membranes Review Solid-Contact Ion-Selective Electrodes: Response Mechanisms, Transducer Materials and Wearable Sensors Yan Lyu 1, Shiyu Gan 1,*, Yu Bao 1, Lijie Zhong 1, Jianan Xu 2,3, Wei Wang 1, Zhenbang Liu 1, Yingming Ma 1, Guifu Yang 4 and Li Niu 1,5,* 1 School of Civil Engineering, c/o Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, China; [email protected] (Y.L.); [email protected] (Y.B.); [email protected] (L.Z.); [email protected] (W.W.); [email protected] (Z.L.); [email protected] (Y.M.) 2 State Key Laboratory of Electroanalytical Chemistry, c/o Engineering Laboratory for Modern Analytical Techniques, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; [email protected] 3 University of Chinese Academy of Sciences, Beijing 100039, China 4 School of Information Science and Technology, Northeast Normal University, Changchun 130117, China; [email protected] 5 MOE Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Guangzhou University, Guangzhou 510006, China * Correspondence: [email protected] (S.G.); [email protected] (L.N.) Received: 28 May 2020; Accepted: 16 June 2020; Published: 23 June 2020 Abstract: Wearable sensors based on solid-contact ion-selective electrodes (SC-ISEs) are currently attracting intensive attention in monitoring human health conditions through real-time and non-invasive analysis of ions in biological fluids. SC-ISEs have gone through a revolution with improvements in potential stability and reproducibility. The introduction of new transducing materials, the understanding of theoretical potentiometric responses, and wearable applications greatly facilitate SC-ISEs. We review recent advances in SC-ISEs including the response mechanism (redox capacitance and electric-double-layer capacitance mechanisms) and crucial solid transducer materials (conducting polymers, carbon and other nanomaterials) and applications in wearable sensors. At the end of the review we illustrate the existing challenges and prospects for future SC-ISEs. We expect this review to provide readers with a general picture of SC-ISEs and appeal to further establishing protocols for evaluating SC-ISEs and accelerating commercial wearable sensors for clinical diagnosis and family practice. Keywords: ion selective electrodes; wearable sensors; solid-contact materials; response mechanism 1. Introduction With the rapid growth of personal healthcare and fitness systems, wearable devices that can provide real-time and continuous monitoring of an individual’s physiological state have attracted great attention in recent years. Conventional applications in medical biomarker detection generally related to separated collection and analysis of blood samples is invasive and costly and needs complicated operations, while failing to provide users with real-time health diagnostics and monitoring. Wearable sensors hold great promise for continuously monitoring an individual’s physiological bio-chemical signals [1–5]. A variety of flexible sensors have recently been developed for non-invasively assessing personal physiological states by detecting analytes of interest (like those in sweat) [6–9]. Potentiometric Membranes 2020, 10, 128; doi:10.3390/membranes10060128 www.mdpi.com/journal/membranes Membranes 2020, 10, x FOR PEER REVIEW 2 of 23 Membranes 2020, 10, 128 2 of 24 A variety of flexible sensors have recently been developed for non-invasively assessing personal physiological states by detecting analytes of interest (like those in sweat) [6–9]. Potentiometric sensors,sensors, particularly particularly for the ionion sensing,sensing, areare oneone of of the the attractive attractive types types for for practical practical application application due due to totheir their high high portability, portability, good sensitivity,good sensitivity, lower energy lower consumption energy consumption and high e ffiandciency. high Potentiometry efficiency. Potentiometryincorporates a incorporates working electrode a working (WE) electrode and a reference (WE) and electrode a reference (RE) electrode and measures (RE) and their measures relative theirpotential relative under potential zero current. under Ion-selective zero current. electrodes Ion-selective (ISEs) are theelectrodes typical potentiometric(ISEs) are the sensor typical for potentiometricselective ion recognition. sensor for selective ion recognition. ClassicClassic liquid liquid-contact-contact ISEs ISEs (LC (LC-ISEs)-ISEs) contain contain an an ion ion-selective-selective membrane membrane (ISM, (ISM, e.g. e.g.,, pH pH glass glass membrane)membrane) andand anan internal internal solution solution (Figure (Figure1A) to1A) form to a form liquid–contact a liquid– interfacecontact [interface10]. The theoretical[10]. The theoreticalfundamental fundamental of ISEs is based of ISEs on is the based relationship on the relationship between ion between activity andion activity output voltageand output according voltage to accordingthe Nernst to equation. the Nernst The equation. electromotive The electromotive force (EMF) force is the (EMF) sum ofis the all thesum phase of all boundarythe phase boundary potentials. potentials.LC-ISEs have LC- beenISEs have commercialized been commercialized and quite popularand quite for popular various for ion various analysis ion in analysis the laboratory in the laboratoryand environmental and environmental analysis. However, analysis. the However, biggest challenge the biggest for the challenge LC-ISEs is for miniaturization the LC-ISEs and is miniaturizationintegration, which and could integration, not satisfy which the requirementscould not satisfy in biological the requirements relative applications, in biological like relative cell or atissue-levelpplications, ion like analysis cell or tissue and wearable-level ion sensors.analysis and Cattrall wearable and Freiser sensors. fabricated Cattrall and the Freiser first solid-contact fabricated theISEs first (SC-ISEs) solid-contact without ISEs the (SC internal-ISEs) without solution the in internal 1971, which solution they in 1971, called which “coated they wire called electrodes” “coated wire(CWEs) electrodes” [11]. A quite (CWEs) simple [11] electrode. A quite structure simple e waslectrode proposed, structure i.e., was a metal proposed, wire directly i.e., a coatedmetal wire with directlyCa2+ ionophore-containing coated with Ca2+ ionophore polymeric-containing sensing membrane. polymeric The sensing CWEs membrane. exhibited theThe exciting CWEs Nernstianexhibited theresponse exciting toward Nernstian Ca2+. response Freiser et toward al. further Ca2+ extended. Freiser theet al CWEs. further for extended other ions the [12 CWEs]. Although for other the largeions [12].potential Although drift isthe attributed large potential to the drift unstable is attributed potential to at the the unstable metal/membrane potential at interface, the metal/membrane the milestone interface,CWEs opened the milestone the way forCWEs the open SC-ISEsed the [13 –way15]. for the SC-ISEs [13–15]. FigureFigure 1. 1. AnAn overview overview from from liquid liquid-contact-contact ion ion-selective-selective electrodes electrodes (LC- (LC-ISEs)ISEs) to solid to solid-contact-contact ISEs ( ISEsSC- ISEs(SC-ISEs)) for wearable for wearable sensors. sensors. (A) (ClassicA) Classic LC- LC-ISEsISEs (e.g., (e.g., pH pH meter) meter) by by a aliquid liquid-contact-contact between between internal internal solutionsolution and and ion ion-selective-selective membrane membrane ( (ISM).ISM). ( (BB)) The The structure structure of of SC SC-ISEs-ISEs by by a a solid solid-contact-contact between between solidsolid ion ion-to-electron-to-electron transducer transducer layer layer and and ISM. ISM. ( (CC)) An An example example of of the the SC SC-ISEs-ISEs for for wearable wearable sensor sensor applicationsapplications [9] [9].. In 1992, Lewenstam and Ivaska et al. further focused on this issue and proposed an intermediate In 1992, Lewenstam and Ivaska et al. further focused on this issue and proposed an intermediate polypyrrole (PPy) [16] solid-contact layer between an ISM and conducting substrate, called polypyrrole (PPy) [16] solid-contact layer between an ISM and conducting substrate, called the “ion- the “ion-to-electron transducer layer” (Figure1B). This transducer can transfer the ion concentration to-electron transducer layer” (Figure 1B). This transducer can transfer the ion concentration to to electron signal and stabilizes the potential at the substrate/ISM interface. This electrode structure electron signal and stabilizes the potential at the substrate/ISM interface. This electrode structure has has become the-state-of-the-art standard model of SC-ISEs. Currently, numerous materials have become the-state-of-the-art standard model of SC-ISEs. Currently, numerous materials have been been developed for the transducer, such as conducting polymers, multifarious carbon materials, developed for the transducer, such as conducting polymers, multifarious carbon materials, nanomaterials, molecular redox couples etc. The potential stability has been remarkably improved and nanomaterials, molecular redox couples etc. The potential stability has been remarkably improved the applications for SC-ISEs are also attracting increasing attention. A representative application is for and the applications for SC-ISEs are also attracting increasing attention. A representative application wearable sensors [9] (Figure1C).