Patent Application
20060140822
The present invention relates to medical analyzers and, in particular, to a device for temperature control or thermostatting of a measuring cell in an analyzer.
It is known that many devices and apparatuses containing sensors show temperature-dependent signal characteristics. Depending on the type of sensor, this effect is due to the temperature dependence of chemical processes, their equilibrium state and/or their kinetics, or, especially in the case of electrochemical sensors, a temperature-dependent change of physical properties, such as electrical conductivity.
Such sensors are frequently used in medical analyzers for the determination of gas partial pressures in blood or for the measurement of the pH-value or ion or metabolite concentrations in body fluids. In particular, such sensors are used in blood gas analyzers, which play an important role in medical diagnostics.
While the temperature coefficients of the sensors may easily be obtained by calibration measurements, a problem arises when the variables to be measured are temperature-dependent, as for instance the partial pressures and pH of blood gases (pO2, pCO2, pH), and when the temperature coefficients of the sample required for computational correction are not known with sufficient accuracy. Computing the values of a blood sample at body temperature (37° C.) from measurement values which have been obtained at ambient temperature will thus be prone to error.
To avoid the temperature-dependent effects mentioned above, it is known to use measuring cells with sensors in controlled temperature environments, i.e., in thermostats. If the measuring cells are to be exchanged after a certain time of use, however, the measuring cell should be easily detachable from the thermostat, which is a fixed component of the analyzer.
In general, the measuring cells are operated in a temperature-controlled chamber of the analyzer, which is kept at constant temperature and usually made from a metal alloy or ceramic material.
Especially in the case of dissolved gases the temperature of the sample during measurement plays an important role. The solubility of gases, e.g. in aqueous media, decreases as temperature increases, and the dissolved gas thus shows a tendency to escape from the solution. The measured value will thus be higher. At lower measuring temperatures a lower measurement value will be obtained.
The analysis of blood gas parameters plays an important part in medical diagnosis, especially in an emergency situation. The collective term of blood gas parameters is used for the value of oxygen partial pressure, carbon dioxide partial pressure (gas dissolved in a physiological sample) and the pH-value of the physiological sample or of an aqueous reference solution.
To obtain an accurate picture of the situation in the body of a patient measurements are carried out at a sample temperature of 37° C. Even if the time span between sample-taking and measurement is small, the blood sample will have significantly cooled off and must very quickly be heated again to body temperature in the analyzer.
The sensors used in the measuring cell are constantly kept at measuring temperature, in this case at 37° C. This is necessary since the massive heating block (large weight) has a very slow reaction to temperature change, and the measuring cell—due to being made from polymeric materials (see EP 1 087 224 A2, for example), which conduct heat poorly or very poorly—will also exhibit a sluggish reaction to temperature change. The thermostatted parts of the housing are made of polycarbonate, for instance, and have wall thicknesses of up to 5 mm, which will also increase heat transfer resistance.
Even if the measuring cell is pressed against one or more thermostatted surfaces of the analyzer, contact with the thermostatted surface is established only at a few points and in a non-reproducible manner. From EP 1 367 392 A1 an analyzer is known in this context, whose temperature controlled measuring cell is provided with electrochemical electrodes not further specified. The measuring cell is thermostatted by Peltier elements, with a flat heat-conducting distributing element being placed between the Peltier elements and the wall of the measuring cell. Due to unavoidable air gaps this arrangement will be equivalent to an air bath, with heat transfer being limited primarily by the thickness of the polymeric material around the electrochemical sensor, which is a poor heat conductor, and by the remaining air gap adjacent to the thermostatted surface.
A consequence of this set-up is a retarded change of temperature of both sample and sensor. It will thus take longer for the device to be ready for measurement at the target temperature. To shorten this delay in actual operation the sample is heated approximately to target temperature in a preheating section preceding the measuring cell. The desired temperature of samples and sensors at the measurement location is thus achieved more easily and quickly.
Some sensors contain constituents whose useful lifetime is limited by the operating temperatures required, such as for instance enzymes which enable necessary sensor reactions at the measurement site. Once these enzymes are partly or totally destroyed by prolonged temperature exposure, i.e., their activity is reduced or deactivated, the sensor can no longer be used. Higher temperatures will thus usually shorten the useful lifetime of enzyme-containing sensors.
It is against the above background that the present invention provides certain unobvious advantages and advancements over the prior art. In particular, the inventors have recognized a need for improvements in a device for thermostatting a measuring cell for insertion in an analyzer. The device, as described herein, if possible without use of a preheating section, is suitable for quick, reproducible thermostatting of the sensors contained in a measuring cell, of the calibrating media, the reference media and the sample, and which ensures an easy and simple exchange of the measuring cell in case of malfunction or at the end of its service life.
In accordance with one embodiment of the present invention, a device for thermostatting a measuring cell in an analyzer is provided, comprising a measuring cell comprising a measuring channel, wherein at least one sensor element is located in the measuring channel; and an analyzer comprising a thermostatted supporting surface, wherein the measuring cell can be inserted in the analyzer in an exchangeable manner and will contact the thermostatted supporting surface at least in a contact area, and the measuring cell has an essentially planar measuring cell wall at least in the contact area.
The inventors have recognized that to improve heat transfer to the measuring cell by means of a heat-conductive, elastic or plastic layer, which adheres at least in the area of contact to at least one wall of the measuring cell or to the thermostatted supporting surface of the analyzer and which can be removed from the measuring cell wall or the opposing thermostatted supporting surface without residue, when the measuring cell is exchanged, and/or by proposing that the measuring cell wall, which carries at least one sensor element on its interior side facing the measuring channel, be made of a heat-conductive metal or metal alloy at least in the area of contact with the thermostatted supporting surface of the analyzer.
These embodiments of the invention (heat-conductive layer or metallic wall of the measuring cell), which can also be applied in combination, will ensure that the heat transfer resistance between the heat source, i.e., the thermostatted supporting surface of the analyzer, and the sensor or sample plane is substantially minimized. A failing measuring cell or a measuring cell that has reached the end of its useful life may be replaced by a new measuring cell without problems and without change of the prevailing thermal conditions.
In a variant of the invention the measuring cell may have two or more planar walls, which are in contact with a thermostatted supporting surface of the analyzer, a heat-conductive, elastic or plastic layer being interposed, which adheres at least in the area of contact to at least one wall of the measuring cell or to the thermostatted supporting surface of the analyzer, and which can be removed from the measuring cell wall or the opposing thermostatted supporting surface without residue, when the measuring cell is replaced.
In the case of a metal wall of the measuring cell, which is made for instance of copper or aluminium, the wall of the measuring cell may be very thin on account of the high strength of metallic materials, e.g., it could have the shape of a platelet with a thickness of typically less than about 2,000 μm, even more typically not more than about 1,000 μm. By making the metal wall very thin its heat capacity will also be minimized, thus permitting the desired temperature of the measuring cell to be attained faster.
If electrochemical sensors are used, the electrically conducting structures can of course not be applied directly to a metal platelet. To avoid short circuits in the case of a metal or metal-alloy wall the at least one electrochemical sensor is placed on the planar wall of the measuring cell facing into the measuring channel, an intermediate layer, which is electrically insulating, being interposed. As an electrically insulating medium a very thin, electrically non-conductive layer, typically less than about 100 μm, and more typically less than about 10 μm thick, is applied on the metal or metal-alloy wall of the measuring cell. This layer may be formed by a thin film, e.g. of a polymeric material, which is applied by laminating or coating techniques.
Examples of electrically non-conductive plastic layers are for instance plastic films of polycarbonate, polyester or polyvinylchloride, which are bonded to the metal platelet, or coatings of polycarbonate and polyester varnishes, which are applied to the metal platelet.
In the case of sensor types which are not based on electrochemical technology and/or do not require electrical leads, in accordance with another embodiment of the present invention, the measuring cell wall, on whose interior side facing the measuring channel the at least one sensor element is located, is made of a heat-conductive metal or metal alloy at least in the area of contact with the thermostatted supporting surface of the analyzer. Sensors of this type are for instance sensors based on optical technologies or on the determination of intrinsic properties of the sample fluid, e.g. its electrical conductivity, since such sensors must also be operated under exactly defined temperature conditions, if highly accurate and reproducible analyte measurements are required.
Since it is typical for rapid and reproducible thermo-staffing to quickly establish the required operating temperature not only in the media introduced into the measuring cell, such as calibrating media, test media or the sample fluids, but also in the sensors contained in the measuring cell, the configuration according to the invention is advantageous as it makes possible particularly fast and reproducible heat transfer to the sensors. In particular, the configuration according to the invention is advantageous as compared with configurations in which a metal layer for heat transfer is applied to the measuring cell wall opposite the sensors, since the limited heat conductivity of the medium between measuring cell wall and sensors will cause slower thermostatting of the sensors. Due to the fact that different media present in the measuring cell, for instance diverse calibrating media, test media or sample fluids, have different heat conductivities, the heat transfer is not exactly reproducible in such configurations. This will be the case especially with gaseous calibrating media, which can for instance be used with sensors for the determination of gaseous analytes such as oxygen. In contrast to this, in the configuration according to the invention heat transfer between the thermostatted supporting surface of the analyzer and the sensors will advantageously occur through defined layers whose heat conductivities are fully known.
Measuring cell walls on whose interior side facing the measuring channel the at least one sensor element is placed and which consist of a heat-conductive metal or metal alloy at least in the region of contact with the thermostatted supporting surface of the analyzer, are not required by the present invention to be configured as continuous metal layers. The present invention also comprises embodiments in which the metal layer has openings in certain regions, for instance in the shape of holes or grid-structures. Such configurations are of particular advantage if optical sensor technologies are used, since such openings in the metal layer, especially if confined to a small part of the area of the metal layer, permit the irradiation of light onto the sensors or the recording of light emitted by the sensors, without substantially impairing the heat transfer to the sensors and into the measuring channel as proposed by the invention. Optical sensor technologies of this kind are for instance described in “Fluorescent optical sensors for critical care analysis” by J. K. Tusa, M. P. Leiner; Ann Biol Clin 2003, 61:183-191. With electrochemical sensor technologies such metal layers with openings of certain shapes may also be advantageously used since contacting the sensors through these openings in the metal layer is possible. It is of course necessary to provide for suitable electrical insulation of the individual parts, for instance by an air gap between metal layer and the electrical lead of the sensor or by applying an insulating layer on the surface of the metal layer in the area of the openings or on the electrical lead of the sensor.
Interposing an intermediate layer between a measuring cell wall consisting of metal or a metal alloy and the measuring channel, or rather the sensors facing the measuring channel, may be of advantage not only for electrochemical sensors, but for all types of sensors. Such an intermediate layer may for instance serve to improve the surface characteristics of the measuring channel, e.g. the hydrophilic properties of the surface, or to improve the surface properties, in particular the adherence characteristics if further layers are to be built up, or to improve corrosion protection of the underlying metal layer, or to avoid undesirable chemical reactions between the metal layer and the fluids contained in the measuring channel.
In accordance with still another embodiment of the present invention, the device for thermostatting of a measuring cell in an analyzer or the measuring cell itself is configured in such a way that the at least one sensor element of the measuring cell is an optical sensor element and is placed on the measuring cell wall, which for instance consists of a metal or a metal alloy, with an optically transparent intermediate layer being interposed between wall and sensor element. If optical sensor technologies are used an intermediate layer between sensors and the adjacent metal layer enhancing heat transfer, may advantageously be configured as an optically transparent layer. It may furthermore be designed such that it can function as an optical fibre. Such an intermediary layer may be used in particular to feed excitation light to the sensors or conduct light emitted by the sensors to suitable detectors. Such embodiments are especially advantageous for optical procedures and assemblies, in which excitation light or emitted light is irradiated or picked up from the side, as described in EP 0 793 090 B1, for instance. Combinations of such a light-guiding intermediate layer with a metal layer, which has openings in the area of the sensors, are possible in an advantageous way, for instance if the radiation emitted by the sensors is detected in a direction normal to the direction of the irradiated excitation light.
According to yet still another embodiment of the present invention, the heat-conductive, elastic or plastic layer is furnished with a certain structure in the form of stripes, naps or the like, at least on its free surface.
In order to improve heat conduction the heat-conductive, elastic or plastic layer may contain particles of a strongly heat-conductive material, typically ceramic particles.
Furthermore, the device consisting of measuring cell, heating or cooling element of the analyzer or of its thermostatted supporting surface, may be miniaturized, such that the desired temperature is attained faster and without the need of a preheating section due to the reduced mass and dimensions.
In order to further improve heat transfer between the heat source and the sample if a heat-conductive, elastic or plastic layer is used, the essentially planar wall of the measuring cell can be made from a highly heat-conductive material, typically a ceramic material or a metal or metal alloy. Suitable materials include ceramics consisting of diverse oxides and nitrides, such as aluminium oxide, aluminium nitride, zirconium oxide, zirconium nitride, boric oxide or boron nitride etc., or metals such as copper or aluminium, etc.
In accordance with yet still another embodiment of the present invention, the measuring cell may be made up of two parts and, in the case of one-sided thermostatting, consist of a lower housing part made of strongly heat-conductive material and forming the measuring cell wall, which is planar at least in the contact area towards the thermostatted supporting surface, and of a thermally insulating upper housing part, which together with interposed sealing elements bounds the measuring channel.
Although the present invention is not limited to specific advantages or functionality, it is noted that:
These and other features and advantages of the present invention will be more fully understood from the following detailed description of the invention taken together with the accompanying claims. It is noted that the scope of the claims is defined by the recitations therein and not by the specific discussion of features and advantages set forth in the present description.
The following detailed description of the embodiments of the present invention can be best understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:
FIGS. 2 to 4 show different variants of the device according to the invention in a sectional view as in
Skilled artisans appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of the embodiment(s) of the present invention.
The device shown in
In the variant shown in
The variant shown in
The upper part of the housing may also be configured as a planar, highly heat-conductive measuring cell wall 5, which is in contact via an intermediary heat-conductive, elastic or plastic layer 11, with a thermostatted supporting surface 3 of the analyzer, such that the measuring cell 1 is temperature controlled either only by the measuring cell wall 5 of the upper housing part or by both measuring cell walls 2 and 5, each of which—as shown in
In the variants of the invention shown in
The lower housing part, respectively the measuring cell wall 2, is provided with a layer of a heat-conductive silicone (e.g., Thermally Conductive RTV Silicone R-2930 of NuSil Technology CA 93013 U.S.A. or ELASTOSIL® RT 675 of Wacker Silicones, Germany) of suitable texture on one side, which is applied by laminating or coating techniques, typically by screen or template printing, and, if so required, with an electrical insulation on the other side.
As shown in three variants in
In the measurement diagram of
It is noted that terms like “preferably”, “commonly”, and “typically” are not utilized herein to limit the scope of the claimed invention or to imply that certain features are critical, essential, or even important to the structure or function of the claimed invention. Rather, these terms are merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the present invention.
For the purposes of describing and defining the present invention it is noted that the term “substantially” is utilized herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. The term “substantially” is also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.
Having described the invention in detail and by reference to specific embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims. More specifically, although some aspects of the present invention are identified herein as preferred or particularly advantageous, it is contemplated that the present invention is not necessarily limited to these preferred aspects of the invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| A 2158/2004 | Dec 2004 | AT | national |
