Thin Layer Coulometry Based on Ion-Exchanger Membranes for Heparin Detection in Undiluted Human BloodClick to copy article linkArticle link copied!
Abstract
We explore here for the first time a potentially calibration-free methodology for the detection of protamine (and, by titration, heparin) in undiluted human blood in the therapeutic concentration range from 20 to 120 mg L–1. The use of a thin layer sample (5.8 μL) confined between a tubular protamine selective membrane (inner diameter, 600 μm) and a Ag/AgCl wire (diameter 400 μm) achieves an exhaustive depletion from the sample. Coulometry detection was chosen for the interrogation of the thin layer, employing a double pulse technique with 120 s for each pulse. Protamine calibration curves were recorded at physiological concentrations and in undiluted human blood. A linear relationship was obtained in both cases, but a diminished sensitivity was observed in contact with blood, which is explained with a partial passivation of the inner Ag/AgCl element. Heparin–protamine titrations were performed in undiluted human blood samples, mimicking the final application with patients undergoing critical care. The observed values correlate satisfactorily with those of an alternative technique, so-called flash-chronopotentiometry on planar membranes.
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Figure 1
Figure 1. Schematic illustration of the thin layer coulometry ion selective electrode for determining protamine in the therapeutic range.
Experimental Section
Materials and Chemicals
Cell Assembly
Electrochemical Measurements
Results and Discussion
Figure 2
Figure 2. Ion transfer charge as a function of the applied potential vs Ag/AgCl wire for different concentrations of protamine (subtracted signal). Note that the inset legend corresponds to protamine concentration in milligram per liter units.
Figure 3
Figure 3. (a) Protamine calibration curve recorded at 120 mV. The sample solution contains from 20 to 120 mg L–1 + 100 mM NaCl. The outer solution contains 100 mg L–1 of protamine + 100 mM NaCl. %RSD = 1%. (b) Correlation between coulometric and chronopotentiometric method. Note that the obtained readout signal for coulometry and chronopotentiometry was normalized by the sensitivity of each method.
Figure 4
Figure 4. Heparin–protamine titration in NaCl 0.1 M at 120 mV.
Figure 5
Figure 5. Coulometric heparin–protamine titration in undiluted human blood.
Supporting Information
Additional information as noted in text. This material is available free of charge via the Internet at http://pubs.acs.org.
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Acknowledgment
The authors thank the Swiss National Science Foundation for supporting this research.
References
This article references 21 other publications.
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- 8Ma, S. C.; Yang, V. C.; Fu, B.; Meyerhoff, M. E. Anal. Chem. 1993, 65, 2078– 2084Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXksVSit7w%253D&md5=8a36c40551eb9d182455351e66ec477dElectrochemical sensor for heparin: further characterization and bioanalytical applicationsMa, Shu Ching; Yang, Victor C.; Fu, Bin; Meyerhoff, Mark E.Analytical Chemistry (1993), 65 (15), 2078-84CODEN: ANCHAM; ISSN:0003-2700.Potentiometric responses to heparin of polymeric membranes doped with lipophilic quaternary ammonium salts are reported. Among a wide range of membrane formulations examd., optimum responses toward macromol. heparin are achieved using tridodecylmethylammonium chloride as the active membrane component within poly(vinylchloride) or poly(vinylchloride)/(vinylacetate) films plasticized with dioctyl sebacate. Although such membranes exhibit a typical Hofmeister potentiometric selectivity pattern toward small inorg. and org. anions, very large and reproducible responses to heparin at submicromolar levels are obsd. in the presence of physiol. saline (0.12-0.15 M NaCl), as well as in citrated whole blood. Equal responses on a mass basis occur with fragments of heparin as small as 2500 Da. Complexation of heparin anionic sites by macromols. that bind heparin with high affinity (protamine and poly(L-lysine)) reduces the membrane electrode heparin responses, indicating that the electrode detects biol. available (unbound) heparin levels in soln. Quant. potentiometric titrns. of protamine with the porcine mucosa heparin followed by the sensor yield stoichiometric values in good agreement with the literature. The biomedical utility of the sensor is demonstrated by measuring its responses in whole blood from patients undergoing open heart surgery before and after heparin therapy and correlating such responses to conventional blood clotting time measurements.
- 9Samec, Z.; Trojanek, A.; Langmaier, J.; Samcova, E. Electrochem. Commun. 2003, 5, 867– 870Google ScholarThere is no corresponding record for this reference.
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- 11Guo, J. D.; Amemiya, S. Anal. Chem. 2006, 78, 6893– 6902Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xoslamu7k%253D&md5=05d2ed1faded15149528a709bd5f587bVoltammetric Heparin-Selective Electrode Based on Thin Liquid Membrane with Conducting Polymer-Modified Solid SupportGuo, Jidong; Amemiya, ShigeruAnalytical Chemistry (2006), 78 (19), 6893-6902CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A novel, solid-supported voltammetric ion-selective electrode to detect anticoagulant/antithrombotic heparin at polarizable poly(vinyl chloride) (PVC) membrane/H2O interfaces was developed. An ∼3-4.5-μm-thick PVC membrane plasticized with 2-nitrophenyl octyl ether was supported on a Au electrode modified with a poly(3-octylthiophene) (POT) film as an ion-to-electron transducer. Charge transport through the PVC-covered POT film is electrochem. reversible, as demonstrated by cyclic voltammetry with nonpolarizable membrane/H2O interfaces. In addn. to the fast charge transport, adequate redox capacity of the POT film and a small ohmic potential drop in the thin PVC membrane enable ion transfer voltammetry at polarizable macroscopic membrane/H2O interfaces in a std. 3-electrode cell. Reversible ClO4- transfer at the interfaces coupled with oxidn. of a neutral POT film was examd. by cyclic voltammetry to det. the distribution of the applied potential to the 2 polarizable interfaces by convolution technique. Interfacial adsorption and desorption of heparin facilitated by octadecyltrimethylammonium were studied also by cyclic voltammetry and convolution technique to demonstrate that the processes are electrochem. irreversible. Stripping voltammetry based on the interfacial processes gives a low detection limit of 0.005 unit/mL heparin in a saline soln., which is slightly lower than the detection limit of most sensitive heparin sensors reported so far (0.01 unit/mL).
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- 14Shvarev, A.; Bakker, E. J. Am. Chem. Soc. 2003, 125, 11192– 11193Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXmsVels7w%253D&md5=45991cec67a2d570cd8865c8760c9adcReversible electrochemical detection of nonelectroactive polyionsShvarev, Alexey; Bakker, EricJournal of the American Chemical Society (2003), 125 (37), 11192-11193CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Selective extn. principles for the recognition of nonelectroactive polyions such as heparin and protamine exist, but the high ionic valency renders the extn. process irreversible. A response principle for the reversible detection of such polyions is proposed here. The extn. of the polyionic analyte to the membrane and its subsequent back-extn. is now controlled electrochem. The principle is established with a protamine electrode, and excellent stability and reproducibility are demonstrated. This method has important implications for the design of chem. recognition principles for polyionic analytes.
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Abstract
Figure 1
Figure 1. Schematic illustration of the thin layer coulometry ion selective electrode for determining protamine in the therapeutic range.
Figure 2
Figure 2. Ion transfer charge as a function of the applied potential vs Ag/AgCl wire for different concentrations of protamine (subtracted signal). Note that the inset legend corresponds to protamine concentration in milligram per liter units.
Figure 3
Figure 3. (a) Protamine calibration curve recorded at 120 mV. The sample solution contains from 20 to 120 mg L–1 + 100 mM NaCl. The outer solution contains 100 mg L–1 of protamine + 100 mM NaCl. %RSD = 1%. (b) Correlation between coulometric and chronopotentiometric method. Note that the obtained readout signal for coulometry and chronopotentiometry was normalized by the sensitivity of each method.
Figure 4
Figure 4. Heparin–protamine titration in NaCl 0.1 M at 120 mV.
Figure 5
Figure 5. Coulometric heparin–protamine titration in undiluted human blood.
References
This article references 21 other publications.
- 1Whitelock, J. M.; Iozzo, R. V. Chem. Rev. 2005, 105, 2745– 2764There is no corresponding record for this reference.
- 2Raymond, P. D.; Ray, M. J.; Callen, S. N.; Marsh, N. A. Perfusion-UK 2003, 18, 269– 2762https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3sris1WnsA%253D%253D&md5=d67bb8cba16f885d98af745f66cf9efcHeparin monitoring during cardiac surgery. Part 1: Validation of whole-blood heparin concentration and activated clotting timeRaymond P D; Ray M J; Callen S N; Marsh N APerfusion (2003), 18 (5), 269-76 ISSN:0267-6591.There is limited published data on the agreement between techniques for monitoring heparin levels. The aim of this study was to validate the Hepcon/HMS, with particular focus on the agreement with laboratory anti-Xa assay. The performances of two ACT instruments--Hemochron and HemoTec--were also evaluated, including an assessment for interchangeability. Blood samples from 42 adult cardiopulmonary bypass (CPB) patients were analysed for activated clotting time (ACT), whole-blood heparin concentration (Hepcon/HMS) and anti-factor Xa (anti-Xa) plasma heparin concentration. Agreement between measures was determined using the method of Bland and Altman. Simple analysis of agreement between the Hepcon and anti-Xa heparin revealed the Hepcon has a mean bias of -0.46 U/mL, with the limits of agreement +/- 1.12 U/mL. The comparison between ACT instruments indicated a mean difference of -96 seconds for the HemoTec, with limits of +/- 265 seconds. The Hepcon/ HMS instrument displayed satisfactory agreement with anti-Xa plasma heparin concentration, as the expected variation would not be expected to cause problems in the clinical setting. Agreement between the two measurements of ACT may be satisfactory, provided each is assigned a different target value.
- 3Frank, R. D.; Brandenburg, V. M.; Lanzmich, R.; Floege, J. Nephrol., Dial., Transplant. 2004, 19, 1552– 15583https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXkt1Sqsrg%253D&md5=eed0fab16eb96d68e9e8961386340cd4Factor Xa-activated whole blood clotting time (Xa-ACT) for bedside monitoring of dalteparin anticoagulation during hemodialysisFrank, Rolf Dario; Brandenburg, Vincent M.; Lanzmich, Regina; Floege, JuergenNephrology, Dialysis, Transplantation (2004), 19 (6), 1552-1558CODEN: NDTREA; ISSN:0931-0509. (Oxford University Press)Background: Low mol. wt. heparins (LMWH) like dalteparin are increasingly used for anticoagulation during haemodialysis (HD). The available lab. tests for monitoring LMWH anticoagulation are time-consuming and expensive, and the suitability of the conventional activated clotting time (ACT) is controversial. A simple and cheap bedside test would be useful. Methods: We studied the factor Xa-activated whole blood clotting time (Xa-ACT) in vitro and in vivo in nine patients undergoing chronic HD with i.v. dalteparin bolus anticoagulation and compared it with the conventional ACT. Plasma anti-factor Xa (antiXa) activity was detd. with a chromogenic assay. Thrombin-antithrombin complexes were measured to detect coagulation activation. Results: Xa-ACT and ACT were prolonged with rising dalteparin concn. In vitro, both clotting times were strongly correlated with the antiXa levels (r = 0.94 and 0.89, resp.). Nevertheless, compared with the ACT, the Xa-ACT was considerably more sensitive to the LMWH in vitro (healthy blood: Xa-ACT 90 s/U vs. ACT 26 s/U; uremic blood: Xa-ACT 96 s/U vs. ACT 31 s/U) as well as in vivo (Xa-ACT 81 s/U vs. ACT 22 s/U) and reflected different intensities of anticoagulation. An initial dalteparin bolus of 80±11 U/kg body wt. was able to prevent coagulation activation for up to 4 h of HD. Conclusion: For monitoring LMWH anticoagulation the Xa-ACT was superior to the conventional ACT in vitro as well as in vivo during HD. The Xa-ACT can be useful as a LMWH bedside test. The ACT was not sensitive enough to serve as a LMWH monitoring tool.
- 4Khaja, W. A.; Bilen, O.; Lukner, R. B.; Edwards, R.; Teruya, J. Am. J. Clin. Pathol. 2010, 134, 950– 9544https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhs1aksL7K&md5=81477dca559c0ee87e2e9b139dcb1f47Evaluation of heparin assay for coagulation management in newborns undergoing ECMOKhaja, Wassia A.; Bilen, Ozlem; Lukner, Ralf B.; Edwards, Rachel; Teruya, JunAmerican Journal of Clinical Pathology (2010), 134 (6), 950-954CODEN: AJCPAI; ISSN:0002-9173. (American Society of Clinical Pathology)The objective was to identify the usefulness of heparin level by anti-factor Xa (anti-Xa) assay vs activated partial thromboplastin time (PTT) or activated clotting time (ACT) in neonates undergoing extracorporeal membrane oxygenation (ECMO). A retrospective record review of 21 patients in the neonatal intensive care unit (mean ECMO initiation age, 2 days; range, 0-4 days; male/female ratio, 1:1) undergoing ECMO from 2006 to 2008 was performed. Linear regression correlations between anti-Xa, PTT, and ACT were detd. by extrapolating PTT and ACT therapeutic ranges that corresponded with the ECMO heparin target range of 0.3 to 0.6 U/mL. Pearson correlation coeffs. between heparin levels and PTT (-0.903 to 0.984), PTT less than 40 s after correction using PTT-heparinase (-0.903 to 1.000), and ACT (-0.951 to 0.891) in this patient population were widely variable. Inconsistency of PTT and ACT therapeutic ranges corresponding to heparin levels of 0.3 to 0.6 U/mL prompts a multifactorial approach to ECMO management because no single lab. test can be used to det. appropriate anticoagulation management.
- 5Hussein, H. M.; Georgiadis, A. L.; Qureshi, A. I. American Journal of Neuroradiology 2012, 33, 1211– 1220There is no corresponding record for this reference.
- 6Vandiver, J. W.; Vondracek, T. G. Pharmacotherapy 2012, 32, 546– 558There is no corresponding record for this reference.
- 7Ma, S. C.; Yang, V. C.; Meyerhoff, M. E. Anal. Chem. 1992, 64, 694– 6977https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XpvVOqug%253D%253D&md5=d8d24217258c14cb76955041ecfaba05Heparin-responsive electrochemical sensor: a preliminary studyMa, Shu Ching; Yang, Victor C.; Meyerhoff, Mark E.Analytical Chemistry (1992), 64 (6), 694-7CODEN: ANCHAM; ISSN:0003-2700.A heparin-responsive electrochem. sensor is prepd. by impregnating a heparin complexing agent, tridodecylmethylammonium chloride, in a plasticized poly(vinyl chloride) membrane. Potentiometric response in saline soln. and undiluted human plasma demonstrate that the sensor exhibits adequate selectivity and sensitivity to detect heparin in the clin. relevant concn. range.
- 8Ma, S. C.; Yang, V. C.; Fu, B.; Meyerhoff, M. E. Anal. Chem. 1993, 65, 2078– 20848https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXksVSit7w%253D&md5=8a36c40551eb9d182455351e66ec477dElectrochemical sensor for heparin: further characterization and bioanalytical applicationsMa, Shu Ching; Yang, Victor C.; Fu, Bin; Meyerhoff, Mark E.Analytical Chemistry (1993), 65 (15), 2078-84CODEN: ANCHAM; ISSN:0003-2700.Potentiometric responses to heparin of polymeric membranes doped with lipophilic quaternary ammonium salts are reported. Among a wide range of membrane formulations examd., optimum responses toward macromol. heparin are achieved using tridodecylmethylammonium chloride as the active membrane component within poly(vinylchloride) or poly(vinylchloride)/(vinylacetate) films plasticized with dioctyl sebacate. Although such membranes exhibit a typical Hofmeister potentiometric selectivity pattern toward small inorg. and org. anions, very large and reproducible responses to heparin at submicromolar levels are obsd. in the presence of physiol. saline (0.12-0.15 M NaCl), as well as in citrated whole blood. Equal responses on a mass basis occur with fragments of heparin as small as 2500 Da. Complexation of heparin anionic sites by macromols. that bind heparin with high affinity (protamine and poly(L-lysine)) reduces the membrane electrode heparin responses, indicating that the electrode detects biol. available (unbound) heparin levels in soln. Quant. potentiometric titrns. of protamine with the porcine mucosa heparin followed by the sensor yield stoichiometric values in good agreement with the literature. The biomedical utility of the sensor is demonstrated by measuring its responses in whole blood from patients undergoing open heart surgery before and after heparin therapy and correlating such responses to conventional blood clotting time measurements.
- 9Samec, Z.; Trojanek, A.; Langmaier, J.; Samcova, E. Electrochem. Commun. 2003, 5, 867– 870There is no corresponding record for this reference.
- 10Guo, J. D.; Yuan, Y.; Amemiya, S. Anal. Chem. 2005, 77, 5711– 5719There is no corresponding record for this reference.
- 11Guo, J. D.; Amemiya, S. Anal. Chem. 2006, 78, 6893– 690211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xoslamu7k%253D&md5=05d2ed1faded15149528a709bd5f587bVoltammetric Heparin-Selective Electrode Based on Thin Liquid Membrane with Conducting Polymer-Modified Solid SupportGuo, Jidong; Amemiya, ShigeruAnalytical Chemistry (2006), 78 (19), 6893-6902CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A novel, solid-supported voltammetric ion-selective electrode to detect anticoagulant/antithrombotic heparin at polarizable poly(vinyl chloride) (PVC) membrane/H2O interfaces was developed. An ∼3-4.5-μm-thick PVC membrane plasticized with 2-nitrophenyl octyl ether was supported on a Au electrode modified with a poly(3-octylthiophene) (POT) film as an ion-to-electron transducer. Charge transport through the PVC-covered POT film is electrochem. reversible, as demonstrated by cyclic voltammetry with nonpolarizable membrane/H2O interfaces. In addn. to the fast charge transport, adequate redox capacity of the POT film and a small ohmic potential drop in the thin PVC membrane enable ion transfer voltammetry at polarizable macroscopic membrane/H2O interfaces in a std. 3-electrode cell. Reversible ClO4- transfer at the interfaces coupled with oxidn. of a neutral POT film was examd. by cyclic voltammetry to det. the distribution of the applied potential to the 2 polarizable interfaces by convolution technique. Interfacial adsorption and desorption of heparin facilitated by octadecyltrimethylammonium were studied also by cyclic voltammetry and convolution technique to demonstrate that the processes are electrochem. irreversible. Stripping voltammetry based on the interfacial processes gives a low detection limit of 0.005 unit/mL heparin in a saline soln., which is slightly lower than the detection limit of most sensitive heparin sensors reported so far (0.01 unit/mL).
- 12Langmaier, J.; Samcova, E.; Samec, Z. Anal. Chem. 2007, 79, 2892– 2900There is no corresponding record for this reference.
- 13Amemiya, S.; Kim, Y.; Ishimatsu, R.; Kabagambe, B. Anal. Bioanal. Chem. 2011, 399, 571– 57913https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtVyqs7bL&md5=1228cc5c9db98f33ec9bc6b37d651f59Electrochemical heparin sensing at liquid/liquid interfaces and polymeric membranesAmemiya, Shigeru; Kim, Yushin; Ishimatsu, Ryoichi; Kabagambe, BenjaminAnalytical and Bioanalytical Chemistry (2011), 399 (2), 571-579CODEN: ABCNBP; ISSN:1618-2642. (Springer)A review. The monitoring of heparin and its derivs. in blood samples is important for the safe usage of these anticoagulants and antithrombotics in many medical procedures. Such an anal. task is, however, highly challenging due to their low therapeutic levels in the complex blood matrix, and it still relies on classical, indirect, clot-based assays. Here we review recent progress in the direct electrochem. sensing of heparin and its analogs at liq./liq. interfaces and polymeric membranes. This progress has been made by utilizing the principle of electrochem. ion transfer at the interface between two immiscible electrolyte solns. (ITIES) to voltammetrically drive the interfacial transfer of polyanionic heparin and monitoring the resulting ionic current as a direct measure of heparin concn. The sensitivity, selectivity, and reproducibility of the ion-transfer voltammetry of heparin are dramatically enhanced compared to those of traditional potentiometry. This voltammetric principle was successfully applied for the detection of heparin in undiluted blood samples, and was used to develop highly sensitive ion-selective electrodes based on thin polymeric membranes that are intended for anal. applications beyond heparin detection. The mechanism of heparin recognition and transfer at liq./liq. interfaces was assessed quant. via sophisticated micropipet techniques, which aided the development of a powerful ionophore that can ext. large heparin mols. into nonpolar org. media. Moreover, the reversible potentiometric detection of a lethal heparin-like contaminant in com. heparin prepns. was achieved through the use of a PVC membrane doped with methyltridodecylammonium chloride, which enables charge d. dependent polyanion selectivity.
- 14Shvarev, A.; Bakker, E. J. Am. Chem. Soc. 2003, 125, 11192– 1119314https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXmsVels7w%253D&md5=45991cec67a2d570cd8865c8760c9adcReversible electrochemical detection of nonelectroactive polyionsShvarev, Alexey; Bakker, EricJournal of the American Chemical Society (2003), 125 (37), 11192-11193CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Selective extn. principles for the recognition of nonelectroactive polyions such as heparin and protamine exist, but the high ionic valency renders the extn. process irreversible. A response principle for the reversible detection of such polyions is proposed here. The extn. of the polyionic analyte to the membrane and its subsequent back-extn. is now controlled electrochem. The principle is established with a protamine electrode, and excellent stability and reproducibility are demonstrated. This method has important implications for the design of chem. recognition principles for polyionic analytes.
- 15Gemene, K. L.; Bakker, E. Anal. Biochem. 2009, 386, 276– 281There is no corresponding record for this reference.
- 16Crespo, G. A.; Afshar, M. G.; Bakker, E. Angew. Chem., Int. Ed. 2012, 51, 12575– 12578There is no corresponding record for this reference.
- 17Bakker, E.; Crespo, G. A.; Afshar, M. G.; Saxer, T.; Bendjelid, K. Chimia 2013, 67, 350– 350There is no corresponding record for this reference.
- 18Grygolowicz-Pawlak, E.; Bakker, E. Anal. Chem. 2010, 82, 4537– 4542There is no corresponding record for this reference.
- 19Shvarev, A.; Neel, B.; Bakker, E. Anal. Chem. 2012, 84, 8038– 804419https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1Gmsr%252FK&md5=c0aed2599e9f2ebfacd08cae0c8716c7Detection Limits of Thin Layer Coulometry with Ionophore Based Ion-Selective MembranesShvarev, Alexey; Neel, Bastien; Bakker, EricAnalytical Chemistry (Washington, DC, United States) (2012), 84 (18), 8038-8044CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The authors report here on a significant improvement in lowering the low detection limit of thin layer coulometric sensors based on liq. ion-selective membranes, using a potassium-selective system as a model example. Various possible processes that may result in an elevated residual current reading after electrolysis were eliminated. Self-dissoln. of AgCl on the Ag/AgCl inner element may result in a residual ion flux that could adversely affect the lower detection limit. It was here replaced with an Ag/AgI inner pseudo-ref. electrode where the self-dissoln. equil. is largely suppressed. Possible residual currents originating from a direct contact between inner element and ion-selective membranes were eliminated by introducing an inert PVDF separator of 50 μm diam. that was coiled around the inner element by a custom-made instrument. Finally, the influence of electrolyte fluxes from the outer soln. across the membrane into the sample was evaluated by altering its lipophilic nature and reducing its concn. This last effect is most likely responsible for the obsd. residual current for the potassium-selective membranes studied here. For the optimized conditions, the calibration curves demonstrated a near zero intercept, thereby paving the way to the coulometric calibration-free sensing of ionic species. A linear calibration curve for the coulometric cell with valinomycin potassium-selective membrane was obtained in the range of 100 nM to 10 μM potassium in the presence of a 10 μM sodium background. In the presence of a higher (100 μM) concn. of sodium, a reliable detection of 1-100 μM of potassium was achieved.
- 20Sohail, M.; De Marco, R.; Lamb, K.; Bakker, E. Anal. Chim. Acta 2012, 744, 39– 44There is no corresponding record for this reference.
- 21Grygolowicz-Pawlak, E.; Bakker, E. Electrochem. Commun. 2010, 12, 1195– 1198There is no corresponding record for this reference.
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