Establishing Meaningful Limits of Detection for Ion-Selective Electrodes and Other Nonlinear Sensors

Abstract

Although IUPAC has recommended a probabilistic approach to determining limit of detection (LOD) based on false-positive and false-negative rates for more than 20 years, the LOD definition for ion-selective electrodes (ISEs) long predates these recommendations and conflicts substantively with them. Although it is well known that the ISE LOD definition does not follow best practice, it continues to be used due to simplicity and a lack of available methods for estimating LOD for nonlinear sensors. Here, we use ISEs as a model system for estimation of LOD for nonlinear sensors that is consistent with broad IUPAC recommendations and justified using statistical theory. Using freely available software, the new approach and updated definition is demonstrated through theory, simulation, and an environmental application. The results show that the current LOD definition for ISEs performs substantially worse than the proposed definition when assessed against IUPAC recommendations, including ignoring sensor noise and LOD uncertainty, leading to bias of an order of magnitude or more. Further, the environmental application shows that the new definition, which includes estimates of LOD uncertainty, allows more objective assessment of sensor response and fitness for purpose. The growing demand for ultrasensitive sensors that operate in complex matrices has pushed the boundaries of traditional calibration approaches. These sensors often operate near their limit of detection (LOD), with additional challenges created if their response is nonlinear. These challenges are amplified when assessing new sensors, since they may be less reproducible and noisier than benchmark techniques.

Concurrent measurement of nitrate and ammonium in water and soil samples using ion‐selective electrodes: Tackling sensitivity and precision issues

“…As a consequence, a significant portion of the signal above noise levels is often neglected. In order to maintain brevity and focus, this somewhat unusual practice originating from the bias created by the current IUPAC definition and treatment of LOD (LOD 1969 ) is discussed in the Supplemental Info (section “Bias in the determination of unknown activity around LOD of ISEs”) and elsewhere 33 . This bias is nicely visible in Figure 2 bottom since the concentration of NH 4 + in almost all samples is between LOD 1969 and the limit of quantification (LOQ; as discussed in SI).…”

“…Recently, we analysed the current IUPAC definition of LOD of ISEs and recommended a new LOD definition for ISEs that would be in line with broader IUPAC recommendations for a LOD 33 . For practitioners, it is important that our recommendations realistic estimates of uncertainty.…”

Discussion on the Relationship and Influence Factors of the Limit of Detection and the Sensitivity of Analytical Methods

“…图1 假设检验法确定检出限 [12] 若测量信号与浓度的对数lgc成正比，此时检出限又该如何计算呢？电位分析法就是一个典型的 例子。Dillingham等人提出了一个与IUPAC推荐相一致的检出限计算方法 [14]…”

Sensing and sensitivity: Computational chemistry of graphene‐based sensors

“…From identifying the underlying chemical mechanisms responsible for the detectable signal to simulations of a model sensor in operation, 48 computational chemistry with its vast array of tools and techniques 50,51 plays an increasingly important role in chemical sensor research. Specific tasks currently addressed in silico include: assessing the scope of analytes and the selectivity of a given sensor; 52 understanding the factors influencing LOD and sensitivity; 52,53 deriving the design criteria for improved sensors 54 …”