In human medicine, it has hitherto been customary practice to send samples of body fluids, e.g. blood, plasma or urine, for analysis to a specialized clinical laboratory possessing the necessary technical equipment and trained staff. Clinical chemical parameters of particular interest are, for example:
pH. PA0 concentrations of electrolytes, such as Li.sup.+, Na.sup.+, K.sup.+, Ca.sup.2+, Mg.sup.2+, Cl.sup.-, HCO.sub.3.sup.- and NH.sub.3 (NH.sub.4.sup.+), PA0 concentrations of dissolved gases, notably oxygen and carbon dioxide (conventionally reported in the form of partial pressures, e.g. pO.sub.2, pCO.sub.2), PA0 haemoglobin concentration, PA0 concentrations of metabolic factors, such as glucose, creatinine, urea (BUN), uric acid, lactic acid, pyruvic acid, ascorbic acid, phosphate, protein, bilirubin, cholesterol, triglycerides, phenylalanine and tyrosine, PA0 concentrations of enzymes, such as lactic acid dehydrogenase (LDH), lipase, amylase, choline esterase, alkaline phosphatase, acid phosphatase, alanine amino transferase (ALAT), aspartate amino transferase (ASAT) and creatinine kinase (CK). PA0 and concentrations of ligands, such as antibodies and nucleotide fragments. PA0 a sensor having a sensing surface part, PA0 and a chamber adapted to contain a conditioning fluid, the chamber being partly defined by a first wall part adapted to allow the sensor to pass through it and establish a seal around the sensor when the sensor traverses the first wall part, the sensor and the chamber being movable relative to each other so as to transfer the sensing surface part of the sensor through the first wall part from a position where the sensing surface part of the sensor is inside the chamber to a position where it is outside the chamber, PA0 exposing the sensing surface part of the sensor to a conditioning fluid in the chamber, PA0 moving the sensor and the chamber relative to each other so as to transfer the sensing surface part of the sensor through the first wall part and position it outside the chamber, PA0 exposing the sensing surface part of the sensor to a sample fluid, PA0 deriving the characteristic on the basis of a response generated by the sensor when the sensing surface part of the sensor is exposed to the sample fluid, and, optionally, a response generated by the sensor when the sensing surface part of the sensor is exposed to the conditioning fluid, PA0 and discarding the measuring device after one measurement of the characteristic. PA0 by keeping the chamber fixed relative to the measuring device as a whole, and moving the sensor, PA0 by keeping the sensor fixed relative to the measuring device as a whole, and moving the chamber. PA0 exposing the sensing surface part of the sensor to a sample fluid, PA0 moving the sensor and the chamber relative to each other so as to transfer the sensing surface part of the sensor through the first wall part and position it inside the chamber, PA0 exposing the sensing surface part of the sensor to a conditioning fluid in the chamber PA0 deriving the characteristic on the basis of a response generated by the sensor when the sensing surface part of the sensor is exposed to the sample fluid, and a response generated by the sensor when the sensing surface part of the sensor is exposed to the conditioning fluid, PA0 and discarding the measuring device after one measurement of the characteristic. PA0 selective interaction with the chemical species of interest, thereby producing a well-defined and measurable response which is a function of the desired characteristic of that chemical species, the desired characteristic thus being derivable therefrom, PA0 response to a bulk property of a fluid, the response not being selective with respect to any specific chemical species, but being a function of the total concentration of one or more chemical species in the fluid, the desired characteristic thus being derivable therefrom. PA0 potentiometric sensors for use in aqueous media, such as ion-selective electrodes for specific measurement of the concentration of selected ionic chemical species [a description of non-limiting examples of some ion-selective electrodes for the selective measurement of the concentrations of a number of cations and anions of frequent interest is provided by Simon (W. Simon, "Ion-Selective Electrodes Based on Neutral Carriers", in H. Freiser, Ed., "Ion-Selective Electrodes in Analytical Chemistry", Plenum, 1978, pp. 211-281)], the response being in the form of an electric potential, PA0 amperometric sensors, such as sensors for the determination of oxygen partial pressure, whose response is in the form of an electric current, PA0 optical sensors, such as sensors producing a colour response to a particular chemical species, the colour intensity being measured by, e.g., reflectometry, PA0 piezoelectric sensors, PA0 thermometric sensors, PA0 pressure-change sensors, PA0 acoustic sensors, PA0 enzyme-based sensors employing an enzymatic reaction and generating a response on the basis of any relevant physical principle, for example any of those principles employed in the sensor types listed above; examples are enzyme-based thermistors and enzyme-based amperometric sensors for use in the measurement of concentrations of metabolic products, e.g. glucose, urea, creatinine or lactate, PA0 and affinity sensors comprising one moiety of an affinity pair, e.g. an antigen/antibody pair or two complementary nucleotide fragments, the other moiety being the chemical species of interest PA0 a calibration fluid for the calibration of the response of the sensor in relation to the magnitude of the characteristic, the calibration fluid containing a known concentration of chemical species, PA0 a fluid for the preparation of the sensor prior to the use of the sensor in measuring the characteristic such that measurement of the characteristic can take place without further treatment of the sensor, PA0 a reference fluid for a reference electrode; PA0 a fluid for establishing a fluid junction between a reference fluid and a sample fluid; PA0 a fluid for establishing a fluid junction between a reference fluid and a conditioning fluid; PA0 such that an aperture matching in size and profile the cross-section of the sensor is provided for the sensor, the perimeter of the aperture being equipped with sealing means which provide the above-mentioned fluid-tight seal around the sensor, the sensor in this case at all times traversing the wall, PA0 such that it initially has no aperture for the sensor, thereby initially constituting an intact boundary between the inside and the outside of the chamber, but is ruptured by the sensor following movement of the sensor and the first wall part relative to each other, an aperture being formed which matches in size and profile the cross-section of the sensor, the perimeter of the aperture providing the above-mentioned fluid-tight seal around the sensor. PA0 permit relative movement of the sensor and the first wall part without excessive frictional resistance to the movement, PA0 and substantially prevent contamination of the sample fluid by the conditioning fluid or vice versa. PA0 in those cases where the conditioning fluid chamber of the measuring device is intended to be filled only once with conditioning fluid (either from a store of conditioning fluid within the measuring device, or by any other means, the measuring device is not discarded after one, but instead is discarded after more than one measurement of the characteristic, the discardment taking place before the conditioning fluid is no longer capable of properly exerting its conditioning function, PA0 in those cases where the measuring device comprises a store of conditioning fluid intended for repeated release of conditioning fluid into the conditioning fluid chamber, the measuring device is not discarded after one measurement of the characteristic, but is re-used such that the conditioning fluid in the chamber is replaced with a fresh portion of conditioning fluid from said store after each measurement of the characteristic, the measuring device being discarded before or when the store of conditioning fluid has been consumed.
In the past, clinical chemical analysis systems have tended to be large in size, expensive and complex to operate, and in general only relatively large medical institutions have been able to afford the purchase, operation and maintenance of such systems. Smaller hospitals, clinics, general practitioners etc. usually have had to employ centralized commercial or hospital laboratories for clinical chemical analyses, leading to unavoidable delays in the procedure.
Since abnormal values of certain clinical chemical parameters are indicative of serious danger to health, the rapid and reliable determination of clinical chemical parameters in general is of crucial importance for proper and effective medical treatment. Furthermore, quite apart from the acute aspects of medical treatment, it is clearly an advantage, both for patients from a psychological viewpoint and for medical staff from an administrative viewpoint, that clinical analysis results are accessible as quickly as possible.
Thus, increasing demands for reduction in costs, more rapid turnover, greater decentralisation and increased staff flexibility in clinical chemical analysis have provided an incentive for the development of easy-to-use, easy-to-maintain, reliable, relatively cheap, compact and, if possible, portable equipment, based in part on discardable components, for the bedside measurement of those characteristics of chemical species which constitute fundamental clinical chemical parameters of body fluids.
Equipment based in part on disposable components may also be of great value in numerous non-medical analytical applications where the ability to carry out decentralised or field analyses is of importance. Examples of such applications are the determination of pH, colour and concentrations of chemical species such as chloride, nitrite, nitrate, sulfate and phosphate in relation to control of the quality of bodies of water used for domestic supplies, and on-site analyses of the contents of process vessels, e.g. in fermentation processes such as the production of beers and wines, in sugar refining and in industrial syntheses.
PCT applications WO 85/02257, WO 85/04719 and WO 86/05590, U.S. Pat. No. 4,436,610, U.S. Pat. No. 4,225,410 and European application EP 0189316, disclose apparatuses, all of which comprise a disposable measuring device and an analyzer, suitable for bedside clinical chemical analyses, notably of blood samples. European patent EP 0012031 discloses a method and apparatus for measuring a chemical characteristic of a liquid, in particular for measuring the pH of a blood sample. The preferred embodiments of the measuring devices disclosed in the first five of the above mentioned sources are intended for discardment after a single use, whereas a preferred embodiment disclosed in EP 0189316 and embodiments disclosed in EP 0012031 are intended to be disposed of after repeated use. In each of these devices the sensor or sensors responsive to the chemical species, and the chamber(s) or passage(s) in which the sensor or sensors are exposed to a calibration fluid or a sample fluid remain fixed with respect to the housing or support of the measuring device as a whole.
British application GB 2 183 041 discloses apparatus comprising an analyzer and a measuring device for analyzing an undiluted body fluid; the measuring device comprises an ion-selective or enzymatic sensing electrode which is mounted on a probe, the probe being movable to transfer the sensing electrode between an open-ended reference wash cell and a sample cup bearing the body fluid specimen to be analyzed. The measuring device disclosed is intended for prolonged repeated use and is rather complex in its construction.
As will be described in detail in the following, the present invention concerns, inter alia, methods using discardable measuring devices for measuring a characteristic which is a function of the concentration of one or more chemical species in a sample fluid, for example a body fluid, the measurement entailing movement of a sensor relative to a sample fluid chamber containing a sample fluid and/or relative to a chamber containing a fluid for conditioning the sensor (e.g. calibrating the sensor response), or movement of said sample fluid chamber and/or said conditioning fluid chamber relative to a sensor. As will become clear from the following, this principle offers a number of advantages in connection with measurements using discardable measuring devices.