Influence of Electrolyte Concentration on Single-Molecule Sensing of Perfluorocarboxylic Acids

Abstract

Perfluorocarboxylic acids (PFCAs) are an emerging class of persistent organic pollutants. During the fabrication process, it is unavoidable to form PFCA homologs or isomers which exhibit distinct occurrence, bioaccumulation, and toxicity. The precision measurement of PFCAs is therefore of significant importance. However, the existing characterization techniques, such as LC-MS/MS, cannot fully meet the requirement of isomer-specific analysis, largely due to the lack of authentic standards. Single-molecule sensors (SMSs) based on nanopore electrochemistry may be a feasible solution for PFCAs determination, thanks to their ultra-high spatiotemporal resolutions. Hence, as a first step, this work was to elucidate the influence of electrolyte concentration on the four most critical indicators of nanopore measurements, and furthermore, performance of nanopore SMSs. More specifically, three of the most representative short-chain PFCAs, perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA), were adopted as the target analytes, aerolysin nanopore was employed as the sensing interface, and 2, 3 and 4 M KCl solutions were used as electrolytes. It was found that, when the concentration of KCl solution increased from 2 to 4 M, the conductance of aerolysin nanopore increased almost linearly at a rate of 0.5 nS per molar KCl within the whole voltage range, the current blockade of PFPeA at −50 mV increased from 61.74 to 66.57% owing to the enhanced steric exclusion effect, the maximum dwell time was more than doubled from 14.5 to 31.5 ms, and the barrier limited capture rate increased by 8.3 times from 0.46 to 3.85 Hz. As a result, when using 4 M KCl as the electrolyte, over 90% of the PFPeA, PFHxA and PFHpA were accurately identified from a mixed sample, and the calculated limit of detection of PFPeA reached 320 nM, more than 24 times lower than in 2 M KCl. It was thus clear that tuning the electrolyte concentration was a simple but very effective approach to improve the performance of nanopore SMSs for PFCAs determination.

Machine learning assisted single-molecule sensing of per- and polyfluoroalkyl carboxylic acids: Quantification without standards

“…It was noted that difference between the current blockade of C2 and C8 was only 9.662%, but at least 452 PFCA 3 (with CAS available) had been identi ed in this range. Hence, to fully resolve all the PFCA above, the standard deviation of blockade has to be smaller than 0.00356% (R = 1.5) 20 , which however was around 0.2% at best for WT AeL. It was thus essential to make the most of other features of single-molecule signals.…”

“…1f, which could triple the resolution of identi cation. One possible reason was the prolonged dwell time of PFCA in WT AeL, caused by the higher cis-to-trans driving force in 4 M KCl (or the lower trans-to-cis electroosmotic force) 20 . Nevertheless, it was noted that the sum of the three sigma of poly-and the adjacent per-uoroalkyl carboxylic acids (highlighted as the error bar in Fig.…”

“…Herein, a nanopore based single-molecule electrochemical sensor is proposed as an emerging technology to bridge the gap between the urgent demand for quantitative PFAS monitoring and the severe shortage of authentic standards. By measuring the change of ion movement through nanopore, single-molecule sensor (SMS) can identify and quantify a speci c analyte with the characteristics and frequency of the resulting current blockade 20 . A linear correlation was established in this work between the magnitude of ionic current and the volume of PFAS simulated by molecular dynamics (MD), and thus the current response of unknown PFAS could be accurately predicted, avoiding the need for standards.…”

Review—Single-Molecule Sensors Based on Protein Nanopores

“…Regarding the second question, the answer is still open to debate, but as mentioned previously, one possibility may be the precision sensing of those extremely low concentration isomers of, e.g., perand poly-fluoroalkyl substances 197 or antibiotic drugs. Determination of those species remains challenging even for the state-of-the-art analytical techniques.…”