Tailoring Functional Interlayers in Organic Field-Effect Transistor Biosensors.

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Tailoring Functional Interlayers in Organic Field-Effect Transistor Biosensors Maria Magliulo, Kyriaki Manoli, Eleonora Macchia, Gerardo Palazzo, and Luisa Torsi* between organic electronics and the world of biology are manifold.[5] Among the others, worth to mention is the possibility to develop advanced label-free biosensors with high selectivity and sensitivity that do not need expensive detection units and can be, in principle, fabricated by printing at low cost. Such systems can be disposable electronic devices fabricated on flexible plastic or paper substrates,[6] with the possibility to tune the organic materials’ properties improving their biocompatibility and biodegradability. These unique features make OTFT sensors also potentially suitable for high throughput and point-of-care applications. Organic bioelectronics hold much promise as a platform to create novel investigation tools to study biochemical interactions but also to realize performing and sophisticated medical devices, able to detect and transduce signals transmitted by biological systems such as tissue and neuron cells. To this aim, a variety of device configurations, with different working principles, have been proposed so far for sensing applications, including electrochemical,[3c,7] electrolyte-gated,[1,8] ion-sensitive,[9] charge-modulated OFETs[10], as well as OFET structures involving a back-gate and a solid dielectric.[11] Organic electrochemical transistors, whose operation mechanism is based on the electrochemical doping of the organic semiconductor (OSC), have attracted particular interest for chemical and biosensing applications due to the possibility to implement biocompatible and water stable OSCs such as poly(3,4ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS), and several contributions could be find in the literature on this topic.[2c,3b,4,5] This report is mainly restricted to the discussion of back-gate OFETs where the biomolecules are integrated into the device structure, either to act as biorecognition elements or to perform as dielectric materials. One interesting study involving a dual-gate device structure integrating a biosystem is also proposed. As schematically depicted in Figure 1, the structure of a backgate OFET comprises a gate electrode, connected to a solid dielectric layer that is interfaced with an OSC. This is electrically contacted by a source and a drain electrode. Similar to most thin-film transistors, OFETs operate in the accumulation mode and the two most relevant interfaces are the dielectric/OSC and the contacts/OSC ones. By applying a gate voltage (VG), charges are accumulated and confined at the interface between the OSC and the dielectric layer forming a 2D conductive channel. Upon

This review aims to provide an update on the development involving dielectric/organic semiconductor (OSC) interfaces for the realization of biofunctional organic field-effect transistors (OFETs). Specific focus is given on biointerfaces and recent technological approaches where biological materials serve as interlayers in back-gated OFETs for biosensing applications. Initially, to better understand the effects produced by the presence of biomolecules deposited at the dielectric/OSC interfacial region, the tuning of the dielectric surface properties by means of self-assembled monolayers is discussed. Afterward, emphasis is given to the modification of solid-state dielectric surfaces, in particular inorganic dielectrics, with biological molecules such as peptides and proteins. Special attention is paid on how the presence of an interlayer of biomolecules and bioreceptors underneath the OSC impacts on the charge transport and sensing performance of the device. Moreover, naturally occurring materials, such as carbohydrates and DNA, used directly as bulk gating materials in OFETs are reviewed. The role of metal contact/OSC interface in the overall performance of OFET-based sensors is also discussed.

1. Introduction Organic field-effect transistors (OFETs) or thin-film transistors (OTFTs) have gained considerable attention over the last years thanks to their steadily improving performance level and amenability for several different applications. OTFTs are a wider class of gated devices that do not necessarily involve a field-effect mechanism.[1] In addition to large-area applications such as digital displays, electronic paper, and radio frequency identification tags, these devices have been widely investigated as label-free sensors.[2] Physical, chemical, and biological OTFT detection platforms have been proposed for a broad range of applications including humidity control, pH measurements, detection of chemical and biological species, monitoring of cells’ growth, and drug delivery.[3] Furthermore, implantable organic devices that can facilitate the tissues regeneration or can control the cell signaling are emerging.[4] The reasons to create synergies Dr. M. Magliulo, Dr. K. Manoli, E. Macchia, Prof. G. Palazzo, Prof. L. Torsi Università degli Studi di Bari “Aldo Moro” Via Orabona 470125, Bari, Italy E-mail: [email protected] E. Macchia Dipartimento Interateneo di Fisica “M. Merlin” Università degli Studi di Bari “A. Moro” Via Orabona 470125, Bari, Italy

DOI: 10.1002/adma.201403477

Adv. Mater. 2014, DOI: 10.1002/adma.201403477

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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Figure 1. Schematic of a p-type OFET structure where the organic semiconductor/dielectric and the organic semiconductors/contact interfaces are highlighted.

the application of a source–drain voltage (VDS), the accumulated charges can drift generating a source–drain current (IDS). Depending on the type of OSC, positive (p-type OSC) or negative (n-type OSC) charges can be accumulated and transported. The OFET sensing process relies on the interaction of chemical and biological species either directly with the OSC or with biological receptor molecules suitably integrated in the OFET structure. Upon interaction, the electronic properties of the OSC and/or the OFET dielectric/OSC interface are modified affecting the field-effect mobility (μFET) of the charges flowing in the device channel as well as the OFET threshold voltage (VT).[2c] Indeed, the electrical and sensing performance of an OFET can be dramatically influenced by the nature of the dielectric/OSC interface. As an OFET is a planar device with the contacts that are exposed to the target molecule, also the contacts resistance can be affected during the interaction and this is a critical issue that needs to be duly taken into account in an OFET sensor to rule out that this contribution is not the predominant one.[12] The search for new functional materials, especially OSCs and dielectrics, along with the engineering of the interfaces, remains the most widely undertaken approach to improve the OFET device performance and to develop highly performing OFET biosensors.[13] The use of OFETs for biosensing applications implies a stable operation of these devices in aqueous media. The instability of the OSCs in the presence of water along with the high operation voltages has limited, at the beginning, the use of OFETs as reliable and reproducible biosensors.[14] In this respect, important advances have been made thanks to the synthesis of new OSC materials characterized by a good stability in water. The (5,5′-bis-(7-dodecyl-9H-fluoren-2-yl)-2,2′-bithiophene, also known as DDFTTF,[15] as well as the isoindigo-basedconjugated polymer with solubilizing siloxane-terminated side chains (PII2T-Si),[16] recently proposed by the Bao's group, are an example of OSCs successfully employed in OFET sensors operating in direct contact with aqueous media. Specifically, it was demonstrated that OFETs fabricated using the PII2T-Si

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Maria Magliulo is a researcher in analytical chemistry at the Department of Chemistry, University of Bari. Her research interests include ultrasensitive labelfree biosensors, organic bioelectronics, and clinical chemistry. She deals with the development of electronic biosensors based on organic field-effect transistors (OFETs) and the study of new supramolecular assembly procedures for the integration of biomolecules in OFET devices. She is involved in several national and European projects aiming at the development of innovative, low-cost, disposable label-free biosensors for clinical applications. She is author of several scientific publications in the field of analytical chemistry, clinical chemistry, and materials science. Kyriaki Manoli did B.Sc. in Chemistry in 2003 from the University of Ioannina, Greece, and M.Sc. and Ph.D. in “Polymer Science and its Applications” from the Chemistry Department of the National and Kapodistrian University of Athens-Greece in 2005 and 2010, respectively. Since 2011 she is a postdoc in the Chemistry Department at the University of Bari-Italy. Her research interests include fabrication and characterization of functional electronic devices that embed biological elements and, in particular, organic field-effect transistors to be used for chemical and biosensing applications.

Luisa Torsi is a full professor of Chemistry since 2005. She received her degree in physics in 1989 and a Ph.D. in chemical science in 1993. She was post-doctoral fellow at Bell Labs and has been awarded with the 2010 HE Merck prize, this marked the first time the award was given to a woman. She is also the elected VicePresident of the European Material Research Society. She is author of more than 130 ISI papers, including contributions published in Science, Nature Materials, and Proceedings of the National Academy of Science.




2. Dielectrics Surface Modification Strategies for Organic–Biological Interfaces The dielectric/OSC interface heavily affects the conducting channel of an OFET as a 2D transport regime is established in the first few monolayers of the OSC, close to the gate dielectric. Consequently, the quality of the OSC ultrathin layer at this interface impacts on the electronic performances of the whole


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OSC can stably operate in both freshwater and seawater and can be used to selectively sense heavy-metal ions in these environments.[17] Natural or nature-inspired OSCs have been also proposed as inexpensive and biodegradable stable materials for OFET sensors fabrication.[18] To overcome important issues such as back-gate OFET large operation voltage, poor stability, especially in aqueous environment, and reduced lifetime, new dielectric materials as well as new strategies enabling the improvement of the dielectric/ OSC interface have been proposed. The reduction of the OFET operation voltage has been obtained also with the aid of new inorganic and organic high-k gate dielectrics such as thermally grown metal-oxide thin films and polymeric materials.[19] The quality of the dielectric/OSC interface depends on properties such as the dielectric surface energy as well as the trap density that can be tuned by properly modifying the dielectric surface. Self-assembled monolayers (SAMs), polymeric compounds, and naturally derived biomaterials such as DNA and proteins have been used for this purpose.[20] Novel OFET configurations with biological receptors directly integrated at the dielectric/ OSC interface, right where the OFET 2D transport occurs, have also been proposed, not only as ultrasensitive label-free biosensors but also to study by means of an electronic probe, protein– ligand interactions.[21] This review aims to provide an overview on the use of biological interlayers that are integrated into back-gate OFETs. Strikingly, the transistors are shown to retain a high level of performance when operated as organic bioelectronic sensors. First, the interfacial effects occurring at the OSC/biodielectric interface are introduced. Afterward, the attention is directed toward the modification of solid dielectric surfaces with biomaterials, such as peptides and DNA, as well as to the strategies that have been proved useful for the integration of biological receptors. A bird's eye view of emerging naturally occurring materials, such as carbohydrates and proteins, used as gating materials in OFETs is included as well. All these topics involve the dielectric/OSC interface. Moreover, the issues connected with the source and drain contacts/OSC interface are also addressed by showing how the right modeling of bio-OFET output characteristics can help in estimating an important parameter such as the contact resistance and its variation upon exposure to a target molecule. The elicited topics are organized and presented along the following sections—Section 1: dielectrics surface modification strategies for organic-biological interfaces; Section 2: OFET devices with a biointerlayer between the gate dielectric and the OSC; Section 3: OFETs based on naturally occurring dielectrics; Section 4: the role of the contacts–OSC interface in the OFET sensing.

device and great efforts have been made so far to reduce any detrimental interfacial effect on the OFET performances. From the viewpoint of the development of electronic sensing devices, the ability to modulate the carrier density in the channel and control the threshold voltage is a rather important issue. In several applications of OFET sensors, the threshold voltage shift is associated with the sensing mechanism. Furthermore, it is has been recently showed that the integration of biological receptors, such as proteins and antibodies, in between the dielectric and the OSC layers can lead to ultrasensitive biosensors.[21] Interfacial effects at the dielectric/biolayer/OSC region are also directly related to the response of the sensor, since this is where the biorecognition event takes place. Hence, understanding the phenomena governing this interface and how its properties influence the electric transport of an OFET can provide useful information for designing reliable and highly sensitive sensors. One of the first strategies exploited to control the dielectric/OSC interface involves the use of SAMs as interlayer. In particular, considering that silicon dioxide (SiO2) is one of the most commonly employed gate insulators, the modification of the chemical and physical properties of the interface using organosilane precursors (i.e., RSiX3, with X = Chlorine (Cl), methoxy (OMe), and ethoxy (OEt) functional groups) has been extensively investigated.[22] Specifically, these precursors can spontaneously react with the –OH terminal groups of hydroxylated dielectric surfaces, such as SiO2, aluminum oxide (Al2O3), and tin-doped indium oxide (ITO), arranging themselves into monolayer structures. The modification of the dielectric by means of SAMs has been demonstrated to cause smoother surface and lower surface energy, resulting in a semiconductor morphology characterized by larger grain size.[23] Consequently, the modification of the dielectric surface with SAMs can result in an enhancement of the OFET field-effect mobility.[24] Virkar et al.[25] recently proved that also the SAMs density strongly affects the mobility of the OFET. In this case the SiO2 dielectric surface was modified with an octadecylsilane (OTS) layer. The hydrophobic nature of OTS is known to improve the OSC crystal quality and to reduce the amount of interfacial traps enhancing the OFET performance. Moreover, it was shown that the higher the density of the OTS layer, the better the mobility. The presence of SAMs impacts also on the threshold voltage VT, which is a crucial parameter to control as any VT deviation from a stable value yields a reduced gain in logic gates, worsening the noise figures of merits in integrated circuits. Kobayashi et al.[26] were among the first to report how to achieve the control of channel carrier density in OFET devices by means of the effects generated by molecular dipoles and weak charge transfer. Specifically, the SiO2 surface was modified with three different SAMs deposited from organosilane compounds such as (CF3)(CF2)7(CH2)2Si(OC2H5)3, (CH3)(CH2)7Si(OC2H5)3, and (NH2)(CH2)3Si(OC2H5)3 used as starting molecules. The SAMs formed by these three molecules are referred to as -F, -CH3, and -NH2 SAMs, respectively. P-type pentacene and n-type fullerene (C60) molecules were used as OSCs, resulting in the structure schematically reported in Figure 2A. As shown in Figure 2B, with both the OSCs, a threshold voltage shift toward positive values has been observed as the SAMs go from -NH2 through –CH3 to –F. These VT shifts are associated with an increase in μFET. In more detail, the CH3-SAMs devices result in VT values



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Figure 2. A) Schematic structure of an OFET embedding SAMs at the gate dielectric/OSC interface. B) Threshold voltage values for n-type C60 and p-type pentacene OFET with untreated SiO2 surface and with three kinds of SAMs molecules. Reproduced with permission.[25] Copyright 2004, Nature Publishing Group. C) Energy level diagrams proposed for untreated and SAM-treated SiO2 surface in a metal-insulator-(p-type) semiconductor structure with i) no applied gate voltage and ii) in the presence of a negative gate voltage. Reproduced with permission.[27] Copyright 2004, AIP Publishing LLC.

closer to the one of the untreated devices, while the F-SAMs and the NH2-SAMs originate positive and negative threshold voltage shifts, respectively. This behavior has been explained assuming that electrons and holes accumulation is improved by the –NH2 and –F SAMs, respectively, while the charge accumulation effect is not significantly affected by the presence of CH3SAMs as in the case of the bare OFET devices. A more exhaustive explanation of these experimental evidences has been presented by Pernstich et al.[27] Here an empirical model based on the device energy level diagram has been proposed, where the measured threshold voltage shift is associated with the built-in electric field generated by the SAMs. Specifically, the authors found that the film morphology affects the charge carrier mobility, while only a weak dependence, with no general trend on the different morphological features, was seen for the threshold voltage. Eventually, the VT shift was associated with the electronegativity of the SAM molecule's functional groups that modify the charge distribution at the interface by forming oriented electric dipoles. Indeed, a dipole field at this interface can produce the same effect of an applied extra gate voltage. When a gate bias is applied, band bending occurs and holes are accumulated in the channel. The extra built-in electric field induced by the permanent dipole field of the SAM results in a further increasing of the band bending, thus increasing

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the hole density in the channel, as reported in Figure 2C. It is worth mentioning that surface charges eventually present at the gate dielectric/OSC interface, due to –OH groups (present on a pristine SiO2 surface), water molecules, or residual mobile ions, influence the charge accumulation in the electronic channel of the OFET devices, affecting the threshold voltage too. Quantitatively, according to the Helmholtz equation (Equation (1)), the potential drop across the dipole layer Δφ dip can be evaluated as[28] Δφdip =

ddipσ dip M dip = ε 0 ε dip ε 0 ε dip A

(1)

where Mdip is the dipole moment associated with a single molecule, A denotes the area of a single molecule deposited on the dielectric surface, and εdip is the effective dielectric constant present in the dipole layer. Therefore the dipole layer acts as an extragating Δφdip, producing an effective gate potential of Veff = VG ± Δϕ dip

(2)

The direction of the Veff shift, going in the opposite direction respect to the VT shift, is related to the dipoles orientation. Though this model provides a nice qualitative explanation for




REVIEW Figure 3. A) Schematic structure of an OFET with photochromic SP-SAMs on SiO2 gate substrate. B) Proposed model for the energy bend diagrams at the insulator/OSC interface. Reproduced with permission.[31] Copyright 2011, American Chemical Society.

the data, the dipole contribution is not sufficient to explain a threshold voltage shifts up to 60 V. In fact, in order to explain such a large threshold voltage shift invoking a dipole layer, the molecular dipole moments must exceed the unrealistic value of 50 debyes. Therefore, as an alternative model to explain VT shifts of the order of tens of volts, SAM-related space charge layers have been recently proposed by Gholamrezaie et al.[29] The surface potential of the gate dielectric modified by an SAM was measured by means of scanning Kelvin probe microscopy (SKPM), proving that the CH3-SAM is inactive as expected for a nonpolar molecules such a –CH3 is. The NH2–SAM traps positive charges, while F–SAM traps negative charges, in line with the NH2 molecule being less electronegative than F ones. This clearly explains the data proposed by Kobayashi. In addition to organosilane SAMs, also phosphonic acids (PAs) have been used as SAM precursors, due to their better stability to moisture and resistance to hydrolysis, as well as robustness toward a wide range of inorganic surfaces, such as SiO2, Hafnium(IV) oxide (HfO2), Al2O3, and ITO. The device architecture, comprising a HfO2 gate dielectric modified with an ultrathin PA-SAMs (2–4 nm), allows pentacene-based OFET to operate at source–drain and gate voltages below −1.5 V with an on/off current ratio in the range of 105–106 and field-effect mobility of 0.22 cm2 V−1 s−1.[30] This significant improvement of the device performance has been imputed to the presence of terminal anthryl group, responsible for the increased polarization and the more densely packed surface, due to the strong π−π interactions between the neighboring anthryl surface groups. As has been shown, the presence of functional terminal groups in SAM molecules can cause profound changes in the


electrical properties of an OFET. Taking into account that the majority of biological systems consist of a number of different functional groups and, most importantly, these groups are often involved in the interaction with the molecules to be detected, it is clear that the knowledge acquired on functional interfaces in OFETs is precious to understand the sensing mechanisms as well as to develop highly performing OFET sensors, as is shown in the following. A first example involves a novel way to modify the dielectric/ OSC interface thorough a photochemical process. This might be seen as an example of photochemical electronic sensor. Zhang et al.[31] were able to achieve a reversible tuning of the channel conductance and of the carrier density, exploiting the interaction between a photochromic molecule and photons of different energy. Specifically, the SiO2 surface was treated with SAMs of spiropyrans (SPs) photochromic molecules as shown in Figure 3A. Such chemical systems are able to switch from a neutral, colorless form to a colored form upon exposure to light. This switching causes a considerable change in the electric dipole moment as the photochromic SP-SAMs undergo a photoisomerization between SP-closed and SP-open structure, upon exposure to UV and visible light, respectively. Interestingly, these two states present different dipole moments. The electrical characteristics of the OFET have been reversibly and optically controlled, thanks to the interfacial properties associated with the molecular dipoles. As reported in Figure 3B, the interesting device features have been explained assuming that the photo-induced increase in the dipole field results in a larger local built-in electric field, responsible for a more pronounced band bending. This leads to an increase of the hole density in the



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electronic channel, explaining the observed threshold voltage shift. Such an approach of interface functionalization sets new perspectives for the development of OFET optical biosensors able to convert molecular conformation changes into a detectable signal. The concepts described so far have also been used to rationalize the features that characterize an OFET whose gate dielectric has been modified by a biolayer. Recent contributions have demonstrated that biomaterials such as peptides or proteins can be used to engineer the dielectric/OSC interface and precisely control the OFET VT. Quartz binding polypeptides (QBPs), a particular type of genetically engineered peptides for inorganics (GEPIs), have been proposed by Dezieck et al. for this aim.[33] The proposed molecules have a strong affinity for silicon dioxide surfaces and different electrical dipoles can be obtained depending on their amino acid sequence. Particularly, the secondary structure of the peptides is affected by the pH of the solution in which they are dissolved as a result of the variation in hydrogen bonding and of the interaction between amino acid residues. Changes in the pH cause modifications in the peptide conformation or structure and affect the electrostatic interactions between amino Figure 4. A) Schematic structure of the pentacene OFET device comprising a SiO2 dielectric acids influencing the formation of dipoles. As layer modified by QBP peptides (panel (a)). According to the deposition conditions, different shown in Figure 4A, the deposition of QPBs peptides orientation is obtained affecting the dipole formation at the dielectric/OSC interface. on the SiO2 dielectric by solutions having By using peptides aqueous solution no permanent dipole is formed at interface (panel (b)); peptides acidic solutions allow the formation of dipoles oriented far from the substrate (panel different pH (from acid to basic) allows the (c)), while using peptides basic solution the dipoles are oriented toward the substrate (panel formation of different dipoles at dielectric/ (d)). B) Current–voltage transfer curves obtained for pentacene OFETs modified with QBP OSC interface. By measuring the I–V transfer assembled under basic (green diamond), neutral (blue circles), and acidic (red triangles) condicharacteristics of the pentacene-based OFET, tions. Reproduced with permission.[32] Copyright 2010, AIP Publishing LLC. a clear shift of the VT is obtained according to the nature and orientation of the dipoles (Figure 4B). A positive VT shift is observed when QBPs were for chemical synthesis, have been widely proposed in OFETs assembled using acid solutions, while a negative shift in VT was devices fabrication as substrates, OSCs, and dielectrics. Furobserved with basic solutions. The advantages of this strategy thermore, these materials allow to simplify the OFET fabriover other dielectric modification methods such as SAM formacation process and, in some cases, to reduce the costs of the tion and polymer adhesion are noteworthy. First, the peptides organic electronics devices production.[15,18a,33] structure could be designed ad hoc to tune their affinity toward More recently, biomaterials such as enzymes, protein recepdifferent dielectric materials. Further, the QBPs deposition is tors, or DNA have also been integrated in OFET sensing platenvironmental friendly (water is used as solvent) and it does not forms as recognition elements to confer selectivity.[3c] In the require any annealing procedure, thus the whole dielectric funcfirst attempts, the biomolecules were anchored on the OSC tionalization process is fully compatible with low-cost printing layer giving rise to the so-called bilayer OFET (BL-OFET) structechniques. It is important to outline that QBPs are molecules ture. In one of the earlier device structures, β-D-glucosidic or that are designed and synthetized artificially and their role is to L-phenylalanine amino acid units have been deposited on the chemically modify a surface as they are capable to undergo an OSC to confer chiral-recognition capability to the OFET sensor. acid-base-type chemical reaction that is not a selective one. The chiral OFET sensor was able to differentiate carvone and citronellol enantiomers at the ppm concentration level.[34] Lately, BL-OFET biosensors have also been proposed for DNA detection by several research groups.[35,11b] Particularly, 3. OFET Devices with a Biointerlayer between the in the device proposed by Bao et al.,[11b] the OSC surface was Gate Dielectric and the OSC modified with a thin maleic anhydride polymer layer, using plasma-enhanced chemical vapor deposition to covalently Biological-inspired materials, thanks to their unique feaattach the peptide nucleic acid strands, which were then used tures such as biodegradability, biocompatibility, and no need

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REVIEW Figure 5. A) FBI-OFET structure embedding three different biological layers, namely phospholipids (PL), purple membrane (PM), and streptavidin (SA). The FBI-OFET devices are fabricated in a bottom gate configuration by depositing the biomaterial right on the silicon oxide dielectric layer. The P3HT organic semiconductor is then spin-coated from a chloroform solution directly on the biodeposit. B) Current–voltage (I–V) output characteristic curves obtained for PL, PM, and SA FBI-OFETs. Reproduced with permission.[21] Copyright 2012, National Academy of Sciences.

for real-time, in-situ detection of the target DNA molecules. The use of a thin polymer dielectric and the integration of a microfluidic system ensured the stable operation of this OFET directly in an aqueous buffer solution. Although efficient, in the BL-OFET biosensors the recognition process takes place far from the dielectric/OSC interface. With the aim to overcome this limitation, a completely novel approach for OFET biosensors development was recently proposed. The new OFET configuration is based on a Functional Biological Interlayer (FBI) directly placed at the interface between the dielectric and the OSC.[21] As show in Figure 5A, three different bio-systems have been integrated in the FBIOFET, namely phospholipids (PL), purple membrane (PM), and streptavidin (SA). The biomolecules were deposited on the silicon oxide (300 or 100-nm thick) dielectric surface and a regioregular poly-3-hexylthiophene (P3HT) OSC was then spread on top of the biological layer. In all the cases FBIOFETs with good level of electrical performance were obtained (Figure 5B), reaching mobility (μFET) and ION/IOFF ratio in the range of 10−3 cm2 V−1 s−1 and 102, respectively. The FBI-OFET successful functioning was not so obvious considering that the dielectric/OSC interface quality plays a pivotal role in the OFET operation, and in the FBI-OFETs the FET electronic channel is forced to work while lying on top of a biological layer. More interestingly, the embedded biomolecules retain their functional activity although the P3HT OSC layer is spread by spin-coating, from a chloroform solution, directly on top of each of the FBI biodeposits. This finding along with the evidence that analytes like biotin, insulin, and even bigger


molecules such as streptavidin (SA) can percolate through the P3HT layer[21] has opened the door to the implementation of FBI-OFETs as ultrasensitive label-free electronic biosensors useful not only to probe biorecognition events but also to study biomolecules interactions. FBI-OFETs integrating PL and PM have been, for instance, proposed for the electronic detection of archetypal volatile anesthetics such as diethyl ether and halothane.[36] In this study it has been demonstrated that by exposing the PL FBI-OFET sensors to the diethyl ether volatile anesthetic, at concentrations in the range of 0.6–3 wt%, good sensitivity is obtained, while very low response was measured in the case of acetone vapors that is a nonanesthetic ketone with a vapor pressure similar to that of diethyl ether (Figure 6A,B). The device exhibited good repeatability, as demonstrated by the low error bars associated with the PL FBI-OFET response to different diethyl ether concentrations. By exposing a bare P3HT-based OFET to both the anesthetic and the acetone, lower biosensor responses have been observed (Figure 6B). This provides evidence that the PL layer confers a certain degree of selectivity toward general anesthetic molecules to the FBI-OFET device. The electronic response of the PL FBI-OFET was also considerably influenced after the exposure to halothane anesthetic vapors (Figure 6C). Specifically, a current decrease was observed after the exposure of PL FBI-OFETs to this anesthetic even at clinically relevant concentrations (2 and 5 wt% in a nitrogen atmosphere). It has been demonstrated that halothane interacts with PLs producing a change in the PL membrane film structure,[37] so it is likely that the FBI-OFET response is due to a disorder



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Figure 6. A) I–V transfer characteristics obtained for a PL FBI-OFET before and after the exposure to diethyl ether at a concentration of 3.0 wt% in a nitrogen (N2) atmosphere. Inset: Schematic illustration of PL FBI-OFET structure. B) Calibration curves obtained for PL FBI-OFETs and bare P3HT OFETs exposed to diethyl ether and acetone vapors; the abscissa represents the analyte concentration expressed as wt% in the N2 atmosphere. C) Differential analytical sensitivities of PL FBI-OFETs and P3HT OFETs exposed to diethyl ether, halothane, and acetone. For all compounds, the maximum concentration tested was half the saturated vapor. Reproduced with permission.[36] Copyright 2013, Elsevier.

induced by the anesthetic interaction with the extremely ordered and smooth PL bilayer, residing underneath the OSC. The anesthetic–PL interaction is thus responsible for affecting the 2D electronic transport at the dielectric/OSC interface. This evidence can be rationalized by taking into account that, among the several theories formulated on the general anesthesia mechanism, there is the hypothesis that anesthetics interact with PL membranes and with the hydrophobic regions of the membrane proteins.[38] However, there is still no clear proof that anesthetic molecules alter the overall structure of the lipid bilayer significantly at clinical concentrations. In this scenario, PL FBI-OFETs represent an extremely powerful tool to probe subtle changes in the PL membrane after anesthetics exposure and to gather insight into the still-controversial general anesthesia mechanism of action. In the case of the PM FBI-OFET, bacteriorhodopsin (bR) proteins into PL nanolamellae were integrated as FBI. This device was proposed to study the proton translocation processes occurring after the exposure of the bioelectronic device to chemical and physical external stimuli such as low concentrations of halothane vapors or light, respectively (Figure 7).[21] The bR is, in fact, a light-driven ion pump capable to translocate protons across the bacterial membrane as photons are absorbed. The protein is also sensitive to anesthetics.[39] Specifically, anesthetics are capable to modify the bR local pKa values causing an amino-acid protonation/deprotonation switch, while, upon exposure to light, the bR protein structure is subjected to both a photo-induced cis/trans isomerization and a deprotonation of

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the bR Schiff base. All the elicited changes can be easily probed by measuring the PM FBI-OFET electrical response to the specific stimuli.[40] As reported in Figure 7A, the interfacial effect of the halothane interaction with the PM generates an increase of the FBI-OFET current, opposite to the response obtained for a PL FBI-OFET (Figure 7B). This effect is explained recalling that halothane generates pKa changes in the side chain amino acids of the bR which eventually triggers a protons release. Protons are finally injected into the p-type channel by the gate-field. A proton injection is also achieved by exposing the PM FBI-OFET to green-yellow light (λ > 500 nm). Upon illumination the current flowing between OFET source and drain increased its intensity, while such an effect was not seen on the bare P3HT OFET (Figure 7C). It was suggested that proton injection from the PM layer into the P3HT OFET channel occurs, causing a current increase due to a doping effect of the OSC. Particularly, the electronic transduction of the protons photo-translocation resulted in a current increase in the p-type channel, only when the device was irradiated with photons known to trigger the bR photocycle. Furthermore, the FBI-OFET ultrasensitive detection capability has been demonstrated by embedding SA as recognition layer and probing its biotin binding.[41] Both a spin-coating deposition process or an electrostatic Layer-by-Layer (LbL) assembly (Figure 8) have been employed to deposit the SA capturing molecules on the silicon oxide dielectric surface.[42] In both cases, the FBI-OFET response has shown a logarithmic dependence spanning over five orders of magnitude of analyte




REVIEW Figure 7. A) I–V transfer curves obtained for a PM FBI-OFET before (black line) and after the exposure to a 2% halothane atmosphere (blue line). B) PM FBI-OFET (blue triangles), P3HT-OFET (black squares), and PL FBI-OFET (red circles) responses to clinically relevant halothane concentrations. The FBI-OFET is reported as relative response (ΔI/I0) over the signal measured for nitrogen vapors. C) The square root of the IDS current versus the gate voltage obtained for a PM FBI-OFET before (black line) and after the exposure to yellow light is reported. Reproduced with permission.[21] Copyright 2012, National Academy of Sciences.

concentration and an extraordinary high sensitivity, reaching detection limits of few tens of pM. This challenges the sensing performances reached with other electronic biosensors technologies such as nanotube- and nanowire-based FET, which however require a much more demanding nanotechnological approach. Indeed, Figure 9A (panel (a)) shows that a systematic and scalable current decrease is observed by exposing the SA FBI-OFET to biotin solutions of different concentrations, demonstrating that the OFET response is connected with the SA–biotin complex formation. A similar effect was also observed by embedding an antibiotin monoclonal antibody as recognition layer (Figure 9A, panel (b)). Most importantly, no response was measured by performing a set of negative control experiments, indicating that the streptavidin/biotin interaction is selectively detected by FBIOFET devices (Figure 9A, panel (d)). The standard deviations associated with the SA FBI-OFET biotin response showed how the current variation was significant even at the lowest concentration (50 pM), most probably because in the FBI-OFET the complex is formed just underneath the OSC (Figure 9A, panel (c)).


The observed current decrease after exposing the SA FBIOFET to biotin can be related to a disorder in the OSC interface. It is known that upon SA–biotin complex formation, the protein undergoes a conformational change causing the characteristic highly mobile string loops to close on the incorporated biotin.[43] The very good functioning of FBI-OFETs also using a microfluidic system (Figure 9B) along with the possibility to integrate biological recognition layers such as antibodies and enzymes[41] allows conceiving FBI-OFET employment in applications such as digital and disposable strip-tests for the determination of clinically relevant biomarkers, even in biological fluids such as saliva or even eye drops, where ultralow detection limits are necessary. The morphology of the SA deposits and of the SA/P3HT assembly in FBI-OFETs was recently investigated by means of a combination of X-ray scattering techniques and scanning electron microscopy.[42] The results indicated that a larger surface covering is obtained in the case of the spin-deposited SA, but a



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Figure 8. A) Scheme of a SA FBI-OFET biosensor structure having the biological interlayer deposited on the silicon oxide dielectric. B) Illustration of the spin-coating procedure for the deposition of the protein layer. C) Illustration of the LbL deposition of the protein layer. In the LbL deposition, the SiO2 substrate is first dipped in a piranha solution to obtain negative charges on the surface (step 1 in panel C), after washing, the substrate is dipped in the positively charged poly(diallyl-dimethyl-ammonium chloride) adhesion polymer solution (step 2 in panel C), finally the substrate is immersed in the negatively charged protein solution and the SA is electrostatically attached (step 3 in panel C). This procedure can be repeated several times to obtain the desired number of SA layers. Reproduced with permission.[42] Copyright 2014, American Chemical Society.

more homogeneous coating is achieved by the LbL deposition. These findings can explain the better detection limit and analytical performances obtained for the SA LbL FBI-OFET sensor compared to the spin-coated one.[41] The FBI-OFET structure in the spin-coated SA is formed by a discontinuous layer of SA agglomerates of different size. These agglomerates are locally forming, at different length scales, 3D islands, 2D patches, or nanoscale networks, with thickness and branching increasing with SA surface coverage, until a compact layer is formed. A bilayer structure with irregular morphology is then created after coating the SA film with the P3HT OSC layer (Figure 10A,B). On the other hand, the LbL-SA deposit features short range paths with bilayer structures similar to the SA ramifications, which should play a role in the sensing mechanism of the FBIOFET device (Figure 10C,D). Importantly, the morphology of the P3HT film showed an edge-on orientation for all the SA layers studied, giving a clear rationale for the consistently observed field-effect mobility invariance values measured on the SA FBI-OFETs. The large voids presented in the P3HT layer, covering both the spin-coated and LbL SA deposits (Figure 10), further confirmed that even insulin or large proteins, such as

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SA, percolate through the P3HT film. Such an observation suggests that the FBI-OFET sensing platform can be used to detect large target molecules. Another interesting topic is to understand how the biochemical interactions or the biomolecules conformational changes occurring at the dielectric/OSC interface impact on the OFET operation mechanism and how the OFET electronic parameters, such as the field effect mobility and the threshold voltage, are affected. To this aim, as a first step, a model for the electrical characteristics of the FBI-OFETs electronic sensors based on an ad hoc designed equivalent circuit was proposed.[44] This study involved also the integration into the FBI-OFET of proteins such as avidin (AV) and neutravidin (NA).[45] The set of SA, AV, and NA proteins was chosen as these proteins all bind biotin with comparable affinity, although differing in the protein structure and isoelectric point (pI). The isoelectric point is the pH at which a protein has no net electrical charge. At a different pH, an overall positive or negative charge is associated with the protein in solution. SA, NA, and AV hold a pI of ≈5–6, 6.3, and 10, respectively.[46] When the protein is deposited (dry state), the overall charge, including the counter




REVIEW Figure 9. A) I–V transfer curves obtained for a SA (panel (a)) and an antibiotin (panel (b)) FBI-OFET biosensors exposed to biotin solutions at different concentrations. The biotin calibration curve for a SA FBI-OFET along with the standard deviations over three replicates measured on different devices is reported in panel (c). Panel (d) reports the response to different biotin concentrations for FBI-OFETs embedding different capturing interlayers: Triangles: saturated streptavidin–biotin complexes; squares: P3HT-OFET; diamonds: bovine serum albumin (BSA) FBI-OFET. B) Picture of SA FBI-OFET chip implemented with a microfluidic system (panel (a)) along with the magnified microscope image of the microfluidic structure (panel (b)). The I–V transfer curves obtained by delivering pure water and biotin at 0.01 ppb (50 pM) on such device are reported in panel (c). Reproduced with permission.[41] Copyright 2013, American Chemical Society.

ions from the solution, is retained. In the present case, all the experiments were carried out at a pH of 5.5, meaning that all the three proteins carried an overall positive charge, though of different intensity. In Figure 11A, the I–V square root of the transfer curves for the bare P3HT OFET and for the FBI-OFETs embedding the three elicited proteins on the SiO2 dielectric is reported. A shift in the threshold voltage was observed, caused by the modification of the SiO2/OSC interface. In particular for the bare P3HT device a VT positive value of 25.40 ± 1.66 V was found (Figure 11B). The positive threshold value was correlated with the presence of deprotonated hydroxyl groups, negatively charged, at the surface of the SiO2. Consequently at VG = 0 a potential is built, across the p-type semiconductor and the SiO2 layer, caused by the interfacial negative charges. In this situation, even if no gate bias is applied, a band bending is set up and holes are induced at the interface between the OSC and the SiO2.[47] Thus, the positive threshold voltage observed is the external applied gate bias that is needed to compensate for the built-in local electric field in the P3HT channel caused by –OH groups. VT shifts toward negative values were observed as the proteins go from streptavidin, through neutravidin to avidin, in agreement with their isoelectric point. The VT value for streptavidin was positive


and close to the threshold voltage estimated for neutravidin, which was approximately zero. The avidin was found to present a negative value of threshold voltage (Figure 11B). The threshold voltage shift induced by the protein layer can be explained considering that the positive net charge at the SiO2/OSC reduces the bend bending and consequently the hole carrier density in the electronic channel. This finding confirms what has been already demonstrated by Deizieck et al. regarding the possibility to tune the VT of OFET devices by modifying the dielectric surface with opportunely charged biomolecules. As already mentioned, the same FBI configuration was employed to probe the structural properties of protein–ligand interactions, by studying the effect of biotin (5 nM) exposure on SA, NA, and AV FBI-OFETs.[45] The protein–biotin complex formation induces similar relative responses in terms of source– drain current of the FBI-OFET for all the embedded proteins upon exposure to 1-ppb biotin, indicating a quantitative biotin binding for all the protein. A reduction of the field effect mobility was also observed in these FBI-OFETs. This effect was attributed to the disorder generated at the OSC interface upon the protein–biotin complex formation. A significant modification of the proteins structure occurs after the analyte binding



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Figure 10. Scanning electron microscope (SEM) images obtained for a SA FBI-OFET fabricated by spin-coating from a 10-µg mL−1 SA solution followed by the deposition of P3HT layer from a 2.5-µg mL−1 solution in chloroform. The images were acquired by tilting the sample of A) 60° and B) 75° at different magnifications. The SEM images obtained for a SA FBI-OFET fabricated by depositing SA using a layer-by-layer assembly procedure acquired by tilting the sample of C) 30° and D) 75° are also reported. Reproduced with permission.[42] Copyright 2014, American Chemical Society.

which is most probably responsible for the modification of the to the pentacene layer were accumulated at the dielectric/OSC OSC electronic propriety. Experiments with bare P3HT OFET interface, increasing the conductivity of the channel and prodevices rule out any influence of biotin-induced degradation of ducing a positive VT shift. By applying a negative gate bias, the the P3HT. The threshold voltage is independent from the anahole carriers are transferred from the dielectric/OSC interface lyte concentration as observed in the absence of biotin and the to the ferritin centers. The trapped hole charges in the ferritins threshold voltage relative responses follow the isoelectric points built up an internal electric field that partially offset the external of the proteins. applied electric field and resulted in low conductivity and a Another interesting approach was recently proposed by Kim negative VT shift. Ferritin-based OFET memory array were also et al.[48] In this work a ferritin protein nanoparticles (NPs) multilayers OFET is proposed as memory device (Figure 12). The OFET is fabricated by depositing anionic ferritin nanoparticles on the silicon dioxide dielectric by an LbL deposition, using pentacene as OSC. Thanks to the presence of redox sites, the protein NPs layer can be used as charge storage gate dielectrics conferring to the OFET device good programmable memory properties, namely, large memory window (ΔVT greater than 20 V), a fast switching speed (10 μs), and high ON/ Figure 11. A) Square rout of the absolute drain current versus the gate voltage for a bare P3HT OFF current ratio (above 104). A significant OFET (green triangles) and FBI-OFET fabricated by depositing streptavidin (black squares), shift in the threshold voltage was observed avidin (red circles), and neutravidin (blue up triangles) on SiO . B) Threshold voltage values 2 after applying an appropriate gate voltage extracted for bare P3HT device, and FBI-OFET embedding the three proteins. The isoelectric (VG). The hole carriers injected from ferritin point for each protein is also reported. 12





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capture sulfate ions, directly deposited on the functionalized polystyrene gate dielectric (Figure 13). Specifically, the thin dielectric layer is modified with maleimide anchor groups that allow the protein receptor binding. By applying a negative gate bias on the bottom gate, positive charges are accumulated at the bottom dielectric/OSC interface. Upon interaction of the protein receptors with sulfate ions, negative charges are trapped at the top dielectric/OSC interface causing an accumulation of positive counter charges in the semiconductor. To deplete the Figure 12. A) Schematic representation of the ferritin NPs OFET memory device fabricated by channel from these positive counter charges, the LbL-assembled procedure using cationic poly(allylamine hydrochloride) (PAH) as adhe- a higher positive bias at the bottom gate is sion polymer and anionic ferritin NPs (PAH/ferritin NP). B) The I–V transfer curves for OFET required to switch on the transistor and a memory devices using PAH/ferritin NP. The protein multilayers act as gate dielectric material shift in the VT is observed. and a shift of the VT is obtained by applying the appropriate gate voltage as a result of the trap/ All the described examples demonstrate detrap charge effect. Reproduced with permission.[48] Copyright 2013, Wiley-VCH Verlag GmbH the potential of OFETs comprising a bioint& Co. KgaA, Weinheim. erlayer between the dielectric and the OSC, to be used as label-free, selective, and ultrasensitive bioelectronic devices. OFETs with desired functionfabricated on a flexible substrate using Al2O3 as high-k dielecalities can be developed by tailoring the dielectric surface. tric instead of silicon dioxide. Memory devices with enzyme as Integrating biofunctional molecules between the dielectric and gate dielectric were also proposed. the semiconductor influences directly the electronic states at Maddalena et al.[49] have proposed a dual gate OFET device the interface, thus controlling the channel conductance. More having as top gate a sulfate binding protein layer, able to

Figure 13. A) Top: Schematic view of the dual gate OFET device having the protein receptor anchored on the top of dielectric layer. Below: A scheme of the charge dielectric/OSC interfacial effect upon application of the gate voltage is also reported. B) Protein binding site for sulfate ions. C) I–V transfer curves obtained for a bare OFET device and for a protein embedding OFET before and after the exposure to sulfate ions. Reproduced with permission.[49] Copyright 2010, AIP Publishing LLC.




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importantly, this methodology offers the possibility to explore and interpret molecular conformation dynamics. Moreover, it is worth noting that back-gate OFET devices are fully compatible with printing fabrication procedures at low cost. A further step would be the fabrication of such devices using new dielectric materials allowing their operation at ultralow voltage. Again biomolecules can be proposed at this aim as discussed in the following section.

4. OFETs Based on Naturally Occurring Dielectrics The incorporation of biocompatible/biological materials in electronic devices unfolds new perspectives for the exploitation of biosystems and holds much promise in bioelectronics application. During the last decade, biomaterials have been exploited successfully as structural layers in OFET architectures. Considering that the majority of naturally occurring biopolymers have insulating properties, they can serve as dielectric layers. However, certain requirements should be ensured so as to obtain high performance and sustainable OFET devices. As already discussed, the surface of the dielectric can modulate the electrical performance of the OSC. It is well established that morphology of the OSC film depends greatly on the dielectric surface. In several cases the nature of the dielectric can be the main cause of the appearance of hysteretic behavior or high gate leakage. Moreover, alternative materials having a high dielectric constant are desired, so as to increase the transconductance of the OFET and allow operation in low voltages. In particular, an ideal gate dielectric should display high dielectric strength, low leakage current, and large breakdown strength, and form a “harmonic” interface with the semiconductor of interest. In addition, the semiconductor industry is nowadays interested in producing environment friendly, disposable, and even bioresorbable electronics of low cost. Biomaterials are biodegradable by nature and are considered extremely promising substitutes of conventional organic or inorganic insulating materials. Furthermore, biomaterials often have unique properties that cannot be easily achieved by means of synthetic chemistry. In the following section, the development of OFETs based on naturally occurring dielectrics is discussed. Among the most used biological compounds employed directly as dielectrics are: deoxyribonucleic acid (DNA) and nucleobases, proteins (i.e., silk, bovine serum albumin (BSA), collagen, etc.), and carbohydrates. Particular attention is paid to state-of-the-art devices providing details regarding their electric properties and their potential to be used for specific applications. Main drawbacks and remaining challenges are also outlined.

4.1. OFET Based on DNA DNA carries the genetic code in all living organisms. This molecule is composed of two long complementary polynucleotide chains, which are coupled forming a double strand helix. Each DNA chain is actually a long polymer made of repeated nucleotide units composed by different nucleobases (adenine

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(A), cytosine (C), guanine (G), or thymine (T)). The nucleotides are covalently bound into a chain through phosphodiester linkages where the 5′-phosphate group of one nucleotide unit is joined to the 3′-hydroxyl group of the next nucleotide. To form the double-helix structure, complementary nucleobases (i.e., A-T, C-G) are linked together by hydrophobic, van der Waals dipole–dipole interactions, and hydrogen bonds.[50] The discovery of the double-helix structure of the DNA set new standards in modern biology. Due to its inimitable structure and composition, DNA exhibits appealing mechanical and electrical properties and has reasonably attracted the interest of material scientists and engineers. Conflicting results are reported regarding the conductivity of DNA, showing insulating to superconductive behavior.[51] The sugar-phosphate backbone is considered insulating, while charge transfer can occur along the π-stacks of the nucleobases. Recently, Genereux et al.[52] suggested that different values of conductivity can be found depending on how DNA is integrated to the measurement's apparatus. Based on the fact that the DNA molecule is sensitive to conformational changes, conductivity can vary over a wide range. Another important factor that can affect the charge transfer is the sequence of the bases and the length of the molecule. In aqueous solutions DNA yields polyelectrolyte properties and positive-charged ions can move along the negatively charged phosphate backbone.[53] In a dry state, DNA leans more toward its insulating nature. Dry DNA films can be easily obtained using different deposition techniques (e.g., spin-coating, dip-coating, doctor blade method). Also membranes with good ionic conductivity have been reported by Pawlicka et al.[54] using DNA plasticized with glycerol. Although, there is still ongoing debate among scientists on the electric properties of DNA, this does not restrict its application in bioelectronics. On the contrary, its versatile behavior may be the key element of constructing all DNA-based electronic devices. Herein, an overview of the use of DNA as alternative gate material in OFETs is given, focusing on the overall performance of the device. Pioneered study of DNA-based biopolymer as bulk gating material in OFETs was reported in 2006 by Grote and coworkers.[55] The proposed solid-state OFET device was based on solution-processed DNA films. DNA was extracted from frozen salmon milt and roe sacs. The molecular weight of this DNA was 8000 kDa, as determined by gel-phase electrophoresis. After purification, DNA was precipitated in water with a cationic surfactant, namely cetyltrimethylammonium (CTMA) chloride, through ion exchange reaction[56] as shown in Figure 14. The obtained DNA–surfactant complex became insoluble in water but could be dissolved in other solvents, particularly in alcohols (e.g., ethanol, methanol, isopropanol, and butanol). Pristine DNA is soluble only in aqueous solutions, but the resulting films from undesired aggregates, are sensitive to moisture and lack of mechanical strength. Moreover DNA is known to denature at ≈90 °C. By tuning the solubility of DNA with the addition of the surfactant, thermally stable up to 230 °C and smoother films can be obtained via spin-coating technique. Moreover, it was shown that the DNA–CTMA complex films exhibited self-organized structures.[56a] It was proposed that the observed ordered structures were due to a perpendicular




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prevent the ion migration and improve the transfer characteristics of the device, crosslinked DNA-CTMA films were fabricated. As a cross-linking agent, poly (phenylisocyanate-co-formaldehyde) (PPIF) was used. The obtained cross-linked DNA-CTMA-PPIF films were more robust than the non-cross-linked DNA-CTMA ones and showed higher resistance to the solvents used during the fabrication of the device. After deposition, the crosslinked films were post-baked at 80 °C for 5 min and cured in a vacuum oven at 175 °C for 15 min. The capacitance per unit area was ≈0.8 nF cm−2 and the relative dielectric constant εDNA/CTMA/PPIF = 5.4. Again n- and p-type-based OFETs were fabricated, using fullerene (C60) and α-sexythiophene (α-6T) OSCs, respectively. Similar values of electron mobilities ≈9 × 10−3 cm2 V−1 s−1, as extracted from the linear regime, were found for the cross-linked and non-cross-linked dielectric for the C60-based OFETs. The hole mobility of α-6T was almost two orders of magnitude higher than the n-type OFETs. Reduced hysteresis was observed for all devices bearing a cross-linked DNA-CTMA-PPIF film as gate insulator. Figure 14. Picture of dried purified DNA extracted from salmon frozen milt and roe sacs, chemPhotocross-linked DNA was used by Kim ical structure of CTMA: hexadecyl trimethyl-ammonium chloride, and a schematic diagram that et al.[60] to gate OFET devices in top contact shows how surfactants are added to the DNA structure. Reproduced with permission.[57] 2009, bottom gate configuration. A homopolymer Springer-Verlag Berlin Heidelberg. of DNA baring photoreactive chalcone moieties (CcDNA) and a copolymer of CTMADNA-co-CcDNA were orientation of the CTMA alkyl chains to the film plane and a synthetized by using purified natural sodium DNA. The photoparallel to the film plane orientation of the DNA helices.[57] reactive DNA acted as a negative photoresist, and was able to Pentacene-based OFETs baring a top contact bottom gate cross-link through a photocycloaddition reaction upon irraconfiguration were fabricated. The thickness of the dielectric diation with UV light. As OSC (5, 5′-(9, 10-bis((4-hexylphenyl) was 200 nm with a capacitance per area of 1.15 nF cm−2 and ethynyl) anthracene-2, 6-yl-diyl) bis(ethyne-2,1-diyl) bis(2-hexan estimated dielectric constant εDNA/CTMA = 7.8. In terms of ylthiophene) HB-ant-THT was used. OFET devices with fieldelectrical performance, the devices exhibit a saturation mobility effect mobilities in the range of 10−1 cm2 V−1 s−1 were obtained μsat = 0.05 cm2 V−1 s−1 and the drain current was amplified by 3 three orders of magnitude (ION/IOFF = 10 ), using gate voltages and low hysteresis was observed on the corresponding transfer I–V characteristic curves. Higher mobility was found for the of less than 10 V. However, a large hysteresis was observed in device prepared with the copolymer CTMADNA-co-CcDNA as the reverse current sweep, shifting the threshold voltage almost gate insulator. Tapping-mode atomic force microscopy (AFM) 7 V. The hysteresis was attributed to migration of ionic mobile revealed different morphologies among the films of the semispecies at the interface between the DNA-based insulator and conductor deposited on the homopolymer and copolymer DNAthe OSC. based dielectric. The film deposited on the copolymer held a In a following work by the same group, a thin charge barrier more ordered structure, consisted of well-dispersed and welllayer of aluminum oxide Al2O3 was introduced after the deposiconnected crystallites. The authors suggested that the hexyl tion of the DNA-CTMA dielectric film.[58] The presence of the peripheral side groups of HB-ant-THT interact with the long Al2O3 layer, in between the semiconductor and dielectric, minialkyl chains present in the CTMA resulting in highly ordered mized the hysteresis and reduced the gate leakage current of HB-ant-THT molecules. the DNA-based OFET device (Figure 15). In this case DNA with The examples given above reveal that the morphological lower molecular weight (Mw = 300 kDa) was used and the thickcharacteristics as well as the electrical and mechanical propness of the film was 1–1.1 μm. Two types of OSCs, pentacene erties of DNA-dielectric films can be tailored, by adjusting (p-type) and 1-[3-(Methoxycarbonyl)propyl]-1-phenyl-[6.6]C61 its molecular weight and the nature or concentration of the (PCBM) (n-type), were employed. Both p- and n-type channels involved reagents. For instance, smoother films are obtained showed good current modulation at operating voltages lower by reducing the MW of DNA. In addition, the electrical resistthan 15 V. An alternative method to obtain hysteresis-free DNA-based ance of the films has been found to be dependent on the moleOFETs was reported a couple of years later.[59] In order to cular weight. Moreover, the presence of surfactants in the DNA




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Figure 15. Schematic illustration of the pentacene-based OFET having A) bare DNA-CTMA as dielectric and B) DNA-CTMA with an additional Al2O3 charge blocking layer; C) I–V transfer characteristics of the two devices. Inset: I–V output characteristic of the pentacene-based OFET with DNA-CTMA and an additional Al2O3 charge blocking layer. Reproduced with permission.[58] 2006, Elsevier.

solution improves the quality of the film. The DNA–surfactant complex chemistry can be used for obtaining functional biomaterials, thus broadening the spectrum of applications. Different molecules can be introduced in the DNA–CTMA matrix so as to provide desired optical or electrical properties.[56a,61] On the other hand, one of the main drawbacks of using DNA as bulk gating material is the presence of injected or inherent mobile charges that lead to increased hysteresis and gate leakage current. To overcome such an issue, the introduction of barrier layers at the interface with the semiconductor and methods to cross-link the films have been proven effective. However, few studies are published after 2010 reporting on DNA as gating material in OFET devices. More recently, it has also been used as a semiconducting layer[62] in OFETs and as an interlayer between metal and OSC to enhance the injection of carriers.[63] Other potential applications include organic photonics[64] (e.g., OLEDs, LCDs), nanoscale robotics,[65] and assembly of graphene nanostructures using DNA as scaffold.[66]

4.2. OFET Based on Proteins The development of OFET devices having a protein layer as dielectric has recently gained increasing interest. Silk fibroin was one of the first proteins reported as gating material in organic transistors.[67] It is a protein extracted from silk worms and is composed by repeated amino acids of glycine (Gly) and alanine

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(Ala) in alternating sequence. The structure consists of polypeptide chains linked together by lateral NH·OC hydrogen bonds and form antiparallel-chain β-pleated sheets. Silk fibroin's secondary structure exhibits a high content of β- sheets leading to a 3D structure of highly ordered fibers.[68] Moreover, silk proteins hold a high relative permittivity value (>5), placing them among the most promising biomaterials in dielectric applications. A silk protein dielectric layer was employed by Capelli et al.[67a] to fabricate both OFET and organic light-emitting transistor (OLET) devices. Silk-based OFETs with both n- and p-type OSCs, N,N'-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (P13), and α,ω-dihexyl-quaterthiophene (DH4T), respectively, were proposed. The electrical figure of merits namely mobility and on/off ratio were comparable with those of more conventional organic transistors based on other dielectrics such as SiO2 and poly(methyl methacrylate) (PMMA). A pentacene-based OFET with silk fibroin as gate dielectric fabricated on flexible substrate was presented by Wang et al.[67b] (Figure 16). An average hole mobility of 21.7 cm2 V−1 s−1 at low gate voltages (−3 V) and an ION/IOFF = 3 × 104 were achieved. Initially, a silk fibroin thin film of 30 nm was spin-coated onto a gate electrode prepatterned plastic substrate. A dip-coating step followed in order to obtain a thicker layer (420 nm). The capacitance per area (Ci) of the protein film was estimated using impedance and quasistatic capacitance–voltage measurements (QSCV). The value of capacitance as obtained by the impedance measurements was 12.8 nF cm−2 (at 1 MHz) and 17.5 nF cm−2 (at 20 Hz), whereas a more accurate value of 30 nF cm−2 was found by the quasistatic mode. The latter was used to calculate the mobility at the saturation regime. Improved performance of the protein-gate OFET device, compared to conventional SiO2 dielectric, was observed and was correlated to the formation of a better interface between the protein and the semiconductor. The protein film exhibited low surface roughness (0.3 nm) as determined by AFM measurements. Moreover, by grazing incidence X-ray diffraction (GIXRD) analysis it was shown that the amount of amorphous phase in pentacene was reduced in the case of protein-gated transistors, giving rise to a more ordered crystalline phase. Low hysteresis and threshold voltage (−0.77 V) was further evidence of low trap density in the semiconductor/protein dielectric interface. Solution-processed poly(3-hexyl thiophene) P3HT-based OFET baring silk fibroin as gating material has also been reported by Shi et al.[69] The silk fibroin film was found to be resistant upon the exposure to the solvent of the semiconductor, thus allowing the deposition of P3HT via spincoating. Low threshold voltage (−0.77 V) and a mobility of 0.21 cm2 V−1 s−1, which is comparable to the highest mobility reported for regioregular P3HT using inorganic dielectrics, were obtained at low operating voltages (−3 V). The authors suggested that the highly ordered fiber-like structure of the protein film leads to reduction of trap sites at the interface with the semiconductor. Indeed silk fibroin reflected a high content of β-sheets, as determined by means of circular dichroism (CD). Another interesting demonstration of silk protein being a potential dielectric for the development of flexible OFETs was the work of Tsai and collaborators.[70] In this study, silk fibroin was employed as gating material for n-type channel OFET. C60 was evaporated on bare protein and after introducing a thin (2 nm) layer of pentacene




REVIEW Figure 16. A) Schematic structure of the pentacene OFET device with silk fibroin as the gate dielectric and cross-sectional FESEM image of the silk fibroin film on the Au gate electrode. B) Schematics showing the growth modes of pentacene on SiO2 and silk fibroin. C) Electrical characteristics of the pentacene OFETs and Metal-Insulator-Metal (MIM) devices with silk fibroin as the dielectric material: (a) output and (b) transfer along with the gate leakage current characteristics for the OFET device. Inset: Square rout of the drain current versus the gated voltage; (c) capacitance versus frequency for the MIM device. Inset: Capacitance–voltage (C–V) curve at 20 Hz. (d) Quasistatic capacitance versus voltage curve taken at a sweep rate of 0.25 V s−1; (e) Double I–V transfer characteristics of the OFET device. Reproduced with permission.[67b] 2011, Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim.

between the OSC and the dielectric. As first reported by Itaka et al.,[71] the pentacene interlayer assists to improve the quality of the C60 crystals, thus enhancing the relative mobility of the device. The devices were measured in vacuum and in air with a relative humidity of 55%. The presence of the 2-nm pentacene interlayer increased the mobility from 0.014 to 1 cm2 V−1 s−1. This enhancement was attributed to the better crystal quality of C60 formed on pentacene's surface. In addition, the mobility of the device was further increased, reaching 10 cm2 V−1 s−1, and the device exhibited an ambipolar behavior, when it was exposed to ambient air due to water absorption in the protein film. The authors ascribed the observed behavior to changes in the capacitance of the protein- based dielectric layer. It was anticipated that in ambient conditions, mobile and immobile charges are found in the protein matrix due to sorption of water molecules. Another interesting approach involving chicken albumen without any purification was reported by Chang et al. The albumen was successfully employed as gating material in high performance OFET devices (Figure 17).[72]


Apart from being a commonly available and inexpensive biomaterial, natural albumen can be easily cross-linked by means of thermal treatment without using additional cross-linking agents. The authors investigated the effect of annealing temperature on the film's morphological characteristics. The degree of cross-linking depends on the annealing temperature and consequently can affect the performance of dielectric. The films of albumen were baked at different temperatures resulting in films of varying hydrophobicity. The higher the temperature used for annealing, the higher the contact angle (more hydrophobic films) of the obtained protein films. For the fabrication of the OFET devices, temperatures above 100 °C were used in order to obtain hydrophobic, smooth, and dense films. Further on, the density and smoothness of the film's surface was correlated to the rate of water evaporation. Albumen proved to be a fairly good gate insulator for both p- and n-type OFET channels. As OSCs, pentacene and C60 were selected. Hole and electron mobility in the saturation regime reached a value of 0.09 and 0.13 cm2 V−1 s−1, respectively, while the devices were biased with



17

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REVIEW


Figure 17. A) The structure of an OFET fabricated with albumen dielectrics. The photograph illustrates the separation of egg white and egg yolk. Output and transfer I–V characteristic curves of B) pentacene-based OFET, C) C60-based OFET with albumen egg-white dielectric. Reproduced with permission.[72] 2011, Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim.

25 V. Low threshold voltage values, leakage current in the order of 10−10 A, and an on/off current ratio of 104 were observed for both types of semiconductors. Furthermore, the capacitance of the protein films was measured at different environmental conditions. The results showed that the capacitance of the albumen remained stable in a wide range of relative humidity due the hydrophobic nature of the protein after the thermal treatment. A comparison between albumen and conventional polymers used as dielectrics in OFETs was also made. The mobility of the protein-based devices was almost two orders of magnitude higher than that found for the polymer-based OFETs. As we already saw, the presence of moisture plays a critical role in the electrical performance of OFETs fabricated with biomaterials. The effect of moisture on OFETs fabricated with BSA was recently investigated by Lee et al.[73] BSA is a natural protein that is known to have a high hydration ability. In vacuum, pentacene-based OFETs with BSA had a saturation mobility of 0.3 cm2 V−1 s−1 and a threshold voltage of −16 V (Figure 18). In a relative humidity of 47%, the mobility value increased to 4.7 cm2 V−1 s−1, whereas the threshold voltage was found −0.7 V. Hydrated BSA can act as a polyelectrolyte, since mobile ions can be generated by dissociation of water molecules through interaction with carboxylic or amine groups of the amino acids. Therefore, in a humid environment BSA dielectric is able to increase the drain current by forming electric double-layer capacitors (EDLCs). The formation of EDLCs upon bias results in the increase of the capacitance value and the reduction of the threshold voltage. On the other hand, the presence of moisture caused an increase in the leakage current and a decrease in the on/off ratio by two orders of magnitude.

18


A similar work was reported by Hsieh et al.[74] regarding the enhancement in mobility of pentacene-based OFETs by water absorption in the protein–dielectric. In this case, collagen hydrolysate was used to gate the device. Collagen hydrolysate is the hydrolyzed form of collagen, which is a bioproduct widely used as food additive and in cosmetics. The pentacene OFET exhibits a field effect mobility of 0.8 cm2 V−1 s−1 and an on/off ratio in the order of 105 in vacuum. The drain current increased upon exposure to air from 10−9 to 10−5 A, resulting in a mobility of 15.5 cm2 V−1 s−1. The threshold voltage was found also to depend on the presence of humidity. A threshold shift toward the positive direction was observed at the time the device was exposed to ambient air increased. The role of water in the performance of n-type N,Ndioctyl-3,4,9,10-perylene tetracarboxylic diimide (PTCDI-C8)based OFETs with gelatin dielectric was also studied.[75] Gelatin aqueous solution was initially spin-coated on polyethylene naphthalate (PEN) flexible substrate. The thickness of the dielectric layer was further increased by subsequent casting so as to reduce the gate leakage current. The device characteristics measured in vacuum and in ambient conditions differed greatly. Although gelatin is considered less hydrophilic than BSA, the amount of sorbed water molecules in gelatin was enough to change dramatically the electrical performance of the device. In general, the PTCDI-C8-based device with gelatin as gate insulator exhibited a mobility of 0.22 cm2 V−1 s−1 in vacuum, which is in agreement with values of mobility reported for inorganic dielectrics. Similar to the effect of moisture on BSA-based OFETs discussed earlier, the capacitance of the gelatin layer is increased when the device is operated in air. The overall enhanced electrical performance of the device




REVIEW Figure 18. A) I–V output and transfer characteristic curves along with the gate leakage current of pentacene-based OFET with BSA dielectric in vacuum and in ambient conditions with a relative humidity of 47%. Inset: Square route of the drain current versus the gated voltage. B) Schematic illustration of the device configuration. C) Capacitance measurement versus vacuum time of the MIM device with BSA as dielectric. Reproduced with permission.[73] 2013, Elsevier.

(higher mobility, lower threshold voltage) was attributed to the presence of mobile ions. Moreover, the trap density at the interface and the hysteresis were found to decrease in air. The authors suggested that mobile hydroxide ions that move toward the PTCDI-C8/gelatin interface upon bias are neutralizing the existent trap sites. Furthermore, the reduction of the threshold value from 55 V in vacuum to 2.6 V in air showed that less voltage is required for electrons to accumulate in PTCDI-C8. On the other hand, the increased of the gate leakage current was assumed to be originated by the formation of conducting paths due to the fixed and mobile ions in the hydrated gelatin. Protein-based OFETs, either baring n-type or p-type OSCs, proved to be excellent dielectrics, resulting in devices with improved electric performance compared to polymeric and inorganic dielectrics. The protein layer seems to wield a significant influence on the degree of crystallinity of the OSC layer. This effect has been correlated with the ability of certain proteins to form a well-ordered structure. It is also worth mentioning that in some cases, voltages down to a few volts were enough to operate the devices. Finally, the humidity affected greatly the electrical performance of the devices, leading to an enhancement of the figures of merit. However, for practical applications, encapsulation of the OFET device is most probably required to ensure a stable environment in which the device is operated.

4.3. OFETs Based on Naturally Occurring Carbohydrates Solution-processed cellulose thin films served as effective gate dielectric for the fabrication of pentacene- and C60-based


OFETs.[76] Cellulose is a well-known polysaccharide and is the main component of most papers. It is composed by a linear chain of linked D-glucose units. Thin films of cellulose were prepared by desilylation of trimethylsilyl cellulose (TMSC) dissolved in chloroform. The desilylation of TMSC was performed by vapor phase acid hydrolysis, resulting in fully regenerated cellulose films. In this case the cellulose film was part of a bilayer dielectric composed by a 16-nm film of cellulose and 8 nm of Al2O3. The oxide layer being introduced, through an oxygen plasma treatment of the aluminum gate, between the gate electrode and the cellulose, holds a dual role. It is first of all a barrier blocking mobile charges to be injected from the gate into the cellulose layer, thus reducing significantly the gate leakage and minimizing the hysteresis. Secondly, it forms along with the cellulose, a hybrid high-k dielectric layer exhibiting a capacitance per area of 310 nF cm−2 at 1 KHz, allowing transistor operation at voltages below 3 V. Above all, combining these two layers leads to more stable and reproducible devices as compared to OFETs with bare cellulose as dielectric. As far as the electrical performance is concerned, the mobility extracted from the saturation regime was 0.08 and 0.1 cm2 V−1 s−1 for C60 and pentacene, respectively. Likewise, glucose and lactose as well as isolated DNA nucleobases have been successfully employed as additional dielectric layer deposited on Al2O3.[77] Cellulose dissolved in ionic liquids has also been utilized as gating material for electrolyte-gated OFETs, with promising properties for developing flexible electronics. The obtained iongel exhibited high capacitance (4–15 μF cm−2) and the OFETs reached mobility values in the order of 102 cm2 V−1 s−1 at operating voltages

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