Recent progress in organic field‐effect transistor‐based chem/bio‐sensors

Recent decades have witnessed the huge successes of organic field‐effect transistors (OFETs) and their applications. Among them, OFET‐based sensors have shown promising applications in the field of food safety, industrial security, environmental, and health monitoring. This is due to their advantages in solution processability, flexibility, light weight, and variety in molecular design. This review highlights recent progress in OFET‐based chemical and biological sensors in gas and liquid phase, especially for the past 5 years. The analytes range from small molecules to large biomolecules. The optimizations of OFET devices for sensors, including the semiconducting layers, dielectric layers, electrodes, and their interfaces etc., are illustrated. And their relationships with sensing parameters (sensitivity, selectivity, and response time) as well as the sensing mechanisms are given. Finally, the remaining challenges are discussed. We expect that this review can offer inspiration for future design of OFET‐based sensors.


INTRODUCTION
Organic field-effect transistors (OFETs) have attracted increasing attention since their invention in 1986 by Tsumura et al. 1 due to their large-area fabrication, good flexibility, and light weight. In the past few decades, OFETs have not only been used in circuits 2 but also in new sensing functional devices, such as chemical sensors, biological sensors, temperature sensors, pH sensors, and press sensors. [3][4][5][6][7][8][9][10][11][12][13] OFET sensors using organic semiconductor (OSC) active layer have attracted increasing attention due to their inherent merits of channel materials and sensor F I G U R E 1 Schematic illustration of typical organic field-effect transistor (OFET) configurations were provided for comparison, and many aspects were discussed. The first consisted of reviewing OFET and their advantages in sensing. The second and third sections summarized the chemical sensors in gas phase and chem/bio-sensors in liquid phase, respectively. The analytes range from small molecules to large biomolecules. The sensing mechanisms include physical absorptions, chemical reactions, or supramolecular interactions etc.
The key sensing positions include semiconducting layers, dielectric layers, gate electrodes, and their interfaces. OFET devices are also optimized for sensing including normal configurations, electrolyte-gated OFET (EG-OFET), and extended-gated OFET etc. We hope that this review would benefit the future design of OFET-based sensors.

PRINCIPLES OF OFETS IN SENSING
OFETs are active devices based on the controllable injection of free carriers into semiconductors. In this process, organic materials, such as small molecules, oligomers, and polymers are used as semiconductor layers. OFET consists of OSC layer, electrodes (source, drain, and gate), and dielectric layer. Among components, the OSC layer is generally made of organic small molecule or polymer thin films and single crystals. The dielectric layer is constructed by inorganic or organic materials with good dielectric properties. The gate electrode is usually composed of a highly doped silicon substrate, and the electrodes are fabricated by high work function metals or conductive polymers. OFETs consist of four typical configurations ( Figure 1): bottom gate/bottom contact (BG/BC), bottom gate/top contact (BG/TC), top gate/bottom contact (TG/BC), and top gate/top contact (TG/TC). The performances of OFETs are usually evaluated by transfer and output characteristic curves. The former provides a plot of source-drain current (I SD ) versus gate voltages (V G ) at different source-drain voltage (V SD ), while the latter produces a plot of I SD versus V SD under different V G s. Applying a gate bias voltage may induce the formation of a charge accumulation layer at the insulator/OSC interface.
The quality of an OFET can be evaluated by addressing key parameters, such as: (1) mobility (μ), which determines the on-currents and processing speed of OFETs; 8,14,[18][19] (2) on-off current ratio (I on /I off ), defined as the ratio of I SD in "on" and "off" states. 20 High I on /I off value means better stability and anti-interference ability; (3) threshhold voltage (V T ), defined as the minimum V G when channel current occurs in a transistor device. Low V T value would reduce the power consumption of the device; (4) subthreshold slope (S), reflecting the degree of reduction of the sourcedrain current value in response to changes in gate voltage.

F I G U R E 2 Four examples of interactions of analytes with organic field-effect transistors (OFETs) at semiconducting layer, dielectric layer or gate electrodes in gas or liquid phase
When an OFET is exposed to environment, analytes can interact with the device in several ways like at the surface of OSC, at the grain boundaries between crystallinity aggregates of OSC film, or at interfaces between OSCs and dielectrics or electrodes. Such analytes could induce local electric fields, or disrupt molecular packing of OSC, which alter the current−voltage relationships in OFETs. However, unlike OFETs used for purely circuit functions, the analyte-induced effects in OFETs-based sensors should be as high as possible and even better if they are selective. The analyte affecting μ should ideally exert such effect throughout the applicable V G range. Therefore, a larger current modulation can be obtained due to the interaction of the analyte. Figure 2 summarizes the OFET-based sensor integrated with analytes delivery system.

GAS SENSORS BASED ON OFETS
We live in a gas-filled environment, and many industrial and biological processes depend on the gas phase reactions. Thus, gas sensors are highly demanded in many fields, such as chemical, pharmaceutical, and disease detection. Since the landmark work of Laurs and Heiland, 21 various gases have been detected with good selectivity and sensitivity using OFET-based sensors, including NH 3 , NO 2 , H 2 S, ethylene etc.

NH 3 and ammonia gas sensors
Ammonia (NH 3 ) is major industrial chemical product that is both caustic and hazardous. The presence of NH 3 in the atmosphere could not only facilitate the formation of hazy weather but also may cause chronic diseases, such as severe respiratory inflammation, asthma, and lung problems. Therefore, the detection of NH 3 and amines has attracted great attention in recent decades. [22][23][24][25][26][27] The presence of NH 3 in the atmosphere often decreases the flowing current (I SD ) in the device channel. As a result, regioregular poly (3-hexylthiophene) (rr-P3HT)-based OFETs have been developed for the detection of NH 3 gas at concentrations below 20 ppm with the excellent recovery of the original state within 6 min. 28 The exposure of the conducting channel to various concentrations of NH 3 reduces I SD /μ and increases V T due to the dedoping effect. Sagdullina et al. used fluorinated alkyl chain containing naphthalene diimide (NDI) as an active layer to fabricate NH 3 gas sensors. The tests revealed good selectivity to amines coupled with high sensitivity and good operational  35 Copyright 2017, SpringerLink stability. 29 Additionally, the sensor devices exhibited a fast response to low NH 3 levels (≤1 ppm) and some aliphatic amines at V SD = 10 V and V G = 11 V. The high sensitivities and operational stabilities of the devices make them promising for food quality control or medical diagnostics.
The change in the morphologies and redox properties of semiconductors would strongly affect the performance of OFETs. In this review, many efforts have been devoted to the study of such changes. This includes modification of OSC film thickness to improve the diffusion of analytes into channel layer, thereby enhancing device response. Noh et al. fabricated uniform ultrathin polymer films (poly[[2,5-bis(2-octyldodecyl)-2,3,5,6-tetrahydro-3,6-dioxopyrrolo [3,4-c]pyrrole-1,4-diyl]-alt-[[2,2′-(2,5thiophene)bis-thieno(3,2-b)thiophene]-5,5′-diyl]] [DPPT-TT]) with thickness below 2.0 and 1.5 nm using a wire-wound bar-coating method ( Figure 3A-C). 30 The dependence of the sensitivity on OSC layer thickness revealed that devices with films thickness below 2 nm showed 82% sensitivity toward the detection of NH 3 , while devices with thicker films displayed sensitivities of 27% (5.0 nm) and 10% (12.8 nm). Moreover, 1000 ppm ethylene and ethanol gases were also successfully detected. Qiu et al. used vertical phase separation of polymer blends to obtain ultrathin P3HT films with thicknesses as low as 2.0 nm by varying the P3HT/poly (methyl methacrylate) (PMMA) blending ratio. 31 The obtained devices achieved NH 3 sensing with 31.1% response sensitivity (10 ppm NH 3 ). Also, the performance of NH 3 sensors was found inversely proportional to the film thickness. Furthermore, the P3HT film thickness could only be controlled by varying the P3HT/PMMA blending ratio. Ponomarenko et al. designed a highly sensitive gas sensor in monolayer device directly exposed the analyte based on Langmuir-Schaefer monolayer as an OSC layer. 32 The OSC layer was organosilicon derivative of benzo[b]benzo [4,5]thieno [2,3-d]thiophene (BTBT). The resulting devices operated well under air with ultrafast detection of NH 3 down to tens of ppb concentrations. It is worth mentioning that the sensor response allowed for distinguishing NH 3 and H 2 S in a single sensing device.
The control over grain size of OSC films is another approach to tailor the sensing performances of gas sensors since the transport of charge carriers can be facilitated by fewer grain boundaries. In this regard, Huang et al. fabricated a series of dinaphtho [2,3- [3,2-b]thiophene (DNTT) films with variable grain sizes by adjusting the substrate temperature during the thermal evaporation process. 33 Although the resulting OFETs with smaller grain sizes exhibited lower I SD , they showed enhanced sensing performances. Chung et al. inserted buffer layers to yield dramatic changes on the semiconductor surface to tune the cohesive energies of semiconductors. 34 The resulting NH 3 gas sensors did not only exhibit high sensitivity and real-time response to NH 3 at concentrations as low as 10 ppm but also maintained the high charge carrier mobility (0.12 cm 2 V -1 s -1 ).
The side chain effects of OSC on OFET-based NH 3 sensors have also been investigated. 35 Huang et al. reported four OFETs made of OSC layers with the same conjugated structure but different alkyl chain lengths ( Figure 3D,E). They investigated the relationship between the film thickness and alkyl chain for sensor sensitivity. In this process, the alkyl side chains could induce layer-by-layer growth of OSC films and hinder the interactions of NH 3 molecules with charges in the conduction channel. Short alkyl chains would be better for sensing. On the other hand, Zhang et al. incorporated tert-butoxycarboxyl (t-boc) groups into the side chains of polymer pDPPBu-BT during fabrication resulted in NH 3 sensors with remarkably sensitivity and selectivity toward the detection of NH 3 down to 10 ppb and volatile amines ( Figure 3F). 36 Thermo gravimetric analysis and fourier transform infrared analysis indicated that t-boc groups (pDPPBu-BT) could be transformed into -COOH groups (pDPPCOOH-BT) during the thermal annealing of polymer film at 240 • C. Meanwhile, nanopores were produced after thermal annealing, and the -COOH groups reacted with NH 3 and other amines to form the respective salts. These features improved the selectivity of the obtained sensors since the presence of nanopores facilitated the diffusion of analytes within OSCs layers, explaining the elevated performances of sensors.
Chemical interaction between the active component and analytes could enhance the selectivity of sensors. Kim et al. fabricated OFET-based sensors using P3HT blended with tris (pentafluorophenyl) borane as an active layer. The as-obtained sensors exhibited a remarkable selectivity to NH 3 with respect to methanol, acetone, and dichloromethane, owing to the chemical interaction between the Lewis acid (TPFB) and Lewis base (NH 3 ). 37 As depicted above, 33 the presence of nanoporous OSCs structure could add adsorption sites and provide addi-tional direct pathways for analytes to interact with charge carriers in the conductive channel. [38][39][40][41] In this review, Huang et al. fabricated porous OFETs with reproducible response to NH 3 (10 ppb) combined with a relative sensitivity up to 340% ppm −1 ( Figure 4A,B). 42 The value is higher than those of previous reported OFETs with the same OSC thickness. The porous OFETs were obtained by vacuum freeze-drying template method by using DNTT with polystyrene (PS) microspheres to yield devices with good selectivity and stability. Solution processing is another way to obtain nanoporous OSCs. For example, Diao et al. fabricated porous OFETbased sensors by introducing nanopores with sizes of 50-700 nm into semiconductor film via solution processing method to yield two porous OFETs-based sensors (DPPT-TT with 11-propylhenicosane alkyl chains or C 8 -BTBT as OSC layer). 43 The nanoporous template was poly(4vinylphenol)/tetrahydrofuran solution with HDA (4,4′-(hexafluoroisopropylidene)-diphthalic anhydride) (crosslinking agent). The as-obtained DPPT-TT-based sensor showed ultrafast and ultrasensitive response toward ammonia at levels below 1 ppb in hundred millisecond time scale. By comparison, porous C 8 -BTBT-based OFET showed a good response toward formaldehyde at concentrations below 1 ppb, equivalent to three-fold improvement over the originally reported values. 44 The excellent performance and simple fabrication look promising for applications in personalized health. Yu, Li, and coworkers used P3HT and PS blends as semiconductor layer to fabricate OFET-based gas sensors. 45 This process creates more interaction interfaces with NH 3 , leading to sensors with more efficient detection of NH 3 even at low concentrations (5 ppm). Qiu, Wu, Yin, and coworkers decreased the detection limit (limit of detection [LOD]) of NH 3 to 0.1 ppm by using a P3HT/insulation block copolymer helical nanofibrils structure in the sensor construction. 46 Compared to devices containing films as active layers, single-crystal or ordered nanowire structures show higher sensitivities to analytes. Sung et al. developed a sensitive NH 3 gas sensor (0.01-25 ppm) by employing P3HT nanowires as OSCs layer ( Figure 4C). 47 The NH 3 -sensing calibration curves, constructed by I air /I NH3 versus NH 3 concentration, showed high NH 3 sensitivity of the single crystal OFETs compared with P3HT thin film OFETs ( Figure 4D). Liu, Song, and Li et al. fabricated a novel single heterostructure NH 3 gas sensor by coating single crystal copper phthalocyanine (CuPc) with metal-organic frameworks (MOFs) (IRMOF-3). The as-obtained sensors demonstrated excellent sensitivity and outstanding selectivity toward NH 3 detection at ≈60% relative humidity and indoor temperature with a limit detection of 52 ppb. 48 The current responses of such CuPc@IRMOF-3 sensors toward NH 3 reached around 34-265 fold higher than that of both reducing volatile organic compounds (VOCs) and  Figure 5A,B). 49 By changing the concentration of NDI3HU-DTYM2, the size of the pores of MMCs can be adjusted during drop-casting strategy. With the increase of the pore size (from 20 to 200 nm), the sensitivity of the sensor can be enhanced. Then sensitivity of such sensors could reach 0.1 ppb (sub-ppb level). Moreover, due to the specificity of MMCs structure (porosity and monolayer), the charge accumulation layer can be directly exposed, and thus the OFET-based MMCs could also sense dopamine as a solid amine-derivative with a detection limit up to 500 ppb. It should be noted the report about solid phase detection is rare. This is due to the diffusion hinder of solid analytes. The solid analytes are difficult to be diffused into the charge accumulation layer. Developing thin (down to monolayer level) or porous OSCs (discussed above) for minimizing the diffusion process may be good strategy for solid analyte detection.
The intrinsic property of OSCs could affect the sensing properties. For example, Zhang, Liu, and coworkers used thieno [3,4- as semiconducting layer to detect NH 3 ( Figure 5C). 50 The FET sensor based on PTTEH showed high sensitivity (down to 10 ppb) and good selectivity toward NH 3 and amines at low driving voltages (−5 V), which is due to good electrical conductivity of PTTEH with the existence of radical state and low bandgap. They further successfully used the sensor for real-time meat spoilage monitoring ( Figure 5D).
Except for OSC layer, the dielectric layer is also an important part of OFET devices, useful for partially determining the device stability, sensitivity, and power consumption. Thus, appropriate dielectric layers are critical in device design and functionality for sensing. Currently, obtaining stable performance and low voltage operation is still challenging, thereby severely hindering the commercialization for sensing. Guo et al. used a low-k nonpolar polymer dielectric layer (295 nm thick poly(vinyl cinnamate) [PVC]) for low operation voltage and realized a long-term and reliable sensing of NH 3 with low power consumption (∼50 nW). 51 In a similar vein, Turner, Rahmanudin, and coworkers developed a bilayer gate dielectrics, which are high-k ferroelectric layer (poly(vinylidenefluoride-trifluorethylene-  52 The as-obtained BG OFET chemical sensors were able of operating at low voltage even in flexible plastic substrates. They also exhibited reliable sensing performances over multiple cycles of exposure to NH 3 (2-50 ppm). Yu, Li, and coworkers used poly (vinyl alcohol) (PVA) as a gas accumulation layer to fabricate an NH 3 gas sensor. The sensor showed current changes of 66.9% and 30.2% under 0.5 and 0.2 ppm NH 3 , respectively. 53 Besides, the resulting sensor can realize both absorption and desorption processes on the hydroxyl dipoles under the applied electrical field. The latter was attributed to the orientation of hydroxyl groups attached to polymer chains in PVA dielectrics ( Figure 6D,E). Katz, Yu, and coworkers fabricated an OFET-based sensor with a hybrid dielectric with graphene oxide (GO) sheets and PMMA. 54 The GO sheets contained many oxygen-based functional groups (hydroxyl, carbonyl, carboxyl, and epoxy groups), which could promote the absorption of NH 3 molecules via hydrogen bonding or van der Waals interactions. Through these charge-dipole interactions, the rate of charge transfer was changed, and thus the sensor performed excellent sensing performance. The response of the sensor to 2 ppm NH 3 was multiple folds higher than that of the PMMA one.

NO 2 gas sensors
Nitrogen dioxide (NO 2 ) is the most common and toxic oxidizing air pollution produced from automotive engine emission and combustion. Hence, many studies have been focused on NO 2 sensing. [55][56][57] For example, Singh et al. fabricated an FET-based sensor to detect NO 2 gas using gate bias as a control unit using poly [N-9′heptadecanyl-2,7-carbazole-alt-5,5-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole] as active layer. 58 The resulting sensor showed high selectivity toward ppm levels of NO 2 gas. In another study, PQT12 and PQTS12 were also used as OSCs to detect NO 2 ( Figure 7A-C). 59 Accordingly, the PQTS12-based FET sensor showed higher sensitivity than PQT12 one with a detection level as low as 1 ppm. Such high sensitivity is attributed to the incorporation of sulfurs  60 Three types of TES-ADT crystal arrays were successfully achieved using engraved polydimethylsiloxane mold ( Figure 7D,E). The type C device with decreased width of TES-ADT pattern displayed the highest NO 2 gas sensing property. This was mainly attributed to the increased area of the crystal interface that facilitated the arrival of gas molecule at the OSC-dielectric interface. The NO 2 gas sensing properties of TES-ADT micro-strip FET were also optimized by incorporating PMMA to yield a highly crystalline TES-ADT: PMMA micro-strip FET with elevated gate-bias stability. 61 This was helpful for the accurate measurement of FET sensor.
On the other hand, optimizing the dielectric/OSC interface could also enhance the sensing performances. For instance, CuPc thin film-based NO 2 sensor with lowcost UV-ozone-treated polymeric gate dielectric was fabricated by Facchetti, Marks, and Yu et al. 62 The gas sensitivity of the resulting FETs sensor under 1 ppm of NO 2 reached about 50-fold than that of the original sen-sors. The LOD of such sensing platforms was around 400 ppb. The reason for this had to do with ultraviolet ozone (UVO), which generated oxygen-containing functional groups capable of strongly interacting with NO 2 shown in Figure 7F. Additionally, a binuclear phthalocyanine dimer-containing double-decker complex was used as an active layer to obtain ambipolar NO 2 gas sensors. 63 The concentration range of 0.5∼3 ppm of NO 2 could be detected at room temperature.
Another major strategy to improve the NO 2 sensing performances consists of combining different materials in OSC films as heterojunction structure. The heterojunction structure cannot only maintain the electronic property but also extends functionality for electronic response to analytes binding. Examples include forming bilayer or multilayer structures. In this review, Yu et al. fabricated dioctyl perylene tetracarboxylic diimide (PTCDI-C8) with various thicknesses on CuPc as active layers. 64 The obtained platforms exhibited high performance when compared to OFETs with a single CuPC layer. In particular, OFET-based sensor with 0.5 nm PTCDI-C8 and 7 nm CuPc displayed the highest sensing performances with one order of magnitude sensing enhancement when compared to CuPc one. Such sensitivity enhancement  Figure 8A-C). 65 The sensitivity of the resulting sensor was improved by 700% when compared to the original PDVT-10-based sensor. Moreover, the device exhibited reproducible performance from 8 ppb to 100 ppm with good stability of ∼6 months under humidity or ambient conditions. As shown in Figure 8D,E, MOF/PDVT-10 OFET was also integrated into a compact analog-to-digital converter (ADC) gas detection system able to not only detecting the NO 2 gas with high selectivity and sensitivity but also generating a five-bit digital output at different NO 2 gas concentrations from 25 ppb to 1 ppm. 66 Some OFET-based NO 2 sensing circuits were also reported with superior humid air stability (LOD: 200 ppb) 67 and environmental stability. 68 Yu et al. fabricated a DNA-based NO 2 sensor by spray-coating DNA between the gate dielectric and OSC layer. 69 The fabricated sensor showed nearly one order of magnitude sensitivity higher than that prepared without DNA interlayer. This enhancement was associated with the negatively charged phosphate groups of DNA molecules interacting with NO 2 . Note that such a biomaterial-based gas sensor was used to verify the potential of biomaterials in organic electronic sensing. Later, a biomolecule guanine/pentacene-based NO 2 gas was constructed by layer-by-layer thermally depositing guanine and pentacene to yield similar sensing performances. 70 As cellulose derivative, methyl cellulose (MC) possesses  75 Copyright 2018, American Chemical Society hydrophilic (OH) and relatively hydrophobic (CH 3 ) groups to provide modulated solubility and water-surface interaction. An, Lee et al. constructed a controllable heterointerface between pentacene and MC buffer layers for OFET-based NO 2 gas sensor. 71 The pentacene layer with MC showed decreased aggregate size that led to higher boundary density. The resulted sensors displayed an LOD toward NO 2 of 1 ppm. Tang 72 for the selective detection of NO 2 , H 2 S, and NO down to ppm levels. 73 Li, Yu et al. reported the synergistic effect of CuPc/Pentacene heterojunction and zinc oxide (ZnO)/PMMA hybrid dielectric. 74 After storage under air atmosphere for 30 days, the resulting sensor showed high stability with more than 10-fold saturation current at 0.5 ppm of NO 2 .
Another effective method for the construction of sensors relies on the use of a single blend as an active layer. In this respect, polymer blends prepared by mixing different ratios of P3HT and PVK (poly(9-vinylcarbazole)) were used to detect NO 2 ( Figure 8F). 75 The good holetransporting/electron-blocking capability of PVK induced sensors with about 20000% response to 30 ppm NO 2 using 1:1 P3HT/PVK blend at V G = 0 V, V SD = -40 V. This value was about 40-fold higher than that obtained with pure P3HT. By comparison, the response at V G = V SD = −40 V increased by 15-fold when compared to pure P3HT (Figure 8G). Note that this example was the first time showing PVK employed as OFET semiconductor layer to enhance the sensing performances. Poly [N, N'-bis (4-butylphenyl) -N, N'-bis (phenyl) benzidine] was also introduced to mixing with P3HT as active layer to detect NO 2 . 76 Yu, Akinwande et al. used P3HT/PVK OFET to explore the influence of the atmosphere on device properties and NO 2 sensing performances. The high sensitivity of 12381% was obtained under dry air saturated with 15 ppm NO 2 . 77 These data related to the gas sensing mechanism of OFET may help in realizing high sensing performance OFETs. Katz et al. used the hybrid active layer zinc oxide-graphene oxide (ZnO@GO) nanoparticles and P3HT to investigate the NO 2 sensing performance. 78 The sensors exhibited 210% sensing response to 5 ppm NO 2 .

H 2 S gas sensors
Hydrogen sulfide (H 2 S) is a highly toxic and flammable pollutant gas with a threshold limit of 10 ppm. 79 Compared to NH 3 and NO 2 , only a handful of reports dealing with H 2 S sensing based on OFETs have been reported. 80 In this review, Chi et al. fabricated sensitive H 2 S FET sensor using spirobifluorene as an active layer. The sensor achieved LOD as low as 1 ppb for the optimized film thickness. 81 Although P3HT and its composites have widely been used in OFET-based gas sensors, P3HT lacks dangling bonds to detect gas molecules. To solve this issue, Rao, Surya et al. combined SnO 2 and ZnO nanoparticles with P3HT to yield gas sensors. The resulting low-cost SnO 2 -based sensor exhibited a better response toward H 2 S at room temperature than ZnO-based sensor. 82 Furthermore, a low power (low operating voltages and currents) and fast approach H 2 S sensor was reported by Ponomarenko et al. 83 The method was on the basis of a metal-containing porphyrin receptor layer used to modify an LS monolayer active layer. The obtained sensor demonstrated high sensitivity toward H 2 S reaching 70-180 ppb under air with relative humidity up to 60%, coupled with good reproducibility. Tang et al. fabricated a flexible Ph5T2 single-crystal OFET H 2 S sensor and investigated the response of different deformation states. 84 The results showed an increase in sensor response toward 1 ppm H 2 S in a tensile state by 400% when compared to a compressive state. Such performances surpassed those of reported flexible H 2 S sensors, attributed to changes in the intermolecular distance of single crystals under deformation conditions. In sum, such a strategy would benefit the development of flexible and portable gas sensors for health diagnosis and environment monitoring.

Other sensors in gas phase
Aromatic VOCs are widely used as solvents and fuels but their vapors are hazardous and may cause various diseases. Therefore, the detection of VOCs is of great importance for human health. To this end, Sonar et al. used high mobility diketopyrrolopyrrole (DPP) copolymers as active layers in OFETs devices to detect VOCs in air ( Figure 9A,B). 85 The discrimination of VOCs with similar structures was realized by combining a pattern recognition algorithm with sensor data. Another sensor based on cyclopentadithiophene-benzothiadiazole (CDT-BTZ) copolymer also distinguished the structural isomer of VOCs (p-xylene, m-xylene, o-xylene, Hexanal, 2-Hexanone, Heptanal, 3-Heptanone) ( Figure 9C-E). 86 A single sensing parameter from transfer curve of OFET could identify the VOCs over a range of concentrations. Katz et al. reported an OFET-based nerve agent simulant dimethyl methylphosphonate (DMMP) sensor by using bi-layer structure. 87 NDI derivative was used as semiconducting layer closed to dielectric layer, and phenolic hydroxy group containing NDI derivative was used as detection layer to form a hydrogen bond with DMMP. The resulting sensor can selectively detect DMMP as low as tens of ppm level. After that, the same group reported more sensitive OFET-based DMMP sensor with the detect limit down to 5 ppm. 88 This is due to the ultra-thin bi-layer structure, which consisted of 4 nm semiconducting layer (6PTTP6, see Figure 3D) and 4 nm detection layer (6PTTP6 and hydroxy containing HO6OPT (6,6′-(([2,2′-bithiophene]-5,5′-diylbis(4,1phenylene))bis(oxy))bis(hexan-1-ol))). Recently, Huang et al. reported an ultra-high sensitive and fast responsive dimethyl carbonate (DMC) sensor with detection limit of 50 ppb. 89 Ionically conductive MOFs (IC-MOFs) thin film was used as the semiconducting layer, which guaranteed the direct interaction between metal ions (in IC-MOFs) with analytes. It should be noted that DMC is one of the main lithium-ion battery (LIB) electrolytes. Therefore, the sensor can also be used to detect LIB electrolyte leakage down to 20 nl.
As mentioned in Section 3.1, nanoporous structures may enhance the OFET sensor performance. In this review, Tisserant et al. reported a methylparaben vapor sensor consisting of calixarene dielectric and nanoporous films of TIPS-Pn (6,13-bis (triisopropylsilylethynyl) pentacene). 90 In this platform, the nanoporous films were fabricated by interfacial self-assembling on a water-air interface. The sensitivity of the sensor toward methylparaben was below  91 The strategy consisted of alternating polymer PDPP-TVT (thiophene flanked diketopyrrolopyrrole and thienylene-vinylenethienylene) and MOF (porous Cd(NDC)0.5(PCA)]⋅Gx (2,6-napthalene dicarboxylic acid for NDC; 4-pyridine caboxylic acid for PCA, guest molecules for G)). The percentage change in the saturated drain current (%ΔI Dsat ) was used to reflect the viable analytes. The resulting sensor exhibited %ΔI Dsat values of 81%, 24%, 50%, −7%, and 2% for TNT, NM, RDX, NB, and DNB, respectively. This demonstrated the great potential of such a sensor for explosive detection. Katz et al. fabricated an OFET-based ethylene gas sensor with a sensitivity reaching up 25 ppm. 92 N-(tert-Butoxycarbonyloxy)-phthalimide was used to increase the F I G U R E 1 0 Schematic illustration of (A) electrolyte-gated organic field-effect transistor (EG-OFET) and (B) extended-gated OFET configurations porosity of P3HT in the semiconducting layer, while palladium particles were employed as receptors for ethylene and P3HT film. Jiang, Ai, Zhang, and coworkers reported a highly selective monolayer molecular crystals (MMCs) flexible OFET sensor toward the detection of dimethoate, a typical organophosphorus pesticides. 93 As shown in Figure 9F, the active layer was NDI3HU-DTYM2. An ultrahigh LOD of 0.6 ppm dimethoate was obtained, thanks to the ultra-thin thickness of MMC combined with a highly crystalline nature ( Figure 9G,H). There are also reported OFET-based gas sensors for SO 2 , ethanol, and methanol etc. 38,72,94,95 The mechanisms are similar to those discussed above.

LIQUID SENSORS BASED ON OFETS
OFET-based liquid sensors have been used for the detection of various biomaterials, health-related molecules, and chiral molecules. [96][97][98][99][100] To this end, different device configurations have been developed, including normal OFET (BG/BC, BG/TC), EG-OFET, and extended-gated OFET. 9,101 In 2011, Khan, Kim, and their coworkers have reported highly sensitive bovine serum albumin (BSA) antibody (Ab) sensor by using normal OFET (BG/BC). 102 However, multiple layers, including semiconducting layer, surface passivation layer, functional layer (covalently attached to BSA), and BSA layer, were used, which needs complex OFET fabrication. In addition, OSCs are normally sensitive to aqueous solutions. It remains challenging to maintain their electrical performances in liquid phase by using normal OFET structure. Here, two structures were mainly discussed: EG-OFET and extended-gate type OFET employed for the detection of biomaterials and healthrelated molecules (Figure 10).

EG-OFET-based liquid sensors
The EG-OFETs are novel platforms used for the detection of large molecular weight biomaterials. In this process, stable and reliable label-free sensing of certain analytes was achieved by proper functionalization of OSCs layers or receptor layers. 101,103-105 Magliulo et al. combined the anti-C-reaction protein (anti-CRP) onto a P3HT semiconductor surface by physical adsorption and realized ultrasensitive label-free detection of CRP in clinically relevant matrix serum with an LOD of 2 pM (220 ng/L) ( Figure 11). 106 Good inter-device reproducibility was also confirmed by measuring three immunosensors from different chips with values ranging between 1% and 14%. Another procalcitonin EG-OFET was fabricated using the same approach to yield sensors with detection limit as low as 2.2 pM, relevant for clinical testing. 107 To obtain label-free and single-molecule detection, they further designed a SiMoT (single molecule with a large transistor) platform based on EG-OFET with multiple sclerosis (miR-182) functionalized gate for a single oligonucleotide (miR-182-5p) detection ( Figure 12). 108 As expected, SiMoT can be used as a label-free platform to detect both genomic and protein markers at the physical limit. Bortolotti et al. designed a novel lab-on chip device by combining a four-gate EG-OFET with 6.5 μl microfluidics for an inflammatory biomarker tumor necrosis factor α (TNFα) detection (as low as 3 pM). 109 Figure 13 illustrates the gate electrode functionalization strategy. The functionalization of the gate electrodes with anti-TNFα peptide aptamer or 11-mercaptoundecyl-triethylene glycol selfassembled monolayer (OEG SAM) resulted in the construction of a sensor able of measuring in triplicate and simultaneously identifying nonspecific response due to the internal reference electrode ( Figure 13F). Mas-Torrent,  (Figure 14). 111 The resulting sensor could standalone operation by a selfpowered smart sensing platform. The sensor was powered by paper-based biofuel cell able of extracting the energy from the analyzed sample itself. This is beneficial for the affordable, sensitive, specific, user-friendly, rapid and robust, equipment free, and deliverable sensor design.
Nickel et al. detected urea by an EG-OFET through enzymatic hydrolysis of urea to yield NH 3 in solution. 113 To this end, a semipermeable parylene membrane (100 nm) was used as top-gate dielectric and functionalized with enzyme urease. The as-obtained sensor was able of detecting physiologically relevant urea concentrations ranging from 0.75 mM to 7.5 mM. Furthermore, fast detection of NH 3 (1 s) was also realized in Volmer-Weber growth mode of DNTT film. 114 Piro et al. reported an innovative strategy for the small molecules detection, such as heterogeneous bisphenol A (BPA). 112 This approach was based on the competitive chemical reaction between BPA and target mime anchored on the sensing surface. As shown in Figure 15, the Ab, hapten anchoring Ab, and alkyl-BPA hapten consisted of the target mime. With the addition of BPA, a competitive exchange occurred between BPA and alkyl-BPA hapten, which upset the equilibrium and detached the Ab from the surface, resulting in the change of electric signal. Other small molecules, such as Dopamine 115 and 2,4dichlorophenoxyacetic acid, 116 were also detected with an LOD of 10 −16 M and 2.5 fM, respectively.

Extended-gated OFET-based liquid sensors
The extended-gated type configuration may provide a dry environment for sensors by moving sensing area away from OSCs layer. Using this configuration, various detection performances toward analytes can be achieved. For instance, Minami et al. achieved a label-free detection of phosphoprotein (α-casein) by functionalizing the extended-gate electrode with an artificial phosphoprotein receptor (Zn II -DPA) (Figure 16). 117 The recognition of α-casein by Zn II -DPA was confirmed by the selectivity toward the analyte, which changed in the presence of α-casein. This was the first example reporting Ab-free sensing of phosphoprotein in water using OFETs with LOD of 0.22 ppm. Another artificial histidine-rich protein receptor (Ni II -nitrilotriacetic acid complex)-functionalized extended-gate OFET demonstrated an LOD of BSA as low as 6.0 × 10 -13 M. 118 Glial fibrillary acidic protein (GFAP) is related to the human brain injury. Katz et al. reported an anti-GFAP modified extended-gated OFET sensor without the use of a reference electrode with a separated  Figure 17). 119 In this process, polyethylene glycols with different molecular weights were mixed to form the bioreceptor layer and help extend the Debye screening length. Note that 100 ng/ml GFAP was successfully determined at different gate potentials.
Lactate (LA) is a biomarker used to assess human physical performances. Hence, wearable LA sensors can be used to monitor the human health status. Minami et al. constructed an LA sensor on the basis of OFET using an extended-gate modified with enzymes and DNTT as semiconducting layer (Figure 18). 120 Osmium-redox polymer was used for the dectection of LA. The resulting sensor realized continuous measurements of LA at the level of 0-10 mM. The same group also reported a non-enzymatic LA sensor with an artificial receptor phenylboronic acid derivative modified extended-gated OFET, which showed LOD of 6.3 μM. 121 The LA detection mechanism relied on the changes in the transfer curves of OFET upon dynamic covalent bonding with LA. Other extended-gated OFET sensors, such as mercury (II) ion (Hg 2+ ), glutathione, and nitrate in liquid phase, were also realized. 99,122.123

Other sensors in liquid phase
Rutin  124 At rutin content of 10 wt%, the resulting sensor showed the best performance with LOD reaching 500 pM. The same group also fabricated a BG/BC OFET-based ROS sensor by introducing nano-clay into binary mixtures of P3HT and rutin at various weight ratios. 125 The resulting sensor was able of sensing 1 nM ROS. The superior performances of these sensing platforms were attributed to the improved crystallinity of P3HT hybrid films. This led to more rutin molecules to protrude on the channel layers to react with superoxide.
Other studies combined β-cyclodextrin (β-CD) derivatives into OFET to enhance the performance of chiral discrimination. [126][127][128][129] Xiao, Wang, and coworkers reported a sensing unit consisting of a β-CD and copper hexadecafluorophthalocyanine (F 16 CuPc) films ( Figure 19). 126 The resulting sensor showed a real-time and fast detection of enantiomer pairs in 10 −9 M aqueous solution. The detection mechanism was linked to the presence of different enantiomer geometries that led to weakened or enhanced surface polarizations. They further fabricated a top-gate OFET with top-gate electrode functionalized with SH-β-CD (thiolated β-cyclodextrin). 127 The resulting sensor exhibited the lowest LOD of 10 -12 M toward various enantiomers, such as pheylalanine, mandelic acid, and phenyllatic acid.
Cioffi et al. combined ZnO nanoparticles with streptavidin as a bio-interlayer between gate dielectric and P3HT semiconducting layer. 130 The bio-interlayer OFETs exhibited a good stability, which could realize the detection of biotin in pM (10 −12 mol L −1 ) range even after being stored for 1 year. Napoli et al. coupled organic charge-modulated field-effect transistors (OCMFETs) and hairpin-shaped probes for presenting the electronic transduction of DNA hybridization. 131 The OCMFETs can separate the OSCs from the sensing area. The as-obtained devices exhibited 100 pM of target concentration. It is the first time for applying hairpin-shaped probes to electronic transduction. There is another device structure for liquid analytes detection, called liquid-solid dual-gate organic transistors (DG-OFETs) structure. 132 Through separating an additional gate from the channel, the V T of the sensing channel can be modified.

CONCLUSION
Recent progress in OFET-based chemical and biological sensors was summarized, and various sensing strategies were discussed. Gas sensors of NH 3 , NO 2 , H 2 S, ethylene, and other molecules were reviewed along with liquid sensors used for genomic biomarkers, antibodies, artificial phosphoprotein receptor. The optimization OFET devices and related materials, and sensing mechanisms are introduced and discussed. The results suggested that OFET-based sensors made great progress over the last few years. Ultrathin films down to monolayer and thin films with nanopores have been demonstrated as effective ways to improve the sensitivity at ppb level in terms of physics. And electrolyte-gated and extended-gated OFETs are more promising OFET configurations used in liquid phase. From the chemistry aspect, introducing chemical  126 Copyright 2018, American Chemical Society reaction sites or molecular recognition units allow the detection in a more selective manner. However, the key parameters of OFET-based sensor, such as device stability, response reproducibility, and speed, still fall behind the inorganic ones. The applications of OFET-based sensors remain challenging. The reason for this had to do first with the difficult molecular design of OSCs with high semiconducting performance and high selectivity. There is a trade-off between functional groups for analyte capture or recognition and charge transport. A good balance should be found. Meanwhile, device optimization in terms of the morphology of the semiconducting layer, nature of the electrode, dielectric layer, and device configuration should be considered synergistically. Finally, fundamental understanding of sensing mechanisms based on physical or chemical processes should be further investigated. It should be noted the construction of related modules and systems by integrating OFET sensors is essential. After all, the arrays and integrated systems based on these optimized OFET devices are really used in practical applications in health and environment monitoring aspect. In sum, we hope that the discussed results could inspire further molecular design, device optimization, and working mechanism for practical applications.

A C K N O W L E D G M E N T S
This work was supported by NSF of China (22175081, 61890943), National Key R&D Program of China (2018YFA0703200), and Beijing National Laboratory for Molecular Sciences (BNLM202010).

C O N F L I C T O F I N T E R E S T
The authors declare no conflict of interest.