Microelectrodes for in-vivo determination of pH - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 259

have also shown that ischemia from reduced cerebral blood fl ow can lead to brain tissue
acidosis, which can cause brain damage [15]. Finally, pH measurements in the eye have
revealed that hyperglycemia induce an acidifi cation of 0.12 pH in the retina, which may
contribute to the development of diabetic retinal disease [16].
The importance of monitoring pH changes during neural stimulation has been dem-
onstrated in studies for cochlear [17], retina [18, 19], spinal dorsal horns [20], and
dopamine cell bodies in the brain [21]. A shift in pH due to electrical stimulation will
change the electrode's corrosion potential and cause electrode materials to dissolve.
More importantly, pH changes will also affect cell function and cause tissue damage,
by altering the structure and activity of proteins, ionic conductance of the neural mem-
brane, and neuronal excitability. Measurements of pH changes are important for study-
ing the tissue/electrode interaction. This aids in the development of neural prostheses
and stimulation protocols to ensure minimal pH changes and provide safe electrical
stimulations.
10.1.2 Techniques of measurement of pH in vivo
A variety of techniques have been used for the measurement of pH. These techniques
range from simple pH dye indicator, to conventional pH electrodes, to very sophis-
ticated pH systems employing spectrometers such as nuclear magnetic resonance
(NMR) spectroscope [22]. Based on the nature of the physical detection used in trans-
ducers, pH measurement systems can be mainly classifi ed as optical, gravimetric,
and electrochemical. Optical detection systems are based on light-sensitive elements.
Gravimetric transducers are based on sensitive detection of mass changes following
concentration changes. Electrochemical detection using pH sensing electrodes is based
on detection of changes in potential, current or impedance.
The optical signal detection of pH can be conducted by spectrophotometric, spec-
trofl uorimetric, or other related techniques [23]. Spectrometric pH sensors consist of
functional organic or inorganic indicator dye incorporated in porous glass beads (e.g.
sol-gel glasses). These sensors are interfaced with a spectrometer, allowing colorimetric
changes with pH to be measured. The indicator dyes are incorporated into the sensor
device by non-covalent entrapment within the sol-gel matrix [24] or by covalent bind-
ing [25]. However, many of these devices suffer from drawbacks such as dye leaching
and slow response times [26].
Various optical detection methods have been used to measure pH in vivo .
Fluorescence ratio imaging microscopy using an inverted microscope was used to
determine intracellular pH in tumor cells [5]. NMR spectroscopy was used to continu-
ously monitor temperature-induced pH changes in fi sh to study the role of intracellular
pH in the maintenance of protein function [27]. Additionally, NMR spectroscopy was
used to map in-vivo extracellular pH in rat brain gliomas [3]. Electron spin resonance
(ESR), which is operated at a lower resonance, has been adapted for in-vivo pH meas-
urements because it provides a suffi cient RF penetration for deep body organs [28].
The non-destructive determination of tissue pH using near-infrared diffuse refl ectance
spectroscopy (NIRS) has been employed for pH measurements in the muscle during