Solid-Contact pH Sensor without CO2 Interference with a Superhydrophobic PEDOT-C14 as Solid Contact: The Ultimate "Water Layer" Test.

The aim of this study was to find a conducting polymer-based solid contact (SC) for ion-selective electrodes (ISEs) that could become the ultimate, generally applicable SC, which in combination with all kinds of ion-selective membranes (ISMs) would match the performance characteristics of conventional ISEs. We present data collected with electrodes utilizing PEDOT-C14, a highly hydrophobic derivative of poly(3,4-ethylenedioxythiophene), PEDOT, as SC and compare its performance characteristics with PEDOT-based SC ISEs. PEDOT-C14 has not been used in SC ISEs previously. The PEDOT-C14-based solid contact (SC) ion-selective electrodes (ISEs) (H+, K+, and Na+) have outstanding performance characteristics (theoretical response slope, short equilibration time, excellent potential stability, etc.). Most importantly, PEDOT-C14-based SC pH sensors have no CO2 interference, an essential pH sensors property when aimed for whole-blood analysis. The superhydrophobic properties (water contact angle: 136 ± 5°) of the PEDOT-C14 SC prevent the detachment of the ion-selective membrane (ISM) from its SC and the accumulation of an aqueous film between the ISM and the SC. The accumulation of an aqueous film between the ISM and its SC has a detrimental effect on the sensor performance. Although there is a test for the presence of an undesirable water layer, if the conditions for this test are not selected properly, it does not provide an unambiguous answer. On the other hand, recording the potential drifts of SC electrodes with pH-sensitive membranes in samples with different CO2 levels can effectively prove the presence or absence of a water layer in a short time period.

Accuracy of commercial blood gas analyzers for monitoring ionized calcium at low concentrations.

BACKGROUND: Variable ionized calcium measurements in post filter blood samples during continuous renal replacement therapy (renal dialysis) using regional citrate anticoagulation (RCA) have been reported using commercial blood gas analyzers, resulting in analyzer-dependent differences in decisions regarding adjustment of citrate dose. METHODS: We evaluated accuracy for measurement of iCa at low concentrations by 4 commercial blood gas analyzers using primary reference solutions formulated down to 0.15mmol/l iCa. RESULTS: Of the 4 analyzers tested, GEM Premier 4000 demonstrates acceptable accuracy for iCa measurement with a median deviation of -6.7% (-0.01mmol/l) at 0.15mmol/l, while other analyzers tested show increasingly positive biases from +40% (+0.06mmol/l) to +60% (+0.09mmol/l) relative to target. These relative differences are consistent with discordant results reported for measurement of iCa in blood during RCA. Interference from sodium with measured iCa and carryover from system rinse solution to sample are likely contributors to variability. CONCLUSIONS: We conclude the GEM Premier 4000 shows acceptable accuracy for measuring iCa at low concentrations required to control citrate dose during RCA. The method presented here may be used to test accuracy of any blood gas analyzer prior to use in clinical applications requiring measurement of iCa at low concentrations.

Integrated quality control: implementation and validation of instrument function checks and procedural controls for a cartridge-based point-of-care system for critical care analysis.

In this article, the process used to develop and validate an integrated quality-control system for a cartridge-based, point-of-care system for critical care analysis is outlined. Application of risk management principles has resulted in a quality control system using a combination of statistical quality control with onboard reference solutions and failure pattern recognition used to flag common failure modes during the analytical phase of the testing process. A combination of traditional external quality control, integrated quality control to monitor ongoing instrument functionality, operator training, and other laboratory-implemented monitors is most effective in controlling known failure modes during the testing process.

Biosensors in clinical chemistry - 2011 update.

Research activity and applications of biosensors for measurement of analytes of clinical interest over the last eight years are reviewed. Nanotechnology has been applied to improve performance of biosensors using electrochemical, optical, mechanical and physical modes of transduction, and to allow arrays of biosensors to be constructed for parallel sensing. Biosensors have been proposed for measurement of cancer biomarkers, cardiac biomarkers as well as biomarkers for autoimmune disease, infectious disease and for DNA analysis. Novel applications of biosensors include measurements in alternate sample types, such as saliva. Biosensors based on immobilized whole cells have found new applications, for example to detect the presence of cancer and to monitor the response of cancer cells to chemotherapeutic agents. The number of research reports describing new biosensors for analytes of clinical interest continues to increase; however, movement of biosensors from the research laboratory to the clinical laboratory has been slow. The greatest impact of biosensors will be felt at point-of-care testing locations without laboratory support. Integration of biosensors into reliable, easy-to-use and rugged instrumentation will be required to assure success of biosensor-based systems at the point-of-care.

IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma.

Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should yield comparable and unbiased results for iMg. This IFCC guideline on sampling, measuring and reporting iMg in plasma provides a prerequisite to achieve this goal [in this document, "plasma" refers to circulating plasma and the forms in which it is sampled, namely the plasma phase of anticoagulated whole blood (or "blood"), plasma separated from blood cells, or serum]. The guideline recommends measuring and reporting ionized magnesium as a substance concentration relative to the substance concentration of magnesium in primary aqueous calibrants with magnesium, sodium, and calcium chloride of physiological ionic strength. The recommended name is "the concentration of ionized magnesium in plasma". Based on this guideline, results will be approximately 3% higher than the true substance concentration and 4% lower than the true molality in plasma. Calcium ions interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus it is necessary to determine both ions simultaneously in each sample and correct the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent. Therefore, pH should be measured simultaneously with iMg to allow adjustment of the result to pH 7.4. The concentration of iMg in plasma may be physiologically and clinically more relevant than the concentration of total magnesium. Furthermore, blood-gas analyzers or instruments for point-of-care testing are able to measure plasma iMg using whole blood (with intact blood cells) as the sample, minimizing turn-around time compared to serum and plasma, which require removal of blood cells.

Approved IFCC recommendation on reporting results for blood glucose: International Federation of Clinical Chemistry and Laboratory Medicine Scientific Division, Working Group on Selective Electrodes and Point-of-Care Testing (IFCC-SD-WG-SEPOCT).

In current clinical practice, plasma and blood glucose are used interchangeably with a consequent risk of clinical misinterpretation. In human blood, glucose is distributed, like water, between erythrocytes and plasma. The molality of glucose (amount of glucose per unit water mass) is the same throughout the sample, but the concentration is higher in plasma, because the concentration of water and therefore glucose is higher in plasma than in erythrocytes. Different devices for the measurement of glucose may detect and report fundamentally different quantities. Different water concentrations in the calibrator, plasma, and erythrocyte fluid can explain some of the differences. Results for glucose measurements depend on the sample type and on whether the method requires sample dilution or uses biosensors in undiluted samples. If the results are mixed up or used indiscriminately, the differences may exceed the maximum allowable error for glucose determinations for diagnosing and monitoring diabetes mellitus, thus complicating patient treatment. The goal of the International Federation of Clinical Chemistry and Laboratory Medicine, Scientific Division, Working Group on Selective Electrodes and Point of Care Testing (IFCC-SD-WG-SEPOCT) is to reach a global consensus on reporting results. The document recommends reporting the concentration of glucose in plasma (in the unit mmol/L), irrespective of sample type or measurement technique. A constant factor of 1.11 is used to convert concentration in whole blood to the equivalent concentration in plasma. The conversion will provide harmonized results, facilitating the classification and care of patients and leading to fewer therapeutic misjudgments.

Recommendation for measuring and reporting chloride by ISEs in undiluted serum, plasma or blood.

The proposed recommendation for measuring and reporting chloride in undiluted plasma or blood by ion-selective electrodes (ISEs) will provide results that are identical to chloride concentrations measured by coulometry for standardized normal plasma or blood samples. It is applicable to all current ISEs dedicated to chloride measurement in undiluted samples that meet the requirements. However, in samples with reduced water concentration, results by coulometry are lower than by ion-selective electrode due to volume displacement. The quantity measured by this standardized ISE procedure is called the ionized chloride concentration. It may be clinically more relevant than the chloride concentration as determined by coulometry, photometry or by ISE after dilution of the sample.

Approved IFCC recommendation on reporting results for blood glucose (abbreviated).

In current clinical practice, plasma and blood glucose are used interchangeably with a consequent risk of clinical misinterpretation. In human blood, glucose, like water, is distributed between erythrocytes and plasma. The molality of glucose (amount of glucose per unit of water mass) is the same throughout the sample, but the concentration is higher in plasma because the concentration of water and, therefore, glucose is higher in plasma than in erythrocytes. Different devices for the measurement of glucose may detect and report fundamentally different quantities. Different water concentrations in calibrators, plasma, and erythrocyte fluid can explain some of the differences. Results of glucose measurements depend on sample type and on whether methods require sample dilution or use biosensors in undiluted samples. If the results are mixed up or used indiscriminately, the differences may exceed the maximum allowable error of glucose determinations for diagnosing and monitoring diabetes mellitus, and complicate the treatment. The goal of the IFCC Scientific Division Working Group on Selective Electrodes and Point of Care Testing (IFCC-SD, WG-SEPOCT) is to reach a global consensus on reporting results. The document recommends reporting the concentration of glucose in plasma (with the unit mmol/L), irrespective of sample type or measurement technique. A constant factor of 1.11 is used to convert concentration in whole blood to the equivalent concentration in the pertinent plasma. The conversion will provide harmonized results, facilitating the classification and care of patients and leading to fewer therapeutic misjudgments.

Guidelines for sampling, measuring and reporting ionized magnesium in undiluted serum, plasma or blood: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC): IFCC Scientific Division, Committee on Point of Care Testing.

All analyzers with ion-selective electrodes for ionized magnesium (iMg) should yield comparable and unbiased results. The prerequisite to achieve this goal is to reach consensus on sampling, measurement and reporting. The recommended guidelines for sampling, measurement and reporting iMg in plasma ("plasma" refers to circulating plasma and the forms in which it is sampled: the plasma phase of anticoagulated whole blood, plasma separated from blood cells, or serum) or blood, referring to the substance concentration of iMg in the calibrants, will provide results for iMg that are approximately 3% greater than its true concentration, and 4% less than its true molality. Binding of magnesium to proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be simultaneously measured to allow adjustment of iMg concentration to pH 7.4. The substance concentration of iMg may be physiologically and consequently clinically more relevant than the substance concentration of total magnesium.

Biosensors in clinical chemistry.

Biosensors are analytical devices composed of a recognition element of biological origin and a physico-chemical transducer. The biological element is capable of sensing the presence, activity or concentration of a chemical analyte in solution. The sensing takes place either as a binding event or a biocatalytical event. These interactions produce a measurable change in a solution property, which the transducer converts into a quantifiable electrical signal. Present-day applications of biosensors to clinical chemistry are reviewed, including basic and applied research, commercial applications and fabrication techniques. Recognition elements include enzymes as biocatalytic recognition elements and immunoagents and DNA segments as affinity ligand recognition elements, coupled to electrochemical and optical modes of transduction. The future will include biosensors based on synthetic recognition elements to allow broad applicability to different classes of analytes and modes of transduction extending lower limits of sensitivity. Microfabrication will permit biosensors to be constructed as arrays and incorporated into lab-on-a-chip devices.