Yellow Springs Instrument Research Articles

Use of an enzyme thermistor for semi-continuous blood glucose measurements

A method to monitor glucose in whole blood is presented. The aim of the project was to develop a prototype for a bedside monitor system for semi-continuous monitoring of the blood glucose concentration, requiring only one calibration. This was made possible by using the special advantage of the thermal sensor technique in combination with the adjustment of flow. The glucose concentration was determined from the difference between the sensor response and an estimated background signal. Using standard addition technique, calibration factors for background and sensitivity were set and remained unchanged during the monitoring. The background signal was 45 ± 8 mV (mean ± S.D., n = 8) and the sensitivity was 28 ± 1 mV/mmol (mean ± S.D., n = 4). Recovery in whole blood was 90–98% (mean 94%, n = 12). With an injection interval of 3 min the precision with the sensor was <3% over more than 100 blood samples. Response time was about 60 s. The calculated glucose values correlated, r = 0.98, with the values obtained with an YSI glucose; analyser (Yellow Springs Instruments, Yellow Springs, OH, USA), over the range 2–20 mmol/l.

Evaluation of the APEC analyzer for whole blood glucose. Testing in a pediatric setting.

The APEC glucose analyzer (APEC, Danvers, MA) was analyzed in a pediatric clinical chemistry laboratory and its performance was compared with glucose determinations on the YSI 2300 STAT analyzer (Yellow Springs Instrument [YSI], Yellow Springs, OH). One hundred sixty-nine samples were simultaneously analyzed by the APEC and the YSI systems. The agreement between the two analyzers was excellent, with r = 0.986, slope = 1.04, and y intercept = -0.094. Analysis of the run-to-run precision yielded a CV of < or = 4.1% for both the APEC and the YSI instruments. Both analyzers displayed a sensitivity to at least 1.1 mmol/L (20 mg/dL) and both produced a linear response up to 27.8 mmol/L (500 mg/dL). Neither instrument was affected by icteric or hemolyzed samples. Variations in the patient's hematocrit did not lower the whole blood glucose values when these were compared with the equivalent plasma levels. In conclusion, the APEC glucose analyzer is suited for whole blood glucose testing in pediatric settings.

The slow penetration of enzyme-based biosensors into clinical chemistry analysis.

In 1972 Yellow Springs Instrument Co., Inc. (YSI) introduced the first commercial instrument which could measure glucose in diluted whole blood by use of an enzyme-based biosensor. Until 1986 YSI had a monopoly of this technology for clinical chemistry. Since 1986 another ten companies have commercialized the technology. Enzyme-based biosensors for clinical chemistry are now available for glucose, lactate, and urea. Until 1975 the annual number of papers on enzyme-based biosensors is sparse, but from then there is a significant increase in the number of publications. The commercial interest in glucose is reflected in the number of patents covering this analyte: close to fifty per cent of the patents cover this type of sensor while less than ten per cent of the scientific papers are on glucose sensors. The major problems in developing enzyme-based biosensors for clinical chemistry have been achievement of the necessary linear range and elimination of interferences from the blood. The slow penetration of enzyme-based biosensors into clinical chemistry analysis is due to the fact that it is difficult to develop sensors which meet the high accuracy and reliability requirements, are manufacturable, and have an acceptable shelf life. The number of commercial products utilizing enzyme-based biosensors will probably remain limited in the future due to the limited number of analytes for which a suitable enzyme exists, and for which the use of an enzyme-based biosensor offers the advantages that can justify the costs of development.

A Ward Comparison Between the One Touch II and Glucometer II Blood Glucose Meters

A 6-week clinical evaluation of the One Touch II blood glucose meter was performed in a medical ward specializing in diabetic patients and compared to the existing Glucometer II system. Nursing staff trained in both methods performed 267 capillary blood glucose measurements using the two meters. A reference capillary blood glucose was performed simultaneously on 129 of these occasions using a Yellow Springs Instrument analyser. The One Touch II correlated better with the reference (r = 0.97) than the Glucometer II (r = 0.86) and was equally close or closer to the Yellow Springs Instrument on 82% of occasions. A greater proportion of samples measured by the One Touch II were within 15% of the reference value (83% vs 66%). There were also 17 cases where the One Touch II was able to give a measurement which was outwith the analytical range of the Glucometer II. A questionnaire revealed the nursing staff unanimously preferred using the One Touch II to their present meter. It is concluded that in a ward setting the One Touch II meter showed improved accuracy, usefulness in its wider analytical range, and a greater user preference in comparison to the Glucometer II.

Lactate Measured in Diluted and Undiluted Whole Blood and Plasma: Comparison of Methods and Effect of Hematocrit

We evaluated a new analyzer that measures lactate in undiluted whole blood by direct (or undiluted) amperometry [Nova Stat Profile 7 Analyzer (SP7); Nova Biomedical, Waltham, MA] by comparing it with two other analyzers, one for measuring lactate in whole blood by indirect (or diluted) amperometry [Model 2300; Yellow Springs Instrument Co. (YSI), Yellow Springs, OH] and another for measuring lactate in plasma by enzymatic colorimetry (aca; Du Pont Co., Wilmington, DE). All between-method comparisons of the three methods showed that the results for plasma were comparable (Sy/x = 0.24-0.33 mmol/L). Within-method comparisons by the YSI differed substantially between plasma and whole blood (Sy/x = 0.48 mmol/L), but within-method comparisons by the SP7 produced better agreement between plasma and whole blood (Sy/x = 0.18 mmol/L). The difference between whole blood and plasma by YSI is related to hematocrit, with the greatest differences noted for samples with the highest hematocrit. Serum lactate measured by SP7 had between-day imprecision (CV) ranging from 12% at 0.5 mmol/L to 4.2% at 3.7 mmol/L, showed a linear standard curve to at least 11.5 mmol/L, and was independent of hematocrit. There was a mean bias of approximately 0.4 mmol/L for results in the reference range for both plasma and whole blood by SP7 compared with plasma results by either aca or YSI.

Improving Lactate Analysis with the YSI 2300 Gl: Hemolyzing Blood Samples Makes Results Comparable with Those for Deproteinized Whole Blood

To obviate the well-documented problem of hematocrit dependency of the Yellow Springs Instruments (YSI) whole-blood lactate analyzer, we modified the dilution buffer by including a lysing reagent. This makes the results comparable with those of methods performed with deproteinized whole-blood samples. No centrifugation step is needed, thus preserving the convenience of the YSI instrument for stat and field use. The modification works equally well on plasma samples. Lactate concentrations measured in nonhemolyzed whole blood are not comparable with results for hemolyzed whole blood or protein-precipitated whole blood. We therefore recommend to all users of YSI equipment to lyse the erythrocytes before lactate determinations.

On-line determination of glucose and lactate concentrations in animal cell culture based on fibre optic detection of oxygen in flow-injection analysis

A flow-injection analysis (FIA) system based on fibre optic detection of oxygen consumption using immobilized glucose oxidase (GOD) and lactate oxidase (LOD) is described for the on-line monitoring of glucose and lactate concentrations in animal cell cultures. The consumption of oxygen was determined via dynamic quenching by molecular oxygen of the fluorescence of an indicator. GOD and LOD were immobilized on controlled pore glass (CPG) in enzyme reactors which were directly linked to a specially designed fibre optic flow-through cell covering the oxygen optrode. The system is linear for 0–30 m m glucose, with an r.s.d. of 5% at 30 m m (five measurements) and for 0–30 m m lactate, with an r.s.d. of 5% at 30 m m (five measurements). The enzyme reactors used were stable for more than 4 weeks in continuous operation, and it was possible to analyse up to 20 samples per hour. The system has been successfully applied to the on-line monitoring of glucose and lactate concentrations of an animal cell culture designed for the production of recombinant human antithrombine III (AT-III). Results of the on-line measurement obtained by the FIA system were compared with the off-line results obtained by a glucose and lactate analyser from Yellow Springs Instrument Company (YSI).

Influence of blood handling techniques on lactic acid concentrations.

Despite the popularity of measuring blood lactic acid concentrations, many of the common variations in technique have not been evaluated. The purposes of this study were to: 1) establish the relationship between plasma and blood lactate concentrations, 2) determine the inter-analyzer reliability, and 3) assess the stability of lactate concentration in blood stored for up to one week. Blood was sampled from 26 volunteers before exercise, at 80% of estimated maximum heart rate, and 5 minutes after a treadmill run to exhaustion. Inter-machine reliability was tested between two Yellow Springs Instruments analyzers with buffer treated with a lysing agent and between two without. Blood lactate levels at all three levels could be predicted from plasma with R2 greater than .95. Correlations between duplicates on the same machine were greater than .96 for blood and .97 for plasma. In the worst cases, between duplicate differences and between machine differences were 2%. Lactate in stored blood was in some cases significantly different after 24 hours of storage. Moderate and high lactate concentrations in plasma were not significantly altered after 2 days of storage.

A system for the on-line determination of glucose concentration

An off-line glucose analyzer, Yellow Springs Instrument (YSI) model 27 was modified and coupled to various peripheral components to produce a fast, fully automated system for the online determination of glucose concentration. The amount of time required to accomplish each measurement was in the order of two minutes. To demonstrate the utility of this system, various tests were performed. First, a stream containing known amounts of glucose was monitored on-line and the system was calibrated. The calibration curve was shown to be described by Michaelis-Menten kinetics. Once the system was properly calibrated, it was used to monitor the glucose concentration in the effluent stream of two different enzyme reactor systems. The glucose concentrations were within experimental error of those obtained via standard off-line techniques.

On-line determination of glucose concentration throughout animal cell cultures based on chemiluminescent detection of hydrogen peroxide coupled with flow-injection analysis

A flow-injection analysis (FIA) system for the on-line determination of glucose in animal cell cultures is described. The system is based on immobilized glucose oxidase (GOD). The hydrogen peroxide generated in the enzyme reaction is determined via a highly sensitive chemiluminescent reaction with luminol. Based on the measurement of the maximum emitted light intensity, the system was able to analyse hydrogen peroxide over the concentration range of 10 −7 to 10 −2 M. For glucose determination, the system has a linear range of 10 −5 to 5 × 10 −2 M glucose, with an r.s.d. of 3% at the 1 mM level (5 measurements). The influence of luminol and buffer concentrations, pH and temperature on the chemiluminescent reaction were investigated. The enzyme reactor used was stable for more than 4 weeks in continuous operation, and it was possible to analyse up to 20 samples per h. The system has been successfully applied to on-line monitoring of glucose concentration during an animal cell culture, designed for the production of human antithrombin III factor. Results obtained with the FIA system were compared with off-line results, obtained with a Yellow Springs Instrument Company Model 27 (YSI).

Determination of malolactic enzyme activity using an immobilized L-lactate oxidase probe

This paper describes a method for bacterial malolactic enzyme assay based on the use of an industrial analyser (YSI (Yellow Springs Instruments Co.) model 27) equipped with an immobilized L-lactate oxidase probe. The method is very reliable and well adapted to estimation of enzyme activities producing L-lactic acid.

"Stat" measurements of L-lactate in whole blood and cerebrospinal fluid assessed.

A first-generation semi-automatic amperometric lactate analyzer (Yellow Springs Instrument Co.) was assessed for urgent ("stat"), rapid laboratory measurements in whole blood and cerebrospinal fluid. For whole blood, measured lactate concentration and hematocrit were linearly correlated. An improved equation is presented for estimating the concentration of lactate in plasma from measurements in whole blood. The 95% reference range for the concentration of lactate in paired samples of capillary and venous whole blood from 40 healthy laboratory adults was found to be 0.4-1.5 mmol/L and 0.3-1.5 mmol/L, respectively. The 95% ranges for lactate in whole blood from 24 uncomplicated vaginal deliveries at term were established for cord venous blood, 1.2-5.0 mmol/L; cord arterial blood, 1.6-5.5 mmol/L; and maternal venous blood, 1.7-6.6 mmol/L. The 95% paired ranges were established for 20 lumbar-anaesthetized urological patients without neurological disorders after induction of anaesthesia for venous whole blood and cerebrospinal fluid (venous blood, 0.5-1.3 mmol/L; cerebrospinal fluid, 1.1-2.4 mmol/L).

Inexpensive Method for Repair of YSI Model 403 Thermistor Probes

Abstract An inexpensive method of refurbishing failed YSI (Yellow Springs Instrument) thermistor probes by use of epoxy resin has been developed. The faulty thermistor is severed, a new one is soldered on, and the unit is sealed with epoxy resin in a glass test tube.

Photodynamic therapy for cutaneous and subcutaneous malignant neoplasms.

Twenty-seven patients with cutaneous and subcutaneous malignant neoplasms were treated with photodynamic therapy. Therapy was administered to 248 areas during a total of 72 separate treatment sessions after patients received a total of 45 injections of sensitizer. Seven patients had basal cell carcinoma, three had squamous cell carcinoma, three had malignant melanoma, one had liposarcoma, and 12 had breast cancers. One patient had Bowen's disease. Treatment was given either by surface radiation or interstitially. One month after treatment, 48 (67%) of the treatment sessions resulted in a complete response (no clinical evidence of tumor), and 19 (26%) resulted in a partial response (greater than 50% reduction in the number or size of tumors). Fifteen patients were examinable 12 months after treatment, and in this group, 31 treatment sessions were evaluated as a complete response one month after therapy, 15 (48%) of which retained this status at one year after treatment. By comparing the ability of different light-delivery instrumentation, it was concluded that the Yellow Springs radiometer (Yellow Springs Instruments, model 65A, Yellow Springs, Ohio) provided the most reliable spot power density readings. Straight-tipped fibers are nonhomogeneous and can result in overtreatment of the central area with necrosis and pain and in undertreatment of the periphery.

Clinical application of a new glucose analyzer in the neonatal intensive care unit: Comparison with other methods

We evaluated the operation of the Yellow Springs Instrument Co. (YSI) glucose analyzer (model 23A) by clinical nurses for the measurement of blood glucose in the intensive care nursery. In vitro performance was determined with the use of aqueous standards; with a 2-point calibration of 0.0 and 200 mg/dl, a precision of better than 1.0% of each standard (25, 50, 100, 200 mg/dl) was achieved, and the linearity was excellent (Y = 0.99X - 0.49, r = 0.99). The YSI correlated well with a manual spectrophotometric glucose oxidase method (r = 0.99) and the Kodak Ektachem analyzer (r = 0.98) using human umbilical cord blood samples. Five trained clinical nurses performed all YSI and glucose reagent strip analyses, including all in vitro and patient samples. Four reagent strip methods were compared with the YSI from 104 neonatal heel-stick blood samples: Glucometer II with memory (r = 0.73), Glucostix (r = 0.74), Dextrostix (r = 0.70), and Chemstrip bG (r = 0.83). We conclude that clinical nurses can and do learn to use the YSI with excellent precision and that the YSI represents an improved method for measuring glucose concentrations in the newborn intensive care nursery.

Metal oxide catalyst membrane electrodes for the determination of hydrogen peroxide

The use of metal oxides as catalysts in electrochemical sensors for hydrogen peroxide is reported. Membrane-immobilised and entrapped catalysts were used with a Yellow Springs Instruments Model 5739 oxygen electrode. The electrodes were studied at high pH in the dip-type mode. The most sensitive electrode using manganese(IV) oxide had a detection limit of <10–6M hydrogen peroxide and did not suffer interference from many components commonly found in industrial waste samples. The manganese(IV) oxide catalyst electrode was adapted as a flow injection technique and showed good responses during continuous use.

Effect of hematocrit concentration on blood glucose value determined on Glucometer II.

Nineteen patient blood samples each with modified hematocrit concentrations of approximately 20, 30, 40, 50, and 60%, were assayed for their glucose concentration by the Glucometer II. Blood removal from the test strip was by the one- and two-blot techniques. The reference method was the Yellow Springs Instruments (YSI) blood glucose analyzer. Glucometer II results were falsely high for the single blot (13-59%, mean 33%) and double blot (12-41%, mean 19%) at 20% hematocrit and falsely low at 60% hematocrit for the single blot (22-44%, mean 37%) and the double blot (26-49%, mean 43%). At 40-50% hematocrit, Glucometer II and YSI results agreed only for the one-blot technique.

Chemically immobilised enzyme electrodes for hydrogen peroxide determination

The use of peroxidase and catalase in electrochemical sensors for hydrogen peroxide is reported. The enzymes are chemically immobilised on nylon net. The peroxidase enzyme electrode is used in a flow injection analysis (FIA) mode as the working electrode in a three-electrode modified Stelte cell with hexacyanoferrate(II) as the redox mediator in a phosphate buffer carrier stream. The low potential used (– 100 mV versus silver-silver chloride) helps to offset the effect of redox-active interferents. The catalase enzyme is used in conjunction with a Yellow Springs Instruments Model 5739 oxygen electrode and has been studied in the dip mode at high pH. The two electrode systems can be calibrated between <10–5 and >10–3M hydrogen peroxide and do not suffer from interference by many of the components commonly found either in industrial samples where hydrogen peroxide is employed, or in wastewater samples.

Water Costs and Water Revenues for Established and Rain-Induced Roots of Agave deserti

Water Costs and Water Revenues for Established and Rain-Induced Roots of Agave deserti

Amperometric enzyme electrode system for the flow injection analysis of glucose.

A flow injection system incorporating an amperometric enzyme electrode is described. Glucose oxidase immobilised on nylon mesh and held over a platinum electrode formed the basis of the electrode, which was incorporated in a three-electrode amperometric Stelte cell, modified for flow injection analysis. The flow and enzymatic reaction conditions have been optimised for maximum glucose response. The system exhibited good linearity (0.01 to 3.0 mM glucose), short response times (<45 s), good capacity (24 h with a continuous flow of 2.5 mM glucose) and long lifetimes (up to 4 months with storage at 4 °C). Data for the determination of glucose in foodstuffs with the enzyme electrode were similar to those obtained by the Yellow Springs Instrument glucose analyser and a soluble enzyme test kit (Boehringer Mannheim method).