Conducting Polymer Nanomaterials For Biomedical Applications: Cellular Interfacing and Biosensing

See discussions, stats, and author profiles for this publication at: https://www.researchgate.
net/publication/262890963
Conducting Polymer Nanomaterials for Biomedical Applications:

Cellular Interfacing and Biosensing
Article in Polymer Reviews · July 2013

DOI: 10.1080/15583724.2013.805771
CITATIONS READS
110 1,565
3 authors, including:
Oh seok Kwon
Yale University
134 PUBLICATIONS 5,687 CITATIONS
SEE PROFILE
All content following this page was uploaded by Oh seok Kwon on 20 January 2015.
The user has requested enhancement of the downloaded file.

This article was downloaded by: [Seoul National University]
On: 08 August 2013, At: 19:14
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Polymer Reviews
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lmsc20
Conducting Polymer Nanomaterials

for Biomedical Applications: Cellular
Interfacing and Biosensing
a a a
Wan-Kyu Oh , Oh Seok Kwon & Jyongsik Jang
a
World Class University (WCU) Program of Chemical Convergence
for Energy & Environment (C2E2), School of Chemical & Biological
Engineering, Seoul National University , Seoul , Korea
To cite this article: Wan-Kyu Oh , Oh Seok Kwon & Jyongsik Jang (2013) Conducting Polymer
Nanomaterials for Biomedical Applications: Cellular Interfacing and Biosensing, Polymer Reviews,
53:3, 407-442
To link to this article: http://dx.doi.org/10.1080/15583724.2013.805771
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions
Polymer Reviews, 53:407–442, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 1558-3724 print / 1558-3716 online
DOI: 10.1080/15583724.2013.805771
Conducting Polymer Nanomaterials for Biomedical

Applications: Cellular Interfacing and Biosensing
WAN-KYU OH∗ , OH SEOK KWON∗ , AND JYONGSIK JANG

World Class University (WCU) Program of Chemical Convergence for Energy
& Environment (C2E2), School of Chemical & Biological Engineering,
Seoul National University, Seoul, Korea
Downloaded by [Seoul National University] at 19:14 08 August 2013
Recently, conducting polymer (CP) nanomaterials have shown outstanding chemical

and physical properties compared with ceramic and metal nanomaterials. Thus, sig-
nificant efforts have been made to fabricate CPs that enable various biomedical ap-
plications, such as high-performance biosensing and cellular interfacing. Although
sensing or measuring devices based on CP nanomaterials have shown excellent elec-
trical and physical properties, their limitations, such as the minimum detectable level
(MDL), cytotoxicity assessments, and reliable synthesis methods, remain challenges
to realizing high-performance biomedical geometries. In this article, we provide the
general information on CP nanomaterials and their biomedical applications focusing
especially on cellular interfacing and biosensing. Moreover, we discuss perspectives for
state-of-the-art biomedical geometries using various CP nanomaterials.
Keywords conducting polymer, nanomaterials, cytotoxicity, biosensor, cellular inter-

facing, biomolecule detection
1. Introduction
Bioapplications of conducting polymer (CP) nanomaterials are attractive because of their
inherent biocompatibility and unique optical and electrical transduction mechanisms.1–3
CPs consisting of conjugated π -electron systems also offer advantages of enhanced chem-
ical and physical properties.4,5 The most attractive characteristic properties of CPs for
biomedical applications include the following: i) CPs are easily fabricated by chemical and
electrochemical polymerization, ii) their polymer structure is readily modified by synthetic
variables, iii) they can be deposited on substrates via electrochemical deposition or drop-
casting methods, and iv) their biocompatibility enables various biomedical applications.
These features make CPs attractive for many biomedical applications.
CP nanomaterials are promising candidates that have shown excellent performance
in biomedical applications.6–13 Nanoscale CPs exhibit outstanding properties compared
to their bulk counterparts. Additionally, they possess unique properties associated with
high surface-to-volume ratios, such as highly sensitive sensing and low impedance with
cells. However, there are still few studies on the effects of interfacing CP nanomaterials in
biological systems: i) charge-transfer via CP nanomaterial arrays, ii) immobilization of CP
Received March 4, 2013; accepted May 10, 2013.

∗
These authors contributed equally to this work.
Address correspondence to Jyongsik Jang, World Class University (WCU) Program of Chemical
Convergence for Energy & Environment (C2E2), School of Chemical & Biological Engineering, Seoul
National University, Gwanak 1, Gwanak-gu, Seoul 151-742, Korea. E-mail: jsjang@plaza.snu.ac.kr
407
408 W.-K. Oh et al.
Table 1
Representative CP structures (undoped form)
Name Structure
PPy
PANi
PT
PEDOT
nanomaterials and biomaterials, iii) cell adhesion properties on CP nanomaterials, and iv)
the cytotoxicity of size and shape-controlled CP nanomaterials. These critical issues should
be evaluated systematically for advanced biomedical technologies.
Here, we focus on four CP nanomaterials, polypyrrole (PPy), polyaniline (PANi),
polythiophene (PT), and poly(3,4-ethylenedioxythiophene) (PEDOT), for biomedical ap-
plications, including cellular interfacing and biosensing. Although other CPs are known, we
have concentrated on the applications of these four common CP nanomaterials. Molecular
structures of typical CPs are illustrated in Table 1.
Section 2 reviews the synthesis methods and provides a general overview of the chem-
ical and physical properties of CP nanomaterials. Although several articles have reported
on recently developed CP nanomaterials, this section describes the introduction of conven-
tional synthetic methodologies and biomedical applications of CP nanomaterials. Section 3
covers interactions between cells and CP nanomaterials, including cytotoxicity, neural in-
terfaces, tissue engineering, and drug delivery. Section 4 introduces biosensor applications,
such as protein receptor-based biosensors, hormone sensors, aptasensors, DNA sensors,
immunoassays, and glucose sensors. Because much research has been conducted in this
field, we focus selectively on representative research on the biomedical applications of CP
nanomaterials. Finally, the Outlook section provides a summary and discussion of future
directions to construct state-of-the-art biomedical geometries.
2. Synthesis and Biomedical Applications of CP Nanomaterials
2.1 Synthesis of CP Nanomaterials

CPs that belong to the class of organic materials were first identified in the 1980s.14 CPs
have facilitated the development of electric devices including organic light-emitting diodes,
supercapacitors, solar cells, fuel cells, field-effect transistors (FETs), and sensors.15–23 Re-
cently, rapid advances in nanotechnology have motivated researchers to achieve significant
Conducting Polymer Nanomaterials for Biomedical Applications 409
developments in various fields due to ultrafine features at the nanometer scale.24–28 CP

nanomaterials have been tailored for unique chemical properties, including facile syn-
thesis, simple functionalization, and structural diversity.29 Moreover, the electrical and
physical characteristics of nanoscale materials, which differ from those of bulk materials
have played a key role in the fabrication of CP nanomaterials. These unique properties
of CP nanomaterials have led to widespread interest in various applications.23,30–33 Thus,
numerous CP nanomaterial fabrication processes have been developed, and the outstanding
performance of CP nanomaterials in the field of electrical devices has been demonstrated.
Although novel and simple manufacturing processes have been proposed, advanced tech-
nical methodologies to tailor and control the properties of CP nanomaterials still remain a
challenge. Here, we introduce versatile strategies for the fabrication of CP nanomaterials:
soft- and hard-template and template-free methods.
2.1.1 Soft-Template Methods. Diverse morphologies of CP nanomaterials have been con-

trolled using various soft-templates, such as surfactants, liquid crystalline polymers, and
cyclodextrin.34–37 Surfactants, including cationic, anionic, and non-ionic amphiphiles, have
been used as nanoreactors to form micelles.38–41 Nanoreactors can be generated in mi-
croemulsions consisting of mixtures (water, oil, and surfactant), leading to a useful matrix
for polymerization reactions (Fig. 1a).40,42–45 Thus, this methodology enables the prepara-
tion of ultrafine nanomaterials within the size range of 10–100 nm in diameter and with
Figure 1. Synthesis processes of CP nanomaterials: a) Soft-template method. b) Hard-template

method. c) Template-Free Method (Color figure available online).
410 W.-K. Oh et al.
a narrow size distribution due to the spherical or cylindrical micelles. We have designed
various CP nanomaterials, including PEDOT nanotubes (NTs), PPy nanoparticles (NPs),
and PPy NTs, using soft-template methods.46–48 Also, useful advantages of these CP nano-
materials were confirmed in various applications. Specifically, to fabricate high-quality
CP nanomaterials, polymerization by soft-template methods should be carefully controlled
because it is kinetically and thermodynamically unstable (Ostwald ripening).
2.1.2 Hard-Template Methods. Hard-template methods, which are among the most facile
synthesis methods, are helpful for controlling the dimensions of nanomaterials.49,50 One-
dimensional (1D) nanomaterials including NTs, nanorods (NRs), and nanofibers (NFs) can
be easily prepared by hard-template methods. There are various kinds of hard-templates,
including anodic aluminum oxide (AAO) and polycarbonate (PC) membranes.51–53 AAO
membranes are among the most commonly used hard templates and have various pore
sizes. Figure 1b shows the fabrication process of CP NTs using an AAO template. Based
on this process, PPy NTs were recently developed,54 and PEDOT NTs and particles in NTs
were also introduced. Moreover, their diameters and lengths were precisely tailored using
various AAO pore sizes.55,56 Hard-template synthesis is able to control the wall thickness
of 1D nanomaterials within a range of a few nanometers and can also be used to construct
CP nanocomposites, with additional processes.
2.1.3 Template-Free Methods. Template-free approaches have been extensively investi-

gated for fabricating diverse CP nanomaterials owing to their simple fabrication process,
which does not require a specific sacrificial template.57–59 Compared with other meth-
ods, template-free methods are suitable for constructing simple, uniform, and high-quality
CP nanomaterials. Especially, remarkable achievements in template-free methods have
been made by the Kaner and Gleason groups.60,61 Recently, we have also demonstrated
a novel template-free process to fabricate shape- and size-controlled CP nanomaterials
(Fig. 1c).62,63 In particular, for the first time, multidimensional CP nanomaterials with
unique nanostructures (NRs and nanonodules) on their surfaces were created using vapor
deposition polymerization (VDP) under optimized temperature and pressure conditions.62
2.2 Biomedical Applications of CP Nanomaterials

To use CP nanomaterials for biomedical applications, cytotoxicity assessments are essen-
tial; however, they have generally been neglected. Although CPs are generally known as
safe materials, the unique physicochemical properties of CP nanomaterials can induce
adverse biological effects on living cells.64 The surface area of nanomaterials increases
exponentially with decreasing size, resulting in increased uptake and interaction with bio-
logical tissues. Only a few papers have been published concerning the cytotoxicity of CP
nanomaterials. Thus, systematic toxicity evaluations of CP nanomaterials will be impor-
tant for understanding toxicological issues associated with nanomaterials and providing
toxicological information regarding biomedical applications.
The investigation of neuronal development and outgrowth has received considerable
attention from biomedical engineers over the past few decades.65–67 Several research groups
have exploited CP nanomaterials to improve the properties of neural interfaces and in tissue
engineering.68,69 Such CP nanomaterials were substituted for metal electrodes because of
their enhanced charge-transfer characteristics, leading to high cell adhesion in biological
assays.69 Because neuronal stimulation and monitoring are required for many clinical
diagnostics and remedies, the unique electrical properties of CP nanomaterials may provide
advantages for therapeutic and other purposes.70,71 Additionally, the electronic properties of
CP nanomaterials can be modified according to the charge transport required for electrical
cellular interfacing.
CPs nanomaterials can be subjected to large strains and have high strength even
though they are light weight, and they can be applied at body temperature and in body
circulation.72–74 Moreover, CP nanomaterials can be actuated or tuned with existing
technologies. Therefore, CP nanomaterials have advantages in drug delivery systems, that
is, the process of releasing a pharmaceutical compound at specifically targeted points in the
living body, which could control administration of a therapy through some physiological
or chemical trigger. To realize such a system, researchers have made efforts in the field of
CP nanomaterials.
Developing high-performance biosensors is of great interest in the fields of national
security, food safety testing, and environmental monitoring.75–77 Thus, the preparation
of well-controlled nanomaterials having sensitive and selective analyte detection is an

important and challenging goal. The following issues require further consideration for
high-performance biosensor design: i) an enlarged surface area for enhanced interactions
with analytes and ii) chemical functionalization for selective responses.23,78–80 Based on
these considerations, NT various carbon-based nanomaterials including graphene and
carbon NTs (CNTs), and metal- or ceramic-based nanomaterials have been shown to
control sensing in devices. Numerous studies on carbon nanomaterial-based biosensors
have been performed to advance the development of next-generation biosensors.81–84
Although carbon-based biosensors offer advantages in biosensing applications, intrinsic
shortcomings still remain due to their inert surfaces.
CP nanomaterials can be used in miniaturized biosensors that enable a cost-efficient,
portable, and high-density design.77,78,80,85,86 In particular, functionalized CP nanomate-
rials exhibit improved sensing performance via the immobilization process.23,78,87–90 The
modification is readily achieved by grafting functional groups onto the polymer backbone,
leading to stability in the liquid state compared with non-covalent bonding. CP nanomate-
rials will open up novel biosensor applications and likely play an expanding role in future
biosensor technology.
3. Cellular Interface
3.1 Cytotoxicity of CP Nanomaterials

Prior to the widespread application of nanomaterials in the biomedical field, biocompatibil-
ity testing is necessary.26,64,91–95 Few researchers have performed toxicological assessments
of nanomaterials that have been proposed for bioapplications, even though the biologi-
cal effects of these nanomaterials are clearly important. In particular, the cytotoxicity of
CP nanomaterials has rarely been reported, even though CP nanomaterials have received
much attention for bioelectronics and biomedical applications, due to their high conductiv-
ity, outstanding stability, and potential biocompatibility.96,97 Size-controlled and uniform
nanomaterials without aggregates are necessary for accurate toxicity assessments. How-
ever, the synthesis of monodisperse CP nanomaterials is still a great challenge in nano
research because of destabilizing mechanisms such as Ostwald ripening, phase inversion,
and cramping.91,98,99
The Jang group has devoted much effort to the fabrication of CP nanomaterials with
various controlled sizes and shapes and to the systematic cytotoxicity testing of these
materials. Jang et al. have reported nano-sized effects of PPy NPs on pulmonary cytotox-
412 W.-K. Oh et al.
icity and innate immune responses in human lung fibroblast (IMR90) and mouse alveolar
macrophage (J774A.1) cells as models (Fig. 2).96 The PPy NPs were generally uptaken
into IMR90 cells via endocytosis. In the J774A.1 cells, the PPy NPs were internalized via
both endocytosis and phagocytosis. In both cell lines, the internalized NPs were delivered
by the endosome network and located at lysosomes. Various assay results, including the
ATP assay, reactive oxygen species (ROS) generation test, and apoptosis assay, indicated
dose- and size-dependent toxicity of PPy NP-treated cells. Moreover, the toxic responses
were inversely proportional to the size of the NPs.
Other studies have shown the biocompatibility of PPy nanomaterials. PPy-cellulose
nanocomposites showed good biocompatibility and stability in mammalian cells over
48 h.100 The main reason for toxicity was believed to be impurities and reactants from
the nanocomposites; indeed, no significant toxicity was observed after thorough washing.
Figure 2. a) SEM images of the PPy NPs with various diameters (20, 40, 60, 80, and 100 nm);
below: size distribution histograms. b) TEM images of PPy NP-treatedIMR90 cells for 24 h (25 mg
mL−1) (scale bar: 2 mm). The left indicates the extended TEM images of the boxed area in (b) (scale
bar: 500 nm). Red arrows indicate the PPy NPs. (N: the nucleus, mi: the mitochondria, and PM:
the plasma membrane). Reproduced from Kim et al.96 with permission from Elsevier (Color figure
available online).
PPy microparticle induction did not show any harmful symptom or immune-related hema-
tological parameters in mice over 6 weeks.101 Based on these results PPy nanomaterials
can generally be used in biomedical applications without harmful effects; however, smaller
particles may be harmful and impurities should be removed carefully before use. Vaitku-
viene et al. reported PPy nanoparticles synthesized by oxidative polymerization could be
cytotoxic for primary mouse embryonic fibroblasts, mouse hepatoma cell line, and human
T lymphocyte Jurkat cell lines at high concentration, while the PPy nanoparticles at low
concentration were biocompatible.102 This article is in conflict with previous reports, which
remains a controversial remark.
PEDOT nanomaterials, which are among the most attractive CPs, are extensively used
in biomedical science. Therefore, their toxicities in the living body should be confirmed be-
fore their widespread use.103–105 Oh et al. reported the cytotoxicity of and immune response
to PEDOT nanomaterials in IMR90 and J774A.1 cells (Fig. 3).99 Systematic investiga-
tions of the toxicity of PEDOT nanomaterials, such as cell morphological changes, risks
to cell viability, apoptosis/necrosis tests, ROS generation, and proinflammatory responses,
Figure 3. a) TEM images of PEDOT nanomaterials (width: (55 ± 20) and (50 ± 10) nm; PEDOT-
1, PEDOT-2, and PEDOT-3). b) Live cell differential interference contrast (DIC) and fluorescence
images of IMR90/J774A.1 cells incubated with PEDOT nanomaterials (25 mg mL−1): Green indicates
apoptosis; red means necrosis. Scale bars: 40 μm. Reproduced from Oh et al.99 with permission from
Wiley-VCH Verlag GmbH & Co. KGaA (Color figure available online).
414 W.-K. Oh et al.
focused on shape dependence. Interestingly, these results indicated that toxicity increased
with the decreasing aspect ratio of the nanomaterials in both cell lines. ROS generation was
dependent on the shape of the PEDOT nanomaterials, demonstrating the shape-dependent
toxicity of nanomaterials. As the concentration of the PEDOT nanomaterials increased, the
viability decreased. Interleukin-1 and interleukin-6 were induced by PEDOT nanomaterials
during short-term exposure; however, they were down-regulated after long-term incubation,
indicating that PEDOT nanomaterials can be considered safe materials in terms of immune
responses.
The toxicity of PANi nanomaterials of four different shapes was evaluated by Jang
and coworkers in human lung fibroblast cells.106 Similar to other CP nanomaterials, the
toxicity increased with decreasing aspect ratio of the nanomaterials. In contrast, the highest-
aspect-ratio PANi nanomaterials exhibited toxicity similar to that of bulk PANi materials,
indicating that the high-aspect-ratio CP nanomaterials did not possess unique properties
compared with bulk materials. The toxic effect of PANi nanomaterials was also proportional
to concentration and treatment time. Other assay results demonstrated that low-aspect-
ratio PANi nanomaterials were the most toxic mainly due to their high surface-area and
reactivity.
Additionally, we designed various CP NPs (PT, PEDOT, PANi, and PPy) with uniform
diameters using seeded polymerization onto silica NPs for accurate and comparative toxicity
assessments of CP NPs. The NPs were systematically estimated with in vitro cellular
uptake and viability tests in mouse macrophage RAW 264.7 and rat pheochromocytoma
PC-12 cells (Fig. 4).97 Cellular internalization of silica/CP core/shell NPs was attributed
to phagocytosis and endocytosis mechanisms. Among four different CP nanomaterials,
the silica/PT core/shell NPs were most cytotoxic toward cell lines because of the cellular
effects of sulfur atoms. Moreover, the Zn-S or Fe-S complexes that naturally form in
the living body generated ROS and may lead to several diseases. On the other hand, the
lowest toxicity was demonstrated by silica/PPy core/shell NPs. This research may offer
Figure 4. a) Schematic illustration of preparation of silica/CP core/shell NSs. b) Viability of RAW

264.7 and PC-12 cells incubated with PT, PEDOT, PANi, and PPy NSs for 24 h. ∗ Statistically
significant difference from control exposed to various NSs (P < 0.05). Reproduced from Jeong
et al.97 with permission from Elsevier (Color figure available online).
new insight into the cellular toxicity mechanism of nanomaterials. The reports regarding
the toxicity of four CP nanomaterials have generally presented no significant effect for cells
so far. In contrast, there have been many conflict results with respect to the nanotoxicity
such as ceria and silver nanomaterials. Various capabilities for bioapplications of the CP
nanomaterials demand urgent evaluation of their biocompatibility. Furthermore, simple and
accurate procedure for toxicity assessments ought to be developed in near future.
3.2 Neural Interfaces

Significant achievements in biological nanoscience have enabled controlled morphologies
of various nanomaterials, including CNTs and silicon nanowires (NWs), for neural in-
terfaces.107–110 Nanostructured materials have exhibited structure function relationships
similar to those of microelectrodes in neural interfaces, overcoming the size and bio-
compatibility issues inherent to microelectrodes.111 Owing to their electronic and ionic

conductivity, CPs have been used as bioelectronic interface materials for neural interfaces
and neuronal cell signaling detection.103 These CP nanomaterials have been used to con-
firm the reactive tissue responses from responsive neuron signaling. CP nanomaterials have
shown advantages compared with metal electrodes, including reduced electrode impedance
and enhanced charge injection capacity.10,112 CP nanomaterial-electrodes improve neuron-
electrode communication due to the high-surface-area of the CP nanomaterials, resulting
in enhanced charge transfer and specific selectivity. Inflammation or toxicity may decrease
the mismatch strain between the neurons and the electrode surface owing to the unique
properties of the CPs as soft materials. Reduced inflammation and toxicity resulted in
decreased thickness of the surrounding non-conductive fibrous tissue, which is believed
to cause low signal-to-noise ratios. In this section, three representative CP nanomaterials
(PEDOT, PPy, and PANi) are introduced as new advanced neural interface materials.
First, PEDOT nanomaterials exhibit high conductivity and chemical stability and have
been reported as useful neural recording materials. Kim et al. introduced MnO2 -decorated
PEDOT (PEDOT/MnO2 ) nanoellipsoids for real-time monitoring of neurons and en-
hanced neurite outgrowth (Fig. 5).113 The MnO2 domains on the surface of the PEDOT
nanomaterials were formed by redox deposition. The MnO2 domains facilitated neuron
cell differentiation, and PEDOT nanomaterials provided a safe matrix for cell growth.
Moreover, PEDOT/MnO2 nanoellipsoids were used for label-free real-time monitoring of
neuron cells, detecting released catecholamines from living cells. This research may open
possibilities for hybrid CP nanomaterials in cellular interfacing. Abidian et al. reported
PEDOT on biodegradable electrospun NFs that exhibited significantly improved electrical
properties (Fig. 6).114 The impedance of the electrodes decreased at 1 kHz, from 783 to
2.5 k. Additionally, PEDOT NT electrodes showed highly selective neural recordings
and high-performance long-term stability over a 7-week period. Significant signals and
high-quality discriminable neural units can be achieved with the lower impedance values
of PEDOT NTs. This can generate large phase lag biases in local field potentials analyzed
from chronic recordings.115
In the case of PPy, a porous nerve growth factor (NGF)-doped PPy nanoarchitecture was
prepared using self-assembly of polystyrene beads as a sacrificial template. The open pore
structure of PPy resulted in amplified actions in NGF release profiles, when combined with
electrical fields. The structure provided free diffusion of neurotrophic factors, favorable cell
adherence, and an electrically conductive surface, leading to enhanced cellular behavior.116
The Jang group introduced PANi micropatterns on polyethylene terephthalate sub-
strates for cell patterning and biomolecule detection from neuronal cells.117 PANi patterns
416 W.-K. Oh et al.
Figure 5. a) Schematic diagram of preparation of the PEDOT/MnO2 nanoellipsoids. b) experimental

setting of a sensor device. Reproduced Kim et al.113 with permission from Wiley-VCH Verlag GmbH
& Co. KGaA (Color figure available online).
were inkjet-printed and further modified with the arginine-glycine-aspartate (RGD) peptide
on the PANi pattern to selectively adhere to rat pheochromocytoma PC-12 cells. Cells were
patterned on the RGD-immobilized PANi pattern with high selectivity and growth. The
attached cells revealed focal adhesion on the pattern. Furthermore, the RGD-immobilized
PANi pattern was applied as a real-time electrical detector of biomolecular release from
the PC12 cells.
Figure 6. The fabrication steps of multifunctional polymer coated-neural electrodes: a) pristine

microelectrode, b) DEX-loaded biodegradable NFs by electrospun, c) alginate hydrogel coating,
d) PEDOT-coated electrodes. Reproduced from Abidian et al.114 with permission from Wiley-VCH
Verlag GmbH & Co. KGaA (Color figure available online).
3.3 Tissue Engineering

CPs have recently received much attention as advantageous substrates for tissue engineer-
ing scaffolds, because they can induce electrical stimuli for various cell types, including
neurons, osteoblasts, fibroblasts, and skeletal myoblasts.118–123 Because the orientation and
diameter of NFs present unique topographical features that affect the behaviors of many
cell types, CP NFs with well-controlled topographical features could be valuable as scaf-
fold materials for translating model studies in tissue engineering.124–127 However, research
on CP NFs for tissue engineering has progressed slowly because of the difficulty of CP
treatment, relatively. State-of-the-art techniques for the use of CP NFs in tissue engineering
are briefly introduced below.
One of the most promising CPs is PPy, which can be prepared by simple processes (in-
situ chemical oxidation or by VDP on a substrate) followed by oxidant treatment.47,128 PPy
418 W.-K. Oh et al.
NFs have shown attractive characteristics such as biocompatibility, facile modulation of

adhesion and differentiation of cell types, and the ability to release and entrap biomolecules
in bioapplications.124 However, PPy performed poorly in a tissue-engineering scaffold
under mechanical forces because of its brittle backbone. Therefore, composites based
on PPy have been constructed to overcome this limitation.6,120 For example, PPy-coated
poly(lactic-co-glycolic acid) (PLGA), prepared by nano-thick deposition, was used for
conducting nanoscaffolds with high surface areas, interconnecting pores, and nanofibrous
topographies.130 In-vitro cell culture using PC-12 cells and embryonic hippocampal neu-
rons demonstrated biocompatible cellular interactions, suitable for neuronal applications.
Additionally, the low electrical potential, 10 mV/cm, facilitated neurite outgrowth on the
aligned PPy-PLGA NFs.
Xie and colleagues developed conductive PCL-PPy and polylactate (PLA)-PPy core-
sheath NFs that facilitated neurite growth and extension (Fig. 7).131 The conductive core-
sheath NFs were prepared by combining electrospinning with aqueous polymerization. The
maximum length of neuritis can be achieved by the synergistic effects of aligned conduc-
tive NFs: 1.83-fold (random NFs) and 1.47-fold (aligned NFs). PPy-polyurethane (PU)
nanocomposites were also designed for tissue engineering scaffolds for C2C12 myoblast
cells.132 The scaffolds were prepared by chemical polymerization in a PU emulsion mixture
with drop-wise addition of an oxidant. The PPy-PU nanocomposites exhibited non-toxic,
conductive, and elastomeric properties, resulting in cellular growth and subsequent cell
differentiation. The dopant placed in the CPs can affect their cytocompatibility and the
delivery of biomolecules.133 Among various dopants, the smallest dopants (para-toluene
sulfonate and dodecylbenzene sulfonate) resulted in the best biocompatibility with the neu-
ral tissue culture. As a result, electrochemically synthesized PPy/para-toluene sulfonate
enhanced the auditory nerve matrix, with release of neurotrophin.
PEDOT-COOH nanodots (NDs) were prepared as a nano-platform for enhanced
cell capturing, synthesized by electropolymerization on indium tin oxide (ITO)-coated
glass (Fig. 8).134 The NDs were modified with the EpCAM antibody, a tumor cell-
binding antibody. The enlarged cell-capturing efficacy resulted in the synergistic effects of
ligand–receptor reactions and structural and mechanical matching between tumor cells and
Figure 7. A,B) Schematic illustration of dorsal root ganglion (DRG) neuron outgrowth upon elec-
trical stimulation on random and uniaxially aligned PCL-PPy core-sheath NFs, respectively. C,D)
Typical DRG neurite field on random PCL-PPy NFs and aligned PCL-PPy NFs. Reproduced from
Xie et al.131 with permission from Wiley-VCH Verlag GmbH & Co. KGaA
Figure 8. Fabrication processes of conjugating epithelial cellular adhesion molecule antibody (anti-
EpCAM) onto PEDOT NDs. Reproduced from Sekine et al.134 with permission from Wiley-VCH
Verlag GmbH & Co. KGaA (Color figure available online).
PEDOT-COOH NDs. The NDs have inherent advantages of facile fabrication, functional
groups, and matching mechanical properties.
PANi NF-collagen composite films were introduced as an electronically conductive
and biocompatible scaffold for mammalian cell culture.135 The conductivity was related
to the weight ratio of PANi NFs. Additionally, a PANi-coated Pt electrode was used to
evaluate the biochemical mechanisms of tissue damage, in terms of both phospholipid
peroxidation and protein denaturation under electrical stimulation.136 PANi was deposited
onto the Pt electrode by in-situ polymerization. PANi NFs exhibited valuable properties,
including inactivity against lipid peroxidation, increased protein adsorption, good stability,
and anti-corrosive effects.
3.4 Drug Delivery

A drug delivery system is designed to deliver medicine at specifically targeted places
in the living body. The medicine can be transported by carriers such as NPs and
biomolecules.137,138 Polymeric microspheres and hydrogel-type compounds have been in-
vestigated before for their ability to target specific points and reduce drug toxicity. Moreover,
controlled release and active targeting delivery systems are required. CP nanomaterials are
biocompatible and can be activated by low voltages or light. The application of CP nano-
materials for drug delivery has currently not been explored in depth, but is promising.
The Martin group developed PEDOT NTs having well-defined internal and external
surface textures, which showed controlled release of dexamethasone by external electrical
stimulation.139 The PEDOT NTs lowered the impedance between the tissue and recording
site by growing the surface area for ionic-to-electronic charge transfer. To produce the
PEDOT NT delivery system, biodegradable PLLA or PLGA was first electrospun onto
the electrode, followed by electrochemical deposition of PEDOT on the electrospun NFs.
Then, the drug was loaded into the NFs after the fiber templates were removed. The neural
probes consisting of PEDOT NTs enabled the electrical stimulation or signal recording of
420 W.-K. Oh et al.
Figure 9. Schematic diagram of the fabrication process of PEDOT: PSS-PEG. Reproduced from
Cheng et al.140 with permission from the American Chemical Society (Color figure available online).
neurons. This methodology opens new pathways for the controlled release of drugs and
biomolecules through electrical stimulation.
PEDOT:PSS NPs were developed as an organic photothermal agent, activated by strong
near-infrared (IR) absorbance, for the photothermal treatment of cancer (Fig. 9).140 Layer-
by-layer coating with charged PEDOT:PSS polymers, followed by grafting with branched
polyethylene glycol (PEG), resulted in PEDOT:PSS-PEG NPs that were highly stable
in the physiological environment and possessed “stealth-like” behavior after intravenous
injection, with a long blood circulation half-life. As a photothermal agent, PEDOT:PSS-
PEG NPs were used for in-vivo cancer treatment and demonstrated excellent therapeutic
efficacy in a mouse tumor model under near-IR irradiation at a low laser power density.
Carbonized PPy NPs for drug delivery were prepared by pyrolysis of PPy NPs
(Fig. 10).141 The final NPs displayed uniform sizes, large micropore volumes, and high
surface-areas. Magnetic phases formed during pyrolysis were useful for selective NP sep-
aration. Hydrophobic medicines, such as ibuprofen, were incorporated into the carbonized
PPy NPs by surface adsorption and pore filling, and further plasma modification enhanced
drug sustainability via surface covalent coupling. Drug-loaded NPs demonstrated sustained
release properties. Additionally, the carbonized PPy NPs showed low toxicity and were
readily incorporated into cells.
4. Biosensors
4.1 CP-Based Biosensor Technology

Advanced biosensing technologies based on CPs have been developed extensively during
recent decades because of the unique chemical and physical characteristics of CP materials.
Figure 10. a) FE-SEM images and size distributions of carbonized PPy NPs. b) Cumulative release
from ibuprofen loaded carbonized PPy NPs in PBS solution (100 mM, pH 7.4, 37◦ C; n = 3).
Reproduced from Oh et al.141 with permission from Elsevier (Color figure available online).
422 W.-K. Oh et al.
Recently, research on CP-based biosensors has provided critical control factors for high-
performance biosensors. To construct advanced CP-based biosensors with high perfor-
mance, the following issues should be considered for further investigation: i) an enlarged
surface area for enhanced interactions, ii) chemical functionality for selective responses,
and iii) structural stabilization for efficient signal transfer.
Recently, specific target biomolecules have been discriminated by various CP
nanomaterial-based sensing systems or devices, which show significant electrical and opti-
cal responses via mechanical or electronic transduction mechanisms. Based on these obser-
vations, attractive biosensing technologies have been developed, such as protein receptor-
related biosensors, aptasensors, DNA sensors, glucose sensors, and immunoassays. The
recognition processes used in these sensing technologies can provide highly sensitive and
selective detection of biological molecules as well as quantitative analysis of analytes.
In this section, we introduce advanced sensing technologies using CP nanomaterials as
transistors in liquid-ion gated FET biosensor systems compared with conventional methods,
and we discuss state-of-the-art biosensors. Moreover, we review the important factors for
next-generation biosensors from a materials point of view.
4.2 Protein Receptor−Based Biosensors

4.2.1 A Bioelectronic Nose. An artificial nose, a so-called “bioelectronic nose,” mim-
ics the human olfactory system.142,143 The bioelectronic nose is designed to discriminate
specific odorants and is advantageous for many applications such as food systems, envi-
ronmental monitoring, and disease diagnosis.144–146 Recently, analytical techniques, such
as luminescence, quartz crystal microbalance, and FET methods, based on semiconducting
electronic sensor arrays, have been introduced to develop human-like bioelectronic noses
that can perceive hundreds of thousands of odorants.79,142,143,147–150 For example, Kim et al.
developed a bioelectronic nose using human olfactory receptor-adsorbed CNTs and demon-
strated excellent single-carbon-atomic-resolution. However, the CNT-based bioelectronic
nose showed limited sensitivity because of the physical adsorption of olfactory receptors on
the CNT surface.142 Therefore, advanced technologies such as immobilization and covalent
bonding are needed for stable transistors in the liquid state. Sankaran et al. demonstrated
a piezoelectric biosensor using olfactory receptors in food safety applications. Although
this biosensor showed excellent performance, the important characteristics, that is, low
sensitivity, cost-efficiency, and portability remain challenges.147
For the first time, a high-performance bioelectronic nose was successfully fabricated
by the introduction of carboxylic groups on the copolymerized PPy NT backbone.151 The
carboxylated PPy NT (CPNT) was attached to a the glass substrate functionalized with (3-
aminopropyl)trimethoxysilane (APS) by a condensation reaction that formed amide bridges
(-CONH) between the carboxylic groups (-COOH) and amino groups (-NH2 ). Moreover,
the olfactory receptor (hOR2AG1) was also anchored to the CPNT using a similar conden-
sation process (Fig. 11). Field-emission scanning electron microscopy (FE-SEM) was used
to confirm the olfactory receptor-immobilized CPNT on the interdigitated microelectrode
substrate (Fig. 12a). Based on the covalent bonding, the FET sensor geometry was success-
fully constructed using a buffer solution as a liquid-ion gate (Fig. 12b). Thus, label-free
recognition of odorants can be achieved using an FET-type bioelectronic configuration.
To investigate the sensing performance of the bioelectronic nose based on the receptor
immobilized-CPNT, the I SD change was monitored in real time at a low operating voltage.
A target odorant at an unprecedentedly low concentration (10 fM, Fig. 12c) was discrim-
inated by field-induced sensitivity via the FET-type bioelectronic nose. The bioelectronic
Figure 11. Fabrication processes of bioelectronic nose (Color figure available online).
nose also displayed excellent selectivity at atomic resolution. To tailor the functionality
of the CPNT, the amount of hOR2AG1 (OR) attached to the CPNTs can be controlled,
leading to increased sensitivity with increasing odorant concentration (1OR-CPNT < 2OR-
CPNT < 4OR-CPNT) (Fig. 12d). On the other hand, we also reproduced the human nose-
like nanobioelectronic nose (nbe-nose), which showed excellent odorant discrimination at
Figure 12. a) FE-SEM image of OR-immobilized CNPT on the microelectrodes. b) Schematic illus-
tration of liquid-ion gated FET-type bioelectronic nose. c) The real-time responses of bioelectronic
nose. d) The sensitivity changes depending on the amount of receptor immobilized on the CPNT.
Reproduced from Yoon et al.80 with permission from Wiley-VCH Verlag GmbH & Co. KGaA (Color
figure available online).
424 W.-K. Oh et al.
extremely low concentrations (0.02 ppt: parts-per-trillion). The detection capability of the
nbe-nose was comparable to that of the nose of a trained human expert.152,153 The fabri-
cation process of the nbe-nose was identical to that for the bioelectronic nose based on
an OR-CPNT transducer; the differences between the nbe-nose and bioelectronic nose
are simply the attached biomaterials and sensing system. The hOR3A1 receptor was used
for the nbe-nose, and a chemiresistive sensory system that determines resistance changes
was employed. Importantly, functionalized CP nanomaterials attached to the interdigitated
microelectrodes were introduced, leading to stable electrical contact. The stable electrical
contacts from immobilized CPNTs and receptors not only provided excellent reproducibil-
ity and reusability but also improved the sensitivity of the biosensor. The receptor attached
to the CPNT substrate interacted with target molecules via rapid diffusion, leading to ul-
trafast response/recovery times with to those of conventional gas-sensing platforms. The
sensitive and rapid responses from the nbe-nose can be explained by changes in the oxida-
tion level of the CPs due to chemical and electrochemical doping/dedoping mechanisms.
Moreover, the nbe-nose clearly displayed excellent reversibility and reproducibility with
respect to target gases for up to 20 recycle tests (Fig. 13a). Furthermore, the antagonism
of the nbe-nose was also investigated using known mixtures of helional and the antagonist
(Fig. 13b). Considering these experimental results, the human-like bioelectronic nose based
on receptor-conjugated CPNTs offers a new paradigm for discriminating odorant gases at
low concentrations, leading to high-resolution analysis of complex odorant gas mixtures
after method optimization.
4.2.2 Nanobioelectronic Tongue. The development of sensory systems discriminating var-

ious tastants, referred to as “electronic tongues,” is an important and challenging task in
the food, drug, and beverage industries.154–156 Artificial taste sensory systems based on
arrays of various materials such as CPs, conductive membranes, and semiconductors have
been investigated since the human taste system was discovered.78,157,158 For example, dis-
criminating techniques with patterned substrates consist of semi-conductive channel or
colorimetric arrays that mimic the biological structures of the human tongue.159,160 Even
with recent technological advances, these conventional approaches have limitations that
prevent them from mimicking the complex biological features of real tongues.
Figure 13. a) Highly reproducible responses of the nbe-nose upon exposure to the helional gases
with various concentrations. b) Antagonism diagram of nbe-nose. Reproduced from Lee et al.153 with
permission from Elsevier. (Color figure available online).
Recently, 1D electronic nanomaterials with well-controlled structures have become at-

tractive components in various fields, including transistors, energy converters, and biosen-
sors, due to their efficient charge transport along the long-axis direction.161,162 In particular,
biosensing technologies based on 1D electronic nanomaterials have been developed by
integration with biological receptors. For example, Kim et al. developed a bioelectronic
super-taster device based on CNTs.163 This taster consisted of a taster receptor and CNTs,
which exhibited high sensitivity and selectivity to tastants. Although the bioelectronic
taster had high-performance sensing capabilities, the MDL was limited by unstable con-
tact due to the physical adsorption between the CNTs and the taster receptor. Generally,
modification of the CNT surface affects the physical and electrical properties, leading to
performance degradation of the sensing device. Compared with physically adsorbed recep-
tor/CNTs, functionalized CPs offer unprecedented sensing performance in bioelectronic
tongue systems. The nanobioelectronic tongue (nbe-tongue) was demonstrated using the
receptor-conjugated CPNT substrate. A high-performance nbe-tongue was constructed us-

ing a human bitter taste receptor hTAS2R38-functionalized CPNT immobilized on the
substrate.78 Interestingly, the nbe-tongue was able to distinguish between the taster (PAV-
type) and nontaster (AVI-type) by recognition of phenylthiocarbamide (PTC) and propylth-
iouracil (PROP) compounds.164 The excellent discriminating capability of the nbe-tongue
was also investigated with real vegetable samples. Specifically, the FET-type nbe-tongue
was successfully fabricated via covalent bonding between the taste receptor and CPNTs
immobilized on the interdigitated microelectrodes and surrounded by a liquid state (Fig.
14a). The nbe-tongue was characterized by p-type stable electrical properties in a liquid-ion
gated FET system (Fig. 14b). Compared with conventional FET-gating methodologies, the
liquid-ion gated FET system provides efficient intimate contact on the NT surface. The
real-time responses in I SD changes were monitored by the specific binding events between
target tastants and taste receptors when the tastants were injected (Fig. 14c). The responses
from the nbe-tongue were highly sensitive and selective to PTC (1 fM) and PROP (10 fM)
concentrations, respectively, whereas there were no significant signals for the AVI-CPNT.
The PAV and AVI-type nbe-tongues also showed similar results for additional tastants,
including goitrin and AI, compared with PTC and PROP (Fig. 14d). Finally, mixtures of
PTC and PROP with various tastants (sweet tastant, umami tastant, and glutamate) were
prepared to investigate the specificity of the nbe-tongue based on CPNTs. The nbe-tongue
showed significant responses to mixtures containing the target tastants (PTC or PROP),
demonstrating excellent selectivity. Thus, a human tongue-like high-performance artificial
tongue was successfully created using bitter taste receptor (hRAS2R38)-conjugated CP-
NTs. The novel and simple nbe-tongue geometry offers an alternative to time-consuming
and labor-intensive sensory systems, leading to next-generation taste sensor technologies.
4.3 Hormone Sensors

The activity of various cells and organs is adjusted and regulated by hormones, even at
low levels; thus, hormone imbalances can cause serious diseases, such as osteoporosis,
adenoma, hyperplasia, and cancer.165,166 In particular, the metabolic activity of the human
parathyroid hormone, one of the peptide hormones, plays a key role in maintaining calcium
homeostasis in human body.167 To recognize low concentrations of hormones in the hu-
man body, various techniques have been developed over the past decade including enzyme
immunoassays, enzyme-linked immunosorbent assays, fluorescence optochemical sensors,
multianalyte immunosensors, and sensors based on surface plasmon resonance.168–172 Al-
though these assays have shown the ability to discriminate hormones, limitations such as
426 W.-K. Oh et al.
Figure 14. a) Schematic diagram of nanobioelectronic tongue. b) I SD -V SD curves of nbe-tongue. c)

Real-time responses of FET using PAV and AVI-type nbe-tongues. d) Dose−response profiles of PAV
and AVI types of hTAS2R38-functionalized CPNT-FETs stimulated with different concentrations of
PTC, PROP, goitrin, and AI. Half maximal responses (EC50) for PTC, PROP, goitrin, and AI were
estimated to be 1.839, 4.122, 1971, and 7829 pM, respectively. Reproduced from Song et al.78 with
permission from the American Chemical Society (Color figure available online).
time consumption, complex treatment, low detection levels, and slow responses still remain
challenges.
Biosensing techniques based on FET systems, which can control the flow of charge
on semiconducting channels, enable allow label-free detection of bio-recognition events in
real-time.22,79 Recently, 1D CP nanomaterials were used as transistors for FET biosensors
because of their efficient electron migration. Although CP NPs have been shown to be
excellent signal transducers with the potential for use in high-performance biosensors, it is
still difficult to use them as transducers in FET-type biosensors because of their inherent
structural instability in the liquid state. To realize high-performance biosensors using NPs,
the arrays of NPs deposited between the electrode gap are controlled to achieve specific
electrical properties required for FET systems that measure changes in conductivity.173
Thus, to form suitable NP arrays, advanced technologies must be developed for fabri-
cating highly uniform, well-ordered, and size-controlled NPs.174,175 From this materials
perspective, highly monodisperse, uniform, and size-tunable carboxylated PPy NPs (CP-
PyNPs) were created by copolymerization of pyrrole with pyrrole-3-carboxylic acid and
pyrrole monomer via a dispersion method. The modified CPPyNPs provide advantages such
as compact CPPyNP arrays immobilized on the substrate and the efficient attachment of
biomolecules on the CPPyNP surface. Figure 15 illustrates the close-packed CPPyNP arrays
and the immobilization process of the hormone receptor. The closed-packed CPPyNP arrays
on the substrate were characterized by FE-SEM (Fig. 16a). The CPPyNP nanobiohybrids
Figure 15. Synthetic processes of close-packed arrays of hPTHR-conjugated CPPyNPs. Reproduced

from Kwon et al.173 with permission from the American Chemical Society (Color figure available
online).
attached to the hormone receptor had a rougher surface compared with pristine CPPyNPs.
To confirm the sensing performance of the close-packed NP arrays, an FET system based
on the nanobiohybrids was constructed by immersion in phosphate-buffered saline solution
(PBS, pH 7.4; Fig. 16b). The hormone sensor based on nanobiohybrids was characterized
by p-type FET behavior and operated under low voltage at room temperature. The real-time
responses from hormone sensors were monitored based on I SD changes. The hormone sen-
sor showed fast response times (< 1 s) and retained linear response values. Importantly, the
MDL was ca. 48 fM (signal-to-noise ratio = 12.5; Fig. 16c), which is approximately 3–6
orders of magnitude better than the MDLs of conventional hormone sensors. Based on these
results, high-performance hormone sensors based on well-designed nanobiohybrid arrays
were successfully demonstrated, showing potential as attractive transducers for FET-type
biosensors.
4.4 Aptasensors
Aptamers are nucleic acids (DNA or RNA) that can selectively bind to small or macro
molecules.176 Aptamers for target molecules are selected by the systematic evolution of
ligands by an exponential enrichment (SELEX) procedure consisting of repeated separation-
amplification cycles.177,178 The single DNA or RNA aptamers identified are commensurate
with the complementary DNA or RNA. Aptamers have also been used as active separation
materials in chromatography, therapeutics, and biosensing applications because of their high
affinity. The introduction of aptamers in electrically detectable biosensing devices offers ad-
vantages, such as simple fabrication, reproducible structures, facile chemical modification,
428 W.-K. Oh et al.
Figure 16. a) FE-SEM images of close-packed arrays of the hPTHR-conjugated CPPyNPs (the
yellow dashed lines indicate boundary lines between gold electrodes). b) Representative diagram
of FET-type hormone sensors using CPPyNP arrays. c) Real-time responses of hormone sensors.
Reproduced from Kwon et al.173 with permission from the American Chemical Society (Color figure
available online).
and real-time monitoring.179 Thus, advances in the electrochemical design of biosensors

necessitate the design of aptasensors that can detect specific molecules, including enzymes,
DNA, and antibodies/antigens.
Aptasensors have been combined with various materials, such as carbon-based mate-
rials, metals, ceramics, and CP materials, to construct sensing devices.180–183 In particular,
CPs are suitable candidates for aptasensor substrates because of their inherent electrical
and physical properties. CPs, as immobilization matrix materials provide attractive ad-
vantages, such as facile modification and stability. For example, Rahman et al. fabricated
Au NP-doped CP NR electrodes (AuNPs/CPNEs) and demonstrated a high-performance
aptamer-based biosensor.184 An aptasensor based on AuNPs/CPNEs was characterized by
cyclic voltammetry (CV) and showed sensitive and selective responses to thrombin. Olowu
et al. developed an electrochemical DNA aptasensor, based on PEDOT doped with AuNPs,
which exhibited a specific affinity to endocrine-disrupting 17β-estradiol.185 Schalkhammer
et al. proposed a functionalized PPy porous film to determine enzyme load.186 Moreover,
they demonstrated an enhanced aptasensor by introducing various functional groups to the
PPy film. Second, 1D CP nanomaterials as transducers have displayed excellent perfor-
mance in FET systems; 1D CP nanomaterials were fabricated by a microemulsion process
and used as a transducer in an FET-type vascular endothelial growth factor (VEGF) ap-
tasensor.181 The authors explained the size-dependent effects of 1D CP nanomaterials in
Figure 17. Synthetic process of flexible PPy-NDFLG film. Reproduced from Kwon et al.173 with
permission from the American Chemical Society (Color figure available online).
the VEGF-aptasensor system. A label-free electrochemical aptasensor based on CP NTs

was proposed by Yoon et al.187 They fabricated functionalized polymer NTs by a simple
approach using cylindrical micelle templates. The aptasensor was constructed by an immo-
bilization process on the electrode surface and showed selective recognition of thrombin.
Additionally, we prepared nitrogen-doped few-layer graphene converted from PPy
(PPy-NDFLG) as a flexible transducer by VDP and chemical vapor deposition (Fig. 17) and
utilized it as a flexible aptasensor.180 A liquid-ion gated FET geometry consisting of PPy-
NDFLG and electrolyte was constructed for use in a high-performance VEGF aptasensor.
The field-induced response from the aptasensor was monitored using the analyte-binding
events, leading to an unprecedented MDL level (100 fM). The aptasensor based on PPy-
NDFLG also showed excellent reusability, durability, and mechanical bendability in a
flexible system.
4.5 DNA Sensors

Detecting specific DNA/RNA sequences is important in the field of diagnostics and clinical
diseases. Recently, novel techniques using biotin, fluorescent dyes, and electrochemical
approaches have been used to demonstrate high-performance DNA sensing systems.188–192
For DNA analysis, precise recognition is necessary to identify a partner sequence to one
strand of the double helix. Wang et al. detected DNA hybridization using an in situ electro-
chemical method. Electropolymerized PPy films doped with nucleic acid probes, were used
to monitor current changes via hybridization interactions.193 However, the doping approach
resulted in unstable stimulations because of the physical interaction between the probes
and the PPy film. Dupont-Filliard et al. prepared a biotinylated PPy film biosensor for
DNA detection. A PPy-biotin/avidin/DNA probe was fabricated using intercalated layers
of avidin for the immobilization of DNA probes.194 This sensing layer showed reproducible
and selective responses without loss of activity. Peng et al. proposed a new functionalized
430 W.-K. Oh et al.
CP to simplify the fabrication process of the sensing substrate. The precursor copolymer
on the electrode surface was easily deposited using a simple electrodeposition method and
displayed highly active CP layers in an aqueous medium.195 The authors also demonstrated
the effect of the film thickness on the DNA sensor; thinner films showed higher sensitivity
than thicker films. Although these DNA probes showed sensitive and selective responses
to target molecules, they were limited by their restricted active surface area, which inter-
acted with target molecules. Therefore, nanomaterials with increased surface areas have
been fabricated. Recent advances in electronic detection using NWs and NTs have enabled
label-free and real-time responses via FET systems. Based on these FET systems, 1D CP
nanomaterials were used as transducers owing to their electronic conductivity, environ-
mental stability, and simple fabrication. Ramanathan et al. demonstrated the fabrication of
single and multiple PPy NWs with controlled dimensions.196 PPy NWs were electrode-
posited within channels between two electrodes and applied as a transducer in a label-free
bioaffinity sensor. The authors also discussed the key factors for designing tailor-made NW
biosensors, including monomers, dopants, electropolymerization conditions, and modes.
As an extended study, bifunctionalized CP NTs were prepared using simple VDP with AAO
membranes (hard-template) consisting of adsorbed Fe+ cations with amine-functionalized
silica NPs attached (Fig. 18).197 The dual-functional CP NTs were used as both a molecular
Figure 18. Synthetic processes of bifunctional CP NTs attached with ssDNA. Reproduced from Jang
et al.197 with permission from Wiley-VCH Verlag GmbH & Co. KGaA.
probe and a DNA carrier by immobilizing DNA via the covalent bonding. Compared with
other conventional DNA sensors, the functionalized CP NTs provide a high-performance
sensing substrate and multi-functional sensing devices.
Immunoassays have been widely used in clinical and analytical laboratories because of
their efficiency.198 Immunosensors are defined as sensing devices consisting of biological
recognition regions that convert the binding event of target molecules into a signal.199–204
A key approach used in immunosensor technology is the attachment of monoclonal anti-
bodies to the substrate surface. Sargent et al. fabricated CP electrodes with antibodies, and
their (antibody–antigen) interactions were observed using impedance spectroscopy tech-
niques.205 Bandodkar and coworkers successfully constructed a nanostructured PANi film
on an ITO-coated glass substrate and used it to determine the capacitance changes in a
parallel-plate capacitor.206 The HIgG-modified parallel-plate sensor showed sensitive and
selective human IgG detection. Moreover, an immunosensor based on a single CP NW was
developed by Bangar et al.207 The CP NWs were synthesized by AAO and assembled using
AC dielectrophoretic alignment. Antibody or antigen-functionalized PPy NWs exhibited
excellent sensitivity at low target biomolecule concentrations.
4.6 Glucose Sensors

Diabetes, a chronic disease, occurs due to uncontrolled changes in the amount of insulin
in the living body and is rarely cured.208,209 Hyperglycemia, which occurs as the glucose
concentration in blood increases, has led to serious concerns for people worldwide. In 2000,
171 million people were affected by diabetes. It is expected that the number of patients
with diabetes will reach 366 million in the near future.210,211 Glucose oxidase (GOx) is a
homodimer containing two flavine adenine dinucleotide (FAD) moieties as a cofactor. The
basic concept of most glucose biosensors is amperometric detection via GOx enzyme elec-
trodes.212,213 Recently, various methodologies for glucose detection have been developed
using CPs. For example, Agarwal et al. fabricated an organic thin-film transistor (OTFT)-
type glucose biosensor based on channels composed of a poly(3,4-ethylenedioxythiophene-
poly(styrene-sulfonate) CP film attached to GOx enzymes.214 Pin-coating techniques were
introduced to immobilize GOx on the CP film. Das et al. also prepared the CP layer with 3-
aminophenyl boronic acid and used it to detect saccharides based on specific binding events
between boronic acid and the diol groups of the saccharide.215 However, it is difficult to
induce a direct oxidation reaction (electron transfer) between an electrode and protein.
Thus, Guo et al. prepared a hollow sphere-nanostructured CP/metal oxide composite and
demonstrated the direct electron transfer behavior of GOx on the materials.216 Compared
with conventional glucose sensors based on CP films, well-controlled CP nanomaterials
showed rapid and selective responses to GO. We also constructed excellent glucose biosen-
sors using a liquid-ion gated FET-type geometry based on enzyme-functionalized PPy
NTs.151 Modified PPy NTs have well-defined functional groups and excellent electrical
properties on electrodes. The covalent immobilization of the modified PPy NTs provided
stable electrical-contact between the NTs and the electrode substrate in the liquid state,
leading to a high-performance glucose sensor. Moreover, Ciftci and coworkers developed
an enzyme-free potentiometric glucose sensor through an electrochemical preparation of
a new poly(3-aminophenyl boronic acid-co-3-octylthiophene) organic electrode.217 The
boronic acid and an alkyl spacer functional group enabled molecular recognition on a
CP film electrode. They also fabricated an immobilized monolayer of AuNPs on poly(3-
octylthiophene) and used it for a non-enzymatic glucose sensor.218 Based on the history of
432 W.-K. Oh et al.
glucose biosensors, novel strategies to create modified CP electrodes or transducers should

be developed to obtain advanced electroanalytical chemistry.
5. Outlook
Based on recent research, CP nanomaterials reveal biocompatible electroactive materials
that offer beneficial properties: i) generally low cytotoxicity toward mammalian cells; ii)
enabling physical substrates for neuronal growth and tissue repair; and iii) providing lo-
cal delivery of an electrical stimulus to propagate cell growth or electrical detection of
live neuronal cells. Furthermore, controlled drug release may be achieved using electrical
activation. The charge-transport properties of CP nanomaterials enable sensitive sensing
by tuning the CP characteristics. The surface functional groups of CP nanomaterials can
be modified covalently using specific bioreceptors, allowing the immobilization of CP

nanomaterials on electrode substrates. CP nanomaterial-based sensing systems have been
classified in this article as protein receptor-related biosensors, aptasensors, DNA sensors,
glucose sensors, and immunoassays. However, biomedical applications using CP nanoma-
terials are still in the early stages. For example, the cellular effects of CP nanomaterials
are still not fully characterized, and reliable synthesis routes for CP nanomaterials are still
required. A simultaneous-measurement technology for complex single-molecule mixtures
should be developed to fabricate human-like artificial bioelectronic noses and tongues. CP
nanomaterials have many unexplored potential uses, and we expect future research will
lead to the development of many new biomedical applications.
Acknowledgments
This research was supported by the National Research Foundation of Korea (NRF) grant
funded by the Korea government (MEST) (no. 2011-0017125), by the WCU (World Class
University) program through the NRF funded by the Ministry of Education, Science and
Technology (R31-10013).
References
1. Yoon, H.; Jang, J. “Conducting-polymer nanomaterials for high-performance sensor applica-
tions: Issues and challenges,” Advanced Functional Materials 2009, 19, 1567–1576.
2. Yoon, H.; Choi, M.; Lee, K.; Jang, J. “Versatile strategies for fabricating polymer nanomaterials
with controlled size and morphology,” Macromolecular Research 2008, 16, 85–102.
3. Jang, J. “Conducting polymer nanomaterials and their applications,” Advances in Polymer
Science. 2006, 199, 189–260.
4. Yoon, H.; Hong, J.-Y.; Jang, J. “Charge-transport behavior in shape-controlled poly(3,4-
ethylenedioxythiophene) nanomaterials: Intrinsic and extrinsic factors,” Small 2007, 3,
1774–1783.
5. Yoon, H.; Chang, M.; Jang, J. “Formation of 1d poly(3,4-ethylenedioxythiophene) nanomateri-
als in reverse microemulsions and their application to chemical sensors,” Advanced Functional
Materials 2007, 17, 431–436.
6. Guimard, N.K.; Gomez, N.; Schmidt, C.E. “Conducting polymers in biomedical engineering,”
Progress in Polymer Science 2007, 32, 876–921.
7. Green, R.A.; Lovell, N.H.; Wallace, G.G.; Poole-Warren, L.A. “Conducting polymers for neural
interfaces: Challenges in developing an effective long-term implant,” Biomaterials 2008, 29,
3393–3399.
8. Bendrea, A.-D.; Cianga, L.; Cianga, I. “Review paper: Progress in the field of conducting
polymers for tissue engineering applications,” Journal of Biomaterials Applications 2011, 26,
3–84.
9. Higgins, M.J.; Molino, P.J.; Yue, Z.; Wallace, G.G. “Organic conducting polymer–protein
interactions,” Chemistry of Materials 2012, 24, 828–839.
10. Svennersten, K.; Larsson, K.C.; Berggren, M.; Richter-Dahlfors, A. “Organic bioelectronics
in nanomedicine,” Biochimica et Biophysica Acta (BBA) - General Subjects 2011, 1810, 276–
285.
11. Sayyar, S.; Murray, E.; Thompson, B.C.; Gambhir, S.; Officer, D.L.; Wallace, G.G. “Covalently
linked biocompatible graphene/polycaprolactone composites for tissue engineering,” Carbon
2013, 52, 296–304.
12. Otero, T.F.; Martinez, J.G.; Arias-Pardilla, J. “Biomimetic electrochemistry from conduct-
ing polymers. A review: Artificial muscles, smart membranes, smart drug delivery and com-
puter/neuron interfaces” Electrochimica Acta 2012, 84, 112–128.
13. Oh, J.K.; Drumright, R.; Siegwart, D.J.; Matyjaszewski, K. “The development of micro-
gels/nanogels for drug delivery applications,” Progress in Polymer Science 2008, 33, 448–477.
14. Gardner, J.W.; Bartlett, P.N., “Application of conducting polymer technology in microsystems,”
Sensors and Actuators A: Physical 1995, 51, 57–66.
15. Kreuer, K. “On the development of proton conducting polymer membranes for hydrogen and
methanol fuel cells,” Journal of Membrane Science 2001, 185, 29–39.
16. Gangopadhyay, R.; De, A. “Conducting polymer nanocomposites: A brief overview,” Chemistry
of Materials 2000, 12, 608–622.
17. Marsella, M.J.; Swager, T.M., “Designing conducting polymer-based sensors: Selective
ionochromic response in crown ether-containing polythiophenes,” Journal of the American
Chemical Society 1993, 115, 12214–12215.
18. Thompson, L.A.; Kowalik, J.; Josowicz, M.; Janata, J. “Label-free DNA hybridization probe
based on a conducting polymer,” Journal of the American Chemical Society 2003, 125, 324–325.
19. Forzani, E.S.; Zhang, H.; Nagahara, L.A.; Amlani, I.; Tsui, R.; Tao, N. “A conducting polymer
nanojunction sensor for glucose detection,” Nano Letters 2004, 4, 1785–1788.
20. Snook, G.A.; Kao, P.; Best, A.S., “Conducting-polymer-based supercapacitor devices and elec-
trodes,” Journal of Power Sources 2011, 196, 1–12.
21. Zou, J.; Yip, H.L.; Hau, S.K.; Jen, A.K.Y. “Metal grid/conducting polymer hybrid transparent
electrode for inverted polymer solar cells,” Applied Physics Letters 2010, 96, 203301–203303.
22. Hangarter, C.M.; Bangar, M.; Mulchandani, A.; Myung, N.V., “Conducting polymer nanowires
for chemiresistive and fet-based bio/chemical sensors,” Journal of Material Chemistry 2010,
20, 3131–3140.
23. Yoon, H.; Jang, J. “Conducting-polymer nanomaterials for high-performance sensor applica-
tions: Issues and challenges,” Advanced Functional Materials 2009, 19, 1567–1576.
24. Bruce, P.G.; Scrosati, B.; Tarascon, J.M. “Nanomaterials for rechargeable lithium batteries,”
Angewandte Chemie International Edition 2008, 47, 2930–2946.
25. Magrez, A.; Kasas, S.; Salicio, V.; Pasquier, N.; Seo, J.W.; Celio, M.; Catsicas, S.; Schwaller, B.;
Forró, L. “Cellular toxicity of carbon-based nanomaterials,” Nano Letters 2006, 6, 1121–1125.
26. Dobrovolskaia, M.A.; Mcneil, S.E. “Immunological properties of engineered nanomaterials,”
Nature Nanotechnology 2007, 2, 469–478.
27. Grimsdale, A.C.; Müllen, K. “The chemistry of organic nanomaterials,” Angewandte Chemie
International Edition 2005, 44, 5592–5629.
28. Zhang, L.; Webster, T.J. “Nanotechnology and nanomaterials: Promises for improved tissue
regeneration,” Nano Today 2009, 4, 66–80.
29. Lee, M.-G.; Lucero, A.; Kim, J.-Y. “One-dimensional nanomaterials for field effect transistor
(FET) type biosensor applications,” Transactions on Electrical and Electronic Materials, 2012,
13, 165–170.
30. Tran, H.D.; Wang, Y.; D’arcy, J.M.; Kaner, R.B. “Toward an understanding of the formation of
conducting polymer nanofibers,” ACS Nano 2008, 2, 1841–1848.
434 W.-K. Oh et al.
31. Huang, J.; Kaner, R.B. “Flash welding of conducting polymer nanofibres,” Nature Materials
2004, 3, 783–786.
32. Lu, X.; Zhang, W.; Wang, C.; Wen, T.C.; Wei, Y. “One-dimensional conducting polymer
nanocomposites: Synthesis, properties and applications,” Progress in Polymer Science 2011,
36, 671–712.
33. Nguyen, T. -D. “Portraits of colloidal hybrid nanostructures: controlled synthesis and potential
applications,” Colloids and Surface B: Biointerfaces. 2013, 103, 326–344.
34. Pan, L.; Qiu, H.; Dou, C.; Li, Y.; Pu, L.; Xu, J.; Shi, Y. “Conducting polymer nanostructures:
Template synthesis and applications in energy storage,” International Journal of Molecular
Sciences 2010, 11, 2636–2657.
35. Jang, J.; Oh, J.H.; Stucky, G.D. “Fabrication of ultrafine conducting polymer and graphite
nanoparticles,” Angewandte Chemie International Edition 2002, 41, 4016–4019.
36. J Heeger, A. “Polyaniline with surfactant counterions: Conducting polymer materials which are
processible in the conducting form,” Synthetic metals 1993, 57, 3471–3482.
37. Fredrickson, G.H. “Surfactant-induced lyotropic behavior of flexible polymer solutions,”

Macromolecules 1993, 26, 2825–2831.
38. Wei, M.; Lee, J.; Kang, B.; Mead, J., “Preparation of core-sheath nanofibers from conducting
polymer blends,” Macromolecular Rapid Communications 2005, 26, 1127–1132.
39. Jang, J.; Yoon, H. “Multigram-scale fabrication of monodisperse conducting polymer and
magnetic carbon nanoparticles,” Small 2005, 1, 1195–1199.
40. Jang, J.; Ha, J.; Kim, S. “Fabrication of polyaniline nanoparticles using microemulsion poly-
merization,” Macromolecular Research 2007, 15, 154–159.
41. Jang, J.; Lim, B.; Lee, J.; Hyeon, T. “Fabrication of a novel polypyrrole/poly (methyl methacry-
late) coaxial nanocable using mesoporous silica as a nanoreactor ,“ Chemical Communications
2001, 83–84.
42. Yan, F.; Xue, G. “Synthesis and characterization of electrically conducting polyaniline in
water–oil microemulsion,” Journal of Materials Chemistry 1999, 9, 3035–3039.
43. Jang, J.; Bae, J. “Fabrication of polymer nanofibers and carbon nanofibers by using a salt-
assisted microemulsion polymerization,” Angewandte Chemie International Edition 2004, 43,
3803–3806.
44. Yan, F.; Xue, G.; Zhou, M. “Preparation of electrically conducting polypyrrole in oil/water
microemulsion,” Journal of Applied Polymer Science 2000, 77, 135–140.
45. Reung-U-Rai, A.; Artita, P.J.U.N.; Prissanaroon-Ouajai, W.; Ouajai, S. “Synthesis of highly
conductive polypyrrole nanoparticles via microemulsion polymerization,” Journal of Metals,
Materials and Minerals 2008, 18, 27–31.
46. Jang, J.; Oh, J.H. “Novel crystalline supramolecular assemblies of amorphous polypyrrole
nanoparticles through surfactant templating,” Chemical Communications 2002, 19, 2200–2201.
47. Jang, J.; Yoon, H. “Formation mechanism of conducting polypyrrole nanotubes in reverse
micelle systems,” Langmuir 2005, 21, 11484–11489.
48. Yoon, H.; Chang, M.; Jang, J. “Sensing behaviors of polypyrrole nanotubes prepared in re-
verse microemulsions: Effects of transducer size and transduction mechanism,” The Journal of
Physical Chemistry B 2006, 110, 14074–14077.
49. Hurst, S.J.; Payne, E.K.; Qin, L.; Mirkin, C.A. “Multisegmented one-dimensional nanorods
prepared by hard-template synthetic methods,” Angewandte Chemie International Edition 2006,
45, 2672–2692.
50. Jackowska, K.; Bieguński, A.T.; Tagowska, M. “Hard template synthesis of conducting poly-
mers: A route to achieve nanostructures,” Journal of Solid State Electrochemistry 2008, 12,
437–443.
51. Prună, A.; Branzoi, V.; Branzoi, F. “Ordered arrays of copper nanowires enveloped in polyaniline
nanotubes,” Journal of Applied Electrochemistry 2011, 41, 77–81.
52. Wang, X.; Han, G.R. “Fabrication and characterization of anodic aluminum oxide template,”
Microelectronic Engineering 2003, 66, 166–170.
53. Smith, A.W. “Porous anodic aluminum oxide membrane,” Journal of the Electrochemical
Society 1973, 120, 1068–1069.
54. Ko, S.; Jang, J. “Controlled amine functionalization on conducting polypyrrole nanotubes as
effective transducers for volatile acetic acid,” Biomacromolecules 2007, 8, 182–187.
55. Park, E.; Kwon, O.S.; Park, S.J.; Lee, J.S.; You, S.; Jang, J. “One-pot synthesis of silver
nanoparticles decorated poly (3, 4-ethylenedioxythiophene) nanotubes for chemical sensor
application,” Journal of Materials Chemistry 2012, 22, 1521–1526.
56. Lee, K.J.; Min, S.H.; Oh, H.; Jang, J. “Fabrication of polymer nanotubes containing nanoparti-
cles and inside functionalization,” Chemical Communications 2011, 47, 9447–9449.
57. Wan, M. “A template-free method towards conducting polymer nanostructures,” Advanced
Materials 2008, 20, 2926–2932.
58. Liu, J.; Wan, M. “Synthesis, characterization and electrical properties of microtubules of
polypyrrole synthesized by a template-free method,” Journal of Materials Chemistry 2001,
11, 404–407.
59. Gupta, S. “Template-free synthesis of conducting-polymer polypyrrole micro/nanostructures

using electrochemistry,” Applied Physics Letters 2006, 88, 063108–063103.
60. Tran, H.D.; Shin, K.; Hong, W.G.; D’arcy, J.M.; Kojima, R.W.; Weiller, B.H.; Kaner, R.B. “A
template-free route to polypyrrole nanofibers,” Macromolecular Rapid Communications 2007,
28, 2289–2293.
61. Alf, M.E.; Asatekin, A.; Barr, M.C.; Baxamusa, S.H.; Chelawat, H.; Ozaydin-Ince, G.; Petruc-
zok, C.D.; Sreenivasan, R.; Tenhaeff, W.E.; Trujillo, N.J. “Chemical vapor deposition of con-
formal, functional, and responsive polymer films,” Advanced Materials 2010, 22, 1993–2027.
62. Kwon, O.S.; Park, S.J.; Lee, J.S.; Park, E.; Kim, T.; Park, H.W.; You, S.A.; Yoon, H.; Jang,
J. “Multidimensional conducting polymer nanotubes for ultrasensitive chemical nerve agent
sensing,” Nano Letters 2012, 12, 2797–2802.
63. Kwon, O.S.; Park, S.J.; Park, H.W.; Kim, T.; Kang, M.; Jang, J.; Yoon, H. “Kinetically controlled
formation of multidimensional poly (3, 4-ethylenedioxythiophene) nanostructures in vapor-
deposition polymerization,” Chemistry of Materials 2012, 24, 4088–4092.
64. Nel, A.; Xia, T.; Mädler, L.; Li, N. “Toxic potential of materials at the nanolevel,” Science 2006,
311, 622–627.
65. Han, D.; Cheung, K.C. “Biodegradable cell-seeded nanofiber scaffolds for neural repair,” Poly-
mers 2011, 3, 1684–1733.
66. Fabbro, A.; Bosi, S.; Ballerini, L.; Prato, M. “Carbon nanotubes: Artificial nanomaterials to
engineer single neurons and neuronal networks,” ACS Chemical Neuroscience 2012, 3, 611–618.
67. Hou, S.T.; Jiang, S.X.; Smith, R.A. Kwang, W.J. “Permissive and repulsive cues and signalling
pathways of axonal outgrowth and regeneration,” International Review of Cell and Molecular
Biology 2008, 267, 125–181.
68. Lu, Y.; Li, T.; Zhao, X.; Li, M.; Cao, Y.; Yang, H.; Duan, Y.Y. “Electrodeposited polypyr-
role/carbon nanotubes composite films electrodes for neural interfaces,” Biomaterials 2010, 31,
5169–5181.
69. Lee, J.Y.; Schmidt, C.E. “Pyrrole–hyaluronic acid conjugates for decreasing cell binding to
metals and conducting polymers,” Acta Biomaterialia 2010, 6, 4396–4404.
70. Thompson, B.C.; Richardson, R.T.; Moulton, S.E.; Evans, A.J.; O’leary, S.; Clark, G.M.;
Wallace, G.G. “Conducting polymers, dual neurotrophins and pulsed electrical stimulation:
Dramatic effects on neurite outgrowth,” Journal of Controlled Release 2010, 141, 161–167.
71. Gelmi, A.; Higgins, M.J.; Wallace, G.G. “Physical surface and electromechanical properties of
doped polypyrrole biomaterials,” Biomaterials 2010, 31, 1974–1983.
72. Svirskis, D.; Travas-Sejdic, J.; Rodgers, A.; Garg, S. “Electrochemically controlled drug delivery
based on intrinsically conducting polymers,” Journal of Controlled Release 2010, 146, 6–15.
73. Jiang, S.; Sun, Y.; Cui, X.; Huang, X.; He, Y.; Ji, S.; Shi, W.; Ge, D. “Enhanced drug loading
capacity of polypyrrole nanowire network for controlled drug release,” Synthetic Metals 2013,
163, 19–23.
436 W.-K. Oh et al.
74. Ge, D.; Ru, X.; Hong, S.; Jiang, S.; Tu, J.; Wang, J.; Zhang, A.; Ji, S.; Linkov, V.; Ren, B.; Shi,
W. “Coating metals on cellulose–polypyrrole composites: A new route to self-powered drug
delivery system,” Electrochemistry Communications 2010, 12, 1367–1370.
75. Gerard, M.; Chaubey, A.; Malhotra, B. “Application of conducting polymers to biosensors”,
Biosensors and Bioelectronics 2002, 17, 345–359.
76. Ramanavičius, A.; Ramanavičienė, A.; Malinauskas, A. “Electrochemical sensors based on
conducting polymer-polypyrrole,” Electrochimica Acta 2006, 51, 6025–6037.
77. Bartlett, P.; Birkin, P. “The application of conducting polymers in biosensors,” Synthetic Metals
1993, 61, 15–21.
78. Song, H.S.; Kwon, O.S.; Lee, S.H.; Park, S.J.; Kim, U.K.; Jang, J.; Park, T.H. “Human taste
receptor-functionalized field effect transistor as a human-like nanobioelectronic tongue,” Nano
Letters 2012, 13, 172–178.
79. Park, S.J.; Kwon, O.S.; Lee, S.H.; Song, H.S.; Park, T.H.; Jang, J. “Ultrasensitive flexible
graphene based fet-type bioelectronic nose,” Nano Letters 2012, 12, 5082–5090.
80. Yoon, H.; Lee, S.H.; Kwon, O.S.; Song, H.S.; Oh, E.H.; Park, T.H.; Jang, J. “Polypyrrole
nanotubes conjugated with human olfactory receptors: High-performance transducers for fet-
type bioelectronic noses,” Angewandte Chemie International Edition 2009, 48, 2755–2758.
81. He, P.; Dai, L. “Carbon nanotube biosensors,” BioMEMS and Biomedical Nanotechnology 2006,
6, 171–201.
82. Balasubramanian, K.; Burghard, M. “Biosensors based on carbon nanotubes,” Analytical and
Bioanalytical Chemistry 2006, 385, 452–468.
83. Sotiropoulou, S.; Chaniotakis, N.A. “Carbon nanotube array-based biosensor,” Analytical and
Bioanalytical Chemistry 2003, 375, 103–105.
84. Sinha, N.; Ma, J.; Yeow, J.T.W. “Carbon nanotube-based sensors,” Journal of Nanoscience and
Nanotechnology 2006, 6, 573–590.
85. Contractor, A.; Sureshkumar, T.N.; Narayanan, R.; Sukeerthi, S.; Lal, R.; Srinivasa, R. “Con-
ducting polymer-based biosensors,” Electrochimica Acta 1994, 39, 1321–1324.
86. Wallace, G.; Smyth, M.; Zhao, H. “Conducting electroactive polymer-based biosensors,” TrAC
Trends in Analytical Chemistry 1999, 18, 245–251.
87. Ahuja, T.; Mir, I.A.; Kumar, D. “Biomolecular immobilization on conducting polymers for
biosensing applications,” Biomaterials 2007, 28, 791–805.
88. Elkaoutit, M.; Naggar, A.H.; Naranjo-Rodriguez, I.; Dominguez, M.; De Cisneros, J.L.H.H.
“Electrochemical AFM investigation of horseradish peroxidase enzyme electro-immobilization
with polypyrrole conducting polymer,” Synthetic Metals 2009, 159, 541–545.
89. Ekiz, F.; Rende, E.; Timur, S.; Toppare, L. “A novel functional conducting polymer: Synthesis
and application to biomolecule immobilization,” Journal of Materials Chemistry 2012, 22,
22517–22525.
90. Yousef Elahi, M.; Bathaie, S.; Kazemi, S.; Mousavi, M. “DNA immobilization on a polypyr-
role nanofiber modified electrode and its interaction with salicylic acid/aspirin,” Analytical
Biochemistry 2011, 411, 176–184.
91. Oh, W.-K.; Kim, S.; Choi, M.; Kim, C.; Jeong, Y.S.; Cho, B.-R.; Hahn, J.-S.; Jang, J. “Cellular
uptake, cytotoxicity, and innate immune response of silica−titania hollow nanoparticles based
on size and surface functionality,” ACS Nano 2010, 4, 5301–5313.
92. Xia, T.; Kovochich, M.; Liong, M.; Mädler, L.; Gilbert, B.; Shi, H.; Yeh, J.I.; Zink, J.I.; Nel,
A.E., “Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles
based on dissolution and oxidative stress properties,” ACS Nano 2008, 2, 2121–2134.
93. Maynard, A.D.; Aitken, R.J.; Butz, T.; Colvin, V.; Donaldson, K.; Oberdörster, G.; Philbert,
M.A.; Ryan, J.; Seaton, A.; Stone, V.; Tinkle, S.S.; Tran, L.; Walker, N.J.; Warheit, D.B. “Safe
handling of nanotechnology,” Nature 2006, 444, 267–269.
94. Jiang, W.; Kim, B.Y.S.; Rutka, J.T.; Chan, W.C.W. “Nanoparticle-mediated cellular response is
size-dependent,” Nature Nanotechnology 2008, 3, 145–150.
95. Dobrovolskaia, M.A.; Germolec, D.R.; Weaver, J.L., “Evaluation of nanoparticle immunotoxi-
city,” Nature Nanotechnology 2009, 4, 411–414.
96. Kim, S.; Oh, W.K.; Jeong, Y.S.; Hong, J.Y.; Cho, B.R.; Hahn, J.S.; Jang, J. “Cytotoxicity of,
and innate immune response to, size-controlled polypyrrole nanoparticles in mammalian cells”,
Biomaterials 2011, 32, 2342–2350.
97. Jeong, Y.S.; Oh, W.-K.; Kim, S.; Jang, J. “Cellular uptake, cytotoxicity, and ros generation with
silica/conducting polymer core/shell nanospheres,” Biomaterials 2011, 32, 7217–7225.
98. Pan, Y.; Neuss, S.; Leifert, A.; Fischler, M.; Wen, F.; Simon, U.; Schmid, G.; Brandau,
W.; Jahnen-Dechent, W. “Size-dependent cytotoxicity of gold nanoparticles,” Small 2007, 3,
1941–1949.
99. Oh, W.-K.; Kim, S.; Yoon, H.; Jang, J. “Shape-dependent cytotoxicity and proinflammatory
response of poly(3,4-ethylenedioxythiophene) nanomaterials,” Small 2010, 6, 872–879.
100. Ramanaviciene, A.; Kausaite, A.; Tautkus, S.; Ramanavicius, A. “Biocompatibility of polypyr-
role particles: An in-vivo study in mice,” Journal of Pharmacy and Pharmacology 2007, 59,
311–315.
101. Ferraz, N.; Strømme, M.; Fellström, B.; Pradhan, S.; Nyholm, L.; Mihranyan, A. “In vitro and in
vivo toxicity of rinsed and aged nanocellulose–polypyrrole composites,” Journal of Biomedical

Materials Research Part A 2012, 100A, 2128–2138.
102. Vaitkuviene, A.; Saseta, V.; Voronic, J.; Ramanauskaite, G.; Biziuleviciene, G.; Ramanavi-
ciene, A.; Ramanavicius, A. “Evaluation of cytotoxicity of polypyrrole nanoparticles synthe-
sized by oxidative polymerization,” Journal of Hazardous Materials 2013, 250–251, 167–
174.
103. Yang, J.; Kim, D.H.; Hendricks, J.L.; Leach, M.; Northey, R.; Martin, D.C. “Ordered surfactant-
templated poly(3,4-ethylenedioxythiophene) (pedot) conducting polymer on microfabricated
neural probes,” Acta Biomaterialia 2005, 1, 125–136.
104. Xiao, Y.; Cui, X.; Martin, D.C. “Electrochemical polymerization and properties of pedot/s-edot
on neural microelectrode arrays,” Journal of Electroanalytical Chemistry 2004, 573, 43–48.
105. Kip, A.L.; Nicholas, B.L.; Mike, D.J.; Sarah, M.R.-B.; Jeffrey, L.H.; Daryl, R.K. “Poly(3,4-
ethylenedioxythiophene) (pedot) polymer coatings facilitate smaller neural recording elec-
trodes,” Journal of Neural Engineering 2011, 8, 014001.
106. Oh, W.-K.; Kim, S.; Kwon, O.; Jang, J., “Shape-dependent cytotoxicity of polyaniline nano-
materials in human fibroblast cells,” Journal of Nanoscience and Nanotechnology 2011, 11,
4254–4260.
107. Xiaoming, L.; Yubo, F.; Fumio, W. “Current investigations into carbon nanotubes for biomedical
application,” Biomedical Materials 2010, 5, 022001.
108. Hu, H.; Ni, Y.; Montana, V.; Haddon, R.C.; Parpura, V. “Chemically functionalized carbon
nanotubes as substrates for neuronal growth,” Nano Letters 2004, 4, 507–511.
109. Harrison, B.S.; Atala, A. “Carbon nanotube applications for tissue engineering,” Biomaterials
2007, 28, 344–353.
110. Correa-Duarte, M.A.; Wagner, N.; Rojas-Chapana, J.; Morsczeck, C.; Thie, M.; Giersig, M.
“Fabrication and biocompatibility of carbon nanotube-based 3d networks as scaffolds for cell
seeding and growth,” Nano Letters 2004, 4, 2233–2236.
111. Brunetti, V.; Maiorano, G.; Rizzello, L.; Sorce, B.; Sabella, S.; Cingolani, R.; Pompa, P.P.
“Neurons sense nanoscale roughness with nanometer sensitivity,” Proceedings of the National
Academy of Sciences 2010, 107, 6264–6269.
112. Lee, J.Y.; Lee, J.-W.; Schmidt, C.E., “Neuroactive conducting scaffolds: Nerve growth factor
conjugation on active ester-functionalized polypyrrole,” Journal of the Royal Society Interface
2009, 6, 801–810.
113. Kim, S.; Oh, W.-K.; Jeong, Y.S.; Jang, J. “Dual-functional poly(3,4-ethylenedioxythiophene)/
mno2 nanoellipsoids for enhancement of neurite outgrowth and exocytosed biomolecule sensing
in pc12 cells,” Advanced Functional Materials 2013, 23, 1947–1956.
114. Abidian, M.R.; Martin, D.C. “Multifunctional nanobiomaterials for neural interfaces,” Advanced
Functional Materials 2009, 19, 573–585.
115. Abidian, M.R.; Ludwig, K.A.; Marzullo, T.C.; Martin, D.C.; Kipke, D.R. “Interfacing con-
ducting polymer nanotubes with the central nervous system: Chronic neural recording
438 W.-K. Oh et al.
using poly(3,4-ethylenedioxythiophene) nanotubes,” Advanced Materials 2009, 21, 3764–

3770.
116. Kang, G.; Borgens, R.B.; Cho, Y. “Well-ordered porous conductive polypyrrole as a new
platform for neural interfaces,” Langmuir 2011, 27, 6179–6184.
117. Oh, W.-K.; Kim, S.; Hwan Shin, K.; Jang, Y.; Choi, M.; Jang, J. “Inkjet-printed polyaniline
patterns for exocytosed molecule detection from live cells,” Talanta, 2013, 105, 333–339.
118. Subramanian, A.; Krishnan, U.; Sethuraman, S. “Development of biomaterial scaffold for nerve
tissue engineering: Biomaterial mediated neural regeneration,” Journal of Biomedical Science
2009, 16, 108–118.
119. Ravichandran, R.; Sundarrajan, S.; Venugopal, J.R.; Mukherjee, S.; Ramakrishna, S., “Applica-
tions of conducting polymers and their issues in biomedical engineering,” Journal of the Royal
Society Interface 2010, 7, S559–S579.
120. Prabhakaran, M.P.; Ghasemi-Mobarakeh, L.; Ramakrishna, S. “Electrospun composite
nanofibers for tissue regeneration,” Journal of Nanoscience and Nanotechnology 2011, 11,
3039–3057.
121. Mawad, D.; Stewart, E.; Officer, D.L.; Romeo, T.; Wagner, P.; Wagner, K.; Wallace, G.G., “A
single component conducting polymer hydrogel as a scaffold for tissue engineering,” Advanced
Functional Materials 2012, 22, 2692–2699.
122. Baosong, L.; Yen, W. “Electroactive conducting polymers for biomedical applications,” Acta
Polymerica Sinica 2010, 010, 1399–1405.
123. Ateh, D.D.; Navsaria, H.A.; Vadgama, P. “Polypyrrole-based conducting polymers and interac-
tions with biological tissues,” Journal of the Royal Society Interface 2006, 3, 741–752.
124. Perez-Madrigal, M.M.; Armelin, E.; Del Valle, L.J.; Estrany, F.; Aleman, C. “Bioactive and elec-
troactive response of flexible polythiophene:Polyester nanomembranes for tissue engineering,”
Polymer Chemistry 2012, 3, 979–991.
125. Lu, Y.; Li, Y.; Pan, J.; Wei, P.; Liu, N.; Wu, B.; Cheng, J.; Lu, C.; Wang, L. “Poly(3,4-
ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol)/poly(acrylic acid) inter-
penetrating polymer networks for improving optrode-neural tissue interface in optogenetics,”
Biomaterials 2012, 33, 378–394.
126. Collins, G.; Federici, J.; Imura, Y.; Catalani, L.H., “Charge generation, charge transport, and
residual charge in the electrospinning of polymers: A review of issues and complications,”
Journal of Applied Physics 2012, 111, 044701–044718.
127. Armelin, E.; Gomes, A.L.; Perez-Madrigal, M.M.; Puiggali, J.; Franco, L.; Valle, L.J. D.;
Rodriguez-Galan, A.; Campos, J.S. D.C.; Ferrer-Anglada, N.; Aleman, C. “Biodegradable free-
standing nanomembranes of conducting polymer: Polyester blends as bioactive platforms for
tissue engineering,” Journal of Materials Chemistry 2012, 22, 585–594.
128. Jang, J.; Oh, J.H. “A facile synthesis of polypyrrole nanotubes using a template-mediated vapor
deposition polymerization and the conversion to carbon nanotubes,” Chemical Communications
2004, 7, 882–883.
129. Long, Y.-Z.; Li, M.-M.; Gu, C.; Wan, M.; Duvail, J.-L.; Liu, Z.; Fan, Z. “Recent advances in syn-
thesis, physical properties and applications of conducting polymer nanotubes and nanofibers,”
Progress in Polymer Science 2011, 36, 1415–1442.
130. Lee, J.Y.; Bashur, C.A.; Goldstein, A.S.; Schmidt, C.E. “Polypyrrole-coated electrospun plga
nanofibers for neural tissue applications,” Biomaterials 2009, 30, 4325–4335.
131. Xie, J.; Macewan, M.R.; Willerth, S.M.; Li, X.; Moran, D.W.; Sakiyama-Elbert, S.E.; Xia, Y.
“Conductive core–sheath nanofibers and their potential application in neural tissue engineering,”
Advanced Functional Materials 2009, 19, 2312–2318.
132. Broda, C.R.; Lee, J.Y.; Sirivisoot, S.; Schmidt, C.E.; Harrison, B.S. “A chemically polymerized
electrically conducting composite of polypyrrole nanoparticles and polyurethane for tissue
engineering,” Journal of Biomedical Materials Research, Part A. 2011, 98A, 509–516.
133. Thompson, B.C.; Moulton, S.E.; Richardson, R.T.; Wallace, G.G. “Effect of the dopant anion
in polypyrrole on nerve growth and release of a neurotrophic protein,” Biomaterials 2011, 32,
3822–3831.
134. Sekine, J.; Luo, S.-C.; Wang, S.; Zhu, B.; Tseng, H.-R.; Yu, H.-H. “Functionalized conducting
polymer nanodots for enhanced cell capturing: The synergistic effect of capture agents and
nanostructures,” Advanced Materials 2011, 23, 4788–4792.
135. Kim, H.-S.; Hobbs, H.L.; Wang, L.; Rutten, M.J.; Wamser, C.C. “Biocompatible composites of
polyaniline nanofibers and collagen,” Synthetic Metals 2009, 159, 1313–1318.
136. Di, L.; Wang, L.P.; Lu, Y.N.; He, L.; Lin, Z.X.; Wu, K.J.; Ren, Q.S.; Wang, J.Y., “Protein
adsorption and peroxidation of rat retinas under stimulation of a neural probe coated with
polyaniline,” Acta Biomaterialia 2011, 7, 3738–3745.
137. Zhang, X.-Q.; Xu, X.; Bertrand, N.; Pridgen, E.; Swami, A.; Farokhzad, O.C. “Interactions of
nanomaterials and biological systems: Implications to personalized nanomedicine,” Advanced
Drug Delivery Reviews 2012, 64, 1363–1384.
138. Shim, M.S.; Kwon, Y.J., “Stimuli-responsive polymers and nanomaterials for gene delivery and
imaging applications,” Advanced Drug Delivery Reviews 2012, 64, 1046–1059.
139. Abidian, M.R.; Kim, D.H.; Martin, D.C. “Conducting-polymer nanotubes for controlled drug
release,” Advanced Materials 2006, 18, 405–409.

140. Cheng, L.; Yang, K.; Chen, Q.; Liu, Z. “Organic stealth nanoparticles for highly effective in
vivo near-infrared photothermal therapy of cancer,” ACS Nano 2012, 6, 5605–5613.
141. Oh, W.K.; Yoon, H.; Jang, J. “Size control of magnetic carbon nanoparticles for drug delivery,”
Biomaterials 2010, 31, 1342–1348.
142. Kim, T.H.; Lee, S.H.; Lee, J.; Song, H.S.; Oh, E.H.; Park, T.H.; Hong, S. “Single-carbon-atomic-
resolution detection of odorant molecules using a human olfactory receptor-based bioelectronic
nose,” Advanced Materials 2009, 21, 91–94.
143. Lee, S.H.; Park, T.H., “Recent advances in the development of bioelectronic nose,” Biotechnol-
ogy and Bioprocess Engineering 2010, 15, 22–29.
144. Vidic, J. Bioelectronic noses based on olfactory receptors. In Intelligent and Biosensors; Som-
erset V.S.; InTech, 2010; Ch. 19.
145. Sanmartı́, M.; Iavicoli, P.; Samitier, J. “Biosensors for diagnostic based on olfactory receptors,”
Nanomedicine in Diagnostics 2012, 120–150.
146. Du, L.; Wu, C.; Liu, Q.; Wang, P. “Recent advances in olfactory receptor-based biosensors,”
Biosensors and Bioelectronics 2012, 42, 570–580.
147. Sankaran, S.; Panigrahi, S.; Mallik, S. “Olfactory receptor based piezoelectric biosensors for
detection of alcohols related to food safety applications,” Sensors and Actuators B: Chemical
2011, 155, 8–18.
148. Hyun Lim, J.; Park, J.; Ho Ahn, J.; Jun Jin, H.; Hong, S.; Hyun Park, T. “A peptide receptor-
based bioelectronic nose for the real-time determination of seafood quality,” Biosensors and
Bioelectronics 2012, 39, 244–249.
149. Zampetti, E.; Pantalei, S.; Macagnano, A.; Proietti, E.; Di Natale, C.; D’amico, A. “Use of a
multiplexed oscillator in a miniaturized electronic nose based on a multichannel quartz crystal
microbalance,” Sensors and Actuators B: Chemical 2008, 131, 159–166.
150. Lee, J.Y.; Ko, H.J.; Lee, S.H.; Park, T.H. “Cell-based measurement of odorant molecules using
surface plasmon resonance,” Enzyme and Microbial Technology 2006, 39, 375–380.
151. Yoon, H.; Ko, S.; Jang, J. “Field-effect-transistor sensor based on enzyme-functionalized
polypyrrole nanotubes for glucose detection,” The Journal of Physical Chemistry B 2008,
112, 9992–9997.
152. Keller, A.; Vosshall, L.B. “Human olfactory psychophysics,” Current Biology 2004, 14,
875–878.
153. Lee, S.H.; Kwon, O.S.; Song, H.S.; Park, S.J.; Sung, J.H.; Jang, J.; Park, T.H. “Mimicking
the human smell sensing mechanism with an artificial nose platform,” Biomaterials 2012, 33,
1722–1729.
154. Winquist, F.; Wide, P.; Lundström, I. “An electronic tongue based on voltammetry,” Analytica
Chimica Acta 1997, 357, 21–31.
155. Winquist, F.; Holmin, S.; Krantz-Rülcker, C.; Wide, P.; Lundström, I. “A hybrid electronic
tongue,” Analytica Chimica Acta 2000, 406, 147–157.
440 W.-K. Oh et al.
156. Riul, A.; Gallardo Soto, A.; Mello, S.; Bone, S.; Taylor, D.; Mattoso, L. “An electronic tongue
using polypyrrole and polyaniline,” Synthetic Metals 2003, 132, 109–116.
157. Ciosek, P.; Wróblewski, W. “Sensor arrays for liquid sensing–electronic tongue systems,”
Analyst 2007, 132, 963–978.
158. Ciosek, P.; Augustyniak, E.; Wróblewski, W. “Polymeric membrane ion-selective and cross-
sensitive electrode-based electronic tongue for qualitative analysis of beverages,” Analyst 2004,
129, 639–644.
159. Krantz-Rülcker, C.; Stenberg, M.; Winquist, F.; Lundström, I. “Electronic tongues for envi-
ronmental monitoring based on sensor arrays and pattern recognition: A review,” Analytica
Chimica Acta 2001, 426, 217–226.
160. Chen, Q.; Zhao, J.; Vittayapadung, S. “Identification of the green tea grade level using electronic
tongue and pattern recognition,” Food Research International 2008, 41, 500–504.
161. Liu, W. “Research on charge transport in one-dimensional organic semiconductors material,”
Advanced Materials Research 2012, 531, 231–234.
162. Law, M.; Goldberger, J.; Yang, P. “Semiconductor nanowires and nanotubes,” Annual Review
of Materials Research 2004, 34, 83–122.
163. Kim, T.H.; Song, H.S.; Jin, H.J.; Lee, S.H.; Namgung, S.; Kim, U.; Park, T.H.; Hong, S.
“Bioelectronic super-taster” device based on taste receptor-carbon nanotube hybrid structures,”
Lab on a Chip 2011, 11, 2262–2267.
164. Kim, U.; Jorgenson, E.; Coon, H.; Leppert, M.; Risch, N.; Drayna, D. “Positional cloning of
the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide,” Science
Signalling 2003, 299, 1221–1225.
165. Lübke, K.; Schillinger, E.; Töpert, M. “Hormone receptors,” Angewandte Chemie International
Edition 2003, 15, 741–748.
166. Schauer, R. “The mode of action of hormones,” Angewandte Chemie International Edition
1972, 11, 7–16.
167. Hodsman, A.B.; Bauer, D.C.; Dempster, D.W.; Dian, L.; Hanley, D.A.; Harris, S.T.; Kendler,
D.L.; Mcclung, M.R.; Miller, P.D.; Olszynski, W.P. “Parathyroid hormone and teriparatide for
the treatment of osteoporosis: A review of the evidence and suggested guidelines for its use,”
Endocrine Reviews 2005, 26, 688–703.
168. Lequin, R.M., “Enzyme immunoassay (eia)/enzyme-linked immunosorbent assay (elisa),” Clin-
ical Chemistry 2005, 51, 2415–2418.
169. Opitz, N.; Lübbers, D. “Electrochromic dyes, enzyme reactions and hormone-protein interac-
tions in fluorescence optic sensor (optode) technology,” Talanta 1988, 35, 123–127.
170. Pritchard, D.; Morgan, H.; Cooper, J. “Simultaneous determination of follicle stimulating
hormone and luteinising hormone using a multianalyte immunosensor,” Analytica Chimica
Acta 1995, 310, 251–256.
171. Matsuura, H.; Sato, Y.; Niwa, O.; Mizutani, F. “Electrochemical enzyme immunoassay of a
peptide hormone at picomolar levels,” Analytical Chemistry 2005, 77, 4235–4240.
172. Harding, P.J.; Hadingham, T.C.; Mcdonnell, J.M.; Watts, A. “Direct analysis of a gpcr-agonist
interaction by surface plasmon resonance,” European Biophysics Journal 2006, 35, 709–712.
173. Kwon, O.S.; Ahn, S.R.; Park, S.J.; Song, H.S.; Lee, S.H.; Lee, J.S.; Hong, J.Y.; You, S.A.; Yoon,
H.; Jang, J. “Ultrasensitive and selective recognition of peptide hormone using close-packed
arrays of hpthr-conjugated polymer nanoparticles,” ACS Nano 2012, 6, 5549–5558.
174. Mandke, R.; Layek, B.; Sharma, G.; Singh, J. “Fabrication and evaluation of nanoparticle-based
biosensors,” Biosensor Nanomaterials 2011, 1, 73–93.
175. Shipway, A.N.; Katz, E.; Willner, I., “Nanoparticle arrays on surfaces for electronic, optical,
and sensor applications,” ChemPhysChem 2000, 1, 18–52.
176. Willner, I.; Zayats, M. “Electronic aptamer-based sensors,” Angewandte Chemie International
Edition 2007, 46, 6408–6418.
177. Mairal, T.; Cengiz zalp, V.; Lozano Sánchez, P.; Mir, M.; Katakis, I.; O’sullivan, C.K. “Aptamers:
Molecular tools for analytical applications,” Analytical and Bioanalytical Chemistry 2008, 390,
989–1007.
178. Wang, Y.; Wei, H.; Li, B.; Ren, W.; Guo, S.; Dong, S.; Wang, E. “Sers opens a new way in
aptasensor for protein recognition with high sensitivity and selectivity,” Chemical Communica-
tions 2007, 46, 5220–5222.
179. Song, S.; Wang, L.; Li, J.; Fan, C.; Zhao, J. “Aptamer-based biosensors,” TrAC Trends in
Analytical Chemistry 2008, 27, 108–117.
180. Kwon, O.S.; Park, S.J.; Hong, J.Y.; Han, A.R.; Lee, J.S.; Oh, J.H.; Jang, J. “Flexible fet-type
VEGF aptasensor based on nitrogen-doped graphene converted from conducting polymer,” ACS
Nano 2012, 6, 1486–1493.
181. Kwon, O.S.; Park, S.J.; Jang, J. “A high-performance VEGF aptamer functionalized polypyrrole
nanotube biosensor,” Biomaterials 2010, 31, 4740–4747.
182. Hernandez, F.J.; Ozalp, V.C. “Graphene and other nanomaterial-based electrochemical aptasen-
sors,” Biosensors 2012, 2, 1–14.
183. Zelada-Guillén, G.A.; Riu, J.; Düzgün, A.; Rius, F.X. “Immediate detection of living bacteria at
ultralow concentrations using a carbon nanotube based potentiometric aptasensor,” Angewandte
Chemie International Edition 2009, 48, 7334–7337.

184. Rahman, M.A.; Son, J.I.; Won, M.S.; Shim, Y.B., “Gold nanoparticles doped conducting poly-
mer nanorod electrodes: Ferrocene catalyzed aptamer-based thrombin immunosensor,” Analyt-
ical chemistry 2009, 81, 6604–6611.
185. Olowu, R.A.; Arotiba, O.; Mailu, S.N.; Waryo, T.T.; Baker, P.; Iwuoha, E. “Electrochemical ap-
tasensor for endocrine disrupting 17β-estradiol based on a poly (3, 4-ethylenedioxylthiopene)-
gold nanocomposite platform,” Sensors 2010, 10, 9872–9890.
186. Schalkhammer, T.; Mann-Buxbaum, E.; Pittner, F.; Urban, G. “Electrochemical glucose sensors
on permselective non-conducting substituted pyrrole polymers,” Sensors and Actuators B:
Chemical 1991, 4, 273–281.
187. Yoon, H.; Kim, J.H.; Lee, N.; Kim, B.G.; Jang, J. “A novel sensor platform based on aptamer-
conjugated polypyrrole nanotubes for label-free electrochemical protein detection,” Chem-
BioChem 2008, 9, 634–641.
188. Cao, Y.W. C.; Jin, R.; Mirkin, C.A. “Nanoparticles with raman spectroscopic fingerprints for
DNA and rna detection,” Science 2002, 297, 1536–1540.
189. Ko, S.; Jang, J. “Label-free target DNA recognition using oligonucleotide-functionalized
polypyrrole nanotubes,” Ultramicroscopy 2008, 108, 1328–1333.
190. Gaylord, B.S.; Heeger, A.J.; Bazan, G.C. “DNA detection using water-soluble conjugated
polymers and peptide nucleic acid probes,” Proceedings of the National Academy of Sciences
2002, 99, 10954–10957.
191. Li, J.; Ng, H.T.; Cassell, A.; Fan, W.; Chen, H.; Ye, Q.; Koehne, J.; Han, J.; Meyyappan, M.
“Carbon nanotube nanoelectrode array for ultrasensitive DNA detection,” Nano Letters 2003,
3, 597–602.
192. Stoeva, S.I.; Lee, J.S.; Thaxton, C.S.; Mirkin, C.A. “Multiplexed DNA detection with biobar-
coded nanoparticle probes,” Angewandte Chemie 2006, 118, 3381–3384.
193. Wang, J.; Jiang, M.; Fortes, A.; Mukherjee, B. “New label-free DNA recognition based on
doping nucleic-acid probes within conducting polymer films,” Analytica Chimica Acta 1999,
402, 7–12.
194. Dupont-Filliard, A.; Billon, M.; Livache, T.; Guillerez, S., “Biotin/avidin system for the genera-
tion of fully renewable DNA sensor based on biotinylated polypyrrole film,” Analytica Chimica
Acta 2004, 515, 271–277.
195. Peng, H.; Soeller, C.; Vigar, N.; Kilmartin, P.A.; Cannell, M.B.; Bowmaker, G.A.; Cooney, R.P.;
Travas-Sejdic, J. “Label-free electrochemical DNA sensor based on functionalised conducting
copolymer,” Biosensors and Bioelectronics 2005, 20, 1821–1828.
196. Ramanathan, K.; Mangesh, A.; Yun, M.; Chen, W.; Myung, N.V.; Mulchandani, A. “Bioaffin-
ity sensing using biologically functionalized conducting-polymer nanowire,” Journal of the
American Chemical Society 2005, 127, 496–497.
197. Jang, J.; Ko, S.; Kim, Y. “Dual-functionalized polymer nanotubes as substrates for molecular-
probe and DNA-carrier applications,” Advanced Functional Materials 2006, 16, 754–759.
442 W.-K. Oh et al.
198. Gosling, J.P. “A decade of development in immunoassay methodology,” Clinical Chemistry

1990, 36, 1408–1427.
199. Bange, A.; Halsall, H.B.; Heineman, W.R. “Microfluidic immunosensor systems,” Biosensors
and Bioelectronics 2005, 20, 2488–2503.
200. Van Weeman, B.; Schuurs, A. “Immunoassay using antigen-enzyme conjugates,” FEBS Letter
1971, 15, 232–235.
201. Ishikawa, E.; Kato, K. “Ultrasensitive enzyme immunoassay,” Scandinavian Journal of Im-
munology 2009, 8, 43–55.
202. Zhao, L.; Sun, L.; Chu, X. “Chemiluminescence immunoassay,” TrAC Trends in Analytical
Chemistry 2009, 28, 404–415.
203. Holt, D.; Rabbany, S.Y.; Kusterbeck, A.W.; Ligler, F.S. “Advances in flow displacement im-
munoassay design,” Reviews in Analytical Chemistry 2011, 18, 107–132.
204. Lu, D.; Wang, J.; Wang, L.; Du, D.; Timchalk, C.; Barry, R.; Lin, Y. “A novel nanoparticle-based
disposable electrochemical immunosensor for diagnosis of exposure to toxic organophosphorus
agents,” Advanced Functional Materials 2011, 21, 4371–4378.

205. Sargent, A.; Sadik, O.A. “Monitoring antibody–antigen reactions at conducting polymer-based
immunosensors using impedance spectroscopy,” Electrochimica Acta 1999, 44, 4667–4675.
206. Bandodkar, A.J.; Dhand, C.; Arya, S.K.; Pandey, M.; Malhotra, B.D. “Nanostructured conduct-
ing polymer based reagentless capacitive immunosensor,” Biomedical Microdevices 2010, 12,
63–70.
207. Bangar, M.A.; Shirale, D.J.; Chen, W.; Myung, N.V.; Mulchandani, A. “Single conducting
polymer nanowire chemiresistive label-free immunosensor for cancer biomarker,” Analytical
Chemistry 2009, 81, 2168–2175.
208. Schultz, J.S.; Mansouri, S.; Goldstein, I.J. “Affinity sensor: A new technique for developing
implantable sensors for glucose and other metabolites,” Diabetes Care 1982, 5, 245–253.
209. Singh, M.; Kathuroju, P.K.; Jampana, N. “Polypyrrole based amperometric glucose biosensors,”
Sensors and Actuators B: Chemical 2009, 143, 430–443.
210. Reaven, G.M. “Role of insulin resistance in human disease,” Diabetes 1988, 37, 1595–1607.
211. Megyesi, C.; Samols, E.; Marks, V. “Glucose tolerance and diabetes in chronic liver disease,”
The Lancet 1967, 290, 1051–1056.
212. Calvo, E.J.; Wolosiuk, A. “Supramolecular architectures of electrostatic self-assembled glucose
oxidase enzyme electrodes,” ChemPhysChem 2004, 5, 235–239.
213. Vidaković-Koch, T.; Ivanov, I.; Falk, M.; Shleev, S.; Ruzgas, T.; Sundmacher, K. “Impact of
the gold support on the electrocatalytic oxidation of sugars at enzyme-modified electrodes,”
Electroanalysis 2011, 23, 927–930.
214. Liu, J.; Agarwal, M.; Varahramyan, K. “Glucose sensor based on organic thin film transistor
using glucose oxidase and conducting polymer,” Sensors and Actuators B: Chemical 2008, 135,
195–199.
215. Das, D.; Kim, D.M.; Park, D.S.; Shim, Y.B. “A glucose sensor based on an aminophenyl boronic
acid bonded conducting polymer,” Electroanalysis 2011, 23, 2036–2041.
216. Guo, C.X.; Li, C.M. “Direct electron transfer of glucose oxidase and biosensing of glucose on
hollow sphere-nanostructured conducting polymer/metal oxide composite,” Physical Chemistry
Chemical Physics 2010, 12, 12153–12159.
217. Iftçi, H.; Tamer, U.; Teker, M.Ş.; Pekmez, N. “An enzyme free potentiometric detection of glu-
cose based on a conducting polymer poly (3-aminophenyl boronic acid-co-3-octylthiophene),”
Electrochimica Acta 2012, 90, 358–365.
218. Iftçi, H.; Tamer, U. “Functional gold nanorod particles on conducting polymer poly
(3−octylthiophene) as non-enzymatic glucose sensor,” Reactive and Functional Polymers 2011,
72, 127–132.
View publication stats

Conducting Polymer Nanomaterials For Biomedical Applications: Cellular Interfacing and Biosensing

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Conducting Polymer Nanomaterials For Biomedical Applications: Cellular Interfacing and Biosensing

Uploaded by

Copyright:

Available Formats

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

Conducting Polymer Nanomaterials for Biomedical Applications:

Article in Polymer Reviews · July 2013

The user has requested enhancement of the downloaded file.

Conducting Polymer Nanomaterials

To link to this article: http://dx.doi.org/10.1080/15583724.2013.805771

PLEASE SCROLL DOWN FOR ARTICLE

Conducting Polymer Nanomaterials for Biomedical

WAN-KYU OH∗ , OH SEOK KWON∗ , AND JYONGSIK JANG

Recently, conducting polymer (CP) nanomaterials have shown outstanding chemical

Keywords conducting polymer, nanomaterials, cytotoxicity, biosensor, cellular inter-

Received March 4, 2013; accepted May 10, 2013.

2. Synthesis and Biomedical Applications of CP Nanomaterials

2.1 Synthesis of CP Nanomaterials

developments in various fields due to ultrafine features at the nanometer scale.24–28 CP

2.1.1 Soft-Template Methods. Diverse morphologies of CP nanomaterials have been con-

Figure 1. Synthesis processes of CP nanomaterials: a) Soft-template method. b) Hard-template

2.1.3 Template-Free Methods. Template-free approaches have been extensively investi-

2.2 Biomedical Applications of CP Nanomaterials

of well-controlled nanomaterials having sensitive and selective analyte detection is an

3.1 Cytotoxicity of CP Nanomaterials

Figure 4. a) Schematic illustration of preparation of silica/CP core/shell NSs. b) Viability of RAW

3.2 Neural Interfaces

compatibility issues inherent to microelectrodes.111 Owing to their electronic and ionic

Figure 5. a) Schematic diagram of preparation of the PEDOT/MnO2 nanoellipsoids. b) experimental

Figure 6. The fabrication steps of multifunctional polymer coated-neural electrodes: a) pristine

3.3 Tissue Engineering

NFs have shown attractive characteristics such as biocompatibility, facile modulation of

3.4 Drug Delivery

4.1 CP-Based Biosensor Technology

4.2 Protein Receptor−Based Biosensors

4.2.2 Nanobioelectronic Tongue. The development of sensory systems discriminating var-

Recently, 1D electronic nanomaterials with well-controlled structures have become at-

receptor-conjugated CPNT substrate. A high-performance nbe-tongue was constructed us-

4.3 Hormone Sensors

Figure 14. a) Schematic diagram of nanobioelectronic tongue. b) I SD -V SD curves of nbe-tongue. c)

Figure 15. Synthetic processes of close-packed arrays of hPTHR-conjugated CPPyNPs. Reproduced

and real-time monitoring.179 Thus, advances in the electrochemical design of biosensors

the VEGF-aptasensor system. A label-free electrochemical aptasensor based on CP NTs

4.5 DNA Sensors

4.6 Glucose Sensors

glucose biosensors, novel strategies to create modified CP electrodes or transducers should

be modified covalently using specific bioreceptors, allowing the immobilization of CP

37. Fredrickson, G.H. “Surfactant-induced lyotropic behavior of flexible polymer solutions,”

59. Gupta, S. “Template-free synthesis of conducting-polymer polypyrrole micro/nanostructures

vivo toxicity of rinsed and aged nanocellulose–polypyrrole composites,” Journal of Biomedical

using poly(3,4-ethylenedioxythiophene) nanotubes,” Advanced Materials 2009, 21, 3764–

release,” Advanced Materials 2006, 18, 405–409.

Chemie International Edition 2009, 48, 7334–7337.

198. Gosling, J.P. “A decade of development in immunoassay methodology,” Clinical Chemistry

agents,” Advanced Functional Materials 2011, 21, 4371–4378.

View publication stats

You might also like