Download Carbon based materials for electronic bio-sensing

Carbon based materials
for electronic bio-sensing
Bio-sensing represents one of the most attractive applications of carbon
material based electronic devices; nevertheless, the complete integration
of bioactive transducing elements still represents a major challenge,
particularly in terms of preserving biological function and specificity while
maintaining the sensor’s electronic performance. This review highlights
recent advances in the realization of field-effect transistor (FET) based
sensors that comprise a bio-receptor within the FET channel. A birds-eye
view will be provided of the most promising classes of active layers as
well as different device architectures and methods of fabrication. Finally,
strategies for interfacing bio-components with organic or carbon nanostructured electronic active layers are reported.
Maria D. Angionea, Rosa Pilollia, Serafina Cotronea, Maria Magliuloa, Antonia Mallardib, Gerardo Palazzoa, Luigia Sabbatinia,
Daniel Finec, Ananth Dodabalapurd, Nicola Cioffia*, and Luisa Torsia*
a Department of Chemistry,University of Bari, Via Orabona, 4, I-70126 Bari, Italy
b CNR–IPCF,Istituto per i Processi Chimico-Fisici -Bari, Italy
c Department of NanoMedicine and BioMedical Engineering, The University of Texas Health Science Center at Houston, TX, USA
d Department of Electrical and Computer Engineering Microelectronics Research Center The University of Texas at Austin, TX USA
* E-mail: [email protected] and [email protected]
Recently, increasing medical and biological interest in cheap
active layer materials that allow for the inclusion of biologically
disposable, analytical, and diagnostic devices has driven research
active bio-receptors while maintaining electronic performance. The
towards the development and adaptation of low-cost electronic
present contribution reviews and compares recent developments
sensing devices. While a lot of effort has been devoted to silicon
in these related fields.
based nanostructured active layers, we focus here on carbon-
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based materials. Organic semiconductors can be implemented
Organic field-effect transistor bio-sensors
in a platform for flexible devices, including those built on
Organic transistor-based devices have previously been demonstrated
biodegradable and resorbable substrates, while carbon based
for gas, vapor, and liquid sensing1-5, as well as for the detection of
nano-structured materials, such as carbon nanotubes and graphene
single ions or ensembles of ions in solution6-12. Organic field-effect
sheets, offer higher performance in terms of field-effect mobility
transistor (OFET) based sensing technologies take advantage of the
and sensitivity. In all cases, the major challenge is to develop
physical or chemical changes taking place in or around the organic
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Carbon based materials for electronic bio-sensing
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(semi)conducting material when exposed to different analytes in
systems involved. These aspects are not dealt with here as they would
gaseous or aqueous environments. Field-effect transistors (FETs) for
require a review of their own. Only recent advances in processing and
their
multi-parametric13
response and multi-functionality-related
integrating natural and synthetic bio-active components into electronic
versatility, comprise the primary functional component in an array of
devices based on both organic or carbon nanostructured materials are
sensing platforms proposed in the field of environmental monitoring8,
considered (excluding whole cell implementations). This includes new
military defense9,10,14-16 and preventative medical care11. The
studies on biodegradable substrates for OFETs as well as bio-species
integration of active organic materials into these devices has allowed
included in gate dielectric materials or on electronic active layers.
for the implementation of electronics with plastic substrates, and thus
low-cost, lightweight, and flexible sensing devices.
Organic thin-film transistors (OTFTs) are three-terminal electronic
OFETs fabricated on resorbable and
biodegradable substrates
devices consisting of a thin organic semiconducting layer, an insulating
Efforts to fabricate flexible electronic circuits have routinely focused on
(dielectric) layer, and three conductive terminals, the source, drain,
developing processes that are compatible with flexible plastic substrate
and gate. The source and drain electrodes are fabricated to be directly
materials such as poly(ethylene terephthalate) (PET)39, poly(imide)40,
in contact with the semiconductor, either on top of the previously
poly(ether sulfone)41, cellulose42, silk fibroin, or other functional
deposited organic semiconductor (top-contact), or on the insulating
fibers for e-textile development43,44. Various organic polymeric
layer to be covered with the semiconductor later (bottom-contact).
systems composed of biodegradable polymers have demonstrated
The “channel” refers to the region in the semiconductor layer between
their usefulness in important applications like temporary medical
the defined source and drain electrodes12. The active semiconductor
implants45,46, and biodegradable products47. However, the realization
layer may consist of small
molecules17-22 polymers23,24,
or organic
of these systems requires fabrication processes that are compatible
nanostructured materials25-27, among others. Contacts are usually
with tight substrate compatibility requirements; in particular, in the
composed of gold; although a vast number of conductive materials
case of PET, a moderate use of aqueous solvent and low-temperature
(e.g., doped conjugated polymers and printed metallic nanoparticles)
post processing, must be taken into account as a limiting step in
are actively being used for this
purpose28,29.
The dielectric layer,
the fabrication procedure. To realize electronic circuits that are not
which electrically isolates the semiconductor from the underlying gate
only flexible but also foldable, materials such as aluminum foil48 and
electrode, may be composed of inorganic oxides30, properly tailored
paper49 have been explored. Paper films were used as substrates with
polymers or composites7, or ultrathin self-assembled layers31.
pentacene-based active layers. This approach was further expanded
Recent advancements in the field of biotechnology have provided
to create complete circuits using foldable paper-based substrates,
systems that are able to efficiently transduce biological events using
motivated by the fact that paper substrates are mechanically flexible
electronic devices32,33. This progress has led to the improvement
and capable of small bending radii. Roll-to-roll processing has also
of biological sensing platforms demonstrating the potential to be
been demonstrated by Siegel and co-workers that allows for the
applied for the rapid screening of biological samples and point-of-
realization of a complete circuit from simple folding and cutting
care diagnostics. Advancements in biomaterial processing and organic
techniques (Fig. 1)34. The relative fragility of paper-based circuits
electronic device fabrication have allowed for the potential integration
could potentially be utilized in security applications. One specific
of biomolecules as active components in all of the materials employed
example is the fabrication of an envelope integrated with a system
in the realization of an organic transistor including the bulk substrate,
that, if compromised via destruction of the envelope, will cease to
the dielectric interface, and even the active semiconducting layers and
function. Paper-based devices also present distinct advantages in
electrodes34.
terms of disposability and environmental biodegradability, the latter
Other interesting aspects of biomolecule integration in organic
being extremely important in the context of medical biomaterials.
electronic devices have been explored in electrochemical bio-
The motivation of this nascent research topic is to improve the
transistors35 that have proven to be quite sensitive and selective. Some
compatibility of biomaterials and electronic devices for applications
limitations persist, however, and are connected to their implementation
including restorable electronically active medical implants45,46.
in large area sensor arrays as it is not clear if the need for a reference
Mechanically robust, water-insoluble, natural proteins have also been
electrode can be ruled out. Significant effort has also been invested in
explored as substrates for silicon electronics. A key example is provided
recent years to develop new hybrid systems in which living cells have
by Kim et al.43 who used silk fibroin as a substrate for traditional
been integrated in electronic field-effect devices36,37.The technological
silicon-based transistors. The performance of these devices is only
impact of these systems is attracting the interest of many research
slightly affected when the substrate is mechanically deformed.
groups as evidenced by the numerous contributions that can be found
Bao’s group recently investigated materials and fabrication
in the literature38. These studies involve major efforts in assessing
strategies for the realization of organic thin-film transistors using a
biocompatibility and bio-functionality of the materials and the bio-
small-molecule semiconductor in combination with a biodegradable
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Carbon based materials for electronic bio-sensing
(a)
(a)
(b)
(b)
(c)
(c)
426
Fig. 1 Paper-based circuits demonstrate remarkable mechanical flexibility
and versatility. (a, b) Trimming and burning fiber-based electronic circuits;
in (b), the paper circuit burned in 3 s. (c). A paper airplane circuit shown
unfolded (top left) and folded (top right) with battery-powered red/green
light-emitting diode (LED) wingtips. The circuit weighs less than 1 g.
Electronic traces for both circuits are comprised of metallic wires (100 % In,
thickness = 2 mm, width = 1 mm, length = 30 – 60 mm total) patterned on
Yasutomo origami paper substrates. Reprinted from34. © Wiley-VCH Verlag
GmbH & Co. KGaA. Reproduced with permission.
Fig. 2 A representation of the device structure and degradation time of the
devices reported by Bao, et al. (a) The chemical structure of the semiconductor
5,5-bis-(7-dodecyl-9H-fluoren-2-yl)-2,2 - bithiophene (DDFTTF), the
dielectric (PVA) and the substrate (PLGA). (b) The top-contact configuration
of the OTFT devices. (c) In vitro degradation studies of the PLGA substrates.
Although initially resistant to mass degradation and water uptake, significant
mass loss and water uptake can be observed after 30 days. Near-total mass
loss and 100 % device hydration were observed at 70 days. Reprinted from50. ©
Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.
polymeric substrate and dielectric50. They demonstrated that these
explicitly studied, degradation mechanisms that decompose melanin51,52,
devices perform stably after exposure to water and, since they are
a conjugated amorphous semiconductor53,54, could potentially act
made of nearly entirely biodegradable materials, are resorbable in a
in a similar manner towards DDFTTF. Poly(vinyl alcohol) was used as
simulated degradation environment in vitro. A schematic image of the
the insulating layer. Devices were fabricated with “non-crosslinked”
device is shown in Fig. 2. The strategy for material selection focused on
PVA (nPVA) and crosslinked PVA (xPVA) in order to demonstrate the
utilizing materials that are not only biocompatible and biodegradable,
improved performance of the xPVA-based device in terms of leakage
but also exhibit adequate electronic properties and a suitable device
current and surface roughness. The substrate, which composed 99.89 %
manufacturing process. The semiconducting molecule utilized in this
of the total mass, consists of poly(L-lactide-co-glycolide) (PLGA), a linear
study, 5,50-bis-(7-dodecyl-9H-fluoren-2-yl)-2,20-bithiophene (DDFTTF),
thermoplastic biodegradable polyester. This polymer contains significant
is a robust small-molecule p-channel semiconductor that exhibits
amounts of lactic acid (PLGA 85:15) and thus allows for processing at
excellent device performance and is resistant to harsh aqueous
elevated temperatures due to the high glass-transition temperature, Tg.
environments. Although the biodegradation of DDFTTF has not been
Thin-film transistors based on p-channel DDFTTF active layers and (PVA)
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dielectrics exhibited electron mobilities as high as 0.253 cm2s-1V-1 and
conditions, such as the pH of the precursor solutions, as demonstrated
on/off current ratios (Ion/Ioff) of up to 9.4 × 103. These devices maintained
by the group of A. K-Y. Jen who fabricated pentacene based OTFTs on
functionality after direct exposure to water and are principally resorbable
top of quartz-binding polypeptide (QBP)-modified SiO2/Si substrates
and biodegradable. To avoid interaction with ionic species eventually
with a 50 nm pentacene active layer. The transfer characteristics for
present in the analyte aqueous solution, an appropriate encapsulation and
these devices are shown in Fig. 3, along with the device structure.
packaging of the device was needed. The potential utilization of resorbable
A shift in Vt of about 30 V compared to the unmodified SiO2 was
organic electronics could serve as a motivating factor for the development
observed upon assembly of the peptide in pH-neutral condition. From
of high-performance dielectrics and semiconducting molecules with the
this point, a positive shift in Vt was observed when the GEPI-QBP was
additional properties of biocompatibility and biodegradability into non-
assembled in different concentrations of HCl, while a negative shift
toxic and environmentally safe monomers.
in Vt was observed when QBP was assembled from a KOH solution at
different concentrations. Although the approach is very interesting, the
OFETs dielectrics modified with biomolecules
Improvements of bio-sensor figures of merit have been realized
stability of the system has not been discussed.
OFETs with functional deoxyribonucleic acids (DNAs) as dielectric
through the development of new high performance dielectrics and
material have been pioneered by the Grote and Sariciftci groups56-58.
device architectures, as well as by tuning device properties via
Specifically, organic-soluble DNA, such as cetyltrimethylammonium
interface engineering. Precise control over the threshold voltage (Vt)
chloride (CTMA)-DNA, have been synthesized and their physical
of pentacene-based organic thin film transistors, desirable for better
and electronic properties have been elucidated. Since CTMA-DNA
integration of OFET devices into electronic circuits, has been achieved
is insoluble in water but soluble in alcohol, solution processing
by inserting well characterized genetically engineered peptides for
methods are suitable for thin-film fabrication. An interesting
inorganics (GEPI) at the semiconductor-dielectric interface55. Further
field-effect carrier transport phenomenon was observed in these
tuning of the Vt can be achieved by controlling the peptide assembly
devices, although an undesired hysteresis could be seen in the
corresponding transfer curves. An additional blocking layer of
(a)
(e)
5,5’-(9,10-bis((4-hexylphenyl)ethynyl)anthracene-2,6-yl-diyl)
bis(ethyne-2,1-diyl)bis(2-hexylthiophene) (HB-ant-THT) molecules
was introduced between the organic semiconductor layer and the DNA
dielectric, to improve the electrical performance, including a reduction
in leakage current. Y. S. Kim59 further reported on the development
(b)
of photo-crosslinkable DNA-based dielectrics detailing the precise
effect of the CTMA units in the copolymer on TFT performance.
Particularly, the TFT device with the CTMA-DNA-co-CcDNA dielectric
(Fig. 4) has a very high field-effect mobility implying that the long alkyl
(c)
chains in the CTMA unit help enhance the ordering of the HB-ant-THT
(f)
molecules.
Bio-functionalization of the organic semiconductor
Many examples have been proposed for the detection of analyte
(d)
vapors using OTFTs, with numerous reports addressing the ability
to identify particular analytes either through the use of a fingerprint
response60,61 or by incorporating selective detection layers4,62.
On the contrary few examples of chemical and bio-detection
in aqueous systems have been demonstrated, the first example
Fig. 3 A schematic representation of a peptide-modified thin-film transistor. (b)
Assembly in water produces no ions to pair with the peptide termini. (c) When
assembled in an HCl solution, the N-termini pair with chloride ions. (d) When
assembled in a KOH solution, the C-termini pair with potassium ions to produce
a dipole pointing toward the substrate surface. The source-drain current vs
source-drain bias (e) and the square root of the source-drain current vs the gate
source voltage (f) for pentacene OTFTs assembled on SiO2 under basic (green
diamonds), neutral (blue circles), and acidic (red triangles) conditions, as well
as with and without peptide (purple squares), are also depicted. Reprinted with
permission from55. © 2010, American Institute of Physics.
being published in 2002 by Someya and co-workers63. Selective
in situ detection with OTFTs requires a versatile method for the
immobilization of various selective molecular probes within close
proximity to the active transport channel. Bao’s et al. reported in
2010 a real-time, in situ selective detection scheme with short-chain
DNA targets employing organic transistors as the electrical transducer
(Fig. 5)64. The device was realized by modifying the OTFT surfaces with
a PECVD (plasma-enhanced chemical vapor deposition)-deposited thin
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Fig. 4 A depiction of an OTFT device configuration along with the chemical structures of HBant- THT, CcDNA, and CTMADNA-co-CcDNA. Capacitance plots for
metal insulator metal devices fabricated with CcDNA and CTMADNA-co-CcDNA. Reprinted with permission from59. © 2010, American Institute of Physics.
maleic anhydride (MA) polymer layer65,66. Such a surface pretreatment
Genetic diagnostic tools have been proposed by Subramaniam’s
allowed for the covalent attachment of the peptide nucleic acid (PNA)
group that integrate OTFT-based DNA sensors with microfluidic
strands, which were then used to selectively detect the target DNA
channels. A novel photolithography-based microfluidics fabrication
molecules within limits approaching 1 nM.
method was used to directly enable on-chip hybridization, a significant
(a)
(b)
(c)
Fig. 5 A schematic representation of an OTFT sensor fabrication process. (a) Fabrication of OTFT with a PVP-HDA (20 nm) dielectric layer, DDFTTF organic
semiconductor (15 nm), and source-drain (S-D) electrodes. (b) PNA and DNA 15-mer sequences and the chemical structure of DDFTTF. (c) Schematics of the
surface modification to immobilize the PNA-15mer probe. Reprinted from64. © Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with permission.
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(a)
(c)
(b)
(d)
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Fig. 6 (a) SEM and (b) AFM images of a biotinylated F8T2-polymer film coated onto an SiO2/Si substrate. (c) Plot of source-drain current versus gate voltage at a
drain voltage of −60 V for biotinylated F8T2 OTFTs. The inset represents the I-V characteristics at various gate biases. (d) Plot of drain current versus gate voltage at
a drain-voltage of −60 V for biotinylated F8T2 OTFTs annealed within a temperature range of 150 °C to 280 °C. © ETRI Journal. Reprinted with permission from68.
advancement in the realization of disposable rapid turn-around tools
Recently, our group proposed the inclusion of a photosynthetic
for field-deployable genetic diagnosis67. Another example of direct
membrane protein, the bacterial reaction center, into a phospholipid
semiconductor functionalization was provided by Lim’s group where an
bilayer formed on top of the active layer of an OTFT for herbicide
organic semiconducting copolymer composed of biotinylatedfluorene
detection69,70. A pictorial view of this sensing device bearing the
and bithiophene was synthesized through a palladium(0)-mediated
membrane protein as a bioreceptor is shown in Fig. 7a. The lipid
Suzuki coupling polymerization. OTFTs were fabricated using this
bilayer facilitates a close association of the protein with the carriers
p-type polymer and electrically characterized in the presence of avidin
(electrons or holes) accumulated in the channel at the semiconductor/
(Fig.
6)68.
The binding of avidin-biotin moieties in the polymer were
gate-dielectric interface. Atomic force microscopy (AFM) (Fig. 7b) and
correlated to changes in the channel chemoresistivity and to the on/off
confocal microscopy (Fig. 7c) have been performed to investigate the
characteristics of the OTFTs. Avidin exposure resulted in a lowering
structure of the lipid-protein layer deposited on top of the organic
of the drain current (Ids) of nearly five orders of magnitude when the
semiconductor and shows a very uniform deposition of biomaterials.
device was operated at a drain voltage of −40 V. Detection in this
Very little electronic performance degradation (Fig. 7d) is seen as
case was done at about 50 ppm, which is quite high considering the
the bioreceptor containing layer is deposited on top of the channel
specificity of the interaction.
material.
(a)
(b)
(c)
(d)
Fig. 7 (a) A schematic representation of a phospholipid embedded membrane protein based OTFT. (b) A confocal microscopy image. (c) An AFM image. (d) Currentvoltage characteristics of the supported bilayer OTFT. The gate biases range from 0 V to −100 V in steps of −20 V. Reprinted with permission from69, © 2009, IEEE.
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Another interesting and very recent architecture that explores organic
(a)
semiconductor functionalization has been presented by Blom’s research
group71. Here a dual gate organic field-effect transistor with integrated
sulfate binding proteins (SBP) for sensing of sulfate ions is proposed.
Fluorescence spectroscopy and tapping mode AFM were used to confirm
the covalent coupling of the SBP receptor to the surface of a maleimide
functionalized polystyrene layer. This system guarantees protein stability
without loss of protein selectivity, as demonstrated by the dissociation
constant measurement of SBP after drying and rehydration showing that
the protein remains active even after being dried.
Organic nanomaterials for biosensing by FET
transduction.
(b)
One promising direction for future transistor technology involves
“nanoelectronics” in which the active part of the device is composed
of nanometer sized materials. In particular the integration of 1D
nanomaterials, such as nanowires and nanotubes, into functional
electronic devices has received considerable attention for application
as highly sensitive tools for biological applications. The comparable
sizes of engineered nanomaterials and natural biological systems
(e.g., antibodies, enzymes, transport proteins, etc.) make this
approach appropriate for creating high throughput sensing probes:
shrinking the dimensions of the materials down to the nanometer
scale maximizes the effect of biochemical changes at the surface of
the device. A single surface binding event will lead to a much larger
change in device conductance than planar FETs as a result of the
(c)
accumulation/depletion of carriers through the entire cross section of
the device versus only a thin region near the surface. Nanomaterial
based electronic devices thus provide a unique class of biosensor,
with intrinsic ultra-sensitivity towards changes in their local chemical
environment. These devices behave as both the sensitizing layer and
the transducer allowing for the direct conversion of bio-chemical
information into an electronic signal without labels allowing for realtime continuous monitoring.
Conducting polymer nanostructures
Given previously reported assessments of three-dimensional conducting
polymers as electronic chemical sensors72, 1D conducting polymer (CP)
nanomaterials present attractive alternatives to carbon nanotubes and
silicon nanowires that merge properties from inorganic, carbonaceous,
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Fig. 8 (a) A schematic illustration of a human olfactory receptor (hOR)
conjugated polypyrrole NT-FET. (b-c) Real-time changes of normalized ISD
upon addition of target odorant (amyl butyrate, AB) and non-target odorants
(butyl butyrate, BB; propyl butyrate, PB; hexyl butyrate, HB), measured at
VSD = 50 mV. Reprinted from82. © Wiley-VCH Verlag GmbH & Co. KGaA.
Reproduced with permission.
and polymeric materials: tunable conductivity, chemical diversity,
functionality not only provides sufficient immobilization sites for
mechanical stability, and biocompatibility73-77. Further advantages
biomolecules, but also assists in the covalent binding of 1D CPs on
include their lightweight, low cost, easy processing/patterning, and
amine-terminated silanized SiO2 substrates, to form stable contacts
scalable production. A crucial factor that needs to be accounted for
with the metal electrodes, as illustrated in Fig. 882. Thrombin78,79,
in designing CP-FET biosensors is the sensitivity of the polymeric
glucose80, human serum albumin81 and odorant molecule82 detection
nanostructure towards contact resistance variation due to exposure to
was demonstrated using recognition probes such as aptamers, glucose
the liquid phase. Usually, in order to overcome this issue, a functional
oxidase enzyme, antibodies and a human olfactory receptor (hOR),
monomer such as a polymeric derivative with carboxylic side-chain
respectively. The study by Yoon et al. deserves further mention,
groups78-82 has been integrated into a copolymer scheme. The acid
since it is the first example of a FET-type bioelectronic nose based
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Carbon based materials for electronic bio-sensing
on hOR-conjugated CP nanotubes82. The authors developed a
reliable chemical immobilization strategy for the fabrication of
REVIEW
(a)
CPNT-FET devices with quantitative control on the degree of hOR
functionalization. Moreover, the feasibility of specific odorant detection
down to concentrations as low as tens of femtomoles was assessed.
Carbon nanotubes
Since their discovery in 1991 by Ijima83, carbon nanotubes (CNTs)
have been regarded as an important nanostructured material derived
from bottom-up chemical synthesis. As such, a great deal of effort
has been devoted towards understanding their electrical, mechanical,
(b)
and chemical properties. In this review we will cover the most
recent applications in electronic sensing proposed in the literature
during the last year. For further details, several previous review
papers covering various aspects of carbon nanotube electronics are
recommended26,84-88.
The first CNT field-effect transistors (CNT-FETs) were independently
obtained in 1998 from both the Dekker group at Delft University89
and the Avouris group at IBM90, with the first biological application
of CNT-FET proposed by the Dai group in 2003 while investigating
specific protein–protein interactions91. Recent rapid development of
(c)
chemical modification approaches and bio-functionalization methods
have allowed a new class of bioactive carbon nanotubes conjugated
with proteins, carbohydrates, nucleic acids or aptamers26,83-90,92,93.
Single walled CNTs (SWNTs) have usually been preferred because
of the availability of each atom in the SWNTs to the surrounding
environment leading to maximized electrical coupling.
An interesting advance in functionalizing carbon nanotubes to
obtain the detection of protein-receptor interactions is reported
in the paper of Star and co-workers94. The authors presented a
(d)
supramolecular approach based on the noncovalent functionalization of
nanotubes, in order to avoid the disadvantage of covalent modification
that impairs physical properties of carbon nanotubes. A PEI/PEG
polymer coating is used both to attach receptor molecules to the
sidewalls of nanotubes and to prevent nonspecific binding of proteins.
The biotin-streptavidin binding has been chosen as a model system to
demonstrate the effectiveness of the device architecture.
As an alternative to biological molecules conjugated directly to
the CNTs, a lipid bilayer-based coating for the CNT channel was
proposed95,96. The coating performed two key roles acting both as a
protective impenetrable barrier between the sensing channel and the
surrounding medium, as well as a dispersive matrix for membrane
proteins. Usually these devices incorporated passive biological elements
which transmitted an environmental change to the CNTs. In 2010
Huang et al. assessed the feasibility of using an adenosine triphosphate
(ATP) powered biological pump to control a nanoelectronic circuit96.
The authors reported on a hybrid bionanoelectronic transistor in
which a local Na+/K+-ATPase protein gate, was embedded in the lipid
membrane (Fig. 9). The ion pump modulated the transistor output
Fig. 9 (a) A schematic illustration of an experimental setup in which a carbon
nanotube channel is covered by a lipid bilayer incorporating a Na+/K+-ATPase
ion pump. Inset: a cross-section of the device showing the directions of
the ion fluxes. (b) A scanning electron microscopy image of the S-D region
of the CNT transistor with a single nanotube bridging the two electrodes.
Inset:a photograph of the device chip (2 × 1 cm) with a PDMS microfluidic
channel. (c) The normalized nanotube conductance recorded over time for the
devices covered with a lipid bilayer with (red trace) and without (blue trace)
Na+/K+-ATPase ion pump incorporated, after the injection of 10 mM ATP
solution. (Applied gate voltage Vg= −0.05 V). (d) The normalized conductance
of the Na+/K+-ATPase containing CNT device recorded at different ATP
concentrations. (Applied gate voltage Vg = −0.2 V). Reprinted with permission
from96, © 2010, American Chemical Society.
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(a)
(c)
(b)
(e)
(d)
Fig. 10 (a) A schematic illustration of the experimental setup of a graphene-FET for biosensing applications. (b) A photograph of a patterned reduced graphene
oxide (rGO) sensing device on a polyethylene terephthalate (PET) film. An optical image (c) and schematic illustration (d) of PC12 cells grown on a poly-L-lysine
coated rGO-FET fabricated on a PET substrate. (e) The real-time response of the rGO-FET to the vesicular secretion of neurotransmitters from PC12 cells stimulated
by a high K+ concentration solution. (Vds = 100 mV, Vg = 0 V, distance between D and S electrodes in the device fixed at 1 cm). Reprinted with permission from107,
© 2010, American Chemical Society.
current by up to 40 % by shifting the pH of the water layer located
between the lipid bilayer and the nanotube surface.
Moreover, aligned CNT-FETs have also been proposed as innovative
platforms to fabricate biosensors with high sensitivity down to the
picomolar
range97,98.
Aptamer functionalized SWNT-film arrays were
Further steps in the development of robust graphene-living cell
interfaces have been accomplished in only the last few months. A
graphene-FET device detected well-defined extracellular signals while
exposed to embryonic chicken cardiomyocytes106. Moreover, hormonal
catecholamine molecules and their dynamic secretion from living
deposited by dielectrophoresis and the surface tension associated with
cells were monitored in real time by biosensors based on a reduced
a water meniscus; an AC voltage (frequency 1 MHz, amplitude 5 Vp-p)
graphene oxide (rGO) film (Fig. 10)107. Noteworthy in this study, the
was applied to align SWNTs in solution, which were then compressed
authors focused their attention on competitively alternative materials
by the surface tension of the water meniscus after slow, careful drying.
of graphene, namely rGO, produced by facile and scalable solution
The attachment of the SWNTs to the electrodes was mediated by
processes to extend the applications of graphene for plastic electronics.
Van der Waals forces. The resulting SWNT-film, suspended between
They proposed the fabrication of centimeter-long, ultrathin (1 – 3 nm),
cantilever electrodes, allowed for a highly specific and real-time
and electrically continuous micropatterns of highly uniform parallel
detection of thrombin97.
arrays of rGO films on various substrates by using the “micromolding
in capillary” method. Remarkable sensitivity was achieved that was
Graphene
shown to be insensitive to substrate binding.
Graphene is highly promising for new types of chemical/biological
432
sensors with excellent sensitivity due to a combination of a high active
Conclusions and future perspectives
surface area (i.e., a 2D material with all the carbon atoms exposed
The incorporation of biomaterials into all of the different structural
to the analyte of interest), exceptional electrical properties, and low
components of organic and nanomaterial based electronic devices has
noise26,99,100,101.
The operational principle of graphene bio-electronic
the potential to be applied towards a range of applications in medicine
sensors is based on the change of graphene electrical conductivity (σ)
and point-of-care diagnostics. Future efforts will need to be focused on
due to adsorption of molecules on its surface. The graphene-FET, based
the development of new hybrid biomaterials integrated into electronic
on a non-functionalized single-sheet, has been shown to exhibit a
devices capable of being processed on flexible substrates. The overall
proportional increase in conductance upon protein adsorption at a sub-
progress of this research field will have enormous implications for both
nanomolar level102. Mohanty and Berry developed a graphene-based
fundamental scientific discovery and technological development. In
bio-sensor capable of single bacterium resolution, investigating for the
particular, novel bio-OFETs could be used to study the fundamentals of
first time the interaction between chemically-modified graphene and
electron transfer in naturally occurring biomolecules. The investigation
bioentities103.
of the interface of biomaterials and organic electronics could also lead
Chemical vapor deposition-grown graphene films have
also been used to detect DNA with single-base mismatch sensitivity104,
to the realization of new classes of electronically active medical devices
as well as carbohydrates and neurotransmitters105.
for use in advancing human health.
SEPTEMBER 2011 | VOLUME 14 | NUMBER 9
Carbon based materials for electronic bio-sensing
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