Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 1. General Characteristics Eric Bakker,* ,† Philippe Bu ¨ hlmann,* ,‡ and Erno ¨ Pretsch* ,§ Department of Chemistry, Auburn University, Auburn, Alabama 36849, Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan, and Department of Organic Chemistry, Swiss Federal Institute of Technology (ETH), Universita ¨ tstrasse 16, CH-8092 Zu ¨ rich, Switzerland Received February 26, 1997 (Revised Manuscript Received July 10, 1997) Contents I. Introduction 3083 II. Characteristics of Potentiometric and Optical Sensors 3087 1. Ion-Selective Electrodes 3087 A. Response Mechanism 3087 B. Selectivity 3090 C. Detection Limit 3098 D. Measuring Range 3101 E. Response Time 3102 2. Ion-Selective Optodes 3103 A. Response Mechanism 3103 B. Selectivity 3107 C. Detection Limits 3109 D. Measuring Range 3111 E. Response Time 3111 3. Comparison of Optical and Potentiometric Transduction Schemes 3112 A. Response Mechanism 3112 B. Selectivity 3113 C. Detection Limit 3114 D. Measuring Range 3114 E. Response Time 3114 F. Lifetime 3115 III. Specific Requirements for Ionophores and Membrane Matrices 3115 1. Ionophores 3115 A. General Considerations 3115 B. Modeling of Ionophores 3118 C. Exchange Kinetics, Reversibility 3120 D. Lipophilicity 3122 2. Other Membrane Components 3123 A. Membrane Solvent (Plasticizer) 3123 B. Ionic Additives 3125 C. The Polymer Matrix 3126 IV. Conclusions 3128 V. Acknowledgments 3128 VI. References 3128 I. Introduction Over the past 30 years, the application of carrier- based ion-selective electrodes (ISEs) has evolved to a well-established routine analytical technique. The College of American Pathologists Comprehensive Chemistry Survey in 1980, for example, showed only 22% of the participating laboratories as making potentiometric Na + or K + measurements. By 1991, on the other hand, the Chemistry Survey listed 96% of 6041 participating laboratories as using Na + ISE analyzers and only 4% as using flame atomic emis- sion spectrometry. 1,2 It was estimated that in the United States about 200 million clinical assays of K + are made every year with valinomycin-based ISEs. 3 Since several other biologically relevant ions are also monitored with solvent polymeric membrane elec- trodes, it can be safely stated that yearly well over a billion ISE measurements are performed world-wide in clinical laboratories alone. Moreover, ISEs are also utilized in many other fields, including physiol- ogy, process control, and environmental analysis. They thus form one of the most important groups of chemical sensors. The analytes for which carrier- based ISEs and their counterparts with optical detec- tion have been developed so far are shown in Table 1 and will be discussed in part 2 of this pair of reviews. The key components of both types of sensors are lipophilic complexing agents capable of reversibly binding ions. They are usually called ionophores or ion carriers. The latter name reflects the fact that these compounds also catalyze ion transport across hydrophobic membranes. As will be shown here, their implementation in ion-selective electrodes or optodes is now straightforward. The essential part of a carrier-based ISE is the ion- sensitive solvent polymeric membrane, physically a water-immiscible liquid of high viscosity that is commonly placed between two aqueous phases, i.e., the sample and the internal electrolyte solution (cf. Figure 1). It contains various constituents, com- monly an ionophore (ion carrier) and a lipophilic salt as ion exchanger. The sensor responds to the activity of the target ion and usually covers an extraordinar- ily large sensitivity range, from about 1 to 10 -6 M. Its selectivity is related to the equilibrium constant of the exchange reaction of target and interfering ions between the organic and aqueous phases. It strongly depends on the ratio of complex formation constants of these ions with the ionophore in the membrane phase (cf. Figure 2 and section II.1.B). Ionophores are in their uncomplexed (or unasso- ciated) form either charged or electrically neutral (cf. Figure 2). The first neutral ionophores used in ISE membranes were antibiotics. 4,5 They were followed by a large number of natural and synthetic, mainly uncharged carriers for cations and a series of charged † Auburn University. ‡ The University of Tokyo. § Swiss Federal Institute of Technology (ETH). 3083 Chem. Rev. 1997, 97, 3083-3132 S0009-2665(94)00394-8 CCC: $28.00 © 1997 American Chemical Society