Development and application of a histidine-selective biomembrane electrode.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M E Meyerhoff.
Explore the source record for details and available documents.
Several new electrochemical devices designed for detecting ammonia and carbon dioxide in physiological samples have in common the elimination of the fragile glass pH internal electrode used in the conventional Severinghaus-design potentiometric gas sensors. In one new approach, the pH glass electrode can be replaced with a neutral carrier-based polymer-membrane pH electrode. Alternatively, to improve response characteristics and selectivity, we have used ion-selective polymer membranes responsive to ammonium and carbonate as internal sensing elements in conjunction with appropriate internal buffer reagents. The use of inner polymer membranes rather than glass membranes enables the fabrication of essentially disposable devices having rapid response times. In addition, we have constructed automated continuous-flow NH3- and CO2-sensing systems involving novel tubular forms of the polymer-membrane electrodes and a simple flow-through gas dialysis arrangement. The polymer electrode-based systems described offer many unique and practical advantages over existing gas-sensing units.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A novel bioselective membrane electrode for L-glutamine has been constructed by coupling living bacteria of the strain Sarcina flava to a potentiometric ammonia gas sensor. Tests in aqueous standards and human serum show that the electrode combines excellent sensitivity and selectivity with rapid response and a useful lifetime of at least 2 weeks.
Explore the source record for details and available documents.
An N-acetylneuraminyl-alpha 2,3(6)lactose-malate dehydrogenase (MDH-Lac-Neu5Ac) conjugate is prepared via an isothiocyanate conjugation method using a p-aminophenethylamino derivative of sialyllactose. The newly synthesized conjugate can be utilized as a reagent in a novel homogeneous lectin-based, enzyme-linked, competitive binding assay (1-3) for probing the specific carbohydrate structure and content of intact glycoproteins. The enzymatic activity of the MDH-Lac-Neu5Ac conjugate is shown to be significantly inhibited (35%) by sialic acid-binding lectin, Limax flavus agglutinin (LFA), and this inhibition is reversed by mucin, a glycoprotein possessing sialic acid terminals. The asialo form of mucin, however, binds weakly to LFA, yielding no substantial increase in the MDH-Lac-Neu5Ac activity at comparable glycoprotein concentrations. Use of the newly synthesized conjugate in conjunction with LFA or other lectins capable of binding sialic acid may provide a rapid and convenient way to detect the presence and relative amount of sialic acid terminal groups within intact glycoprotein structures.
The development of an ion-selective electrode heparin sensor consisting of a specially formulated polymer membrane doped with tridodecylmethylammonium chloride as the heparin complexing agent was recently reported. Because of the simple nature of the membrane technology used, the authors envisioned that the sensor could be configured as a disposable single-use device for rapid clinical or bedside measurement of heparin in a small, discrete sample. To explore this possibility, an inexpensive, disposable heparin sensor was created by dip-coating a copper wire with the specially formulated heparin-sensing polymeric membrane. Coated wire heparin sensors with a broad range of membrane thicknesses, prepared by repeatedly dipping the wire in the membrane solution for various times, were examined. Data show that increasing the membrane thickness of the sensor to a certain degree (more than 10 microns) enhanced the sensor's potentiometric response to heparin, although the time required to achieve 90% of the steady-state potential change was also prolonged. In addition, increasing membrane thickness also magnified the stirring effect on the sensor's response. In undiluted plasma samples, the coated-wire sensor with an optimized membrane thickness yielded a significant (5 to 30 mV) and reproducible response to heparin in a clinically relevant concentration range (0.5 to 12 units/ml, respectively). The clinical utility of the coated wire heparin sensor was shown using the sensor during protamine titration of heparinized plasma to assess the titration end-point. Preliminary results showed that the titration end-points determined by the heparin sensor strongly correlated with those determined by the activated partial thromboplastin time clotting assay. The overall time requirement to complete the titration process using a set of prefabricated coated wire heparin sensors, however, was less than 3 minutes. Further titration studies using undiluted clinical whole blood samples are in progress.
Heparin is one of the most important clinical drugs, and is employed universally during surgical procedures and extra-corporeal therapies to prevent blood from clotting. Its clinical use, however, is often associated with serious hemorrhagic complications. Because of this life threatening bleeding risk, there is a need for a simple sensing device that can rapidly and directly monitor heparin levels during extra-corporeal therapies to provide a safeguard during these procedures. Current heparin assays are all based on the measurement of blood clotting time, and none of them are suitable for direct and rapid determination of heparin. We describe applying conventional ion selective electrode (ISE) polymer membrane technology and using a specifically formulated membrane doped with tridodecylmethylammonium chloride (TDMAC) as the heparin complexing agent, to devise the first electrochemical sensor for heparin measurement. The sensor is capable of detecting directly and rather selectively the free heparin concentrations in both physiologic saline and undiluted plasma samples. In addition, the clinical utility of the sensor has been demonstrated by monitoring the levels of heparin in undiluted whole blood specimens obtained from patients undergoing open heart operations. It is envisioned that the sensor could be configured as an in-line device within extracorporeal blood loops to monitor current extracorporeal therapy, or as a convenient single use disposable device for rapid bedside or laboratory measurements of heparin in small discrete samples of undiluted whole blood. Preliminary studies concerning the feasibility of designing a mass fabricated, solid state, disposable heparin sensor also have been conducted.
The authors previously reported the development of an ion selective electrode type heparin sensor consisting of a specially formulated polymer membrane doped with tridodecylmethylammonium chloride as the heparin complexing agent. They also demonstrated the feasibility of measuring blood heparin levels by protamine titration, using a disposable copper wire sensor coated with the heparin sensing membrane to probe the titration end point. In this article, the results of further titration studies conducted on 44 clinical whole blood specimens obtained from 8 patients undergoing open heart surgery were reviewed. Samples were taken from patients at four different stages during the bypass surgery: 1) before heparin administration; 2) immediately after heparin administration; 3) within 30 min to 3 hr after heparin administration; and 4) within 30 min after protamine administration. Heparin anticoagulant activity in these samples was monitored by the activated clotting time assay, whereas heparin concentrations were measured by protamine titration using either the Hepcon HMS Titrator (Medtronic HemoTec Inc., Englewood, CO) or the coated wire heparin sensor to determine titration end points. Results indicate that heparin levels determined by the sensor method were in good agreement with those determined by the Hepcon HMS Titrator. When the heparin concentrations estimated by the two methods show significant discrepancy (> 1.0 unit/ml), the sensor method seems to provide more precise values, as verified by an additional chromogenic heparin assay. The overall time required to complete the titration process and heparin measurement with a pre made heparin sensor was less than 3 min. Clinically, the heparin sensor could be used as a safeguard to precisely monitor heparin levels during surgical procedures. Alternatively, the sensor could be used to assess the accurate protamine dose required for full heparin reversal.