Device for determining concentration of organic substance in organic tissue

The invention relates to medical technique and is used for determining the concentration of at least one existing substance in organic tissue, preferably the glucose concentration.

In medicine, there is the need for continuous analysis of the composition of body fluids to be able to register and to eliminate disturbances of homeostasis. To make unnecessary frequent blood samples, has for many years conducted experiments on the placement of the sensitive elements in the body of patients to receive continuous information.

It is particularly widely used continuous determination of glucose concentration in the body. There are, for example, methods and apparatus for dialysis in which at least a hollow needle or catheter is introduced into the bloodstream. With the help of dialysis membrane is achieved by balancing the complete measuring liquid blood, which is then analyzed for the presence of the substance of interest, for example glucose. However, when loaded on the one hand, the measuring fluid and, on the other hand, the body fluid membranes that for sufficient equilibration should be large enough, it will soon lead to membrane fouling or clogging substances of the organism, so that exchange rapidly broken substance of interest. In addition, when introduced into the bloodstream using a foreign body, for example hollow needles and catheters, there is a constant risk of infection, thrombosis or embolism. Furthermore, to continue over a long treatment time are available only a few blood vessels are clogged soon so that the method can not be used further.

A device which eliminates the mentioned drawbacks. Called "glucose pen" example embodiment has in this case formed as a rod body which at one end has a hypodermic needle. Inside the housing is a piston pump to a reservoir for perfusion fluid, which by means of the piston as the perfusate can be pumped by the piston from the displacement space and absorbed in the releasing piston for receiving tank. By means of the lever device the piston can be moved manually through the required anyway gear and pervuzionnaya fluid via a first internal channel hypodermic needle is applied to the holes in the wall thereof, and simultaneously with a second location, for example concentrically with respect to the first inner conduit through pdsasyvaniyu It collected in the receiving vessel. At the same time the possibility of a hypodermic needle is located at the Join the drain pipe to the assay device for measuring capillaries defined substance and marker values. Thus, for a short time, for example of the order of one minute or less, the liquid is pumped by means of a hypodermic needle after its partial equilibration again collected. Already after a short time with the help of optical and acoustic indication or indications may be recorded actual concentration of substance of interest, such as blood sugar, which is calculated by the analytical unit of the concentration of the marker substance and the substance of interest. In order for the necessary time to obtain a uniform tissue perfusion flow rate, there are several process steps. Thus, for example, via a lever device, which lever during the period of perfusion continuously actuated, uniform perfusion rate is achieved. The lever for this purpose, for example, by a spring or other energy storage and again can be driven to the initial position. In this perfusion rate during collecting period is in the range from 1 to 10 l / min. However, a disadvantage is that a complex design "glucose pen", and, in particular, the production of multi hypodermic needle is technically complicated and costly.

The technical result from the use of the invention is to provide a device which, based on the above prior art, can be made simpler and less expensive, while maintaining the functions and advantages of the closest analogue.

The technical result is achieved due to the fact that provides single-channel hypodermic needle, an inner channel which is connected to the analyzer, the analyzer on the output side is connected to the injection-aspirated means and hypodermic needle is a single-channel analyzer connected to the plug connection for communication with the needle and injection-suction means and is provided with an electrical contact for connection with the evaluation unit, multi-code valve is installed in the connecting pipe and connected thereto two channels between the injection-suction means and the analyzer, and a third valve passage communicates with a reservoir for perfusion fluid. With this device, after the introduction of a hypodermic needle several l perfusate is pumped into the hypodermic needle, and the perfusion solution passes the analyzer and can be accurate zeroing. After partial equilibration with the perfusate which is near tissue perfusate hypodermic needle is withdrawn from the needle and again brought into contact with the sensitive elements of the analyzer, the measured substance and the marker determined value, eg electrical conductivity, and from these calculated actual values ​​of the concentration, such as glucose concentration. For accurate zeroing perfusion fluid in this example, basically would not have to contain ions and glucose.

As other advantages of the device according to the invention should result in that the single-channel hypodermic needle can be made thinner, respectively, so that the patient, for example, repeatedly conducted daily blood glucose fabric must endure less pain.

To increase the area of ​​exchange of a hypodermic needle provided that the hypodermic needle along the axis of the needle has shlitse- shaped extension or hypodermic needle along with the end opening has at least one or the other hole in the wall area. Preferably, circumferential needle in several rows have several openings.

In one embodiment of the invention provides that the analyzer on both sides has a conical plug-in connection, by which it is on one side connected to the subcutaneous needle and on the other side by a connection pipe - with injection-suction means, with the connector via the break contacts creates an electrical connection between the evaluation unit and the analyzer. Connectors provide a simple shift of a needle or instrument.

To partially counterbalanced perfusion fluid could be mixed with a perfusion fluid into the piston pump, in the example of the invention provides that between the pressure-suction means and the analyzer is a multi-way valve, through which injection-suction means at a first position of the valve is connected to a hypodermic needle and in the second position of the valve - with an opening for outside air. The intake valve via an air bubble separates then both the liquid column.

In one embodiment of the invention provides that the injection-suction means has a piston pump, the piston kotorggo space is designed as a reservoir for the perfusion fluid, and that the suction stroke is provided a charged during the pumping stroke energy accumulator. When using the preferred hand-operated piston pump only when the patient should press the piercing lever unit, and then let go, so that the review process takes place automatically. As the energy accumulator is, for example, a spring. Due to the small nagnetaeniya move during the process of balancing the flow of perfusate in the internal bore of a hypodermic needle can be repeatedly changed, and thus a higher level of trim.

A preferred development of the invention is that the pump is provided in the drive mechanism that move between the discharge and suction phase equilibration perfusion fluid provides insignificant nye nagnetaenii movement when suction piston and reciprocating pump. Thus, when moving the discharge phase balancing mechanism executed, the necessary energy to which can also be fed by a discharge stroke of the lever causes the device.

In an improved embodiment of the invention provides a reservoir for the perfusion fluid and at least one tank administered drug, and that the discharge-suction means in the third position of the changeover valve is connected to a reservoir for perfusion fluid and at least one-DREG position - with the appropriate reservoir for the medicament.

Thus, in accordance with the invention may be provided for the fast-acting insulin reservoir, a reservoir for slow-acting insulin and a reservoir for enhancing blood sugar hormone.

An improved embodiment of the invention provides that a reservoir for the perfusion fluid and a reservoir for medication are easily deformable packages of synthetic material and with the multi-port valve and the respective connecting tubes form an interchangeable unit. Thus can be used required, determined on the basis of the measured value determined by the concentration of the substance, the amount of the drug via a hypodermic needle has entered the patient's fatigue without other punctures. After the perfusion fluid reservoir or a reservoir for medicament emptied, they can, together with multi-way valve and the necessary connecting pipes integrally replaced with new ones.

In the embodiment of the invention provides that the refill assembly by tight connection, preferably through a puncture septum or seal rings, coupled with the injection-suction means, with its inner space located between the multi-way valve and a hermetic connection portion of the connection tube It corresponds to the volume of at least the suction stroke. Situated between the septum and the O-ring portion of the tube due to its internal volume can fully perceive the intake stroke, thereby Affiliated injection-suction tool is not dirty. The required amount may be implemented or via coiled capillary tube, or by appropriate roomy expansions in the tube, the capillary tube razuemeetsya has the advantage that it provides full functioning of the device regardless of the position, as a column of liquid in the capillaries not inadvertently mixed with the air.

In order to reliably prevent contamination of the injection-suction means, provided that the refill assembly between a sealed connection and multi-port valve is supplied with a pressure deformable elastic membrane. It is also possible to use a gas permeable membrane in place of bacterial fil- ter, which is impervious to the Jew; dkostey.

If the device for a long time should be on the patient, the advantage is achieved when the conical plug-in connection between the changeover valve and to the analytical device includes a deformable connecting pipe and an electrical connection. In this case a hypodermic needle and the analyzer together form a unit which is movably connected to the rest of the components comprising the device housing.

For the case where not all used perfusion fluid can be fed into the fabric, preferably, the receptacle is provided for the perfusion fluid, which via the position of the changeover valve connected to the delivery and suction device.

Thus, pumping and suction device without cleaning and maintenance for a long time can remain in the body, thus can be used by a microprocessor-controlled precision pump that meets high demands in terms of reliability and repeatability. Simultaneously, the microprocessor also controls the multi-way valve, and at an appropriate screen to appear only ispolzovatelya instructions such as "implant needle", "insert the needle", "remove the needle", etc.

Use of slow acting insulin, rapid-acting insulin, and improves blood sugar substance may preferably be controlled by a microprocessor evaluation unit. Thus the advantage is obtained if the quantity of sugar in the tissue and the amount of insulin introduced accumulate as much as possible for a long time in the memory device to a period of time can be improved by training the calculated effect of the algorithm for insulin. It is also possible to control the discharge and suction performance by the microprocessor so that the marker value, for example conductivity, remains largely constant. After equilibration in the desired range of from 5 to 20% concentration of tissue suction device may be disabled.

Furthermore, according to the invention provides that in order to rapidly change the direction of flow of the perfusion fluid during loading mode precision injection pump reduced pressure pump chamber into the suction mode may be connected in another position of the valve by a connecting tube with a hypodermic needle.

First of all, when the analyzer via a flexible connecting tube is connected to the body of the device and has a long propagation path in accordance with the invention, provided that the analyzer is mounted preamplifier.

In all exemplary embodiments analyzer for better mixing the measured liquid on the inlet side can be a device for changing the flow cross section, for example in the form of bulges, which acts in the perfusate stream and the perfusion fluid swirls.

To better protect the measurement analyzer initially determined by the concentration of the marker value, and then the concentration of interest substance and then at least once again concentration of marker size or two independent measuring circuits can be measured simultaneously or continuously marker value and the concentration of interest substance and from these measurement results It can be calculated from the actual concentration of the substance of interest, such as sugars in the tissue.

Finally, according to the invention provides that the analyzer includes a combined sensor for determining ions or conductivity, and the sensor for determining glucose, wherein the analyzer with the combined sensors has a governmental filling volume of about 10 L or less.

FIG. 1 schematically shows a device; FIG. 2 and 3 - examples of embodiment according to FIG. 1; FIG. 4 and 5 - Examples of the device in detail; FIG. 6 - measurement schedule.

FIG. 1, the apparatus has a housing 1 mounted on a single channel hypodermic needle 2 with an end opening in the wall of which there are three holes for tissue located around 4. The body 1 consists of a piston arranged pump 5 and the lever device 6 injection-suction means 7 for supplying liquid refuzionnoy. The connecting pipe 8 between the piston chamber 9 of the pump piston 5 and the inner conduit 10 of a hypodermic needle 2 directly from the output of a hypodermic needle 2 is associated with the analyzer 11 not shown here in more detail the sensor elements for recording the measured concentration value of the marker substance and the perfusion fluid.

Moved with the push button 12 in the direction of the injection piston 13 piston pump 5 displaces a few microliters of perfusion fluid from the piston chamber 9, and perfusate on its way to the hypodermic needle 2 passes analyzer 11 in order to calibrate zero. At the same time compressed adjacent to the housing 1 and push button 12 spring 14. Due to small movements with the lever on the injection device may be provided by additional repeated changes in the direction of flow of the perfusate in the inner channel 10 of a hypodermic needle 2, thus achieving sufficient trim. After releasing the button 12 of the lever device 6 by a spring 14 is carried out suction stroke and is partially balanced perfusate again in contact with the analyzer 11 and measured.

To prevent mixing of already balanced fresh perfusate and perfusate from the piston chamber 9 in the connecting tube 8 is a multi-way valve 15, via which through an opening 16 in the housing 1 can be sucked air bubble 17 to separate the various fluids into the connection tube 8.

After connected to the analyzer 1, the evaluation unit 18 and display the measured values ​​fall to the indicator device.

As shown in FIG. 2 embodiment, the injection-suction device 7 consists of a precision pump 20, the piston 13 is actuated by stepper motor 21. Control Individual movements at precise discharge and suction pump 20, and accordingly the necessary provisions changeover valve 15 is performed by the microprocessor 22 . While the design in accordance with FIG. One tank for the perfusion fluid is realized by means of the piston chamber 9 of the piston pump, in this case, a separate reservoir 23 for the perfusion fluid and a reservoir 24 for the input of the medicament form together with the multi-port valve 15 refill assembly 25 which via portion 26 of connecting pipe 8 is connected to a precision pump 20.

To protect precision pump 20 from contamination before the partition 27 can be mounted elastically deformable membrane 43.

When using more than one drug in order to correct the violation can be set more reservoirs 24 for medicines. For example, in the case of measuring the sugar could be fitted tank fast acting insulin, the other reservoir for slow release of insulin and rdin medicament reservoir in order to increase blood sugar, such as glucagon.

Portion 26 of the connection tube 8 is closed peregopodkoy 27 with which the assembly 25 is attached to needle 28 equipped with the working space 29 precision pump 20. That precision pump can be made by analogy with known microliter pipettes, such as a bulb, which is sealed relative to the housing via one or more rings.

It can also be used other pumps such as a roller pump, which compresses the deformable sleeve, diaphragm pump, or a pressure vessel with pressure medium. Convenient location for the roller pump 44 there would be executed on the deformable portion 26 of the tube, as there may be undergoing the process of suction and discharge, not inadvertently pumping liquid into the needle 2 or perform other unnecessary functions.

Dimensions of internal space of the tube portion 26 between the valve 15 and the baffle 27 are selected so that the volume can be seen the suction stroke of the pump precision without contaminating the precision pump 20 with its remaining parts in the housing 1 a Fluid. Using a precision valve 15 pump 20 in certain operating positions may be connected to a hypodermic needle 2, a reservoir 23 for the perfusion liquid to reservoir 24 for medication, as well as with an opening 16 for supplying outdoor air.

Furthermore, it is also possible by means of valve 15 and FIG. 2 a dotted line to connect the connection tube 40 with a hypodermic needle 2 is located behind the piston 13, piston chamber 41 of the pump 20. In this case, created during the pumping stroke in the piston chamber 41 negative pressure ensures a rapid change in the direction of flow of the perfusate into the subcutaneous needle 2.

Aanalizator 11 with a sensing element 31 for determining ions or conductivity with a sensor 32 for the determination of glucose is connected with the replaceable part 25 via a conical plug connection 30, preferably via the mouthpiece lock. By means of the conical plug-in connection 30 of the same design hypodermic needle 2 is connected to the analyzer 11.

This can be done automatically and the electric soezhinenie 34 between the analyzer 11 with a sensor 32 for the determination of the glucose meter 31 and conductivity on the one hand and the evaluation unit 18, and it could be, for example, a plug connection or a sliding contact 35. The microprocessor 22 via line 40 connected to the evaluation unit 18.

The at least one tank 24 for the applied drug (insulin) or in a separate tank may be added a small amount of the substance being measured (glucose), and the marker substance (e.g., sodium chloride), and their concentration is in the range usually observed concentrations.

FIG. 3 shows another possible embodiment of the device, which is specially designed to provide a long connection with artificial pancreas patient. This exemplary embodiment differs mainly from that shown in FIG. 2 only in that between the plug connector 30, which creates a connection with the multi-way valve 15, on the one hand, and the device 11, on the other hand, there is a flexible connection tube 33 so that the needle 2, which in one case can consist, for example, atraumaticheskogo soft material can easily be placed in the subcutaneous tissue, and other devices attached elsewhere on the body. This has the advantage that changing the position of the device does not have the needle 2 is no pulling or compressive force. Apparatus 11 as possible should be located close to a hypodermic needle, wherein the connector 30 between the device 11 and the needle 2 allows the replacement unit 11, and the needle 2 although it may remain in the tissue. In another case, the device 11 could also be connected directly to the needle 2. In addition to conveying liquid connecting tube 33 must also have an electrical connection 34 to the evaluation unit 18, for example electrical contacts 35, such as connector or sliding contacts, which are closed simultaneously with the merger the plug connection 30. If the signals from the device 11 is often very weak, and susceptible to interference, the apparatus 11 may also be placed preamplifier 36. In order to better mixing of the perfusate prior to the measurement at the input device 11 may be disposed thickening 39 for changing the flow cross section .

For longer leaving the device in the body using, for example, as an artificial pancreas, or other systems as "closed loop" might also be advantageous to create an additional receiving vessel 37 which receives the measurement after the perfusate used to not need was pumped into his body. This receptacle 37 may also be made from easily deformable material. Also the sealing ring 38 of circular cross section can be used instead of a pierceable septum 27 and needle 28, and by installing a closing lid, which is not shown, may be provided in front of the nozzle sterility refill assembly 25. This closing lid is removed only immediately prior to installation into the angle 25 .

As shown in FIG. 4-5, hypodermic needle 2 in the zone of the front opening 2 may have shlitseobraznoe extension 42, thereby similarly increasing the exchange surface of a hypodermic needle 2. In accordance with FIG. 4 extension can also directly adjacent to the front opening 2.

In the proposed device can automatically submit the following proceeding stages: 1. Before hypodermic needle 2 is introduced into the body through the device 11 is sent to a solution which contains the approximate number of defined substance and the marker substance, which is then expected at the measurement date, so can be determined slope sensor elements. For this example, a solution of a medicament, for example insulin, a substance may be added is determined, for example, glucose, and a marker substance such as sodium chloride. Then the valve 15 is sucked through the air and the connecting tube 8, and the device 11 is cleaned by ejection of air. Then the perfusate which is free from the substance and determined marekernoy substance is injected through the apparatus 11 to produce an accurate zeroing.

2. When pushed on and the introduction of a hypodermic needle is injected into the perfusate and the needle very quickly to the hypodermic needle is applied negative pressure to regain the injected the needle perfusate, before it can seep into the body. Perhaps as a result of additional short distances while injecting perfusate in the internal bore of a hypodermic needle can make reciprocating motion, until a partial equilibration. During a subsequent suction stroke measured concentration of substance of interest, such as glucose, and a marker value, for example the conductivity as a measure of the degree of equilibration.

3. Inert perfusate can then be injected into the body, or as shown in FIG. 3 in its own receptacle.

4. Then the multi-way valve switched and the required amount of medicament, such as insulin, or also increases blood sugar substances, such as glucagon, is injected into the tissue. At the same time as the microprocessor 19 on the basis of the collected measured values ​​can rasschityvatchya optimum amount of the drug without the participation of the patient, the patient can then confirm the suggested amount of medication by pressing a button.

5. After the application of the medicament via valve 15 again creates a connection to the outside air or to a reservoir for perfusion fluid and the residue of the medicament from the perfusion fluid or air is washed out of the needle into the subcutaneous tissue.

6. When using the device as an artificial pancreas needle may remain in the body, and the measurement process and the use of insulin may be repeated at appropriate intervals, the needle due to periodic washing perfusion solution can be kept free from obstructions and can be added to the perfusion solution also prevents clotting substances .

In practice, have proved suitable in the following volumes, lengths of time and pressure to achieve as quickly as possible achieved equilibration perfusion fluid to the tissue: - injection of about 20 to 150 l, and most preferably from about 50 to 100 l of the perfusion fluid with a hypodermic needle with an external cross-section of about 0.4 mm and a length of 10 to 20 mm for approximately 1 second; - Immediate application of reduced pressure of 200 to 700 mbar, preferably 400 mbar (or absolute pressure of 300 to 800 mbar, preferably 600 mbar); - During 20 leads inside the sensor capacity of about 10 l to equilibration in the range of 5 to 20%, to avoid suction of air by selecting the proper pressure.

FIG. 5 shows an exponential characteristic about balancing on the sensor, the observed mathematical function is designed to calculate the actual concentration of the measured substance. Dotted lines show reached after 10 or 40 seconds equilibration is 5% or 10% of the tissue fluid. By controlling the injection-suction means of the degree of equilibration can be maintained constant, as shown, for example, a dotted line.