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Why Ammonium Detection Is Particularly Challenging But Analyst View Article Online CRITICAL REVIEW View Journal | View Issue Why ammonium detection is particularly challenging but insightful with ionophore-based Cite this: Analyst, 2020, 145, 3188 potentiometric sensors – an overview of the progress in the last 20 years María Cuartero, * Noemi Colozza, Bibiana M. Fernández-Pérez and Gastón A. Crespo * The monitoring of ammonium ion concentration has gained the attention of researchers from multiple fields since it is a crucial parameter with respect to environmental and biomedical applications. For example, ammonium is considered to be a quality indicator of natural waters as well as a potential bio- marker of an enzymatic byproduct in key physiological reactions. Among the classical analytical methods used for the detection of ammonium ions, potentiometric ion-selective electrodes (ISEs) have attracted Creative Commons Attribution-NonCommercial 3.0 Unported Licence. special attention in the scientific community because of their advantages such as cost-effectiveness, user-friendly features, and miniaturization ability, which facilitate easy portable measurements. Regarding the analytical performance, the key component of ISEs is the selective receptor, labelled as an ionophore in ISE jargon. Indeed, the preference of an ionophore for ammonium amongst other ions (i.e., selectivity) is a factor that primarily dictates the limit of detection of the electrode when performing measurements in real samples. A careful assessment of the literature for the last 20 years reveals that nonactin is by far the most employed ammonium ionophore to date. Despite the remarkable cross-interference of potass- ium over the ammonium response of nonactin-based ISEs, analytical applications comprising water quality assessment, clinical tests in biological fluids, and sweat monitoring during sports practice have This article is licensed under a been successfully researched. Nevertheless, there is evident difficulty in the determination of close-to- micromolar levels of ammonium in real samples with a significant potassium background level (i.e., milli- molar concentration). This fact has fostered the search for a large variety of ammonium ionophores over Open Access Article. Published on 12 March 2020. Downloaded 9/26/2021 7:44:23 AM. Received 13th February 2020, the years, which are critically inspected herein. Overall, we provide an easily readable state of the art Accepted 11th March 2020 accompanied by a comprehensive description of other types of ammonium electrodes, including com- DOI: 10.1039/d0an00327a mercially available units. We conclude that newer breakthroughs are still required in the field to reach the rsc.li/analyst desired analytical applications. 1. Introduction are the membrane-based design of a sensor and have been applied for ion determination mainly in water quality – In the last few decades, potentiometric ion-selective electrodes assessment,1,6,7 clinical analyses,8 11 and monitoring of sport – (ISEs) have been proposed as effective analytical tools in multi- practices.2,12 14 faceted applications where ion detection is essential. Indeed, Looking back at the development history of ISEs, the inte- the utilization of ISEs is currently preferred over other analyti- gration of ion-selective membranes (ISMs) as the sensing cal techniques because of their cost-effectiveness, user-friendly element has undoubtedly been a disruptive event in this features, and miniaturization capability. Moreover, ISEs are field.15 Today, the technology involving ISM fabrication is well some of the few analytical techniques that provide in situ real- entrenched and the criteria for selecting components/ time measurements of the target concentration with total materials as well as the necessary features have been known – reliability.1 5 Major examples that evidence the success of ISEs for decades.15 One remarkable aspect is the tuning of mem- brane selectivity towards the target ions by the incorporation of a specific receptor (labelled as ionophore in ISE terminol- ogy) in the ISM. Traditionally, ionophores are embedded into a Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, 10044 Stockholm, plasticized polymeric matrix with intrinsic ion-exchange pro- Sweden. E-mail: [email protected], [email protected] perties, which is provided by a mixture of a polymer, plastici- 3188 | Analyst,2020,145,3188–3210 This journal is © The Royal Society of Chemistry 2020 View Article Online Analyst Critical Review 16,17 + zer, and ion exchanger. The selectivity pattern of the iono- The accurate detection of NH4 is needed in samples com- phore is the primary factor that dictates the limit of detection prising many different compositions and from totally different (LOD) of ISE measurements for any sample. fields, ranging from agricultural water to tissues and cell 30,31 + + Essentially, the role of the ionophore is to promote a drastic media. In all these samples, the molar ratio of NH4 /K change in the response pattern found in ionophore-free mem- (and probably other side-interfering ions) dictates the suit- + branes exclusively containing the polymer, plasticizer, and ion ability of nonactin-based NH4 -selective electrodes for the con- exchanger.16,17 Therefore, the ion-exchange process at the sequent analysis. Hence, in this review, we firstly investigate – + sample membrane interphase relies on the extraction of the the performances of nonactin implemented as NH4 iono- target ion from the solution (i.e., solvated state of the ion in phore in ISMs with different architectures. A comprehensive the aqueous phase) to the ISM (i.e., formation of the ion–iono- evaluation of collected papers reported in the last 20 years can phore complex at the organic phase). If the formation of the shed light on certain samples that are still inaccessible due to ion–ionophore complex is sufficiently accessible thermo- the intrinsic selectivity limitations of nonactin. On the other dynamically, the hydration energy of ions in the aqueous hand, other receptors and strategies have been explored, as phase can be overcome and ion exchange becomes an assisted evident in the literature, in an attempt to provide alternatives process.16 As a result, the order for ion preference to be to the use of nonactin as an ionophore. Herein, we report the + exchanged at the sample–membrane interphase is not based entire scenario created for NH4 sensing using potentiometric anymore on regular lipophilicity distribution (i.e., following electrodes designed over the last 20 years, mainly focusing on the Hofmeister series) as that occurring in ionophore-free the use of ionophores, but also discussing certain other high- membranes or even with ionophores that are not sufficiently lighted contributions and commercially available devices. – selective for a single ion.17 19 Beyond providing an updated collection of published papers + Ideally, to ensure the reliable analytical detection of an on NH4 potentiometric detection until now, this review criti- individual ion (i.e., no interference) using the corresponding cally analyzes the advantages and drawbacks of the selected Creative Commons Attribution-NonCommercial 3.0 Unported Licence. ISE, the ionophore should uniquely bind with that ion. papers in order to provide guidance toward the definitive solu- + Unfortunately, this is beyond reality and every ISM—compris- tion for NH4 detection in the presence of primary ing a distinct ionophore—presents a response (or selectivity) interferences. pattern toward the ion analyte together with a number of inter- It should be noted that we do not intend to deviate from + ferences. Notably, it is typically more challenging to develop our discussions any of the manuscripts related to NH4 electro- effective ISEs for highly hydrophilic small ions (for example, des over the selected period; if this has inadvertently been the fluorides and sulfates with high hydration energies).20 These case, the aim was not to undervalue any of the related publi- species have to overcome the enthalpically unfavorable phase cations. Overall, we consider that the selected papers offer a transfer from an aqueous solution into the membrane owing true vision of the field. In addition, all the analytical para- This article is licensed under a to the presence of the ionophore. However, it is challenging to meters discussed throughout this review were obtained from access receptors (particularly for anions) that fulfill such a the original sources (published papers), and the main aim requirement. Consequently, as a general trend, the literature when analyzing them was not to criticize the manner in which Open Access Article. Published on 12 March 2020. Downloaded 9/26/2021 7:44:23 AM. comprises several studies regarding cation ionophores, these values were calculated. However, selectivity coefficients whereas there is a lack of studies on effective anion require special attention; accordingly, the reader should care- – ionophores.18,21 23 fully consider our discussions. It is rather common in the lit- Among the cation ionophores, the case of the ammonium erature to find biased calculations if the experiments were not + ion (NH4 ) is particularly interesting. Even though research meticulously performed and the equations were not used + on the provision of NH4 -selective electrodes has been really appropriately (e.g., the necessity of considering any deviation active over the past few decades, the very first ionophore from the Nernstian slope of the interfering
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