Organic Transistor-Based Chemical Sensors for WearableBioelectronicsPublished as part of the Accounts of Chemical Research special issue “Wearable Bioelectronics: Chemistry,Materials, Devices, and Systems”.

Moo Yeol Lee,†,‡,§ Hae Rang Lee,†,‡,§ Cheol Hee Park,†,‡ Seul Gi Han,†,‡ and Joon Hak Oh*,‡

†Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu,Pohang, Gyeongsangbuk-do 37673, South Korea‡School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro,Gwanak-gu, Seoul 08826, South Korea

CONSPECTUS: Bioelectronics for healthcare that monitor the health information on users in real time have stepped into thelimelight as crucial electronic devices for the future due to the increased demand for “point-of-care” testing, which is defined asmedical diagnostic testing at the time and place of patient care. In contrast to traditional diagnostic testing, which is generallyconducted at medical institutions with diagnostic instruments and requires a long time for specimen analysis, point-of-caretesting can be accomplished personally at the bedside, and health information on users can be monitored in real time. Advancesin materials science and device technology have enabled next-generation electronics, including flexible, stretchable, andbiocompatible electronic devices, bringing the commercialization of personalized healthcare devices increasingly within reach,e.g., wearable bioelectronics attached to the body that monitor the health information on users in real time. Additionally, themonitoring of harmful factors in the environment surrounding the user, such as air pollutants, chemicals, and ultraviolet light, isalso important for health maintenance because such factors can have short- and long-term detrimental effects on the humanbody. The precise detection of chemical species from both the human body and the surrounding environment is crucial forpersonal health care because of the abundant information that such factors can provide when determining a person’s healthcondition. In this respect, sensor applications based on an organic-transistor platform have various advantages, including signalamplification, molecular design capability, low cost, and mechanical robustness (e.g., flexibility and stretchability).This Account covers recent progress in organic transistor-based chemical sensors that detect various chemical species in thehuman body or the surrounding environment, which will be the core elements of wearable electronic devices. There has beenconsiderable effort to develop high-performance chemical sensors based on organic-transistor platforms through material designand device engineering. Various experimental approaches have been adopted to develop chemical sensors with high sensitivity,selectivity, and stability, including the synthesis of new materials, structural engineering, surface functionalization, and deviceengineering. In this Account, we first provide a brief introduction to the operating principles of transistor-based chemicalsensors. Then we summarize the progress in the fabrication of transistor-based chemical sensors that detect chemical speciesfrom the human body (e.g., molecules in sweat, saliva, urine, tears, etc.). We then highlight examples of chemical sensors fordetecting harmful chemicals in the environment surrounding the user (e.g., nitrogen oxides, sulfur dioxide, volatile organiccompounds, liquid-phase organic solvents, and heavy metal ions). Finally, we conclude this Account with a perspective on thewearable bioelectronics, especially focusing on organic electronic materials and devices.

1. INTRODUCTIONContinuous and selective detection of chemicals in body fluidsor gaseous pollutants, without invasive and expensive analytical

Received: September 14, 2018Published: November 7, 2018

Article

pubs.acs.org/accountsCite This: Acc. Chem. Res. 2018, 51, 2829−2838

© 2018 American Chemical Society 2829 DOI: 10.1021/acs.accounts.8b00465Acc. Chem. Res. 2018, 51, 2829−2838

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Inorganic, silicon-based electronic devices have been extensivelydeveloped for applications in the bioelectronics. However,because electrons are mostly used as charge carriers in electronicdevices, they often exhibit limitations when applied to biologicalsystems, which mostly rely on ionic transport instead of elec-trons.2 In recent decades, to combine biology with conventionalelectronics and convert biological signals to electronic signals andvice versa, conducting and semiconducting organic materials haveemerged as excellent tools enabling both electronic and ionicconduction. Also, they can be easily synthesized to include specificreceptors or anchoring sites for highly sensitive and selectivechemical detection. Thanks to these advantages, organic bioelec-tronics has become a general platform for biological recordingand applications in life sciences and healthcare system.3

In 1984, the first use of organic materials as an active com-ponent of transistors was reported by White et al., who inves-tigated the conductivity changes in polypyrrole by electro-chemical doping.4 After that, Koezuka et al. developed the firstsolid-state organic field-effect transistor (OFET) by using poly-thiophene as an active material.5 Since then, organic transistorshave emerged as a feasible solution for high-performance chemi-cal sensors by converting chemical information into electricalsignal. Organic transistors can operate at low voltages, satisfyingoperation in aqueous environments and applications ininexpensive chemical or biological sensors.6,7 Transistor-basedsensors have the combined device structure of a sensor and anamplifier, in which imperceptible electrical changes induced byspecific analytes can lead to a pronounced change in channelcurrent, resulting in high sensitivity compared with other typesof sensors. Also, transistor-based sensors show various advan-tages, including fast response, feasibility for miniaturization, easyprocessing, and high throughput.8 In particular, organic transistor-based sensors are considered a key platform for flexible andwearable sensors for “point-of-care” health monitoring by mini-mizing the discomfort of wearing.1,9−11

In this Account, we review the status of the development oforganic transistor-based detection of not only chemicalsexcreted from the body in the form of biofluids and exhaledbreath, but also those detrimental to health. Reflecting theincreasing demand for wearable bioelectronic chemical sensorsthat directly interface with living and moving human bodies, we

specifically discuss the application of organic transistor-basedchemical sensors to wearable electronics (Figure 1).

2. OPERATION PRINCIPLES OF TRANSISTOR-BASEDCHEMICAL SENSORS

Organic transistors have been spotlighted as a tool of choice forwearable bioelectronics applications involving chemical sensors,particularly due to their biocompatibility and easy integrationinto portable and wearable electronic devices. The main advant-age of organic transistor-based sensors is higher sensitivity thantwo-terminal-based sensors, due to the signal amplification andcontrol ability by modulating the gate voltage.12 In this section,the working principles of chemical sensors based on two types oforganic transistors, conventionalOFETs in thin-film structure andorganic electrochemical transistors (OECTs), are introduced.A typical OFET is composed of three electrodes, a gate

dielectric layer, and an organic semiconductor film. The channelcurrent flows between the source and drain electrodes, wherecharge carrier transport occurs near the interface between thesemiconductor and dielectric layers. This can be controlled bymodulating the voltage applied to the gate electrode (VG),resulting in field-effect behaviors. The channel current (IDS) ofOFETs can be derived by the following equations:13

IWL

C V V V V V V( ) ,DS lin i G T DS DS G Tμ= − < −

IW

LC V V V V V

2( ) ,DS sat i G T

2DS G Tμ= − > −

where W and L are the width and length of a channel,respectively, μ is the field-effect mobility, Ci is the capacitance ofthe gate insulator, VT is the threshold voltage of the device, andVDS is the applied voltage between drain and source electrodes.When OFETs are used as chemical sensors, analyte diffusionthrough semiconductor grain boundaries can change μ, and thedoping effect can change VT, affecting IDS. In most OFET-basedsensors, the semiconducting layers are exposed to the targetanalytes. In this case, the organic semiconductor layer acts asboth the electronic transport material and the chemical sensinglayer (Figure 2a).In the case of OECTs, an electrolyte medium is used instead

of a dielectric layer, and the gate electrode is connected to the

Figure 1.Wearable bioelectronics applications of organic transistor-based sensors for noninvasive detection of chemicals excreted from the body andexogenous chemicals detrimental to health.

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active layer via an electrolyte, in which ionic species penetratethe active layer and modulate IDS via changes in the doping state(Figure 2b).14,15 The changes in electrical current of an OECTcan be derived by the following equations:8

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eff is the effective gate voltage, and Voffset isthe offset voltage related to the potential drop of the OECT.Most OECT-based chemical sensors operate via changes inpotential drop across the gate/electrolyte or electrolyte/channelinterfaces, with exposure to the analytes. Both OFETs andOECTs utilize a method of introducing functional receptors intothe device structure for selective and sensitive chemical detec-tion.16 Three approachesactive/receptor bilayer structure,assembly of active layer-receptor, and active/receptor compo-siteare commonly used for receptor implantation (Figure 2c).

3. RECENT PROGRESS IN TRANSISTOR-TYPEORGANIC CHEMICAL SENSORS FOR HEALTHSELF-MONITORING

3.1. Sensors Detecting Chemicals from the Human Body

The history of biosensors for detecting chemicals from thehuman body began in 1962 with Clark et al., who successfullymonitored glucose concentrations in blood by employingglucose oxidase (GOx).17 Since then, a variety of chemical sens-ors that monitor specific chemicals secreted from the humanbody have been developed for biological and medical diagnosticapplications.10 Here, we focus on wearable healthcare systemssatisfying the demand for easy, rapid, inexpensive, and portablechemical detection (Figure 3). Subsection 3.1.1 focuses onwearable organic transistor-based sensors for detecting chem-icals in bodily excreted products, and in subsection 3.1.2 otherkinds of wearable sensors are described.

3.1.1. Chemicals in Sweat, Saliva, Urine, and Tears.Sweat, a representative noninvasive biofluid, is a useful analytebecause it can be detected in real time without human intentionthrough sensors worn on the body. Because blood glucose isdiffused at a certain rate into sweat, the sweat glucose sensor is apromising noninvasive diagnostic platform for diabetes.You and Pak demonstrated a graphene FET enzymatic wear-

able sensor that can detect glucose.18 Using silk fibroin film asboth an enzyme immobilization matrix and substrate, the sensorcould be attached to human skin, such as the wrist (Figure 4a). TheGOx-immobilized sensor was selectively responsive to glucose insweat at a range of 0.1−10 mM due to the enzymatic reaction.Minami et al. reported an enzyme-based OFET sensor with

an extended gate electrode on a flexible polyethylene

Figure 2. Schematic illustration of typical (a) organic field-effect transistors, (b) organic electrochemical transistors, and (c) the receptor implantationapproaches for chemical sensor applications.

Figure 3. Wearable organic transistor-based sensors that detectchemicals in body secretions, breathing, or body fluids.

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naphthalate (PEN) substrate for detecting lactate,19 which is auseful biomarker of anaerobic metabolism in circulatory failure.To directly expose the sensor to sweat, the extended gate,on which lactate oxidase (LOx) was immobilized, was usedas a sensing unit (Figure 4b). The drain current changedupon stepwise changes in lactate concentration, due to theenzymatic redox chain reaction on the extended gateelectrode. The detection limit was estimated to be as low as66 nM.Promisingly, highly sensitive biological sensors can be used to

sense various chemicals in saliva for noninvasive healthcare.20

Liao et al. developed OECT-based uric acid (UA) sensorsby modifying platinum (Pt) gate electrodes with positivelycharged polyaniline (PANI) and negatively charged Nafion−graphene flake bilayer films with the enzyme uricase (UOx)(Figure 4c).21 The fabricated sensors demonstrated outstandingselectivity and a detection limit of ∼10 nM UA in saliva byblocking the interfering materials using a charged bilayerfilm. Also, long-term stable performance was observed during1000 times of bending.Selective sensing of salivary glucose was reported with

an OECT-based sensor.22 Ji et al. modified a gate electrode

with GOx and poly(n-vinyl-2-pyrrolidone)-capped Pt nano-particles (NPs) and used a microfluidic channel. High sensitivitydown to 10−7 M as well as enhanced glucose selectivity wasachieved by depositing a negatively charged Nafion layer onthe gate electrode, which suppressed the diffusion of othercompounds with electrostatic interactions. A prototype portablesensor for real-time glucose sensing was demonstrated(Figure 4d).Conventional analytical methods for detecting drugs require

long operation time, expensive equipment, and complex experi-mental procedures. Jang et al. successfully demonstrated an easy,fast, and inexpensive detection method for amphetamine-typestimulant (ATS) via the synergistic effects of selective supra-molecular chemistry andOFETplatform.9Cucurbit[7]uril (CB[7])derivatives with the cavity and carbonyl-laced portals that caninteract with ammonium groups on ATS by ion−dipole intera-ctions were deposited on a 5,5′-bis(7-dodecyl-9H-fluoren-2-yl)-2,2′-bithiophene (DDFTTF) layer (Figure 5a). The ampero-metric OFET sensors showed a detection limit for ATS as low as1 pM in DI water and 1 nM in real urine. Furthermore, a wear-able wristband-type drug sensor was demonstrated for stable andrepeatable real-time detection of ATS in urine.

Figure 4. (a) Photograph and schematic illustration of silk/GOx functionalized graphene FET sensors. (b) Schematic illustration of an extended-gatetype OFET biosensor for detecting lactate. (c) Schematic diagram of an OECT with a UOx-GO/PANI/Nafion-graphene/Pt gate (left) andphotographs of OECTs attached on different surfaces (right). (d) Schematic illustration of a functionalized gate electrode for glucose detection (top),glucose sensor based on OECT integrated with a microfluidic channel, and photograph of a portable glucose sensor (bottom). Reproduced withpermission from (a) ref 18, Copyright 2014 Elsevier B.V.; (b) ref 19, Copyright 2015 Elsevier B.V.; (c) from ref 21, Copyright 2015 Wiley-VCH;(d) ref 22, Copyright 2016 Wiley-VCH.

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Yang et al. developed OECT-based biosensors in which Cr/Auand poly(3,4-ethylene dioxythiophene):poly(styrenesulfon-ate) (PEDOT:PSS) layers were deposited on nylon fibers(Figure 5b).23 The fabricated Cr/Au/PEDOT:PSS-coated fiberswere functionalized and woven together, resulting in flexible andstretchable fabric biosensors. Upon exposure to biological inter-faces, such as phosphate-buffered saline (PBS) solution and artifi-cial urine, the woven OECT sensors showed superior selectivityand low detection limits for glucose (30 nM), dopamine (10 nM),and UA (30 nM).Kim et al. reported a graphene FET-based wearable soft

contact lens for wireless detection of glucose in tears, with highsensitivity.24 The graphene−AgNWs hybrid served as both theantenna coil and source/drain electrodes of an graphene-basedFET. To provide reliable and comfortable vision, all the com-ponents were sufficiently transparent and a real soft contact lenswas used as the template (Figure 5c). GOx was immobilized onthe graphene channel, allowing selective binding with glucose.Integrated into a resistance, inductance, and capacitance (RLC)circuit, the sensor exhibited real-time in vivo glucose detectionwhen attached directly to a living rabbit eye.3.1.2. Chemicals in Breath and Other Internal Body

Fluids. Analysis of breath chemicals is a state-of-the-art methodin healthcare and disease diagnostics. Various methods have beenintroduced to detect chemicals in the breath.25,26 For example,ammonia in the breath can be used as a biomarker of renalfailure. Zhang et al. developed a nanoporous-structured OFET-based ammonia sensor.27 Nanopores were introduced intopoly(diketopyrrolopyrrole-thiophene-thieno[3,2,b]thiophene-thiophene) (DPP2T-TT) thin film, providing direct access tothereactive sites (Figure 5d). The sensor showed a detection limitof ammonia below 1 ppb and a reduced response time at the

hundred-millisecond time scale. Moreover, the sensor fabricatedon a flexible substrate showed real-time breath-sensing perform-ance in the range from 10 ppb to 10 ppm.Lactate, typically produced by increased metabolic activity,

has been suggested as a biomarker for cancer. Braendlein et al.reported an in vitro OECT circuit for sensitive and accuratemetabolite detection in highly complex cell culture media.28 Theyadopted the Wheatstone bridge sensor platform for inherentbackground subtraction. Chitosan−ferrocene complex was utilizedwith nonspecific protein on the reference OECT and LOx wasattached to the sensing OECT (Figure 5e). They estimatedthe detection limit of lactate to be∼10 μM. In addition, chrono-potentiometric recording was conducted with exposure to com-plex cell media of malignant samples. This was the first demon-stration of a miniaturized sensor circuit for cancer diagnosis.Thus, far, even though many biosensors have used enzyme

immobilization methods, these approaches have been found tobe expensive, and have slow responses and complicatedfabrication processes. Solving these problems, Jang et al.demonstrated OFET-based biosensors that can detect theacetylcholine (ACh+) by using biological recognition elements,a cucurbit[6]uril (CB[6]) derivative.29 They focused oncombining the high sensitivity of the transistor configurationand the high selectivity of synthetic receptors. The CB[6]-derivative film was deposited on the surface of a water-stablesemiconductor (DDFTTF) layer. The fabricated biosensorshowed a low ACh+ detection limit of ∼1 pM with excellentdiscrimination over choline (Ch+) in real-time. Furthermore,flexible sensor was fabricated using indium tin oxide (ITO)-coated PEN substrates (Figure 5f), which could detect ACh+

with an identical detection limit (∼1 pM) in PBS solution underlow-voltage operation.

Figure 5. (a) Chemical structure of drug-specific host molecule and schematic illustration of a flexible OFET-based sensor (left). Photograph of thebracelet-type wearable ATS sensor (right). (b) Core−shell conductive nylon fiber and its photograph with different bending statues (left). Schematicillustration of a fabricOECT sensor (right). (c) Schematic diagram of the wearable contact lens glucose sensor. (d) Schematic diagram and photographof a nanoporous flexible gas sensor. (e) Schematic depiction of the biofunctionalization and lactate sensing platform. (f) Schematic illustration offlexible DDFTTFOFET-based sensors with a synthetic receptor and their real-time responses. Reproduced with permission from (a) ref 9, Copyright2017 Elsevier B.V.; (b) ref 23, Copyright 2018 Wiley-VCH; (c) from ref 24, Copyright 2017 Nature Publishing Group; (d) ref 27, Copyright 2017Wiley-VCH; (e) ref 28, Copyright 2017 Wiley-VCH; (f) ref 29, Copyright 2015 Wiley-VCH.

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3.2. Sensors Detecting Chemicals Detrimental to theHuman Body

In the applications of chemical sensors in bioelectronics, thedetection of chemical compounds that significantly affect thehuman body is a crucial application area for wearable electronics.With rapid industrialization, humans have been ubiquitouslyexposed to various harmful pollutants.30 These pollutants seri-ously affect the health of human respiratory, cardiovascular,nervous, and other systems. Therefore, the demand for real-timemonitoring devices that detect pollutants in the atmosphere andthe water has risen. In this section, we introduce the recent pro-gress in organic transistor-based chemical sensors that detectchemicals detrimental to human health, including volatile organiccompounds (VOCs); gaseous pollutants such as nitrogen oxides(NOx) and sulfur dioxides (SO2); liquid-phase organic solvents;and heavy metal ions. Specifically, subsection 3.2.1. deals withchemical sensors for VOCs and subsection 3.2.2. focuses onsensors that detect gaseous pollutants. Then, recent progress inorganic transistor-based chemical sensors that detect liquid-phase organic solvents and heavy metal ions is described insubsections 3.2.3. and 3.2.4., respectively.3.2.1. Volatile Organic Compounds (VOCs). With the

increasing use of chemicals in various products, the generation ofharmful chemical vapors is receiving considerable attention as arising source of chemical pollutants. VOCs are classified asorganic compounds that have a boiling point between 50 and260 °C, including various chemicals such as benzene, ammonia,and acetone.31 Because these chemicals have been used in manycommercial products for various purposes, VOCs can begenerated from any products containing them, even frommost household products such as paints, detergents, andfurniture.32 Due to the growing threat posed by VOCs whichcan affect health (e.g., irritation, headaches, nausea, liver/kidneydamage, and central nervous system damage), research onOFET-based sensors for the detection of VOCs is graduallyincreasing.The development of a high-performance pentacene-based

OFET-type methanol sensor was reported by Kang et al.33

Sequential evaporation ofm-bis(triphenylsilyl) benzene (TSB3)as a rubbery small-molecule dielectric layer and pentacene as theactive material on n-octadecyltrimethoxysilane (OTS)-treatedSiO2 substrate produced a macroporous pentacene/TSB3layer. For chemical sensing applications, macroporouspentacene/TSB3-based OFET sensors showed high sensitivitytoward methanol vapor, with facilitated diffusion of analyte mole-cules into the channel region via the macropores (Figure 6a).Cheon et al. reported graphene oxide (GO)-functionalizedOFET-based sensors for the detection of VOC gas.34 DPP-selenophene-vinylene-selenophene (DPP-SVS) doped withfunctional GO was utilized as an active GO-OFET structurefor the detection of various analytes including ethanol, acetone,and acetonitrile. Due to its many polar functional groups andhigh surface-to-volume ratio, GO functioned as a gas-adsorbingdopant. Compared with OFET sensors based on pristine DPP-SVS, GO-functionalized OFET-based sensors exhibited highlyenhanced gas sensing properties by showing significant changesin on-current and threshold voltage.Nkeita-Yawson et al. reported the development of highly

sensitive and flexible ammonia sensors based on organic printedtransistors.35 Flexible OFET sensors based on an ultrathin filmof a poly(4-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b′]di-thiophen-2-yl)-7-(4,4-bis(2-ethylhexyl)-6-(thiophen-2-yl)-4H-silolo[3,2-b:4,5-b′]dithiophen-2-yl)-5,6-difluorobenzo[c]

[1,2,5]thiadiazole) (PDFDT) active layer were fabricated andutilized for ammonia vapor sensing. High sensitivity was demon-strated with hydrogen bonding and electrostatic interactionsbetween fluorine on PDFDT and ammonia. Fabricated sensorsshowed significant changes in electrical properties under thecondition of a small amount of ammonia gas exposure as low as1 ppm (Figure 6b). A study on the sensing mechanism indicatedthat hydrogen bonding and electrostatic interactions betweenthe fluorinated aromatic backbone of PDFDT and ammoniamolecules lowered the highest occupied molecular orbital(HOMO) level of PDFDT, which produced more hole trapsto hinder charge transport in the channel.Lee et al. demonstrated the development of an OFET-type

flexible chemical sensor array based on semiconducting poly-mers with high chemical robustness.36 DPP-selenophene copoly-mers with siloxane-terminated chains (PTDPPSe-SiC4)-basedOFETs showed high insolubility in chemical solvents and couldoperate after immersion in various solvents for 1 day. Based onits chemical robustness, semiconducting PTDPPSe-SiC4 wasapplied to a conventional photolithography process for the fabri-cation of a flexible OFETs patterned array. The fabricated OFETsarray operated well after undergoing the harsh photolithographyprocess and showed long-term stable acetone vapor sensingbehaviors (Figure 6c).

3.2.2. Gaseous Pollutants. Air pollution negativelyimpacting human health is primarily due to the combustion offossil fuels used for energy generation and transportation. Amongthe various gaseous products from fuel combustion, NOx and SO2are the main causes of human health problems such as respi-ratory problems, premature death, and preterm birth.37

For organic transistor-based NOx sensors, various approachesto enhance the sensitivity of the sensors have been proposed.Huang et al. increased the sensitivity of the NO2 sensors bymodifying the interface between the semiconducting layer anddielectric layer using UV-ozone (UVO) treatment.38 The UVO-treated sensors showed ∼400 and ∼50 times higher sensitivitytoward 30 and 1 ppm of NO2, respectively (Figure 6d). Zanget al. suggested OFET-based gas sensors for detecting gasanalytes, including NO2, based on chemical reactions betweengas analytes and semiconductors (Figure 6e).39 Interestingly, incomparison with the distinct signal change of a sensor toward10 ppm of NO2, no obvious signal responses were observedtoward 10 ppm of SO2 gas, likely due to the rather weakerelectron withdrawing ability of SO2 than of NO2, suggesting theselectivity of the sensors. For SO2 sensors, Liu and co-workersdemonstrated gas dielectric transistors based on single crys-talline metal phthalocyanines (i.e., CuPc nanowire and ZnPcnanobelt), which have been widely utilized as the sensing layer ingas sensors due to their high thermal and chemical stability.40,41

OFET-based SO2 sensors with gas dielectrics showed highersensitivity than those with a solid-state dielectric (i.e., PMMA).40

Gas dielectric SO2 sensors with CuPc nanowire exhibited asensitivity and detection limit of 119% and 0.5 ppm, respectively(Figure 6f). For ZnPc-based SO2 sensors, a detection limit of50 ppb and signal response of 910% with 10 ppm of SO2 gaswere observed.41

3.2.3. Liquid-Phase Organic Solvents. Although gaseouspollutants in the atmosphere mainly affect human health throughrespiration or skin contact, liquid-phase chemicals are also noxiousto the human body through ingestion or skin absorption. As publicconcerns about water contamination have increased, the demandfor portable or wearable sensors that detect liquid-phase organicsolvents has risen rapidly. There is a substantial limitation of

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OFET-based chemical sensors in that organic semiconductorshave poor resistance toward liquid-phase organic solvents,hindering further applications in detecting liquid-phase solvents.Thus, far, there have been various approaches to enhance thesolvent resistance of organic semiconductors, such as passivationand cross-linking of semiconductors.36,42,43

The chemical cross-linking of the semiconducting layers of thesensors could enhance solvent resistance toward liquid-phaseorganic solvents. Lee et al. reported solvent-resistant OFET-basedchemical sensors that detect liquid-phase organic solvents viadirect injection.42 They utilized specially functionalized polymersemiconductor, P3HT-azide, where azide helps an efficient photo-cross-linking to generate OFETs with high solvent resistance.Furthermore, the surface of the P3HT-azide layer was modifiedwith the container molecule, calix[8]arene (C[8]A), in order toenhance the sensing performance of the sensors (Figure 7a).The surface-functionalized P3HT-azide sensors showed distinctsensing responses toward various liquid-phase organic solvents(Figure 7b). To demonstrate the potential of the sensors as port-able and wearable sensors, a flexible sensor was fabricated using aflexible substrate (PEN) and a polymer dielectric (cross-linked

poly-4-vinylphenol [PVP]), showing an identical sensing trendtoward liquid-phase organic solvents (Figure 7c).

3.2.4. Heavy Metal Ions. Environmental concerns aboutheavy metal ions in water waste and the ocean have risen withincreasing industrialization. High levels of exposure to heavymetals generally increase serious health risks, such as cancer andnervous system damage.46 Knopfmacher et al. developed water-stable OFET-based chemical sensors to detect mercury ions(Hg2+) in the marine environment (Figure 7d).44 The surface ofthe semiconducting layer (PII2T-Si) was modified with theDNA-functionalized Au NPs to introduce selectivity of thesensors toward Hg2+, showing a distinct signal response underHg2+ exposure compared with other heavy metal ions (i.e., Zn2+

and Pb2+, Figure 7e). Flexible Hg2+ sensors were also demon-strated using polyimide and cross-linked PVP as the substrateand dielectric layer, respectively. Sudibya et al. demonstratedchemical sensors that detect various metal ions including Hg2+ andCd2+ based on micropatterned reduced GO (rGO).45 After pat-terning the GO on the substrate, the GO was reduced to rGO andutilized as the sensing layer of the sensors (Figure 7f). The detectionlimits of the sensors toward Hg2+ and Cd2+ were both 1 nM.

Figure 6. (a) Schematic illustration of pentacene/TSB3 OFET-based sensor and the real-time sensing result toward methanol vapor. (b) FlexiblePDFDT sensors and current responses of PDFDT sensors toward ammonia gas. (c) Photograph of flexible 10 × 10 sensor array and current changesupon acetone vapor exposure. (d) Device configuration of the CuPc-basedNO2 sensor, real-time sensitivity (S) of the sensors towardNO2 gas, and thesensitivity comparison of UVO-treated and pristine sensors. (e) Molecular structures of semiconductors used for the NO2 sensors, the real-timesensing of NO2 and SO2 (top), and the current change (ΔI/I0) toward the gas analytes (bottom). f) Device configuration of the gas dielectric transistorbased on CuPc nanowire, the real-time sensing results toward SO2 gas, and the sensitivity comparison of the sensors based on gas and solid-statedielectric (top). Device configuration and the real-time signal change towardNO2 and SO2 gas of ZnPc nanobelt-based sensors (bottom). Reproducedwith permission from (a) ref 33, Copyright 2014 Nature Publishing Group; (b) ref 35, Copyright 2017 American Chemical Society; (c) ref 36,Copyright 2017Wiley-VCH; (d) ref 38, Copyright 2017Wiley-VCH; (e) ref 39, Copyright 2014Wiley-VCH; (f) ref 40, Copyright 2013Wiley-VCH;ref 41, Copyright 2017 IEEE.

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4. CONCLUSIONS AND PERSPECTIVESIn this Account, we introduced the working principles andrecent progress in organic transistor-based chemical sensors,mainly focusing on the wearable organic sensors for detection ofthe chemicals from human body as well as harmful exogenouschemicals. Unlike most previously reported wearable sensorsdetecting physical movements, the new generation of wearablechemical sensors aims for real-time detection of health-relatedchemicals. The key features of wearable organic chemicalsensors include enhanced flexibility, stretchability, biocompat-ibility, low-cost production, and point-of-care monitoring. Withcontinuing development, organic bioelectronic devices are nowcomplementing inorganic counterparts.Although the electrical performance of organic electronics has

caught up to or even exceeded that of amorphous silicon devices,there are still issues to be improved for commercialization, suchas operational and environmental long-term stability.47 Variousdemonstrations of organic transistor-based chemical sensorshave been reported for human health monitoring devices, asstated above. However, many issues still remain to be resolvedfor practical applications. For example, selectivity toward certain

target analytes can easily be decreased in the real operatingenvironment, because various surrounding factors may interferewith the sensing results. The long-term stability of the chemicalsensors, inter alia, is a critical issue in organic sensors because thesensing layer is generally exposed to the external environment inorder to interact with target analytes. In recent years, however,there has been considerable progress in enhancing theenvironmental robustness of organic electronics. As huge effortshave been made to understand the degradation mechanisms oforganic electronic devices and improve their operational andenvironmental long-term stability, the potential applications oforganic electronic devices in wearable electronic devices haveincreased accordingly. A number of strategies have also beendeveloped to overcome such weaknesses by optimizing materialdesign, device geometry, circuit design, and analytical method.Along with the development of the Internet of things (IoT) andbig data technologies, wearable devices based on organicchemical sensors are envisioned to facilitate point-of-care healthmonitoring and enable saving lives and disease prevention withinterdevice communication. Combined with the physical sensortechnologies, wearable chemical sensors are expected to

Figure 7. (a) Scheme of flexible solvent resistant chemical sensors based on the cross-linked P3HT-azide copolymer. (b) Molecular structures ofP3HT-azide and C[8]A and the comparison of the signal response of the sensors with and without C[8]A. (c) Sensing responses of the cross-linkedP3HT-azide sensors toward various liquid-phase analytes and a photographic image of the flexible sensor. (d) Device configuration of the flexible Hg2+

sensors based on PII2T-Si, the molecular structure of PII2T-Si, and a photographic image of flexible sensors. (e) Real-time sensing responses of theHg2+ sensor for alternatively injected Hg2+ and pure seawater (left) and various heavymetal ions and nonfunctionalized sensors (right). (f) Fabricationprocess and device configuration of the micropatterned rGO-based sensors for detection of heavy metal ions and signal changes upon the exposure ofHg2+ and Cd2+. Reproduced with permission from (a−c) ref 42, Copyright 2015Wiley-VCH; (d, e) ref 44, Copyright 2014 Nature Publishing Group;(f) ref 45, Copyright 2011 American Chemical Society.

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construct useful diagnostic data for human health monitoringand future nano−bio information technologies.

■ AUTHOR INFORMATIONCorresponding Author

*E-mail: joonhoh@snu.ac.kr.ORCID

Joon Hak Oh: 0000-0003-0481-6069Author Contributions§M.Y.L. and H.R.L. contributed equally.Notes

The authors declare no competing financial interest.

Biographies

Moo Yeol Lee is currently a Ph.D. candidate in Department ofChemical Engineering at POSTECH.

Hae Rang Lee is currently a Ph.D. candidate in Department ofChemical Engineering at POSTECH.

Cheol Hee Park is currently a Ph.D. candidate in Department ofChemical Engineering at POSTECH.

Seul Gi Han is currently an M.S. candidate in Department of ChemicalEngineering at POSTECH.

Joon Hak Oh is an associate professor in School of Chemical andBiological Engineering at Seoul National University. He received hisPh.D. degree (2004) from Seoul National University. He worked onflexible displays as a senior engineer at Samsung Electronics (2004−2006). He then continued his postdoctoral research at StanfordUniversity (2006−2010). He was a faculty at Ulsan National Instituteof Science and Technology (2010−2014) and Pohang University ofScience and Technology (2014−2018). His research focuses onorganic electronics and flexible electronics.

■ ACKNOWLEDGMENTSThis work was supported by the National Research Founda-tion of Korea (NRF) grant (No. 2017R1E1A1A01074090),the Nano Material Technology Development Program(No. 2017M3A7B8063825), and the Center for AdvancedSoft Electronics under the Global Frontier Research Program(No. 2013M3A6A5073175) funded by the Ministry of Scienceand ICT (MSIT), Korea.

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