ITUD20100230A1 - DEVICE FOR REALIZING CLINICAL TESTS ON BIOLOGICAL LIQUIDS AND ITS PROCEDURE - Google Patents

Description

Description

"DEVICE FOR CARRYING OUT CLINICAL TESTS ON BIOLOGICAL LIQUIDS AND RELATED PROCEDURE"

FIELD OF APPLICATION

The present invention relates to a device for carrying out two or more combined clinical tests on biological liquids.

More generally, the present invention refers to a device suitable for carrying out two or more clinical tests of different types, for example a first test that can be performed using biosensors (biochips) and a second test that can be performed by means of detection and / or optical reading performed by a suitable vision equipment and / or after appropriate treatment, for example lysis, of the biological liquid sample.

In particular, but not only, the invention is applied advantageously to simultaneously perform combined glycemic tests, such as the measurement of direct glycemia and the measurement of glycated or glycosylated hemoglobin. Another application is that of tests carried out with a biosensor combined with the measurement of the ESR (Erythrocyte sedimentation speed) in the reading cell.

The present invention also refers to the related method and to the machine which uses said device and carries out the aforementioned method.

STATE OF THE TECHNIQUE

It is known that diabetic patients use to monitor their blood sugar level in order to control and adjust the diet so that they can possibly adjust and in any case monitor the insulin dosage.

It is also known that self-monitoring, a fundamental element in the educational process of the diabetic subject, is now mainly conducted using pocket meters.

The meters are electronic instruments, of small dimensions, which have a test strip on which a drop of blood is deposited, using which it is possible to obtain the blood glucose concentration with good approximation.

However, for a diabetic subject it is also useful to have a cognitive factor that indicates the average quality of glycemic control achieved in the previous weeks. This is achieved through the evaluation of glycated or glycosylated hemoglobin.

The dosage of glycated hemoglobin requires, through a special reagent, the lysis of red blood cells and then the use of another reagent, such as a latex or similar, to obtain a suitable solution for measuring the glycosylated hemoglobin contained in them by reading optics.

The problem therefore arises for the diabetic patient of needing two tests, both useful and necessary not only for the control of the glycemic state by the diabetic center but also in the diagnosis; these tests can currently be carried out using separate devices, both with the use of small portable meters and with the use of laboratory instruments.

The Applicant therefore posed the problem of being able to carry out both of the aforementioned clinical tests with a single device designed to collect the two blood samples to perform, for example, the examination of glycemia and glycated hemoglobin in a single instrument. This device is disposable, simplifying and automating the whole procedure, and at the same time minimizing the risk of people coming into contact with potentially infected liquids.

The problem has also arisen of carrying out these tests with a simple, inexpensive device and with equipment that can be found in pharmacies, or similar places (the so-called Point of Care - POC), yes it can be used at any time, in a short time, minimizing the need for the intervention of specialized personnel.

In general, the Applicant has set itself the problem of realizing a device capable of performing two or more combined clinical tests on biological liquids, such as blood, urine, plasma, serum or other, for example a first test that can be performed by means of simple contact of the biological liquid sample with suitable detectors, for example a biosensor, biochip or the like, and a second test, for example, of the enzymatic type with the use of antibodies coated with latex or Elisa test, or even test for measuring the VES.

To achieve these objects, and other and further advantages as highlighted below, the Applicant has devised, tested and implemented the present invention.

EXPOSURE OF THE FOUND

The present invention is expressed and characterized in the respective independent claims. The dependent claims define variants to the main solution idea.

According to the invention, the device for carrying out combined clinical tests comprises a double-channel biological liquid withdrawal and dispensing element and a cartridge container having the function of an optical reading cell.

The withdrawal and dispensing element performs both the function of temporary withdrawal and containment of the biological liquid samples, for example blood or other, of the patient to be analyzed, and the function of closing cap of the container.

In particular, the sampling and dispensing element comprises at least two distinct and separate channels of the capillary type for the withdrawal, for example from a finger of a patient, of two distinct samples of biological liquid to perform two different tests.

The cartridge container in turn comprises at least two, advantageously three, distinct ways or channels, and in particular:

- a first way that can be associated with a first capillary of the sampling and dispensing element, for the collection of the first sample of biological liquid to be subjected to direct analysis, for example through contact with at least one suitable biosensor or biochip;

a possible second way that can be associated with the second capillary of the sampling and dispensing element to perform, in a first phase of the analysis process, the lysis of the red blood cells, the dilution or other suitable pre-treatment procedure, on the second sample of biological liquid , this pre-treatment being preparatory to a subsequent reading and analysis on the treated sample through the use of photometry in the third way, or reading chamber;

a channel, which can be associated with the aforementioned third way, or reading chamber, for the introduction of suitable reagents, such as latexes or other suitable reagent, to be mixed with the second sample of pre-treated biological liquid so as to allow the optical reading of the sample of biological liquid possibly pre-treated, and mixed with the reagents, in order to perform the second analysis.

In one solution of the invention, the biological liquid is blood, the first direct analysis is performed through contact with at least one biosensor for the direct measurement of the glycemic value of the blood, and the second analysis relates to the measurement of hemoglobin by means of an optical reading. glycemic value for measuring the blood glucose value over an average period of time.

In this case, the container having the function of reading cell necessarily includes three ways, since it is necessary to proceed with the lysis (breakdown of red blood cells) of the blood sample before subjecting it to reaction with chemical reagents, for example lactic agents, and then to subsequent reading. optics for the measurement of glycated hemoglobin.

The device as a whole is in the form of a disposable cartridge and is the only part that is discarded after the analysis is performed. In fact, the device according to the invention allows not to contaminate the optical reading equipment with biological liquids, nor does the entire analysis cycle generate waste or other material to be eliminated from the optical equipment itself.

The withdrawal and dispensing element, according to a variant, is configured to have two different mounting positions with respect to the container, to respectively associate the second channel of the capillary type in a first phase with the second way of the container, for example to perform the lysis or dilution of the biological sample contained therein, and then, advantageously by rotation of 180 °, to arrange it in a vertical line to the third way, or reading chamber, of the container, for example to carry out the mixing reaction with the reagent which then allows the optical reading of the sample.

The present invention also allows to save on the quantity of reagents used. In fact, it should be noted that the U sante reagent is in the ratio between 15 and 30 times the volume of blood, advantageously around 20. The dispersion and reading reagent is in the ratio between 40 and 60 times the volume of lysed blood, advantageously around 50 times.

With the present invention, only the part contained in the capillary and aspirated after lysis is then subjected to reaction with the appropriate reagent, so that the quantities of reagent to be used are reduced.

ILLUSTRATION OF DRAWINGS

These and other characteristics of the present invention will become clear from the following description of a preferential embodiment, given by way of non-limiting example, with reference to the attached drawings in which:

- fig. 1 illustrates a device for carrying out clinical tests on a biological liquid according to the present invention;

- figs. 2 to 7 illustrate in sequence the steps for carrying out tests on biological samples using the device of fig. 1;

- fig. 8 schematically illustrates and for the essential part an analysis machine in which the device of fig. 1.

DESCRIPTION OF A PREFERENTIAL FORM OF

REALIZATION

With reference to the figures, the number 10 indicates a disposable type device for carrying out two or more combined clinical tests on biological liquids.

The device 10 consists of a capillary and dispensing pickup element 11 and a cartridge-type container 12 having the function of a reading cell, and can be associated with a machine 24 (fig. 8) suitable for carrying out optical analyzes. of biological liquid samples.

The withdrawal and dispensing element 11 consists of a body, made for example of silicone material, in which two autonomous and separate capillaries, 16 and 17 respectively, are embedded, for example made of glass. The capillaries 16 and 17 are connected with openings or mouths, respectively 31 and 32, communicating with the upper central opening 37 of the withdrawal and dispensing element 11 (Figs. 3a and 3b).

The body made of silicone material has a shape and dimensions such as to act as a cap (see for example Figs. 1 and 2) of the container 12, both in the non-use phase and in the analysis phase.

The container 12 has respective flow channels or channels, three in this case, 21, 22 and 23 (fig. 1), which communicate with respective underlying chambers to perform the different analyzes with the methods explained in detail below.

Following the sequence indicated in the figures, in the phase of fig. 2 the withdrawal and dispensing element 11 is separated from the container 12 to perform the withdrawal of a respective drop of blood, respectively in the capillary 16 (fig.

3a) and in capillary 17 (fig.3b). The fact that the sampling and dispensing element 11 does not have needles, but carries out the withdrawal by capillarity, is advantageous as it avoids possible accidents and infectious contaminations.

The way or channel 22 of the container 12, placed in a central position, to which the first capillary 17 is coupled, is terminally connected to a biochip 13, a biosensor, or other meter suitable for the purpose.

When air is injected through the opening 32, for example temporally associated with a first central injector 18 and with a pump 29 of the analysis machine 24 (see Fig. 8), the blood is expelled from the first capillary 17 and goes to contact with the biochip 13, arranged in this case on the bottom of the container 12, through which it is possible to read the precise blood sugar value.

The biochip 13, in a suitable way, will for example be connected with two diodes on the external surface of the container 12 to detect the variation of electrons determined by the measurement of the sugar through the deposition of glucose oxidase enzyme on the biochip 13 itself.

In the schematic solution illustrated in fig. 8, the first injector 18 is brought into the correct position with respect to the opening 32 and the capillary 17 by a first actuator element 35a.

Simultaneously, or in rapid sequence, a second actuator element 35b brings into position a second injector 19, by means of which a lysing agent, taken from a suitable tank 27, is introduced into the capillary 16, by coupling the aforementioned second injector 19 with the opening 31 connected to the second capillary 16.

Advantageously, in this phase of injection of the U sant, air is also introduced into the capillary 16 which thus creates turbulence and facilitates and improves the reaction, expelling the blood-lysant assembly that comes out of the capillary 16, crosses the second way or channel 23 and is placed in the collection and lysis chamber 39 below the way 23 (fig. 4).

When the action of sending the reagent 1 ends, the capillary 16 automatically recalls the blood.

In order to prevent the capillary 16 from sucking blood not before the lysis has taken place, a positive air pressure is applied through the second injector 19 for all the time necessary for the lysis. Once the required lysis time is over, the positive pressure applied through the silicone sampling and dispensing element 11 and the capillary 16 will suck blood suitable for the second dispensing phase. In a preferential embodiment, the capillary 16 is dimensioned in its suction volume by capillarity exactly in relation to the quantity of reagent, for example to the latex, for the antibody reaction suitable for the analysis of the glycated hemoglobin which is carried out in the phase subsequent as described below.

In the illustrated case, at this point, the withdrawal and dispensing element 11 is separated from the container 12, rotated by 180 ° and then applied again on the container 12 (Fig. 5). In this position the capillary 16, filled with blood, is arranged in correspondence with the third way or channel 21 of the container 12 (Fig. 6).

Then, a third injector 20 of the machine 24 operated by a suitable third actuator 35c, is connected to the second capillary 16 through the opening 31, to inject inside a suitable reagent, taken from the relative tank 28, and push the blood mixture. and reagent in an underlying collection and dispersion chamber 38 (Fig. 7). This collection and dispersion chamber 38 has a light transit compartment 14 at the end. When the mixture of blood and reagent is in correspondence with the light transit compartment 14, the light source 26 is activated (fig. 8) which allows optical reading, in known per se, of glycosylated hemoglobin.

The reading and recording of the blood sugar and glycosylated hemoglobin values are made possible by the machine 24 with the methods described above. This machine 24 comprises at least one processing unit 36 (schematically illustrated in Fig. 8), which receives at least the signals coming from the electrical connection 25 with the bio-chip 13 and from a light source system 26 or optical reading means, for produce appropriate and requested outgoing information.

This information can be viewed on a display 30 and / or printed in a printer 31 which can output a printout made accessible through a special opening 34 obtained on the front of the machine 24.

Furthermore, the machine 24, through the processing unit 36, controls the actuation of the three injectors 18, 19, 20 which can be associated from time to time to the device 10 by means of the respective three actuator elements 35a, 35b and 35c, to inject air respectively , lysing agent and reagent for optical reading.

The three injectors 18, 19 and 20 are fed by air coming from the air pump 29 included in the machine 24.

It is clear that modifications and / or additions of parts can be made to what has been described up to now, without thereby departing from the scope of the present invention.

For example, the device described above could be used on biological liquids other than blood such as urine, serum, plasma, etc., to perform combined clinical tests, one that simply requires contact of the liquid with a suitable biosensor of the type indicated with 13, the other that requires an optical type analysis. The pre-treatment required in the second measurement phase could be, for example, a dilution, a marking, or other, by means of a suitable diluting agent or marker, injected by arranging the sampling and dispensing element 11 in a first position with respect to the container 12 with respect to the position it then assumes in the third measurement phase when the reagent, for example a latex, is injected, which favors the optical analysis in the collection and dispersion chamber 38 of the container 12.

In a possible further evolution of the invention, the second test which uses the collection and dispersion chamber 38 of the container 12 is a test for measuring the erythrocyte sedimentation rate (ESR), in which the blood sample contained in the capillary 17 is subjected to application of a positive pressure, for example through the injector 20. The applied pressure is such as to guarantee a laminar regime in order to break up any rollers formed in the sampling capillary 17 during the inactivity of the device. As already seen previously, the collection and dispersion chamber 38 is coupled to the optical detection system which determines its photometric attenuation with respect to a reference value in a specific time unit, thus detecting an aggregation kinetics related to the subsequent phase. of sedimentation. This optical system also controls the application of positive pressure through the injector 20, stopping this pressure when the presence of the sample is detected inside the collection and dispersion chamber 38 and thus starting the acquisition phase.

Claims (11)

CLAIMS 1. Device for carrying out combined clinical tests on biological liquids, characterized in that it comprises at least one sampling and dispensing element (11) having at least two capillaries (16, 17) for containing a respective sample of biological liquid, and a container (12) of the cartridge type, to which said withdrawal and dispensing element (11) can be selectively associated, said container (12) having at least one sensor element (13) for measuring at least one first parameter of the biological liquid contained in a first (17) of said capillaries, and a mixing and optical reading zone (38) which can be associated with an optical reading device (26) for measuring at least a second parameter of the biological liquid contained in the second (16) of said capillaries . 2. Device as in claim 1, characterized in that said container (12) comprises at least two ways or channels (21, 22) for liquid passage, respectively a first way (22) which connects said first capillary (17) with said sensor element (13), and a second way (21) which connects said second capillary (16) with said mixing and optical reading zone (38). 3. Device as in claim 2, characterized in that said container (12) also comprises a third way or channel for the liquid passage (23), which connects said second capillary (16) with a pre-treatment zone of the biological liquid when the The withdrawal and dispensing element (11) is arranged, with respect to the container (12), in a second position different from a first position in which said second capillary (16) is connected to said mixing and optical reading zone ( 38). 4. Device as in claim 3, characterized in that said pre-treatment zone is a lysis chamber (39) of the blood contained in said second capillary (16). 5. Device as claimed in either of the preceding claims, characterized in that the container (12) has a transparent area at least in correspondence with the mixing and optical reading area (38), said transparent area being associated with a transit compartment light (14). 6. Machine for carrying out combined clinical tests on a biological liquid, in which a device (10) as in one or the other of the preceding claims is used, characterized in that it has injection means (18, 19, 20) connected to at least one pump (29) and selectively associable, through respective actuators (35a, 35b, 35c), to the capillaries (16, 17) of the sampling and dispensing element (11) to selectively inject air and / or reactive agents for the carrying out treatments or surveys on the biological liquid inside the container (12) of said device. 7. Machine as in claim 6 characterized in that it comprises at least one tank (27, 28) of the reagent substance which can be selectively connected to a respective injection means (18, 19, 20). 8. Machine as claimed in claim 6 or 7, characterized in that it comprises at least one light source (26) which can be combined with said mixing and optical reading zone (38) of the container (12) for carrying out optical readings on the biological liquid. 9. Machine as claimed in one or the other of claims 6 onwards, characterized in that it has a processing unit (36) connected at least to the biosensor (13), to the light source (26) and to the actuators (35a, 35b, 35c) for carrying out the sequence of introducing air and / or reactive agents into the aforementioned capillaries (16, 17) and for processing and displaying the data relating to the measurements performed. 10. Process for carrying out combined clinical tests on biological liquids, using a device as per one or the other of claims 1 to 5 and a machine (24) as per one or other of claims 6 to 9, characterized by the fact which involves the following stages: - using the sampling and dispensing element (11) two samples of biological liquid are loaded into the respective capillaries (16, 17) the withdrawal and dispensing element (11) is applied to the container (12), and the assembly thus obtained is inserted into the machine (24); an air flow is introduced into the first capillary (17) to bring the relative sample of biological liquid into contact with the biosensor (13) arranged in the container (12); - a flow of reagent is introduced into the second capillary (16) to determine a reaction of biological liquid sample and to allow the execution of an optical reading through the light source (26) of the machine (24). 11. Process as in claim 10, characterized in that it provides a pre-treatment step of the biological liquid sample before introducing the reagent flow into the second capillary (16) to allow optical reading, in which said pre-treatment step -treatment includes the following stages: positioning of the withdrawal and dispensing element (11) on the container (12), with the capillary (16) full, in a first position, and introduction into said second capillary (16) of a pre-treatment agent such as a consuming agent , diluent, or other; interruption of the introduction of the pre-treatment agent and subsequent filling of the second capillary (16) with the sample of pre-treated biological liquid; removal of the withdrawal and dispensing element (11) from the container (12) and its subsequent repositioning on the container (12) in a second position different from the first position; injection into the second capillary (16) of the reagent to mix the reagent with the pre-treated biological liquid, thus obtaining a sample suitable for optical reading.