Microelectrodes for in-vivo determination of pH - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 290

10.5.6 Measurement of pH under skin
The pH of intact skin ranges from about 4.8 to 6.0, while interstitial fl uid exhibits a
pH that is near neutral. The low pH on skin is attributed mainly to the presence of
the so-called “acid mantle”, a natural skin barrier to the external environment [172].
Wagner et al. [173] measured both in-vivo and in-vitro pH profi les across human stra-
tum corneum (SC) using the tape stripping technique and a fl at surface pH electrode
(InLab 426 from Mettler Toledo). They found a steep pH increase from pH 6 to 8 in

the fi rst 100 m after the removal of the SC.

Transdermal drug delivery based on iontophoresis delivers drugs across the skin and
into the body through the application of an electric current or voltage. Iontophoretic
transportation of drugs in ionized (charged) or molecular (neutral) form through the
skin may occur through diffusion driven by a concentration gradient, migration driven
by an electric fi eld, and convection driven by electroosmotic solvent fl ow [174]. The
pH in the drug carrier, as well as the pH across the skin, are both important for the
effective penetration of the drugs.
The effect of pH on skin permeability, accumulation, and penetration was studied
for some important drugs such as insulin for glucose control [175], acyclovir for HIV-
related conditions [176] and 5-fl uorouracil for cancer treatment [177].
Safety is an important factor when determining the quality of any iontophoresis
electrode. During transdermal iontophoretic delivery using metal electrodes, an applied
DC current will induce pH changes on the electrode/skin interface [178]. pH measure-
ment is used to eliminate the possibility of unsafe pH changes (chemical burns). It has
been reported that the pH shift caused by platinum electrodes has a signifi cant infl u-
ence on the permeation and stability of insulin [175].
Another application of pH measurement in skin is for the development of non-invasive
glucose biosensor. Reverse iontophoresis has been used to extract glucose from inter-
stitial fl uid across skin for non-invasive glucose measurement in diabetes management.
The amount of glucose extracted through electroosmotic fl ow at the glucose biosen-
sor has been demonstrated to correlate with blood glucose in diabetic patients [179].
Tamada and Comyns [174] have investigated the impact of the buffer type, pH, ionic
strength, and buffer concentration on the magnitude of electroosmotic extraction
through the skin in human subjects. They demonstrated that electroosmotic extraction
was signifi cantly enhanced with an increase in pH or a decrease in the ionic strength of
a carrier solution.

µ

10.5.7 Measurement of pH in the eye
pH is strictly regulated in the retina to maintain normal functions. Neuronal activity
and energy metabolism activities can result in signifi cant pH shifts. Severe pH fl uctua-
tions or changes in retinas can have devastating consequences [180, 181].
pH sensitive microelectrodes have been used to obtain spatial pH profi les in retina
and to examine the effects of acute hypoxemia and hyperglycemia on retinal pH, to