Sensors clinical

Smith, R. H. et al. (1999) Development of kinetic ligand-binding assays using a fiber optic sensor. Clinical Chemistry 45 1683-1685. 

The range of sample characteristics and manner of their detection, is much larger than can be realistically addressed in the space of a single chapter. We will confine this chapter mainly to the chemical sensor research areas discussed in other chapters in this volume, dividing them into electrical, optical, and mass and thermal measurements. Our focus will furthermore be on the generic chemical and physical phenomena upon which such measurements can be based, as opposed to the alternative organization that would address chemical sensors in the context of their application (i.e, auto exhaust sensor, clinical diagnostic sensor, environmental sensor) or of the kinds of samples detected (i.e, CO sensors, humidity sensor, biosensor, etc.), as used in a previous ACS Symposium Series volume on Chemical Sensors (D. Schuetzle, R. Hammerle, Eds., ACS Sympos. Ser. 309, 1986). 

The majoiity of the various analyte measurements made in automated clinical chemistry analyzers involve optical techniques such as absorbance, reflectance, luminescence, and turbidimetric and nephelometric detection means. Some of these ate illustrated in Figure 3. The measurement of electrolytes such as sodium and potassium have generally been accomphshed by flame photometry or ion-selective electrode sensors (qv). However, the development of chromogenic ionophores permits these measurements to be done by absorbance photometry also. 

Campbell, M. (ed.J (1996) Sensor System for Environmental Monitoring, Kluwer Academic Publishers, The Hague. Carson, P.A., and Dent, N.J. (ed.) (1990) Good Laboratory and Clinical Practices, Hememann Newnes, Oxford. Carson, P.A., and Mumford, C.J. (1988) The Safe Handling of Chemicals in Industry (Vols 1 and 2), Longman Scientific and Technical, Harlow. 

Miniaturized catheter-type ISE sensors, such as the implantable probe shown in Figure 5-20 represent the preferred approach for routine clinical in-vivo monitoring of blood electrolytes. For these intravascular measurements the reference electrode is placed outside die artery (in die external arm of die catheter), tints obviating biocompatability and drift problems associated with its direct contact with the blood. 

Electrochemical sensors play a crucial role in environmental and industrial monitoring, as well as in medical and clinical analysis. The common feature of all electroanalytical sensors is that they rely on the detection of an electrical property (i.e., potential, resistance, current) so that they are normally classified according to the mode of measurement (i.e., potentiometric, conductometric, amperometric). A number of surveys have been published on this immense field. The reader may find the major part of the older and recent bibliography in the comprehensive reviews of Bakker et al. [109-111]. Pejcic and De Marco have presented an interesting survey... 

Based on many of the advances described above in electrochemical approaches to immunoassay, it is tempting to conclude that commercialization of some of the approaches is imminent. This may be true, but the historical use of optical methods for many clinical chemistry tests coupled with their rapidly growing use in immunoassay is a difficult barrier for any radically different method to overcome, though electrochemical sensors have become more important in the clinical chemistry laboratory over the last decade. In any event, to be successful ECIA methods will have to demonstrate clear superiority over existing and emerging technologies in both cost and performance. Some of the more recently described approaches such as those using enzyme amplified amperometric detection and ecLIA appear... 

Wienke D, Lucasius C, Ehrlich M, Kateman G (1993) Multicriteria target vector optimization of analytical procedures using a genetic algorithm. Part II. Polyoptimization of the photometric calibration graph of dry glucose sensors for quantitative clinical analysis. Anal Chim Acta 271 253... 

This is the first Cys fluorescent sensor derived from FONs, in which the fluorescence enhancing property is in conjunction with a remarkable red-shifted fluorescence emission. Despite the potential sources of error when considering complicated clinical samples, the authors believe that this probe can be applied to study the effects of Cys in a biological system. 

There is an increasing interest in the development of electrochemical sensors and microsensors for detecting and monitoring NO or N02, due to their importance in clinical and environmental analysis. It has been suggested that transition metal electrocatalysts active for NO or N02 coordination and reduction could be exploited for the development of metal-complex film electrodes for N02 and NO sensing. However, most of the sensory devices reported so... 

The ion sensing scheme based on the use of potential-sensitive or polarity-sensitive dyes (PSDs) was extended to other anions. Both the clinically significant chloride ion124 and the environmentally important nitrate anion125 can be sensed in the desired concentration ranges. Such sensors have the unique advantage of having a virtually pH-insensitive response. 

Optical sensors for oxygen are among the few sensors, which have found practical application for process-monitoring and clinical diagnostics. They are generally based on compounds such as platinum porphyrins or ruthenium phenanthroline derivatives (Table 17) which show a decrease in luminescence upon exposure to molecular oxygen15. 

Muller C., Hitzmann B., Schubert F., Scheper T., Optical chemo- and biosensors for use in clinical applications, Sensor Actuat B-Chem. 1997 40 71-77... 

Reliable measurements of L-lactate are of great interest in clinical chemistry, the dairy and vine industry, biotechnology, or sport medicine. In particular, blood lactate levels are indicative of various pathological states, including shock, respiratory insufficiencies, and heart and liver diseases. Silica sol-gel encapsulation of the lactate dehydrogenase and its cofactor was employed as a disposable sensor for L-lactate51. The sensor utilized the changes in absorbance or fluorescence from reduced cofactor nicotinamide adenine dinucleotide (NADH) upon exposure to L-lactate. 

On the other hand some problems regarding the intravascular use of this sensor have emerged during clinical trials on volunteers in critical care and on surgical patients20 ... 

Center for Healthcare Technologies at Lawrence Livermore National Laboratory in Livermore, potentially capable to measure pH at or near the stroke site29. The probe is the distal end of a 125 pm fibre tapered up to a diameter of 50 pm. A fluorescent pH-indicator, seminaphthorhodamine-1-carboxylate, is embedded inside a silica sol-gel matrix which is fixed to the fibre tip. Excitation of the dye takes place at 533 nm and the emission in correspondence of the acid (580 nm) and basic (640 nm) bands are separately detected. The use of this ratiometric technique obviates worrying about source fluctuations, which have the same effects on the two detected signals. The pH sensor developed was first characterised in the laboratory, where it showed fast response time (of the order of tens of seconds) and an accuracy of 0.05 pH units, well below the limit of detection necessary for this clinical application (0.1 pH units). The pH sensor was also tested in vivo on rats, by placing the pH sensor in the brain of a Spraque-Dawley rat at a depth of approximately 5 mm30. 

First clinical results were obtained by using a combined catheter which included both the optical fibre sensor and the Tonocap balloon (Figure 8) A typical result obtained on an intensive care patient, is shown in Figure 9. In the graph the tracing of the end-tidal CO2 (EtCC>2), i.e. the CO2 concentration in the expiration at the end of the expiratory phase, and the values of the arterial CO2 (PaC02), obtained from blood samples drawn from the patient, are also shown. As expected, a rapid CO2 peak was detected only by the optical fibre sensor, and was not seen by Tonocap (as in the measurements carried out on volunteers). Moreover, the optical fibre sensor seems to follow better the end-tidal CO2. 

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