Sandwich-type measuring cell

Abstract

The invention relates to a sandwich-type measuring cell (1) for measuring a sample liquid, in particular a body fluid, preferably blood, comprising: a first sensor support element (2) on which at least one first sensor element (4a, 4b) for measuring the sample liquid is provided, a second sensor support element (3) on which at least one second sensor element (4c-41) for measuring the sample liquid is provided; a sandwich element (5) between the first sensor support element (2) and the second sensor support element (3); and a sample liquid channel (6) which is formed by the first sensor support element (2), the second sensor support element (3) and the sandwich element (5), wherein a multi-component injection-molded part is provided as the sandwich element (5), preferably a two-component injection-molded part with a soft component (7) and a hard component (8) which encloses the soft component (7), said soft component (7) having two lateral walls (9a, 9b) each of which is positioned between the first sensor support element (2) and the second sensor support element (3) and which laterally delimit the sample liquid channel (6). The invention further relates to an analysis device (28) for analyzing a sample liquid and to a method for measuring a sample liquid.

Description

[0001] Sandwich measuring cell The invention relates to a sandwich measuring cell for measuring a sample fluid, in particular a body fluid, preferably blood, comprising: a first sensor carrier element on which at least one first sensor element for measuring the sample fluid is arranged, a second sensor carrier element on which at least one second sensor element for measuring the sample fluid is arranged, a sandwich element between the first and the second sensor carrier element, a sample fluid channel which is delimited by the first sensor carrier element, the second sensor carrier element and the sandwich element. Furthermore, the invention relates to an analysis device for analyzing a sample fluid and a method for measuring a sample fluid, in particular a body fluid, preferably blood. Point-of-care diagnostics is becoming increasingly important in modern healthcare systems.POC diagnostics typically refers to medical diagnostic procedures performed directly on the patient or in the vicinity of the patient. In contrast to traditional laboratory tests, which can often take several days, POC diagnostics allows for rapid collection of diagnostic data, thus enabling immediate medical intervention. However, simpler and faster measurement methods are also gaining importance in conventional laboratory diagnostics. In in-vitro diagnostics (IVD), particularly in the area of ​​point-of-care (POC), high demands are placed on the measuring devices. This particularly applies to the fluidic path of the measuring devices. The measuring cells that hold the sample fluids must be mechanically robust but also fluidically tight.Especially with biological samples, the goal is to be able to analyze the smallest possible sample volume without having to accept significant limitations in measurement accuracy, the number of measured parameters, or the duration of the measurement. Therefore, there are increasing efforts to make fluid channels in measuring cells as small as possible. For example, WO 2008 / 131767 A1 pursues the goal of providing a measuring system with a compact sensor arrangement that requires only a minimal amount of sample fluid for measuring several different parameters without reducing the number of sensors in the sensor arrangement. A sandwich structure is proposed with a measuring cell defined by two printed circuit board substrates and a spacer arranged between them, with both printed circuit board substrates having sensors.By placing sensors on opposite walls of a measuring cell, a larger number of sensors can be brought into contact with the sample liquid while maintaining a constant sample volume. WO 2008 / 131767 A1 thus offers a significant improvement over traditional measuring cells known from the prior art and, thanks to the sensor arrangement described, enables, in particular, the use of smaller sample volumes. However, these small sample volumes present challenges that are not yet adequately addressed in the prior art. For example, a smaller sample volume requires a larger ratio between the surface area and volume of the sample liquid in the measuring cell. Gas exchange that takes place across the surface of the sample liquid therefore leads to a larger relative change in the gas partial pressures in the sample liquid.This can falsify measurements, particularly when the gas partial pressures themselves are the subject of the measurement (e.g., in a blood gas analysis), but also indirectly when measuring other parameters. The object of the present invention is to alleviate or eliminate at least some of the disadvantages of the prior art. The invention particularly aims to provide measuring cells that enable the use of a small sample volume while simultaneously achieving high measurement accuracy and good fluid sealing. This object is achieved by a sandwich measuring cell according to claim 1, an analytical device according to claim 13, and a method according to claim 14. Preferred embodiments are specified in the dependent claims.In the sandwich measuring cell according to the invention, a multi-component injection-molded part, preferably a two-component injection-molded part, with a soft component and a hard component enclosing the soft component is provided as the sandwich element, wherein the soft component has two side walls, each of which is arranged between the first sensor carrier element and the second sensor carrier element and laterally delimits the sample liquid channel. Optionally, the multi-component injection-molded part can comprise at least one further component, which differs from the hard component and / or the soft component, in particular in its hardness, for example in its Shore hardness, and / or in its optical properties. Particularly preferably, one component of the multi-component injection-molded part, for example the soft component, the hard component, or the further component, can be transparent.The at least one further component can, in particular, be enclosed by the soft component or the hard component. For the purposes of this disclosure, all location and direction specifications, such as "horizontal," "vertical," "top," and "bottom," refer to a proper use state of the sandwich measuring cell, in which the measuring cell rests on a horizontal surface such that the main plane of the first sensor carrier element is parallel to this surface. Of course, the sandwich measuring cell can also be positioned differently, in which case the location and direction specifications must be transferred accordingly. Designing the sandwich element as a two-component injection-molded part makes it possible to combine advantageous properties of different materials in one component. The soft component can, in particular, enable good sealing of the sample fluid channel.By being encased in the hard component, it is held in shape, enabling precise joining with the two sensor carrier elements and thus a particularly good seal. Enclosing it in the hard component also allows for good gas tightness. Soft materials, which have good sealing properties, generally exhibit high gas permeability, in contrast to harder materials. Designing the sandwich element as a two-component injection-molded part makes it possible to advantageously combine the good sealing properties of a soft material with the good gas seal of a hard material. Good gas sealing reduces gas exchange between the sample liquid and the environment, thus enabling more precise measurements, particularly measurements of gas partial pressures themselves, but also measurements of other parameters that are indirectly influenced by changes in the gas partial pressures in the sample.A further advantage of the two-component injection-molded part is that it allows for a particularly thin design of the soft component. If the sandwich element consists only of a soft material, for example in the form of a simple insert seal, greater wall thicknesses are required to form a robust sample fluid channel. However, the larger volume of the soft material also entails a greater gas storage capacity, so that gases from the sample fluid can pass into the insert seal and vice versa. This, in turn, can lead to falsifications as described above. In the aforementioned WO 2008 / 131767 A1, a fluid seal between the spacer and the two substrates is to be achieved either by making the spacer of a sealing material, i.e., by designing it as an insert seal, or by providing separate sealing means between the spacer and the substrates.Both have significant disadvantages compared to the two-component injection-molded part provided according to the invention. As explained above, the use of an insert seal, in addition to the poorer robustness and dimensional stability, has the disadvantage of increased gas exchange from the sample liquid into and through the seal. The provision of separate sealing means is also disadvantageous, as the additional parts make manufacturing more complex, reduce robustness, and make it difficult to precisely join the individual parts and ensure a good seal. Two-component injection molding is known from the prior art and has already been described in another context for the production of measuring devices.WO 2019 / 090370 A1 describes a sensor cassette insertable into an analysis module, comprising a sensor carrier that is essentially planar and carries a plurality of sensor elements, and a cover part arranged on the sensor carrier, in which at least one groove-shaped measuring channel is formed, open toward the sensor carrier. The cover part is designed as a two-component injection-molded part comprising a hard component and a soft component, with the at least one measuring channel being formed in the soft component over its entire length. According to WO 2019 / 090370 A1, since the at least one measuring channel is formed entirely in the soft component of a two-component injection-molded part, the latter can be formed in one piece, thus avoiding dead spaces and gaps, as well as carryover and cross-contamination between different measurements.A significant disadvantage of the sensor cassette described in WO 2019 / 090370 A1, however, is that sensor elements can only be placed on one side of the measuring channel. The design of the measuring channel in the soft component of the two-component injection-molded part prevents the wall of the measuring channel opposite the sensor carrier from being used for sensor elements. This would require integrating sensor elements into the soft component, which would be incompatible with two-component injection molding. The sensor cassette therefore does not allow for a sandwich measuring cell with two sensor carrier elements. To achieve the same number of sensors, the length of the measuring channel must effectively be doubled, which inevitably leads to a higher required sample volume.The sandwich measuring cell is preferably a cassette with a main extension plane, wherein the main plane of the first sensor support element and / or the second sensor support element is substantially parallel to the main extension plane of the sandwich measuring cell. The first sensor support element and the second sensor support element are each preferably designed as sensor support plates. The sensor support plates are preferably substantially planar. Preferably, the main plane of the first sensor support element or the first sensor support plate is substantially parallel to the main plane of the second sensor support element or the second sensor support plate. The sandwich measuring cell according to the invention has a two-component injection-molded part as a sandwich element, which comprises a soft component and a hard component enclosing the soft component. The term "enclosing" is preferably understood here to mean that the hard component holds the soft component.Preferably, the soft component is laterally enclosed or held by the hard component. This preferably means that the hard component laterally limits the soft component, in particular that the hard component laterally limits the dynamic expansion of the soft component. To connect the sandwich element to the sensor carrier elements and form a fluid-tight sample fluid channel, methods such as riveting, riveting, clamping, snap-fastening, welding, screwing, nailing, positive connection, and / or gluing can be used. Preferably, the two side walls each have sealing lips running along the side walls, which are in contact with the inner sides of the first and second sensor carrier elements facing the sample fluid channel. This enables particularly good sealing of the sample fluid channel.In a preferred embodiment, the soft component of the sandwich element has a liquid inlet part and a liquid outlet part, each of which is fluidly connected to the sample liquid channel. The integration of the inlet and outlet parts into the soft component offers significant advantages, as separate seals at the connection areas can be avoided. This enables simpler production and simultaneously improves sealing, which is more difficult to ensure at material transitions and when using separate seals. Preferably, the liquid inlet part and the liquid outlet part are each configured for fluid connection to an analytical device, preferably the analytical device according to the invention.In a preferred embodiment of the sandwich measuring cell according to the invention, the liquid inlet part and the liquid outlet part are arranged on different, in particular opposite, sides of the sandwich measuring cell, wherein the sample liquid channel preferably has exactly one longitudinal section extending from the liquid inlet part to the liquid outlet part. This enables particularly uniform flow behavior of the sample liquid and reduces the risk of deposits or blockages. In an alternative, likewise preferred embodiment, the liquid inlet part and the liquid outlet part are arranged on the same side of the sandwich measuring cell, wherein the sample liquid channel preferably has at least two longitudinal sections and at least one deflection section, in particular a U-section, connecting the two longitudinal sections.The arrangement of the inlet and outlet sections on the same side enables an even simpler fluidic connection to an analytical device. Preferably, the liquid inlet section and the liquid outlet section each have a cylindrical section whose central axis is the liquid inlet or liquid outlet axis. Preferably, the liquid inlet section and the liquid outlet section each have a flange, in particular a flat flange or an annular flange projecting from the cylindrical section. Advantageously, the annular flange is configured for fluidic connection to an analytical device. In measuring cells known from the prior art, inlets and outlets are often formed at right angles to sample liquid channels.In connection with the sandwich measuring cell according to the invention, however, it has been found that such deflections of the sample liquid in the area of ​​the liquid inlet and outlet sections can have adverse effects. It has been shown that a right-angled inlet or outlet can lead to poorer flow behavior and blockages. This disadvantage is particularly significant for biological samples, especially blood samples, which contain fibrins and are therefore even more prone to blockages. Therefore, it is preferred if the liquid inlet section has an inlet channel with an inlet axis, wherein the inlet axis runs essentially parallel to a longitudinal axis of a longitudinal section of the sample liquid channel.Likewise, it is preferred if the liquid drainage part has a drainage channel with a drainage axis, wherein the drainage axis runs essentially parallel to a longitudinal axis of a longitudinal section of the sample liquid channel. It is particularly preferred if both the inlet axis of the inlet channel and the drainage axis of the drainage channel run essentially parallel to a longitudinal axis of a longitudinal section of the sample liquid channel. It has been shown that such an arrangement leads to improved flow behavior and significantly reduces the risk of blockages. This effect is particularly pronounced in the inlet region, but the described arrangement has also proven advantageous in the outlet region. The first and second sensor carrier elements are preferably free of liquid connections.In other words, it is preferred that the sample liquid is not passed through either the first sensor carrier element or the second sensor carrier element. This significantly simplifies the manufacture of the sandwich measuring cell, particularly when the liquid inlet part and the liquid outlet part are integrated into the soft component, as described above. In a preferred embodiment, the liquid inlet part and / or the liquid outlet part each have at least one sealing nose, which rests against an inner side of the first and / or second sensor carrier element facing the sample liquid channel, wherein the inlet or outlet axis is offset in the radial direction from the longitudinal axis of the longitudinal section of the sample liquid channel. This enables even better sealing of the sample liquid channel and reduces the risk of sample liquid leakage.At the same time, no strong fluid deflection is required, which would increase the risk of blockages. In particular, it can be provided that a first sealing lug of the at least one sealing lug rests on the inside of the first sensor carrier element facing the sample liquid channel, and a second sealing lug of the at least one sealing lug rests on the inside of the second sensor carrier element facing the sample liquid channel. As explained above, the sandwich measuring cell according to the invention enables measurements of particularly small sample volumes. It is therefore preferred if the sample liquid channel has a volume of less than 100 µl, preferably less than 80 µl, more preferably less than 60 µl, more preferably less than 50 µl, in particular less than 40 µl.The volume of the sample liquid channel is preferably between 10 µl and 100 µl, preferably between 15 µl and 80 µl, more preferably between 20 µl and 60 µl, more preferably between 25 µl and 50 µl, in particular between 30 µl and 40 µl. The sample liquid channel preferably has a minimum width of more than 0.1 mm, preferably more than 0.2 mm, more preferably more than 0.3 mm, in particular more than 0.4 mm. The minimum width is preferably from 0.1 mm to 1.0 mm, more preferably from 0.2 mm to 0.9 mm, more preferably from 0.3 mm to 0.8 mm, in particular from 0.4 mm to 0.7 mm. Preferably, the sample fluid channel has a maximum width of less than 5 mm, preferably less than 4 mm, more preferably less than 3 mm, in particular less than 2.5 mm. Preferably, the maximum width is from 1.0 mm to 5 mm, more preferably from 1.5 mm to 4 mm, more preferably from 1.8 mm to 3 mm, in particular from 2 mm to 2.5 mm.The minimum width preferably refers to the width at the narrowest point of the sample liquid channel, and the maximum width preferably refers to the width at the widest point of the sample liquid channel. The sample liquid channel preferably has a height of less than 3 mm, preferably less than 2 mm, more preferably less than 1.5 mm, more preferably less than 1 mm, in particular less than 0.8 mm. The height is preferably from 0.1 mm to 3 mm, preferably from 0.15 mm to 2 mm, more preferably from 0.2 mm to 1.5 mm, more preferably from 0.25 mm to 1 mm, in particular from 0.3 mm to 0.8 mm. The height is preferably substantially constant along the entire sample liquid channel. The sample liquid channel preferably has a length of more than 24 mm, preferably more than 26 mm, more preferably more than 28 mm, in particular more than 30 mm.On the other hand, it is preferred if the sample liquid channel has a length of less than 70 mm, preferably less than 60 mm, more preferably less than 50 mm, in particular less than 40 mm. It is particularly preferred if the sample liquid channel has a length of 24 mm to 70 mm, more preferably from 26 mm to 60 mm, more preferably from 28 mm to 50 mm, in particular from 30 mm to 40 mm. In a preferred embodiment, the sample liquid channel is widened in the region of at least one sensor element relative to a region of the sample liquid channel without a sensor element. The sample liquid channel can thus widen in the region of a sensor element and then narrow again. Such a local widening makes it possible to provide larger sensor elements without significantly increasing the volume of the sample liquid channel and therefore the sample volume.This is particularly preferred if the at least one sensor element is an optical sensor element, as this allows a wider optical window to be formed. Preferably, the sample fluid channel is widened by 20% to 200%, in particular by 30% to 130%, at the widest point in the region of the at least one sensor element. Within the scope of the invention, a hard and a soft component are understood to mean plastics that can preferably be processed by injection molding, with the hard component having a higher hardness than the soft component. Hardness is preferably understood to mean the mechanical resistance that the respective component offers to the mechanical penetration of another body. Unless otherwise stated, hardness, as used herein, refers to the ball indentation hardness, preferably determined according to the standard DIN EN ISO 2039-1:2003-06.Alternatively, the Shore hardness, preferably determined according to DIN ISO 48-4:2021-02 or ASTM D 2240:2015-08, can also be used as hardness. Suitable materials for the hard component are, in particular, those plastics which can be thermoplastically processed during the injection molding process, such as polycarbonate (PC). Alternatively, plastics or combinations thereof can be used, such as polyvinyl chloride (PVC), styrene-acrylonitrile copolymer (SAN), acrylonitrile-styrene-acrylate (ASA), acrylonitrile-butadiene-styrene copolymer (ABS), polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polyoxymethylene (POM), cellulose acetate (CA), polystyrene (PS), polyphenylene ether (PPE), polymethyl methacrylate (PMMA), polypropylene (PP), high-density polyethylene (HDPE), ethylene-vinyl acetate copolymer (EVOH), liquid crystalline polymers (LCP) or polyamides (PA) of various types, preferably type 6 (PA6), type 11 (PA11) or Type 66 (PA66).Suitable materials for the soft component are, in particular, those plastics that can be thermoplastically processed during the injection molding process and can be combined with at least one or more plastics of the hard component during the injection molding process, such as thermoplastic polyurethanes (TPU). Alternatively, low-density polyethylene (LDPE) can also be used. Further alternatives include plastics from the group of thermoplastic elastomers (TPE), preferably thermoplastic polyamide elastomers (TPA), thermoplastic copolyester elastomers (TPC), olefin-based thermoplastic elastomers (TPO), thermoplastic vulcanizates (TPV), or thermoplastic styrene block copolymers (TPS). The sensor carrier elements preferably have comparable properties to those of the hard component.In addition to the plastics used for the hard component, styrene methyl methacrylate (SMMA), polyethylene (PE), cycloolefin copolymers (COC / COP), or polyimide (PI) can be used as materials. Resins can also serve as sensor carrier elements, preferably polyester resins (UP) or epoxy resins (EP). Alternatively, ceramics or glass, or a combination of the described materials, can also be used. Furthermore, the polymers mentioned can also be provided in a modified form, for example, with carbon fibers, glass fibers, glass beads, broken glass, carbon black, and / or mineral fillers. Aluminum oxide, for example, can be used as a material for a ceramic. The ceramic can also be transparent, for example, comprising magnesium spinel MgAl2O4. Thermoplastic polyurethane (TPU) and polycarbonate (PC) have proven particularly suitable materials in connection with the invention.The combination of these materials has proven particularly advantageous with regard to sealing with respect to the sample liquid, robustness, and gas sealing. Furthermore, these materials are particularly suitable for the two-component injection molding process due to their thermal properties and can be easily bonded together. Therefore, the soft component is preferably made of thermoplastic polyurethane (TPU) and / or the hard component is made of polycarbonate (PC). In a particularly preferred embodiment, the soft component has a Shore hardness of less than 100 Shore A, preferably less than 95 Shore A, more preferably less than 90 Shore A, in particular less than 85 Shore A. The Shore hardness of the soft component is preferably from 30 Shore A to 100 Shore A, preferably from 40 Shore A to 95 Shore A, more preferably from 50 Shore A to 90 Shore A, in particular from 55 Shore A to 85 Shore A.The Shore hardness is preferably determined according to the standard DIN ISO 48-4:2021-02. Alternatively, but also preferably, the Shore hardness is determined according to the standard ASTM D 2240:2015-08. Preferably, the soft component has a Shore hardness of less than 58 Shore D, preferably less than 46 Shore D, more preferably less than 39 Shore D, in particular less than 33 Shore D. The Shore hardness of the soft component is preferably from 6 Shore D to 58 Shore D, preferably from 8 Shore D to 46 Shore D, more preferably from 12 Shore D to 39 Shore D, in particular from 14 Shore D to 33 Shore D. The soft component preferably has a lower Shore D hardness than the hard component. Preferably, the Shore hardness is determined according to DIN ISO 48-4:2021-02 or ASTM D 2240:2015-08.The hard component preferably has a hardness of more than 50 MPa H358 / 30, preferably more than 60 MPa H358 / 30, more preferably more than 70 MPa H358 / 30, more preferably more than 80 MPa H358 / 30, in particular more than 90 MPa H358 / 30. The hardness of the hard component is preferably from 50 MPa H358 / 30 to 200 MPa H358 / 30, preferably from 60 MPa H358 / 30 to 170 MPa H358 / 30, more preferably from 70 MPa H358 / 30 to 140 MPa H358 / 30, more preferably from 80 MPa H358 / 30 to 120 MPa H358 / 30, in particular from 90 MPa H358 / 30 to 100 MPa H358 / 30. The specified values ​​are preferably the ball indentation hardness according to DIN EN ISO 2039-1:2003-06. The hardness is preferably determined by a ball indentation test according to the standard DIN EN ISO 2039-1:2003-06. The hard component preferably has a Shore hardness of more than 39 Shore D, preferably more than 46 Shore D, more preferably more than 58 Shore D, in particular more than 65 Shore D.The hard component preferably has a higher Shore D hardness than the soft component. The Shore hardness is preferably determined according to the standard DIN ISO 48-4:2021-02 or ASTM D 2240:2015-08. The hard component preferably has a greater hardness than the soft component, preferably a greater Shore hardness, in particular a greater Shore D hardness, preferably determined according to the standard DIN ISO 48-4:2021-02 or ASTM D 2240:2015-08. In a preferred embodiment, a first thermal actuator is arranged on the first sensor carrier element and / or a second thermal actuator is arranged on the second sensor carrier element. This makes it possible to bring the sample liquid as well as the sensor elements to a specific temperature and / or to maintain them at such a temperature. It is particularly preferred if thermal actuators are arranged on both sensor carrier elements.This enables uniform thermostatting of both sensor carrier elements, thus creating particularly reproducible and uniform thermal conditions. Optionally, a third thermal actuator can be arranged on the first sensor carrier element and / or a further thermal actuator on the second sensor carrier element. The thermal actuators can be, for example, heating coil systems. Preferably, the thermal actuators comprise temperature probes. Preferably, the first and / or the second and / or the third and / or the further thermal actuator is configured to keep the sample at 37°C. A sensor element is preferably understood herein to be a measuring arrangement that can be used to determine chemical and / or physical parameters of the sample liquid.Preferably, the first sensor element is a first sensor configured to measure a first measurement parameter, and the second sensor element is a second sensor configured to measure a second measurement parameter different from the first measurement parameter. Preferably, each sensor element or each sensor is assigned to exactly one sensor carrier element. It is therefore preferred that all components of a sensor element or a sensor are located on the same sensor carrier element. Preferably, the first sensor element or the first sensor is therefore arranged entirely on the first sensor carrier element, and no components thereof are located on the second sensor carrier element. Likewise, it is preferred that the second sensor element or the second sensor is arranged entirely on the second sensor carrier element, and no components thereof are located on the first sensor carrier element.Preferably, the first and second sensor carrier elements each have at least two sensor elements, preferably at least three sensor elements each, more preferably at least four sensor elements each. Preferably, exactly one sensor element is configured to measure exactly one measurement parameter. Preferably, each sensor element or each sensor is assigned to exactly one sensor carrier element, as described above. The sensor elements of the sandwich measuring cell according to the invention can be configured to measure different measurement parameters. Preferably, the measurement parameters are selected from the group consisting of blood gases, in particular pO2 (oxygen partial pressure), pCO2 (carbon dioxide partial pressure), pH value, HCO3- (bicarbonate); electrolyte concentrations, in particular Na+ (sodium), K. + (potassium), Ca 2+ (calcium), Cl- (chloride), NH4 + (ammonium), Mg 2+(Magnesium); Hct (hematocrit); metabolite concentrations, especially Glu (glucose), Lac (lactate), urea, creatinine; hemoglobin derivatives, especially O2Hb (oxyhemaglobin), HHb (deoxyhemaglobin), COHb (carboxyhemaglobin), MetHb (methhemaglobin); Blood coagulation values ​​and bilirubin. In a particularly preferred embodiment, the first sensor element and / or the second sensor element is configured to measure at least one blood gas value, preferably the oxygen partial pressure (pO2), the carbon dioxide partial pressure (pCO2), the pH value, and / or bicarbonate (HCO3-). These values ​​can be particularly severely distorted by gas exchange between the sample liquid and its environment, which is advantageously reduced by the sandwich measuring cell according to the invention, as explained above.It is particularly preferred if the sandwich measuring cell has sensor elements for measuring at least two, preferably at least three, more preferably at least four blood gas values, preferably selected from pO -2, pCO2, pH and HCO3 . In a particularly preferred embodiment, the sandwich measuring cell has sensor elements for measuring pO2, pCO2, pH and HCO3-. The sensor elements are preferably electrical, chemical or optical sensors, or a combination thereof. Particularly preferred are several potentiometric sensors with ion-selective electrodes for the measurement parameters used (e.g. Na+, K+, Ca2+, Cl-, H+, Li+, NH + 2+4 , Mg , etc., but also pCO2 with a Severinghaus-type sensor or urea with urease enzyme) and at least one reference electrode using thick-film technology. The ion-selective electrodes can contain, among other things, ionophores that reversibly bind the measuring ions and thus cause a potential change.Also preferred are amperometric sensors consisting of a working, counter, and reference electrode (or just a working and counter-reference electrode) for determining metabolite concentrations or oxygen partial pressure (Clark sensor). Metabolite sensors preferably use oxidases (e.g., glucose oxidase) that produce hydrogen peroxide, which is then converted to oxygen, H, at the working electrode. +and electrodes. The resulting current is then proportional to the concentration of the metabolite. This can be used to determine, for example, glucose, lactate, and creatinine. For pO2 measurement, an optical sensor with a dye is preferred, the luminescence or fluorescence of which is quenched to varying degrees, in particular increasingly suppressed, depending on the oxygen partial pressure. Other preferred optical sensors are based on pH-sensitive or acid / base-sensitive luminescent dyes or fluorescent dyes, for example pH fluorescent dyes, which change their optical signal, in particular the intensity, proportional to the pH value, pCO2 value, or NH+4 value, thereby enabling a measurement of the pH value, the pCO2 value, or the NH+4 + -content of the sample. Optical sensors can also be used to measure metabolites such as glucose, lactate, urea or creatinine if they contain O2, NH4 +or other components measurable by the optical sensors are released or consumed during an enzymatic conversion. In this case, a material suitable for the enzymatic conversion of the metabolite is integrated into the optical sensor or arranged in geometric proximity to it. The sample fluid is preferably a blood sample (in particular whole blood, serum or plasma), urine or pleural fluid. Alternatively, aqueous fluids can also be introduced into the analyzer like a sample fluid for calibration, washing, cleaning and / or quality control. The analyzer according to the invention for analyzing a sample fluid comprises: a sandwich measuring cell according to the invention, a computing and control unit for analyzing the sample fluid using sensor data from the sandwich measuring cell.The analysis device preferably has a measuring cell receptacle for the sandwich measuring cell, which is configured to establish a detachable fluidic and electrical connection with the sandwich measuring cell. The method according to the invention for measuring a sample fluid, in particular a body fluid, preferably blood, comprises the following steps: providing a sandwich measuring cell according to the invention, introducing the sample fluid into the sample fluid channel, and measuring the sample fluid with the first and second sensor element (or with the sensor elements). All features and embodiments described herein with reference to the sandwich measuring cell according to the invention are also preferred for the analysis device according to the invention and the method according to the invention.In a preferred embodiment of the method according to the invention, the sample fluid is measured to determine at least one, preferably at least two, more preferably at least three, more preferably at least four blood gas values, preferably selected from oxygen partial pressure (pO2), carbon dioxide partial pressure (pCO2), pH, and bicarbonate (HCO3-). The present disclosure also relates to a method for producing a sandwich measuring cell in one of the embodiments described above, wherein the sandwich element is manufactured by two-component injection molding with a soft component and a hard component enclosing the soft component. The invention is further explained below with reference to exemplary embodiments illustrated in the drawings. Fig. 1 shows an exploded view of an embodiment of the sandwich measuring cell according to the invention. Fig. 2A shows a sectional view of the embodiment from Fig.1 along a longitudinal axis of the sample liquid channel. Fig. 2B schematically shows a longitudinal section of the same embodiment in the region of the liquid inlet part. Fig. 3 and Fig. 4 show exploded views of alternative embodiments of the sandwich measuring cell according to the invention. Fig. 5A and Fig. 5B schematically show plan views of the first and second sensor carrier elements of a further embodiment of the sandwich measuring cell according to the invention. Fig. 6 schematically shows the structure of an embodiment of the analytical device according to the invention. Fig. 1, Fig. 2A and Fig. 2B show a first embodiment of a sandwich measuring cell 1 for measuring a sample liquid, in particular a body fluid, preferably blood. The sandwich measuring cell 1 has a first sensor carrier element 2 and a second sensor carrier element 3. Sensor elements 4a-4l for measuring the sample liquid are arranged on the first sensor carrier element 2 and the second sensor carrier element 3, respectively.A sandwich element 5 is arranged between the first sensor carrier element 2 and the second sensor carrier element 3. The sensor carrier elements 2, 3 and the sandwich element 5 form the walls of a sample fluid channel 6. A two-component injection-molded part with a soft component 7 and a hard component 8 enclosing the soft component 7 is provided as the sandwich element 5. The soft component 7 has two side walls 9a, 9b, each arranged between the first and second sensor carrier elements 2, 3 and laterally delimiting the sample fluid channel 6. The sample fluid channel 6 is delimited at the top and bottom by the inner sides of the sensor carrier elements 2, 3.The two side walls 9a, 9b each have sealing lips 10a, 10b extending along the side walls 9a, 9b, which are in contact with the inner sides of the first sensor carrier element 2 and the second sensor carrier element 3 facing the sample liquid channel 6 to ensure a good seal of the sample liquid channel 6. The sensor elements 4a-4l are arranged on the inner sides of the sensor carrier elements 2, 3 facing the sample liquid channel 6, so that they come into contact with a sample liquid introduced into the sample liquid channel 6. In the embodiment shown, the soft component 7 of the sandwich element 5 has a liquid inlet part 11 and a liquid outlet part 12, each of which is fluidly connected to the sample liquid channel 6.The liquid inlet part 11 and the liquid outlet part 12 have an inlet channel 13 with an inlet axis 13a and an outlet channel 14 with an outlet axis 14a, each of which runs substantially parallel to a longitudinal axis 16c of a longitudinal section 16 of the sample liquid channel 6. The liquid inlet part 11 and the liquid outlet part 12 each have a cylindrical section 11a, 12a, the central axis of which is the inlet axis 13a or the outlet axis 14a, respectively, and each have an annular flange 15a, 15b projecting from the cylindrical section 11a, 12a. The sample liquid channel 6 is widened in the region of the sensor elements 4a, 4b relative to a region of the sample liquid channel 6 without a sensor element. A thermal actuator 17, 18 is arranged on each of the sensor carrier elements 2, 3.Preferably, the sensor elements 4c-4l arranged on the second sensor carrier element 3 comprise a plurality of sensor elements 4c, 4d, 4k, 4l for detecting conductances, such as the sensor contacts 27a to 27d for conductance measurement described below in connection with Fig. 5B. The sensor elements 4c-d, 4k-l for detecting conductances can be arranged in particular along the longitudinal axis 16c of the sample liquid channel 6, wherein a first sensor element 4l of the plurality of sensor elements 4c, 4d, 4k, 4l for detecting conductances is positioned immediately downstream of the liquid inlet part 11 in the flow direction and upstream of the remaining sensor elements 4c-4k of the sensor elements 4c-4l for detecting conductances in the flow direction.Analogously, a last sensor element 4c of the plurality of sensor elements 4c, 4d, 4k, 4l for detecting conductivity values ​​is positioned immediately upstream of the liquid outlet section 12 in the flow direction and downstream of the remaining sensor elements 4d-4l of the plurality of sensor elements 4c-4l in the flow direction. This enables the filling of the sample liquid channel 6 with sample liquid to be stopped when a front of sample liquid reaches the last sensor element 4c. Thus, complete filling of the sample liquid channel 6 is not required. In this context, the flow direction is understood to be a direction along the longitudinal axis 16c from the liquid inlet section 11 to the liquid outlet section 12.Particularly preferably, at least one further sensor element 4d, 4k for detecting conductance values ​​is arranged between the first sensor element 4l and the last sensor element 4c, so that filling of the sample liquid channel 6 can be stopped when the front sample liquid front reaches the at least one further sensor element 4d, 4k. This allows a required sample liquid volume to be further reduced. However, only those sensor elements 4a-4l that are located along the longitudinal axis 16c between the first sensor element 4l and the at least one further sensor element 4c, 4k can be used. This means that a measurement can only be performed for a limited selection of measurement parameters. In general, it can be provided that not the entire sample liquid channel 6 is filled with sample liquid.For example, it can be provided that a sample liquid in the sample liquid channel extends only between two pairs of selected sensor elements 4c, 4d, 4k, 4l, with a measurement being carried out with the sensor elements located in between and / or wetted by the sample liquid. It can also be provided that the sample liquid is filled beyond the last sensor element 4c into the sample liquid channel 6, so that the liquid outlet part 12 is at least partially filled with sample liquid. In this case, it can be provided, in particular, that the sample liquid channel 6 is only partially filled, i.e., not up to the liquid inlet part 11. Analogously, it can also be provided that the sample liquid extends into the sample liquid channel 6 up to one of the sensor elements 4c, 4d, 4k, 4l for detecting conductivity values, and the liquid inlet part 11 is at least partially filled with sample liquid. In the embodiment shown in Fig.In the embodiment shown in Fig. 2A, the liquid inlet part 11 has a first sealing nose 19a and a second sealing nose 19b, which are shown in detail in Fig. 2B. The first sealing nose 19a shown in Fig. 2B rests on an inner side of the second sensor carrier element 3 facing the sample liquid channel 6, wherein the inlet axis 13a is offset in the radial direction from the longitudinal axis 16c of the longitudinal section 16 of the sample liquid channel 6. Furthermore, the second sealing nose 19b shown in Fig. 2B rests on an inner side of the first sensor carrier element 2 facing the sample liquid channel 6. The embodiment shown in Fig. 3 corresponds to the embodiment of Fig. 1, wherein the sample liquid channel 6 has a lateral bulge 20. The bulge 20 can be used for an additional sensor or reference sensor element.For example, the lateral bulge 20 can be filled with a preferably gel-like or liquid reference electrolyte in which a reference electrode is arranged, which can be used for potentiometric measurements. In the embodiment shown, the sample liquid channel 6 is delimited only in the region of the longitudinal section 16, both at the top and at the bottom, by the inner sides of the sensor carrier elements 2, 3. In the region of the bulge 20, the sample liquid channel 6 is delimited at the top by the hard component 8 of the two-component injection-molded part, while it is delimited at the bottom by the second sensor carrier element 3. In the embodiment shown, an upwardly directed connection 21 is also provided in the region of the bulge 20, which connection allows access to a sensor element provided in the bulge or a reference electrode provided therein. In the embodiments shown in Fig. 1, Fig. 2 and Fig.In the embodiments shown in Fig. 3, the liquid inlet part 11 and the liquid outlet part 12 are arranged on opposite sides of the sandwich measuring cell 1, with the sample liquid channel 6 having exactly one longitudinal section 16 extending from the liquid inlet part 11 to the liquid outlet part 12. In the alternative embodiment shown in Fig. 4, the liquid inlet part 11 and the liquid outlet part 12 are arranged on the same side of the sandwich measuring cell 1. The sample liquid channel 6 has two longitudinal sections 16a, 16b and a deflection section connecting the two longitudinal sections 16a, 16b, which is designed as a U-section 22. In the embodiment shown in Fig. 4, the sample liquid channel 6 is delimited both at the top and bottom by the inner sides of the sensor carrier elements 2, 3 only in the region of the first longitudinal section 16a.In the area of ​​the U-section 22 and the second longitudinal section 16b, the sample fluid channel 6 is delimited at the top by the hard component 8 of the two-component injection-molded part, while it is delimited at the bottom by the second sensor carrier element 3. Consequently, the sensor elements 4a, 4b of the first sensor carrier element 2 are arranged only in the area of ​​the first longitudinal section 16a of the sample fluid channel 6, since there they can come into contact with the sample fluid introduced into the sample fluid channel 6. An exemplary distribution of sensor elements on the sensor carrier elements 2, 3 can be seen in Fig. 5A and Fig. 5B. In the embodiment shown in Fig. 5A, the sensor path of the first sensor carrier element 2 consists of optical sensors 24a, 24b for measuring pO2 (oxygen partial pressure) or pCO2 (carbon dioxide partial pressure) and metabolite-sensitive sensors 25a, 25b for measuring glucose and lactate.The sensor section of the second sensor carrier element 3, as shown in Fig. 5B, comprises ion-sensitive sensors 26a-26f for measuring electrolyte concentrations, in particular Na. + (sodium), K + (potassium), Ca 2+ (calcium), Cl- (chloride), NH4 +(ammonium), pH value, or Mg2+ (magnesium), and sensor contacts for conductivity measurement 27a-27d for measuring Hct (hematocrit value). An inventive embodiment of the sandwich measuring cell 1 is not limited to the arrangement shown in Fig. 5A and Fig. 5B, in which several optical sensors 24a, 24b are located closer to the liquid inlet part 11 and several metabolite-sensitive sensors 25a, 25b are located closer to the liquid outlet part 12. On the one hand, positions close to the liquid inlet part 11 have the advantage that the influence of components of the measuring cell arranged upstream in the flow direction on the composition of the sample liquid, in particular on the amount of gases dissolved therein, is lower compared to positions arranged downstream in the flow direction.Furthermore, it is advantageous that a larger portion of the sample is passed through the respective sensor element 4a to 4l, so that the exchange of the analyte between the sensor element 4a to 4l and the sample liquid can take place more effectively. On the other hand, positions close to the liquid outlet section 12 have the advantage that the sample liquid can be better regulated to a desired temperature there. Depending on which advantage is more important for which sensor element 4a to 4l, different arrangements may be particularly preferred. Sensor elements 4a to 4l with a similar measuring principle, i.e., optical sensors 24a, 24b, metabolite-sensitive sensor elements 25a, 25b, and ion-sensitive sensors 26a to 26f, can each be arranged side by side, in particular on the same sensor carrier element 2, 3.Sensor elements 4a to 4l with a similar measuring principle can also be distributed across both sensor carrier elements 2, 3 or across the entire length of the sandwich measuring cell 1. In a particularly preferred embodiment, the sensor elements 4a to 4l for pCO2 and pH are located as close as possible to one another, so that these parameters, which are closely physiologically related to one another, can be determined from a region of the sample liquid that is as similar as possible. In another particularly preferred embodiment, those sensor elements 4a to 4l that could potentially release components into the sample that could interfere with other sensor elements 4a to 4l are located as far away as possible from other sensor elements 4a to 4l or are arranged downstream of other sensor elements 4a to 4l in the flow direction. Fig. 6 schematically shows an embodiment of an analysis device 28 for analyzing a sample liquid. The analysis device 28 has the components shown in Fig. 1 and Fig.2. The sensor data from the sandwich measuring cell 1 are transmitted to a computing and control unit 29 for analyzing the sample fluid. The analysis device 28 has a measuring cell receptacle 30 for the sandwich measuring cell 1, which enables a detachable fluidic and electrical connection to the sandwich measuring cell 1. The movement of the fluids in the analysis device 28 is achieved by fluid pumps 31a, 31b, which are controlled by the computing and control unit 29. To perform a measurement, a sample fluid to be analyzed is introduced via a sample input device 32. The sample input device is controlled by the user interface 33 and subsequently by the computing and control unit 29. The sample input device 32 contains a preferably movable sample container connector 37.Sample fluids from syringes, capillaries, and / or blood collection tubes, for example, can be collected via the sample container connector 37 and fed via the fluid inlet part 11 into the sample fluid channel 6, where they come into contact with the sensor elements 4a-4l. The signal from the sensor elements 4a-4l is transmitted to the computing and control unit 29, evaluated, and output via a user interface 33, for example, comprising a display. The sample fluid is transported from the sample fluid channel 6 via the fluid outlet part 12 and directed into a disposal container 34. If necessary, calibration and / or rinsing with an internal operating solution can be performed before, during, and / or after the measurement. The internal operating solution can be selected from various internal operating solution containers 36a-36e using a movable multi-way valve 35.Specifically, the fluidic paths of the internal operating solutions of the operating solution containers 36a-36e are determined by the need for the solutions to be fed via the multi-way valve 35 and the liquid pump 31a, 31b directly into the discharge container 34 and / or via the sample input device 32 and the sandwich measuring cell 1 into the discharge container 34 and / or via the sample input device 32 into the discharge container. If the internal operating solutions are fed via the sandwich measuring cell 1, the internal operating solutions can be used to flush the fluidic paths, in particular the sample liquid channel 6 and / or the sample input device 32, preferably the sample container connector 37. Furthermore, the internal operating solutions can be used for calibration and / or quality control of the sensor elements 4a-4l.

[0002] List of reference numbers: 1 Sandwich measuring cell 2 First sensor carrier element 3 Second sensor carrier element 4a-l Sensor element 5 Sandwich element 6 Sample liquid channel 7 Soft component 8 Hard component 9a,b Side wall 10a,b Sealing lip 11 Liquid inlet part 11a Cylinder section of the liquid inlet part 12 Liquid outlet part 12a Cylinder section of the liquid outlet part 13 Inlet channel 13a Inlet axis 14 Outlet channel 14a Outlet axis 15a,b Ring flange 16,16a,b Longitudinal section 16c Longitudinal axis 17 First thermal actuator 18 Second thermal actuator 19a,b Sealing nose 20 Bulge 21 Connection 22 U-section 24a,b Optical sensor 25a,b Metabolite-sensitive sensor 26a-f Ion-sensitive sensor 27a-d Sensor contact for conductivity measurement 28 Analyzer 29 Computing and control unit 30 Measuring cell holder 31a,b Liquid pump 32 Sample input device 33 User interface 34 Disposal container Reusable valves Working solution container Sample container connector

Claims

Claims:

1. Sandwich measuring cell (1) for measuring a sample fluid, in particular a body fluid, preferably blood, comprising: a first sensor carrier element (2) on which at least one first sensor element (4a, 4b) for measuring the sample fluid is arranged, a second sensor carrier element (3) on which at least one second sensor element (4c-4l) for measuring the sample fluid is arranged, a sandwich element (5) between the first sensor carrier element (2) and the second sensor carrier element (3), a sample fluid channel (6) which is delimited by the first sensor carrier element (2), the second sensor carrier element (3) and the sandwich element (5), characterized in that a multi-component injection-molded part, preferably a two-component injection-molded part, with a soft component (7) and a hard component (8) enclosing the soft component (7) is provided as the sandwich element (5), wherein the soft component (7) has two side walls (9a,9b), which are each arranged between the first sensor carrier element (2) and the second sensor carrier element (3) and laterally delimit the sample liquid channel (6).

2. Sandwich measuring cell (1) according to claim 1, characterized in that the two side walls (9a, 9b) each have sealing lips (10a, 10b) running along the side walls (9a, 9b), which are in contact with the inner sides of the first sensor carrier element (2) and the second sensor carrier element (3) facing the sample liquid channel (6).

3. Sandwich measuring cell (1) according to claim 1 or 2, characterized in that the soft component (7) of the sandwich element (5) has a liquid inlet part (11) and a liquid outlet part (12), which are each fluid-conductingly connected to the sample liquid channel (6). Sandwich measuring cell (1) according to claim 3, characterized in that the liquid inlet part (11) and the liquid outlet part (12) are arranged at different,in particular are arranged on opposite sides of the sandwich measuring cell (1), wherein the sample liquid channel (6) preferably has exactly one longitudinal section (16) extending from the liquid inlet part (11) to the liquid outlet part (12), orii. are arranged on the same side of the sandwich measuring cell (1), wherein the sample liquid channel (6) preferably has at least two longitudinal sections (16a, 16b) and at least one deflection section, in particular a U-section (22), connecting the two longitudinal sections (16a, 16b).

5. Sandwich measuring cell (1) according to claim 3 or 4, characterized in that the liquid inlet part (11) has an inlet channel (13) with an inlet axis (13a), wherein the inlet axis (13a) runs substantially parallel to a longitudinal axis (16c) of a longitudinal section (16) of the sample liquid channel (6).

6. Sandwich measuring cell (1) according to one of claims 3 to 5, characterized in thatthat the liquid outlet part (12) has a drain channel (14) with a drain axis (14a), wherein the drain axis (14a) runs substantially parallel to a longitudinal axis (16c) of a longitudinal section (16) of the sample liquid channel (6).

7. Sandwich measuring cell (1) according to one of claims 3 to 6, characterized in that the liquid inlet part (11) and / or the liquid outlet part (12) each have at least one sealing nose (19a, 19b) which bears against an inner side of the first sensor carrier element (2) and / or the second sensor carrier element (3) facing the sample liquid channel (6), wherein the inlet (13a) or drain axis (14a) is offset in the radial direction from the longitudinal axis (16c) of the longitudinal section (16) of the sample liquid channel (6). Sandwich measuring cell (1) according to one of claims 1 to 7, characterized in that the sample liquid channel (6) has a volume of less than 100 µl.

9. Sandwich measuring cell (1) according to one of claims 1 to 8, characterized in that the sample liquid channel (6) is widened in the region of at least one sensor element (4a-4l) relative to a region of the sample liquid channel (6) without a sensor element.

10. Sandwich measuring cell (1) according to one of claims 1 to 9, characterized in that the soft component (7) is made of thermoplastic polyurethane (TPU) and / or the hard component (8) is made of polycarbonate (PC).

11. Sandwich measuring cell (1) according to one of claims 1 to 10, characterized in that a first thermal actuator (17) is arranged on the first sensor carrier element (2) and / or a second thermal actuator (18) is arranged on the second sensor carrier element (3). 12.Sandwich measuring cell (1) according to one of claims 1 to 11, characterized in that the first sensor element (4a, 4b) and / or the second sensor element (4c-4l) is configured to measure at least one blood gas value, preferably to measure the oxygen partial pressure (pO2), the carbon dioxide partial pressure. (pCO - 2), the pH value and / or bicarbonate (HCO3).

13. Analysis device (28) for analyzing a sample liquid, comprising: a sandwich measuring cell (1) according to one of claims 1 to 12, a computing and control unit (29) for analyzing the sample liquid with sensor data of the sandwich measuring cell (1).

14. Method for measuring a sample liquid, in particular a body fluid, preferably blood, comprising the steps of: providing a sandwich measuring cell (1) according to one of claims 1 to 12, introducing the sample liquid into the sample liquid channel (6), and measuring the sample liquid with the first and second Sensor element (4a-4l).

15. Method according to claim 14, characterized in that the sample fluid is measured to determine at least one blood gas value, preferably selected from oxygen partial pressure (pO2), carbon dioxide partial pressure (pCO2), pH value, and bicarbonate (HCO3-).

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