Device for determining the concentration of at least one substance in organic tissue

(42) Date of commencement of the patent: 15. 6.1994 (45) Date of issue: 25. 1.1995 (56) Documentation:

WO-Al 86/5402 WO-Al 88/5643 EP-Al 293958 EP-Al 362484 EP-Al 367752 EP-B1 14006 (73) Patentee:

AVL COMPANY FOR COMBUSTION ENGINES AND MEASUREMENT TECHNOLOGY MBH. PROF.DR.DR.HC HANS LIST A-8010 GRAZ, STEIERMARK (AT).

(72) Inventor:

MÖSTL ANTON DIPL.ING. GRAZ, STYRIA (AT). MAYER MICHAEL GRAZ, STEIERMARK (AT). SKRABAL FALKO DR.

GRAZ, STYRIA (AT).

(54) DEVICE FOR DETERMINING THE CONCENTRATION OF AT LEAST ONE ORGANIC TISSUE SUBSTANCE (57) In a device for determining the concentration of at least one organic tissue substance having a subcutaneous needle insertable into the tissue, wherein a microprocessor-controlled pumping and suction device is provided in a housing for supplying a perfusion fluid and for removing it after its partial equilibration with the tissue, with a sensor unit connected to the microprocessor for detecting the concentration of the substance to be determined, and at least one marker size, and with containers for the perfusion fluid, for a calibration solution and at least one drug, is being proposed, that de perfusion fluid, the calibration solution and the medication are each in exchangeable, pre-sealed dosing vials (3,3 ', 12,13) ​​with membranes CQ (14), which capillary tubes (11) penetrating via the membranes (14) communicate with a collecting capillary (10) leading from the pumping and suction device (8; 8 ') to the subcutaneous needle (4), the ampoules having metering pistons (15), which can be actuated by means of a drive unit (7) controlled by the microprocessor (5).

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AT 398 694

INR € 078318

AT 398 694 Β

The invention relates to a device for determining the concentration of at least one substance present in organic tissue with a single-lumen subcutaneous needle that can be introduced into the tissue, wherein a microprocessor-controlled pumping and suction device is provided in a housing for supplying a perfusion fluid and for removing it after its partial equilibration with the tissue, with a sensor unit connected to the microprocessor for detecting the concentration of the substance to be determined, and at least one marker size, and with containers for the perfusion fluid, for a calibration solution and at least one drug.

In the medical field, there is often a need for a continuous or frequent analysis of the composition of body fluids in order to detect and eliminate disorders of homeostasis. In order to obviate frequent blood loss, devices have been developed which allow to obtain information about the patient on an ongoing basis.

From WO 88/05643, for example, a pen-shaped device known as a glucose pen has become known, which has at one end a subcutaneous needle which can be introduced into the tissue. Inside the pen-shaped housing is a piston pump with a reservoir for the perfusion fluid, from which both the perfusate can be pumped out with the aid of the piston, as well as sucked into the collecting container which is released behind the piston. The perfusion fluid is brought by means of a first lumen in the subcutaneous needle at openings in the wall, where it comes into contact with the tissue and passes through a second, for example, concentrically arranged lumen by the resulting suction into the receptacle. As close as possible to the subcutaneous needle, an analysis device with a measuring capillary for the substance to be determined and a marker size is attached to the line which leads away the perfusion fluid. As a marker size, for example, the conductivity or the ion concentration of the perfusion fluid can be determined, whereby even with only partial equilibration of the perfusion fluid with the tissue, the degree of interaction calculated and from the true concentration of the substance to be determined (eg the glucose) can be determined.

With a known from EP-A 0 367 752 device of the type mentioned, a further development of the subject of WO 88/05643, it is possible to dispense with technically difficult to produce, multi-lumen Subcutahnadeln. The device uses a single-lumen needle whose lumen directly with the analyzer or the sensor unit is in communication. To the analysis device a piston pump is angeiossen, with which the flow direction of the perfusion fluid in the lumen of the subcutaneous needle can be reversed. With this very simple device, after the insertion of the subcutaneous needle, a few μl of perfusate are pumped into the subcutaneous needle, whereby the perfusion solution passes through the analysis device and a zero point calibration can be carried out. After partial equilibration of the perfusate with the tissue abutting the subcutaneous needle, the perfusate is aspirated from the needle and brought back into contact with the analyzer sensors, measuring the analyte and marker size and calculating the actual concentration from these values.

A disadvantage of this fully functional device is only the handling or refilling of the fluids used as calibration and perfusion, and the drug used.

The object of the invention is to develop a device of the type mentioned in such a way that medical or technical laymen can operate the device easily, or that simple maintenance tasks such as refilling and replacing consumables can be performed quickly.

This object is achieved according to the invention that the perfusion fluid, the calibration solution and the drug each in exchangeable, be present in known sealed with membranes metering vials, whose metering pistons can be actuated by means of a drive unit controlled by the microprocessor, and in that the metering ampoules communicate via the membranes penetrating capillary tubes with a collecting capillary leading from the pumping and suction device to the subcutaneous needle. This not only simplifies handling, but also makes the device more cost effective, as available on the market drug vials, such as insulin vials, are directly applicable. The perfusion fluid and the calibration solution can be filled at least in ampoules of standardized size, special products are thus obsolete.

A further simplification of the device according to the invention is given by the fact that check valves are arranged at the points of confluence of the capillary tubes in the collecting capillary, which open at defined overpressure in the capillary tube. By this measure, the necessary, for example, in the device according to EP-A 0 367 752 multi-way valve with drive is obsolete.

For example, the check valve may have an inserted into the collecting capillary, elastic hose piece, that the check valve inserted into the collecting capillary, elastic

AT 398 694 B

Has hose piece, which is arranged at the junction of the capillary tube, this closes and releases at overpressure in the capillary tube. It is of course also possible to provide other non-driven, pressure-controlled valves, for example a spring-loaded, pressed against a valve seat ball, which opens at pending overpressure.

It is particularly advantageous if the device according to the invention is designed essentially in four parts. It consists of:

1. the housing containing the microprocessor together with a communication unit connected thereto, the drive unit for the metering ampoules and the pumping and suction device, a receiving position for at least one metering ampoule for the medicament and the energy supply,

Second a replaceable unit which can be inserted into the housing and accommodates the sensor unit, the collecting capillary and the capillary tubes branching off from it and the dosing vials for the perfusion fluid and the calibration solution,

Third at least one can be inserted into the receiving position of the housing, can be brought into the replaceable unit in contact with the capillary tube provided for this purpose Dosierampulle for the drug, and

4th a subcutaneous needle attachable to the interchangeable unit.

In terms of ease of use, the device according to the invention thus consists of a minimum number of loose components: a housing, drug ampoules, a replaceable unit (hereinafter referred to as KIT) and a needle. Except for the housing, which includes the microprocessor, the communication unit and the mechanics as well as the pumping and suction device of the device, all other components are consumables, which are easy to replace by the user. The patient only has to replace the empty drug vials, the KIT (with empty doses of ampoules or defective sensors) or a blunt or no longer sterile needle.

Furthermore, the invention provides that the pumping and suction device is designed as a piston pump, which is arranged together with drive in the housing of the device, wherein the piston chamber communicates via a coupling with the collecting capillary in the replaceable unit.

As with the device known from EP-A 0 367 752, it is also advantageous here to separate the different fluids of the system by an air bubble, for which a microprocessor-controlled valve for ventilating the collecting capillary may be provided in the area of ​​the pumping and suction device.

In a particularly simple embodiment, it is provided that the ventilation valve has a preferably electromagnetically movable into two end positions movable element, the pump and suction device is in an end position of the movable element with the subcutaneous needle and in the other end position with the ambient air in combination.

To further reduce mechanical or electrical connections between the housing and replaceable unit, it is proposed that the movable element of the ventilation valve and at least one electromagnet actuating the movable element are arranged in the housing of the device.

A particularly advantageous embodiment of the invention provides that the pumping and suction device is designed as a peristaltic pump, which is arranged together with drive in the housing of the device, wherein one end of the hose pump via the hose via a coupling with the collecting capillary in the interchangeable unit and the other end communicates with a filter-covered opening to the ambient air.

in the sense of a modular design, it is provided that the drive unit per metering ampoule has a motor controlled by the microprocessor, including a gearbox, and a drive stamp acting on the metering piston in the ampoule.

The device according to the invention is eminently suitable, for example, for determining the glucose concentration and for the automatic administration of insulin if sensors are provided in the sensor device for measuring the glucose concentration and for measuring the conductivity of the perfusion fluid and dosing ampoules for receiving insulin Alt and / or insulin NPH are present ,

The invention is explained in more detail below with reference to schematic drawings. 1 shows a device according to the invention in a partially sectioned illustration, FIGS. 2a and 2b and 3a and 3b each show a detail of the invention in two operating states, and FIG. 4 shows a detail of an embodiment variant according to FIG.

The device shown in Fig. 1 shows a glucose insulin pen without limiting the application to this application example.

AT 398 694 Β

The device consists of a housing 1, an insertable into the housing 1, replaceable unit 2, drug vials 3, 3 'and one on the replaceable unit (KIT) attachable Subcutannadel. 4

The housing 1 receives a microprocessor 5, which communicates with a communication unit 6, via which the device is controlled by the patient by pressing a button and optical / acoustic display. Furthermore, in the device 1, a drive unit 7 for the metering ampoules 3, 3 'for the drug, for the still to be described metering ampoules in the KIT and for in FIG. 1 provided as piston pump pumping and suction device. The housing 1 further has a receiving position for the drug ampoules 3, 3 'and the power supply, not shown (eg Batteries or rechargeable batteries).

The KIT which can be inserted into the housing 1 is a compact plastic part which has a collecting capillary 10 leading from the attachable subcutaneous needle 4 to the pumping and suction device 8, into which opening the individual capillary tubes 11. The KIT takes a dosing ampoule 12 for the perfusion solution, which is used simultaneously as a zero point solution (N solution) and a dosing ampoule 13 for the calibration solution (S solution).

The individual metering ampoules 3, 3 ', 12 and 13 are closed with membranes 14 which, when inserted into the receiving position 9 or into the KIT 2, are pierced by the capillary tubes 11, whereby a connection to the collecting capillary 10 is established. The ampoules have metering 15, which - controlled by the microprocessor 5 - are actuated by the drive unit 7.

At the points of interchange 16 of the capillary tubes 11 into the collecting capillary 10, FIGS. 2a and 2b closer check valves 17 arranged, which open at a defined pressure. Furthermore, a microprocessor-controlled ventilation valve 18 is provided in the collecting capillary 10 in the area of ​​piston pump 8. At the needle-side end of the KIT, the collecting capillary 10 leads through the sensor unit 19 with sensors for determining the glucose concentration and the conductivity. However, it is also possible, for example, the sensor unit at another point of the collecting capillary 10 to be arranged in dashed lines positions 19 '. The electrical connection of the sensor 19 to the housing 1 is hergestelit when inserting the KIT 2 in the housing 1 via a contact point 30.

As shown in Fig. 1, the pumping and suction device may be designed as a piston pump 8, the drive 20 is arranged together with the piston 21 in the housing 1 and their standing with the collecting capillary 10 Koibenraum 22 in the interchangeable unit 2.

The drive unit has per metering ampoule 3, 3 ', 12, 13, a motor not shown here, including gear and acting on the metering piston 15 drive stamp 23, which may be either components of the housing 1 or the respective metering ampoule.

FIGS. 2 a and 2 b show a variant embodiment of a check valve 17, which has an elastic hose piece 24 inserted into the collecting capillary 10, which is arranged at the point of interchange 16 of the capillary tube 11. In the event of overpressure (FIG. 2 b), the piece of tubing is deformed and the opening of the capillary tube 11 is released. In principle, however, any type of check valve (eg ball plus spring) is suitable.

It is advantageous - as shown in one embodiment variant in the two operating states 3a and 3b - when both the venting valve 18 and the piston pump 8 are arranged in the housing 1 of the device. The Koibenraum 22 of the piston pump 8 is connected via a coupling 28 with the Sammelkapiilare 10 in the replaceable unit 2 in connection, wherein upon insertion of the unit 2 in the housing 1, a gas- and liquid-tight connection is made.

The vent valve 18 has an engageable in two end positions, designed as a slider element 25, which is moved by a disposed in the housing 1 electromagnet 26 against the force of a spring 27 and the piston pump 8 in an end position (Fig. 3a) with the subcutaneous needle leading collecting capillary 10 and connects in the other end position via the opening 29 with the ambient air. Again, other known two-way valves are applicable.

According to a variant of FIG. 4 can be provided as a pumping and suction device and a peristaltic pump 8 ', which is arranged together with drive 20 in the housing 1 of the device. One end of the hose 31 guided via the hose pump 8 'is connected via the coupling 28 to the collecting capillary 10 in the exchangeable unit 2; the other end leads to a covered with a bacterial filter 32 opening 29, via which ambient air can be sucked. A controllable valve is not necessary in this embodiment.

In the apparatus described with reference to FIG. 1 receiving positions for two insulin ampoules are provided. Depending on the type of treatment required for diabetics of type I or type II, the appropriate insulin ampules can be inserted into these receiving positions.

AT 398 694 B

The consumption period of the insulin ampules is determined by the number of applications and the insulin doses. Normally, the insulin ampules will be used up rather than the KIT 2. In the device according to the invention, the replacement of the insulin ampules is independent of the KIT change. The device indicates a necessary change over the communication unit 6 and releases the relevant vials automatically for removal.

The patient only has to remove the empty ampoules from the device and dispose of them, insert new ampoules and make the device ready by pressing a button.

The patient must replace the KIT with a new one from time to time. This change is dependent on the consumption of calibration solution or perfusion fluid per measurement and the dimensioning of the corresponding metering ampoules.

The device displays a necessary KIT replacement and simultaneously releases the empty KIT for removal. After the KIT exchange, the device is switched back to operation by pressing a button.

The KiT and the subcutaneous needle are delivered to the patient in sterile packaging. The delivery of insulin ampoules takes place in the commercial form.