Nanoelectrochemistry: Fundamentals and Applications in Biology and Medicine - Applications of Electrochemistry and Nanotechnology in Biology and Medicine - page 51

onto the surface of interest. Using this approach, Beck et al. creat-
ed gold interdigitated electrodes, with electrodes as narrow as 200
nm being made on a 2-in wafer scale in one step. 205 This approach
offers an appealing alternative to lithographic processing.
2. Probing Cells
The use of electrodes for detection of neurotransmitters in-vivo has
a long history beginning with the pioneering work of Adams,
where the direct electrochemistry of catecholamines in the central
nervous system was first demonstrated. 206, 207 With the advent of
UMEs in the early 1980s, the spatio-temporal resolution of these
methods was greatly extended in both in-vivo as well as cultured
cells, and Wightman's group demonstrated that individual exocy-
totic events could be directly monitored on the millisecond time-
scale by use of amperometric measurements. 208 Since then, cellular
exocytosis has been investigated on a variety of cell types, includ-
ing adrenal chromaffin cells, rat pheochromocytoma (PC12) cells
and human or mouse pancreatic ȕ-cells. The candidate cell systems
are limited to those that release an oxidizable substance, which are
often catecholamines, serotonin or tyrosine/tryptophan-type com-
pounds. The most common measurement techniques employed are
amperometry and fast-scan cyclic voltammetry (FSCV). FSCV is
more suitable for in-vivo studies, since the cyclic voltammograms
of species serve as signatures useful for identification. Amperome-
try is more suitable for direct measurement of exocytosis in culture
cells.
Since the literature in this area is enormous we will only deal
briefly with the possibilities of using nanoelectrodes in such am-
perometric measurements. For more background information, the
reader is directed to several recent reviews. 209-212 Nanoelectrodes
are expected to yield several benefits over UMEs for the studies of
exocytosis. As mentioned earlier, by virtue of a faster RC time-
constant, the temporal resolution of amperometric measurements
can be lowered to the sub-millisecond domain. Most studies of
exocytosis are conducted on nonsynaptic cell models that have
large vesicles (0.25-1 ȝm diameter). With nanoelectrodes one can
hope to measure release from synaptic vesicles (20-50 nm diame-
ter). Because of reduced effects of uncompensated resistance ( iR
drop), they can also help mitigate peak distortions in FSCV. Spa-