Biosensing Detection - Bioinspired Approaches for Human-Centric Technologies - page 80

an all-organic biomedical device fashion. The most employed materials are
polyanilines (PANI), polypyrroles (PPy), and polythiophenes (Guimard
et al. 2007 ; Muskovich and Bettinger 2012 ). A fundamental requirement limiting
the use of polymers for prolonged in vitro operation or in vivo conditions is that
they must retain conductivity under physiological conditions (pH

¼

7 in aqueous
media): this is verified in PPy but not in PANI, which has therefore limited its
application in bioelectrodes; conversely, PPy has been extensively used for the
electrical stimulation of neuronal lines, in neural probes, and in bio-actuators
(George et al. 2005 ). Unfortunately, PPy is subjected to irreversible oxidation.
Compared to PPy and PANI, polythiophenes offer the advantage of superior
electrical properties, easier biochemical functionalization, better processability,
and improved electrochemical stability under physiological conditions. These fea-
tures have determined an increasing interest for this material. Biocompatibility has
been widely demonstrated in a number of cells, such as PC12, fibroblasts, endo-
thelial cells, neuroblastoma cells, and cortical neural cell lines as well as living
neurons. PEDOT:PSS in particular is a heavily doped p-type organic semiconduc-
tor, in which holes on the PEDOT chains (the semiconductor) are compensated by
sulfonate anions on the PSS (the dopant). Thanks to its optimal properties of
conductivity, chemical and electrical long-term stability, relatively low interfacial
impedance, and processability easiness, PEDOT:PSS have emerged as the “golden
material” for neural interfaces applications, and it is currently in process for FDA
approval.
The first demonstration of inherent PEDOT cytocompatibility was reported by
Martin and co-workers: they were able to develop integrated systems made between
the polymer and living cells, by means of in situ polymerization. They reported an
integrated neuro-electrode interface with neuroblastoma cells characterized by
impedance values one order of magnitude lower than PEDOT films prepared ex
vitro; the same group demonstrated polymerization of a PEDOT network around
living neuronal cells (Richardson-Burns et al. 2007a ) and finally throughout living
brain tissue (Richardson-Burns et al. 2007b ). The reduced impedance of the contact
prompted use of PEDOT:PSS for the fabrication of single electrodes as well as
microelectrode arrays (MEAs).
In 2011 Malliaras and co-workers (Yang et al. 2011 ) realized PEDOT:PSS
microelectrodes used as sensitive sensors for the detection of individual transmitter
release events from single cells. In other words, they were able to fabricate a
“semiartificial synapsis” in which individual exocytosis event is electrochemically
detected by the polymer microelectrode. The possibility of using conducting poly-
mers for such an application relies on three constraints: (1) they must have adequate
temporal resolution; (2) they must be patterned to single cell dimensions; and
(3) they must be carefully insulated to reduce background noise and to resolve
the small currents associated with detection of individual release events. It was
demonstrated that the PEDOT:PSS microelectrode, properly covered by a
fluoropolymer and insulated by a photoresist, matches all these requirements,
with a detection capability in the same range of standard recording devices based
on carbon fibers electrodes.