this line, previous evidences have demonstrated the feasibility of sensors devices inserted in different tissues, including vascular system [10][11][12][13], brain [14][15][16][17], gastric system [18], subcutaneous or intramuscular [19][20][21][22], to monitor and detect acid-base status. However, most of these sensors are not designed to be used in fetuses during intrauterine period.…”

Novel Self-Calibrating Amperometric and Ratiometric Electrochemical Nanotip Microsensor for pH Measurement in Rat Brain

“…The past decades have witnessed progressive developments in pH monitoring technologies, such as nuclear magnetic resonance, − fluorescence, − surface-enhanced Raman scattering, , and electrochemical methods. − At present, the most common method for measuring pH is the electrochemical assay based on conventional microelectrodes with high spatial resolution, simplicity, and high sensitivity. However, most pH detections were performed using potentiometric sensors, and only a few of them were used to measure the pH e of cells, and even fewer were used to in vivo measure the pH e of mammalian cells. − Recently, a different approach for pH measurement involves the use of voltammetric techniques.…”

“…However, most pH detections were performed using potentiometric sensors, and only a few of them were used to measure the pH e of cells, and even fewer were used to in vivo measure the pH e of mammalian cells. − Recently, a different approach for pH measurement involves the use of voltammetric techniques. There are two ways to introduce pH sensitivity to voltammetric pH probes: chemically modifying an electrode surface with a pH-responsive chemical species or using intrinsic functional groups on the surfaces of carbon electrodes. − In this case, a pH-dependent mediator is selected, and its electrochemical activity is monitored (reduction or oxidation). A popular choice is quinone moieties, which have been previously utilized in the literature. − For example, the pioneering work of Wightman’s group, which depended on fast-scan cyclic voltammetry, opened a great way for characterizing the local pH changes in brains .…”

“…There are two ways to introduce pH sensitivity to voltammetric pH probes: chemically modifying an electrode surface with a pH-responsive chemical species or using intrinsic functional groups on the surfaces of carbon electrodes. − In this case, a pH-dependent mediator is selected, and its electrochemical activity is monitored (reduction or oxidation). A popular choice is quinone moieties, which have been previously utilized in the literature. − For example, the pioneering work of Wightman’s group, which depended on fast-scan cyclic voltammetry, opened a great way for characterizing the local pH changes in brains . However, such devices often suffer from instabilities and/or drifts and therefore require constant recalibration.…”