WO1997021381A2 - Cartouche de mesure utilisee pour effectuer des mesures analytico-chimiques et procede d'utilisation de ladite cartouche de mesure - Google Patents

Cartouche de mesure utilisee pour effectuer des mesures analytico-chimiques et procede d'utilisation de ladite cartouche de mesure Download PDF

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Publication number
WO1997021381A2
WO1997021381A2 PCT/DE1996/002393 DE9602393W WO9721381A2 WO 1997021381 A2 WO1997021381 A2 WO 1997021381A2 DE 9602393 W DE9602393 W DE 9602393W WO 9721381 A2 WO9721381 A2 WO 9721381A2
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WO
WIPO (PCT)
Prior art keywords
measuring cartridge
measuring
calibration
sensor
chamber
Prior art date
Application number
PCT/DE1996/002393
Other languages
German (de)
English (en)
Other versions
WO1997021381A3 (fr
Inventor
Karl Cammann
Stefan Adam
Michael Borchardt
Original Assignee
Institut für Chemo- und Biosensorik Münster E.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institut für Chemo- und Biosensorik Münster E.V. filed Critical Institut für Chemo- und Biosensorik Münster E.V.
Publication of WO1997021381A2 publication Critical patent/WO1997021381A2/fr
Publication of WO1997021381A3 publication Critical patent/WO1997021381A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/153—Devices specially adapted for taking samples of venous or arterial blood, e.g. with syringes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150015—Source of blood
    • A61B5/15003—Source of blood for venous or arterial blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/157—Devices characterised by integrated means for measuring characteristics of blood
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons

Definitions

  • the invention relates to a measuring cartridge for analytical-chemical measurements and a method for operating the measuring cartridge.
  • the cartridge enables simple and contamination-free analyzes, preferably of body fluids such as blood with integrated sample preparation, sensor calibration, validation and quality assurance.
  • Table machines which contain ion-selective electrodes. Although such devices are ready for immediate use, the blood samples to be analyzed must first be sent to a laboratory. This is due to the fact that these devices can only be operated in a stationary manner and that qualified personnel and a high level of work are required for the necessary quality assurance.
  • US Pat. No. 5,096,669 describes a disposable device for real-time liquid analysis, which has to be plugged into a hand-held device for reading out the data.
  • a disadvantage of this flat-mounted measuring cartridge is the sample application.
  • a certain amount of blood must be placed in a small receiving trough, from which the sample is then transported into the measuring section by capillary forces.
  • the sample can be sprayed, which can, for example, endanger the operating personnel in the case of infectious blood.
  • the structure of the device is complicated due to its complex construction, and the production is correspondingly expensive.
  • the sensor surface is attacked by means of a cleaning zone, which is intended to prevent a transfer of sample into the individual calibration solutions and vice versa. Potential-distorting protein deposits cannot be removed in this way either. Electrode poisons are thus transferred from one sample to the next. Disadvantageous with Such a device also involves the cumbersome handling during the evaluation.
  • a disadvantage of this device is the integration of the individual mostly planar sensors in the usually cylindrical piston wall of the syringe, which makes the necessary vacuum-tight piston guide difficult. Also, before using this device for taking blood, the space behind the syringe plunger must be filled with the calibration solution. In addition, the necessary heparin units must be placed in front of the syringe plunger before the blood is drawn. This results in design-related problems, which under certain circumstances can only be solved by a rectangular syringe structure. Such syringes are not yet known in medical technology, they will probably have sealing problems and because of the
  • the object of the invention is to create a measuring cartridge and method for operating the measuring cartridge which, in a simple and inexpensive manner, exclude on-site analyzes of liquid or gaseous samples of air contact and with integrated calibration.
  • a method for operating the measuring cartridges relates to claims 10, 11, 14 and 15.
  • a measuring cartridge with at least one first connection for a sampling device, at least one second connection for a pump device and at least two chambers arranged in the flow direction between the first connection and the second connection, in which at least one of the chambers one or more calibrators - and / or conditioning solutions (calibration chamber) and at least one chemical or biochemical sensor is arranged in the area of at least one of the chambers (sensor chamber), with between individual chambers and the two connections and / or between individual chambers themselves
  • Fluidic control elements are arranged, ensures the possibility of a simple sensor calibration in connection with an on-site analysis of gaseous or liquid samples. Another calibration or conditioning liquid can also be found in the
  • the chambers are areas in which liquid or gas volumes exclude air contact. collects, transported or procedural steps to be subjected.
  • fluidic control elements are arranged between the individual chambers and the two connections or between individual chambers themselves and in particular between the chamber containing one or more calibration solutions and the chamber containing at least one sensor, it is possible to use the sensors to be brought into contact with at least one calibration solution before measuring the sample.
  • the measuring cartridge according to the invention can be used to perform a sensor calibration preceding the sample measurement without the sample, which is preferably already in the measuring cartridge before calibration, being contacted with air.
  • Suitable fluidic control elements are, for example, connecting channels between individual chambers, deflections, valves such as sliding, rotating, deflecting and returning. Impact valves and / or displaceable recesses in spacers, which are positioned sealingly between two surfaces. So-called "crack valves" which open at a certain pressure can also be used.
  • the measuring cartridge is preferably arranged between a hypodermic needle and a syringe and the individual chambers of the measuring cartridge are arranged parallel to one another. In this way, the outer shape of the measuring cartridge can be adapted to the diameter of the syringe body. This ensures ergonomic operation of the device.
  • other pump devices generating negative pressure for example peristaltic pumps, could also be used.
  • the fluidic control elements are preferably each formed as a termination at opposite ends of the individual chambers and between the respective ones
  • the fluidic control elements are preferably passive, movable and simply constructed elements such as, for example, slide valves, which ensure, for example, a connection or separation of the sensor chamber with other measuring cartridge chambers depending on the course of the method.
  • the fluidic control is preferably designed such that it is exerted by mechanical means exerted on the measuring cartridge
  • Pressure can be switched between two different settings. For example, a certain valve position can be useful during sampling, but a different valve position is required for the evaluation and measurement of the sample become.
  • the measuring cartridge advantageously comprises an additional sample collection chamber.
  • the sample collection chamber can be filled with the sample to be taken in a first process step (sampling). After the sample has been taken, the measuring cartridge can then be inserted into an external device, preferably a hand-held measuring device, for measurement, if appropriate together with the sampling device and the pumping device.
  • the sample is then passed from the sample collection chamber into the sensor chamber for measurement.
  • the measuring cartridge can, if necessary, still another
  • Contain collection chamber in which the individual liquid volumes of sample, one or more calibration solutions, etc. are collected as a mixture after the individual process steps have been carried out.
  • the chamber can be filled with an adsorber material.
  • the measuring cartridge advantageously also comprises a second chamber with a second calibration solution.
  • the preferred calibration solutions are the
  • the measuring cartridge can be designed in such a way that the sensor chamber is connected to a calibration chamber, which in turn is connected to a sample collection chamber, and that, in addition, at least one calibration solution is passed between at least two in the calibration chamber
  • Pressure-displaceable stamps or pistons is arranged.
  • Two calibration solutions are preferably separated in the calibration chamber by means of three displaceable stamps or pistons.
  • the sample collection chamber and sensor chamber are advantageously in the area opposite one another. lying calibration chamber ends connected to this.
  • the volume of the calibration chamber should be significantly larger than the sensor chamber volume. Due to the vacuum or pressure generated by the pump device or due to the pressure exerted by the sample on a stamp, the stamps with the calibration solutions arranged between them are displaced in the direction of the connection between the sensor chamber and the calibration chamber and the calibration solution or the calibration solutions are successively transferred to the sensor chamber. The one-point or two-point calibration takes place. The sample then reaches the sensor chamber and is measured there.
  • the sample collection chamber can also be connected directly to the sensor chamber via a fluidic control element.
  • the function of the sample collection chamber can also be performed by a syringe, for example.
  • a method for operating a measuring cartridge according to the invention contains at least the three steps of sampling, calibration and evaluation.
  • the calibration can take place before or after the sampling.
  • the measuring cartridge Before or after filling the sample collection chamber or the pumping device via a sampling device, the measuring cartridge is placed in a measuring device and the at least one sensor is brought into contact with a calibration or conditioning solution.
  • the measuring device is preferably a hand-held measuring device for rapid on-site analyzes.
  • the sensor can then be brought into contact with a second calibration solution.
  • the second supplants Calibration solution the first calibration solution from the sample collection chamber.
  • the sample from the sample collection chamber or the pump device then displaces the second calibration solution in the sensor chamber and comes into contact with at least one sensor.
  • the sample and the individual calibration solutions can flow through the measuring cartridge, for example in the form of air-separated liquid segments.
  • the sample and calibration solutions can also be separated using a stamp or piston.
  • Sampling can take place, for example, by drawing the sample into a syringe with the fluid control elements in the appropriate position.
  • the syringe plunger is moved automatically or manually up to an intended stop or the maximum syringe volume.
  • a sample collection chamber can also be filled with the sample if necessary.
  • the sampling device is preferably inserted into a portable hand-held measuring device together with the sampling device and the pump device. Due to the fitting pressure associated with inserting the cartridge, an automatic switchover of the
  • Fluidics control take place.
  • the syringe plunger is then moved in the direction of emptying.
  • the calibration and / or evaluation of the sample takes place.
  • a measuring cartridge according to the invention can also have a first connection for a sampling device, a second connection for a pump device and at least one chamber arranged between the first connection and the second connection, wherein the chamber contains one or more calibration solutions and at least one chemical or biochemical sensor is additionally arranged in the area of the chamber.
  • Fluidic control elements can also be arranged in the measuring cartridge.
  • the sensors are already in contact with the calibration solution by the manufacturer.
  • the connections for the sampling device and pump device are advantageously closed with a film until just before the sampling.
  • a method for operating this measuring cartridge comprises the steps of calibration, sampling and evaluation. First, the measuring cartridge is placed in a measuring device and the calibration of the at least one sensor in contact with the calibration solution is carried out. This is a one-point calibration. The measuring cartridge is then removed from the hand-held measuring device and the sampling is carried out. The drawn sample displaces the calibration solution from the chamber, and the two mix in the pump device. Following this, the measuring cartridge is reinserted in the hand-held measuring device and the sample is measured by means of the at least one sensor in contact with the sample.
  • Standard addition evaluation method can be carried out.
  • the sample mixed with the calibration solution is conveyed back out of the pump device into the sensor chamber and then measured again.
  • the connections for the sampling device and the pump device preferably have a circular cross section
  • the sensor chamber preferably has a rectangular cross section. If a large number of sensors are to be arranged in the sensor chamber, it can be advantageous if the sensor chamber is configured in a meandering shape.
  • the volume of the sensor chamber and the other chambers is typically 1 to 1000 ⁇ l.
  • the measuring cartridge can have a one-piece construction or consist of two cartridge halves. In the latter case, it is conceivable that one or more chambers, but preferably the sensor chamber, is formed only by inserting a measuring cartridge insert provided with a chamber recess into a recess of a basic measuring cartridge body. In this way, for example, the accessibility of the sensor chamber is guaranteed before individual process steps are initiated.
  • Both the measuring cartridge insert and the measuring cartridge base body can be equipped with sensors, so that the individual sensors of the sensor chamber are later opposite one another after the two halves have been joined together. In this way, typically up to ten sensors can be accommodated per centimeter.
  • a spacer can be arranged between the measuring cartridge insert and the measuring cartridge base body, which serves to press on and to seal the sensor film.
  • Measuring cartridge chambers can also be formed in that the spacer arranged between two cartridge halves has at least one chamber recess.
  • the individual sensors are connected via electrical sensor leads and sensor leads in the area of the measuring card. ink housing or connected directly to the housing contacts.
  • the sensor-specific contacts of the individual sensors for the measurement can be closed precisely and reliably by means of a suitable insertion technique, for example a nipple in the measuring cartridge and a corresponding recess in the opening of a hand-held measuring device.
  • the sensor supply and sensor lines and the contacts attached to the measuring cartridge housing preferably consist of a non-metallic electron conductor such as, for example, graphite, glassy carbon, carbon paste or a conductive polymer.
  • a redox system and / or cavities filled with electrolyte gel can be arranged between the at least one sensor and the electrical sensor feed and sensor leads.
  • the cavities can be configured, for example, as depressions in the sensor chamber. The one arranged on the back of the measuring electrodes
  • the redox system or the depression filled with electrolyte gel can represent the derivation of a planar ion-selective and gas-permeable membrane and can be covered by the appropriate sensor measuring strip.
  • This structure is particularly suitable for amperometric sensors.
  • a thermodynamically reversible internal potential derivation for all electrochemical chemo- and biosensors can be achieved in that in an ion-selective membrane, an inner electrolyte solution and one in the
  • Phase of the electron-conducting connection for example graphite, graphite plus polypyrene, polypyrene, polyethylene, stable and easily disposable redox systems with high standard exchange current densities in a concentration range of 0.1% to saturated.
  • Suitable sensors according to the invention are, for example, impedimetric, amperometric, potentiometric or else optical sensors, optionally in conjunction with immunological or enzymatic detection methods.
  • the measuring cartridge can also contain chambers for immunological rinsing buffers and enzyme substrate solutions as well as solid phases loaded with antibodies or antigens. Immunoassays can thus also be carried out, for example using the ELISA method.
  • At least one reference electrode can be arranged in the sensor chamber.
  • a single sensor reference electrode can be provided for a large number of sensors. It is also conceivable to use a separate reference electrode for each sensor.
  • the individual chemical or biochemical sensors are preferably designed to be easily disposable and miniaturized and are in electrical connection with contacts on the outer surface of the measuring cartridge with corresponding counter-contacts in an associated measuring device. In principle, it is possible to operate a number of differently constructed sensors in the measuring cartridge. However, uniform electrochemical microsensors are preferably used, which are printed on paper-like carriers using a particularly inexpensive technology (for example double-matrix membrane sensors).
  • the pH value, pC0 2 value and the electrolytes Li + , Na + , K + , Ca 2+ , Mg 2+ , Cl " and others are potentiated with ion-selective electrodes. metrically recorded.
  • Glucose, acetate and others are preferably determined using amperometric biosensors.
  • the individual sensors are preferably positioned in series in the sensor chamber and are in direct contact with the drawn sample with their analyte-sensitive measuring surface after corresponding calibration.
  • a preferred and inexpensive production technology for sensors is screen printing technology (eg low-temperature thick film technology) or the automatic printing of nonwoven or filter paper or materials with similar properties by means of a dispenser (cf. DE 41 32 761). It could be shown that the batch scattering is so small that a single-point calibration is often sufficient when using such sensors.
  • sensors which can be mass-produced by silicon technology can also be pressed or glued into corresponding recesses in the sensor chamber.
  • the sensor chamber itself can also be designed using silicon technology. With such an embodiment, a very high number of sensors can be arranged in the sensor chamber. The individual microsensors are brought into contact with the relevant connection to the external contacts on the back. In the case of minimally invasive sampling (e.g. in infants), silicon technology is preferred.
  • impedimetric sensors can also be used. These work with alternating current at different frequencies. When measuring the samples, the complex AC resistance level is evaluated at higher frequencies.
  • impedance sensors In addition to a very thin analyte-selective membrane, impedance sensors only require two electron-conducting micro-discharge electrodes and no potential-constant reference electrodes. Impedimetric sensors are also extremely inexpensive to manufacture in planar form.
  • measuring cartridges can be used as disposable cartridges. Since the sensors can be mass produced and are only used for a single sample measurement, good reproducibility of the analyzes is guaranteed. Because the sensors are arranged in the area of the sensor chamber, the structure and the fit of the planar sensors are not important. Sealing problems therefore do not occur in connection with the sensor structure, which considerably simplifies the manufacture of the sensors. When disposing of the disposable measuring cartridge used in terms of combustion technology, it is advantageous that the cartridge contains little or no metal when using non-metallic electron conductors. With some sensors of an amperometric type, gold and
  • Membrane chemicals for the potentiometeric microelectrodes are in the microgram range and contain no CFCs, so that there is no fear of dioxin formation during combustion.
  • Double-matrix membrane sensors are preferably used, since they reach their equilibrium potential after only a few seconds. This ensures that the procedure runs quickly. Due to the degree of automation, the technical maturity of the planar double matrix membrane sensors is so high that the specimen scattering ranges are well known and allow single-point calibrations (constant calibration curve slope). As soon as a sensor leaves this area, the hand-held measuring device could indicate which parameter could possibly be less reliable. This results in automatic quality assurance.
  • the measuring cartridge can consist of a non-conductive material which can be mass-produced inexpensively in any shape and easily disposed of.
  • the cartridge preferably consists of extrudable plastics (injection molding technology), from which medical articles such as, for example, are also made
  • Syringes exist. Particularly suitable materials are combustible and residue-free combustible polymers such as polycarbonates, polypropylene, polymethyl methacrylate (plexiglass) etc.
  • the measuring cartridge or parts of the measuring cartridge, such as the fluidic control elements or individual chambers, can also consist of microstructurable silicon.
  • the calibration solution may contain various ingredients such as conditioning substances, heparin or poorly soluble salts. These substances can also be arranged in separate chambers.
  • the chambers are preferably filled with multi-analyte calibration, multi-standard and / or conditioning solutions.
  • the measuring cartridge can be characterized in such a way that the hand-held measuring device can take over the respective sensor equipment and data of the calibration or conditioning solution when it is first inserted. This can be done by mechanical or electrical devices, but also by means of a barcode reader.
  • the measuring cartridge is preferably used to measure body fluids such as blood or urine in particular for common parameters such as electrolytes (eg Li + ,
  • metabolic factors such as glucose, acetate, urea (BUN), uric acid, Creatinine, pyruvate, ascorbin, phosphate, cholesterol, blood lipids, triglycerides, phenylalanine, bil
  • the measuring cartridge according to the invention is particularly suitable for use in a hand-held measuring device without annoying connecting cables.
  • the measuring cartridge When used in connection with a hand-held measuring device, the measuring cartridge is preferably equipped with a hypodermic needle and a syringe. This complete arrangement is placed in a measuring device, the fluidic control being switched over by automatic fitting pressure in such a way that one or more calibration solutions can first come into contact with the sensors when the syringe plunger is moved in the direction of emptying.
  • the needle can pierce a septum and behind it into a gel-consolidated or non-consolidated stream.
  • the measurement process in the analysis can be started by closing a resistance measuring circuit with a contact zone in the sensor area when this electrolytic connection between the sensor chamber in the cartridge and the external reference electrode is closed (drastic reduction in resistance).
  • the offset voltage between the reference electrodes in the measuring cartridge, which due to the design cannot have a larger current key, and the reference electrode in the hand-held measuring device is known to within a few microvolts. This is taken into account in a microprocessor evaluation.
  • the automatic measuring process is started when a perfect electrolytic connection has been established. The syringe plunger is then replaced by an
  • the hand-held measuring device integrated mechanism eg spring-tensioning mechanism
  • the hand-held measuring device integrated mechanism is pressed into the syringe under constant pressure so that there is enough time for the formation and acquisition of the measurement signals under the influence of the calibration solutions.
  • an actuator can also move the push rod of the syringe plunger in the desired direction.
  • the sample reaches the sensors and is analyzed there accordingly.
  • samples of calibration solutions are passed into a collecting chamber which is preferably arranged in the measuring cartridge.
  • the measuring cartridges can because of the known and minimal Dilution of the sample arranged in the collecting chamber can also be transported to a laboratory for the determination of other parameters.
  • the measuring cartridge is preferably filled by the manufacturer with a suitable calibration solution which is common to all sensors and is sterile as far as possible.
  • FIG. 4 shows the structure and the mode of operation of a measuring cartridge for a two-point calibration by means of movable pistons.
  • Embodiment 1 outlines the structure of a measuring cartridge 1 with laminated paper sensors 4a to 4z.
  • the measuring cartridge 1 is suitable for connection to a hypodermic needle via the Luer connection 2a and to a syringe via the Luer connection 2b.
  • the two halves la, lb of the measuring cartridge 1 can be made in this shape with sufficient production tolerance from an easily disposable plastic material. rial inexpensive. For reasons of handling, they are not significantly larger than the syringe body itself.
  • the sensors 4a to 4z are preferably double-matrix membrane sensors. It is advantageous that because of the known construction of the double matrix membrane sensors, it is not necessary to insert a metallic conductor that is difficult to dispose of into the plastic material.
  • the sensor strip with any number of laminated paper sensors 4a to 4z has a shape which ensures that the contact surfaces extend into the correspondingly shaped housing half la as far as the recess 7 in the cover 1b and thereby form the contact surfaces 5 .
  • the cartridge half lb In the cartridge half lb, three chambers 8, 9 and 10 are introduced by injection molding. However, the sensor chamber 6 is only formed by joining the two cartridge halves la and lb together. Another chamber, not shown in the illustration, below the sensor level is large enough to accommodate all chamber volumes and the sample volume together.
  • the chambers 8 and 9 contain defined multi-analyte calibration solutions, corresponding to the analytes in a lower and upper concentration range, so that the important slope of the calibration line and its position can be reliably determined by a two-point calibration. If certain minimum criteria installed in software in a hand-held measuring device for the sample evaluation are not met, an unreliability indicator for this parameter is signaled.
  • the calibration solutions contain for the purpose of conditioning and preservation 81 PO7DE96 / 02393
  • the sample is also mixed with a constant ion concentration of these ions which corresponds to the solubility product and which is normally not contained in the sample.
  • an additional micro-reference electrode can be built up without a disturbing diffusion potential.
  • the addition of a lanthanum fluoride suspension may be mentioned as an example.
  • the measuring electrode here is a fluoride-selective electrode.
  • At least the chambers 8 and 9 are sealed gas-tight after filling, which can be done, for example, with the aid of a metallized film, which then breaks through for use at a defined pressure.
  • the entire measuring cartridge is welded into a gas-tight film and some calibration solution is also bound or introduced into this film to compensate for the particle pressure of the measuring gases in question.
  • the chamber 10 serves to temporarily store part of the sample. If necessary, a small amount of the sparingly soluble salt is stored here by the manufacturer.
  • the chamber 10 and the sensor chamber 6 are on both
  • Ends open. They are closed or opened by the fluid control 3 introduced into a further recess in the cartridge half 1.
  • the fluidic control 3 adjusts itself by mechanical counterpressure when the measuring cartridge 1 is inserted into Hand-held measuring device in accordance with the requirements of the respective method (cf., for example, FIG. 2).
  • the two measuring cartridge halves Ia and Ib are brought together and glued together with a sealing plastic spacer.
  • the two Luer connections are then sealed gas-tight with a needle and syringe.
  • the automated sequence of the measuring method according to the invention is schematically outlined in FIG. 2. From the content and the sequence of the method steps described below, the person skilled in the art can infer the configuration of the required fluidic control elements (deflections, valves).
  • the uppermost representation a shows the measuring cartridge 1
  • a first calibration liquid 11 is filled into the chamber 8 and a second calibration liquid 12 is filled into the chamber 9.
  • the sensors 4 are arranged in the area of the sensor chamber 6.
  • the sample collection chamber 10 is still empty.
  • the syringe conveys a defined amount of air into the measuring cartridge 1, whereby the first calibration solution 11 is transported into the sensor chamber 6 via a corresponding valve control.
  • the fluid control 3 takes the sample 13 through the chamber 10. Part of the sample 13 also gets into the syringe.
  • the measuring cartridge 1, together with the syringe and needle is inserted into a corresponding opening of the hand-held measuring device, the fluidics control 3 being switched over at the same time in accordance with the subsequent method steps and the individual chemical and biosensors 4a to 4z being connected via one Snap mechanism on their contacts with the corresponding ones Mating contacts of the handheld measuring device can be contacted.
  • the needle tip is pushed through the septum into the current key electrolyte of the external reference electrode.
  • the automated measuring process is started by detecting a perfect electrolytic connection.
  • the double matrix membrane sensors which are still in contact with the first calibration liquid 11, have already reached their stable measured value after these minimal operating operations.
  • a software logic installed in the hand-held measuring device then compares all sensor signals which occur in contact with the first calibration solution 11 with the known variations in the production technology and signals any deviations already in this process step. After a waiting time of a few seconds, the syringe plunger automatically moves in the direction of the emptying by the mechanism integrated in the hand-held measuring device and thus presses the sample
  • the sample 13 flows back through the fluid control 3 through the chamber 10 and from the fluid control 3 at the needle end into the chamber 9 deflected and displaced there, protected from mixing by an air bubble, the second calibration solution 12.
  • the second calibration solution 12 in turn flows through the fluidics control 3 at the syringe end (deflection) into the sensor chamber and pushes past the sensors the first calibration solution 11 back into the chamber 8 before it also enters the chamber 8 through the fluidics control (deflection) at the needle exit.
  • the final state is shown in representation e.
  • the sample liquid 13 has the second Calibration solution 12 is completely displaced from sensor chamber 6 and can be measured.
  • a microsensor-equipped flow construction with silicon technology and contacts on the back is pressed and glued into a recess in the two measuring cartridge halves. It must be ensured that the rear contacts are conductively connected to the corresponding measuring cartridge bushings.
  • Embodiment 3 outlines a device for performing a single-point calibration in connection with a standard addition.
  • FIG. 3 shows an advantageous device for carrying out this alternative method by means of the measurement value assurance using the standard addition / evaluation method.
  • a fluidic control can be dispensed with here if the needle tip penetrates through the
  • the septum is given a flow resistance by a sealed gel, so that a simple slit overpressure valve in the measuring cartridge is opened when the sample is re-injected, which allows the calibration solution to flow into the chamber.
  • the calibration solution is already in contact with the sensors in the sensor chamber 6 by the manufacturer.
  • the measuring cartridge 1 is measured in a measuring device for calibration alone. Then, after removing the gas-tight caps, it is filled with needle and syringe via the Luer connections 2a and 2b, and the sample is taken. The calibration fluid is displaced from the sensor chamber into the syringe.
  • the subsequent installation of the complete arrangement in the hand-held measuring device is analogous to the first embodiment. Due to the small volume of the sensor chamber 6, the sample located there does not mix very quickly with the syringe content. Therefore, the sample can be measured first and then the mixture of sample and standard solution. If the volume of the sensor chamber 6 and thus that of the standard solution (calibration solution) can be neglected compared to the amount of sample taken, the evaluation is simplified.
  • a further preferred embodiment on this basis results when the sample is drawn into the syringe via a second valve-controlled bypass.
  • the handling remains as described above.
  • the multi-analyte calibration solution which has a concentration suitable for the expected analyte concentration range, is first measured.
  • a logic software checks the plausibility of these values on the basis of the known sample variations. Only then can the mechanism of syringe emptying be activated. The sample and standard mix after the calibration solution has been displaced from the
  • the syringe plunger moves again in the direction of the filling and brings the sample standard mixture from the chamber back into the sensor chamber, where a further measurement takes place.
  • Exemplary embodiment 4 describes a measuring cartridge and a method with two-point calibration by means of piston-separated calibration solutions 11, 12. As sketched in FIG. 4 above and in illustration a, sensor chamber 6 and calibration chamber 18 are above one
  • the volume of the sensor chamber 6 is significantly less than the volume of the calibration chamber 18 (e.g. 300 ⁇ l to 3 ml).
  • the sample 13 is drawn into a sample collection chamber (not shown) or into a syringe.
  • the measuring cartridge is then placed in a hand-held measuring device, where the method steps described below take place. Due to the syringe pressure when emptying the measuring cartridge, the sample 13 is passed through the opening

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Abstract

L'invention concerne une cartouche de mesure utilisée pour effectuer des mesures analytico-chimiques, ainsi qu'un procédé d'utilisation de ladite cartouche de mesure. Cette cartouche de mesure pour échantillons liquides ou gazeux comprend un premier raccord pour un dispositif de prélèvement d'échantillons, tel que notamment une aiguille hypodermique, un second raccord pour un dispositif de pompage, tel qu'une seringue, au moins deux chambres disposées entre le premier et le second raccord, dont au moins une contient une ou plusieurs solutions d'étalonnage (chambre d'étalonnage), et dans la zone d'au moins une des chambres (chambre de détection), au moins un détecteur chimique ou biochimique. En outre, il est prévu des éléments de commande de fluidique, disposés entre des chambres individuelles et les deux raccords et/ou entre des chambres individuelles.
PCT/DE1996/002393 1995-12-13 1996-12-13 Cartouche de mesure utilisee pour effectuer des mesures analytico-chimiques et procede d'utilisation de ladite cartouche de mesure WO1997021381A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19546535.0 1995-12-13
DE19546535A DE19546535C2 (de) 1995-12-13 1995-12-13 Meßkartusche für flüssige oder gasförmige Proben, Verfahren zu deren Betreiben und deren Verwendung

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WO1997021381A2 true WO1997021381A2 (fr) 1997-06-19
WO1997021381A3 WO1997021381A3 (fr) 1997-08-14

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WO2009146163A1 (fr) * 2008-05-30 2009-12-03 General Electric Company Dispositif d'embout de cathéter et son procédé de fabrication
DE102011056273A1 (de) 2011-12-12 2013-06-13 sense2care GmbH Fluidreservoir für eine Vorrichtung zur Analyse von Patientenproben
DE102011056271A1 (de) 2011-12-12 2013-06-13 sense2care GmbH Vorrichtung zur Analyse von Patientenproben
CN110403612A (zh) * 2019-08-22 2019-11-05 南京嘉恒仪器设备有限公司 血气分析仪校准试验气体张力平衡装置
CN113588755A (zh) * 2020-04-30 2021-11-02 恩德莱斯和豪瑟尔分析仪表两合公司 校准设备、包含其部件的柔性袋和校准传感器的方法

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DE19736641A1 (de) * 1997-08-22 1999-03-11 Michael G Dr Weller Verfahren und Vorrichtung zur parallelen Messung von mehreren Analyten in komplexen Mischungen
DE19747572C1 (de) * 1997-10-28 1999-04-08 Inst Chemo Biosensorik Vorrichtung und Verfahren zur Durchführung von Fluoreszenzimmuntests
JP3389106B2 (ja) * 1998-06-11 2003-03-24 松下電器産業株式会社 電気化学分析素子
DE10111457B4 (de) 2001-03-09 2006-12-14 Siemens Ag Diagnoseeinrichtung
US6814938B2 (en) 2001-05-23 2004-11-09 Nanostream, Inc. Non-planar microfluidic devices and methods for their manufacture
WO2003019165A2 (fr) 2001-08-22 2003-03-06 Instrumentation Laboratory Company Systeme automatise servant a calibrer automatiquement et en continu des capteurs electrochimiques
US20030199739A1 (en) * 2001-12-17 2003-10-23 Gordon Tim H. Printing device for personal medical monitors
US7972279B2 (en) 2005-01-27 2011-07-05 Instrumentation Laboratory Company Method and system for managing patient data
DE102005017364B4 (de) 2005-04-14 2007-02-01 Roche Diagnostics Gmbh Analysegerät mit auswechselbarem Testfeldträger
GB0612834D0 (en) 2006-06-28 2006-08-09 Glysure Ltd Sensor calibration
DE102008017196B4 (de) 2008-04-04 2010-10-07 Dräger Safety AG & Co. KGaA Verfahren zur Inbetriebnahme und zum Betrieb einer Messvorrichtung
EP2233210A1 (fr) * 2009-03-23 2010-09-29 Aleria Biodevices, S. L. Dispositif pour la distribution séquentielle de réactifs liquides sur une chambre à réaction
US8746031B2 (en) 2009-05-18 2014-06-10 Lightship Medical Limited Glucose sensor calibration
DE102012011411B3 (de) * 2012-06-08 2013-11-28 Dräger Safety AG & Co. KGaA Testsystem zum Portionieren, Mischen und Verteilen von biologischen Probenflüssigkeiten
GB201401878D0 (en) 2014-02-04 2014-03-19 Lightship Medical Ltd Calibration method
PL3714822T3 (pl) 2019-03-25 2023-03-27 Erbe Elektromedizin Gmbh Układ sterowania płynem do urządzenia medycznego
CN112029821A (zh) * 2020-08-18 2020-12-04 美康生物科技股份有限公司 一种血脂测试卡及其应用

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Publication number Priority date Publication date Assignee Title
WO2009146163A1 (fr) * 2008-05-30 2009-12-03 General Electric Company Dispositif d'embout de cathéter et son procédé de fabrication
US8140146B2 (en) 2008-05-30 2012-03-20 General Electric Company Catheter tip device and method for manufacturing same
DE102011056273A1 (de) 2011-12-12 2013-06-13 sense2care GmbH Fluidreservoir für eine Vorrichtung zur Analyse von Patientenproben
DE102011056271A1 (de) 2011-12-12 2013-06-13 sense2care GmbH Vorrichtung zur Analyse von Patientenproben
WO2013087573A2 (fr) 2011-12-12 2013-06-20 sense2care GmbH Dispositif pour l'analyse d'échantillons prélevés sur des patients
WO2013087567A1 (fr) 2011-12-12 2013-06-20 sense2care GmbH Réservoir à fluide pour un dispositif d'analyse d'échantillons prélevés sur des patients
DE102011056273B4 (de) * 2011-12-12 2013-11-21 sense2care GmbH Fluidreservoir für eine Vorrichtung zur Analyse von Patientenproben
CN110403612A (zh) * 2019-08-22 2019-11-05 南京嘉恒仪器设备有限公司 血气分析仪校准试验气体张力平衡装置
CN113588755A (zh) * 2020-04-30 2021-11-02 恩德莱斯和豪瑟尔分析仪表两合公司 校准设备、包含其部件的柔性袋和校准传感器的方法

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DE19546535C2 (de) 2000-02-03
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