Patent Application
20140148669
As indicated by its title, the object of the invention relates to a device for continuous measuring of an analyte which allows continuous monitoring of the blood or interstitial glucose level in a minimally invasive, minimally detrimental and painless manner.
Said device, which allows measuring in real time, likewise comprises systems for managing, processing and telematically linking data to external reading means with two-directional communications such that it allows sending commands to the processor of the fixed part to reprogram and configure the operation of the puncturing units for sampling the analyte, according to the evolution of the patient and according to the guidelines established by the doctor.
As is known, Diabetes Mellitus (DM) is a metabolic disease which is characterized by a persistent increase of glycemia (blood glucose) above 125 mg/dl. This increase of the blood sugar (hyperglycemia) is the cause of the acute and chronic complications of the disease.
Diabetes mellitus is a common disease and it increases more each day. The problem is caused by different factors, the most significant being: the inheritance and the action of acquired factors, unhealthy habits which lead to obesity the cause of which is usually physical inactivity (lacks of physical exercise), and a fat and sugar rich diet. Among other elements which are responsible for the metabolic syndrome which tends to lead in many years to the onset of diabetes include at the same time other factors such as arterial hypertension, the increase of fats in blood, smoking habit and stresses.
In the last decades an extraordinary increase of the diabetes mellitus cases has been produced worldwide. It is estimated that the diabetic population is duplicating every 15 years, causing a negative impact on the global health quality; with severe personal, family and social repercussions. This disease is a serious and very costly public health problem which does not discriminate ages or socio-economic levels. It is necessary to put-up a containment barrier against that expected avalanche of diabetics and their complications. This task must be carried out by means of a suitable primary prevention structure and an exhaustive control of the disease such as secondary prevention.
With the treatment and successive controls by means of formation, self control and those made by the doctor, fasting blood sugar ideally lower than 120 mg/dl and at one hour after eating lower than 160 mg/dl must be achieved.
Glycemic control is fundamental for controlling diabetes, therefore the self-monitoring of glucose (AGS) forms a primordial and effective component within the factors surrounding disease control providing the patients with an individual evaluation system for evaluating the response to his/her individualized therapy together with the other guidelines of his/her environment.
The AGS scanning and its frequency must be established after an individualized study of the patient and his/her environment, providing confidence, necessity and clear benefit, being fundamental in patients with type I diabetes and with guidelines adapted to type II patients, closing the circle of the variables of the disease.
Current standard diabetes control systems use self-analysis of blood glucose and urine glucose (currently displaced by that of blood) by means of reactive strips having the incorporated glucose reagent.
The self-analysis of blood sugar by means of reactive strips requires first positioning the reactive strip in an equipment called glucometer (which measures and gives the result of the amount of glucose) and positioning the self-puncturing device by means of a blood lancet or needle in the fleshy part of the finger to obtain a drop of blood and to deposit it in the inlet of the strip.
There are 2 types of glucometers, according to the technique used:
Reflectometers: they measure the light reflected from the reagent after it has gone through a chemical reaction (enzymatic oxidation of the glucose). In the reactions a chromatic product is produced. The intensity of the color is proportional to the amount of glucose present.
Electrochemical biosensors: they measure the electric current generated in the enzymatic reaction of glucose oxidation with the reagent.
These self-analysis by means of the reactive strips located in glucometers have a series of advantages including:
They facilitate the modifications of the treatment by the doctor.
They facilitate self-adjusting the treatment depending on the daily circumstances and thereby the self-control of the patient.
They prevent and detect hypoglycemia.
They detect and treat severe hyperglycemia.
They improve appeal and therefore facilitate compliance.
They provide autonomy to the patient and his/her family.
However, there are also a series of drawbacks meaning that this technique is not the best for the whole world. Among the more common drawbacks that can be found are the followings:
To solve some of these problems in the recent years, different systems have been developed for determining over time with more or less frequency, the values of glucose in the so-called interstitial fluid, i.e., at subcutaneous level.
These systems however in no case substitute the common measurement of capillary blood sugar due to the fact that the determination of the interstitial glucose entails a delay with the figures of the blood glucose level, using mathematical algorithms being necessary to determine the figure of blood glucose which was there some time ago. Nevertheless, the published results of the studies performed prove the observation of more hyperglycemia peaks as well as hidden hypoglycemia peaks when measurements at interstitial level are used than when the common method for measuring capillary blood sugar is used, leading one to think that the determination of blood glucose is a temporal method of the figures of blood sugar, but incomplete from a scientific point of view. It must be mentioned that from a physiological point of view the control in the blood sugar regulation is established from glucose located in interstitial space and from its specific transport (GLUT2) into the β-cells of the pancreas.
On the other hand, there are the so-called “monitoring system” which attempt to monitor the evolution of the glucose levels for several days to detect hypoglycemia, specially at night, the hyperglycemia peaks and oscillations following a similar hourly pattern and thus adjusts the insulin treatment, involving an advance use of personalized algorithms to automatically modify the infusion dose from the insulin pumps.
Currently, there are many glucose monitoring system which could be grouped according to the characteristics thereof. These characteristics include:
a) Harmfulness.
b) Analysis System.
c) Frequency and Duration of the Registration:
d) Calibration:
All the monitoring system need to incorporate to its register at least one blood sugar value, generally capillary blood sugar value to be used as a reference and to be calibrated. The number of blood sugars needed varies from 1 to 4 in 24 hours.
However, the current systems for monitoring the glucose levels over time are based on the sampling at interstitial level, with the aforementioned problems, to which the short average life of the sensor which tends to be between 3 and 7 days, the exaggeration at the times of being placed or the fact that they tend to need the change of puncture site to prevent cutaneous or other pathology reactions needs to be added.
Devices and systems based on some of the preceding techniques which attempt to solve some of the mentioned drawbacks with the aid, for example, of micorsystems such as micro-needles for puncturing are known in the state of the art.
In this sense, the Spanish patent application 200402373 based on a microsystem for the controlled extraction and injection of fluid can be mentioned for example. This system relates to the extraction of interstitial fluid, i.e., the fluid found in the extracellular space between one cell and another at a depth which is usually less than 0.5 mm, not penetrating the surface vessels which are usually found at a distance between 1 and 4 mm. Thus, since there is a negative pressure under the epidermis with respect to the outer part of the skin, a sample extraction mechanism is necessary to compensate said pressure difference. On the other hand, since the amount of sample extracted by this system is very small, said document describes the use of several micro-needles each time.
Another example described in the state of the art is that of the European patent EP1144078, in which it describes a cartridge with a plurality of micro-needles all of which penetrate the patient at the same time collaborating the extraction of a single sample, therefore said cartridge being of a single use. In this case said cartridge is intended to extract a sample at blood vessel level, i.e., not needing any extraction system since the breakage of said blood vessel and the extravasation of blood increases the inner pressure with respect to the outer pressure, causing the ascent of the sample through the needle by capillarity. Other examples of the state of the art can bee seen on WO2007041287, U.S. Pat. No. 7,225,008, WO2010011805 and WO2007041244.
The device for sequential measurement of the present invention solves the aforementioned problems, forming a device capable of performing, in a temporal manner, a continuous temporal monitoring of blood glucose or interstitial glucose by means of a minimally invasive, minimally detrimental and painless system, allowing the measurement in real time and including telematic link systems for linking data to an external reading means and transmitting the dose of insulin to be administered to dispensation devices.
To that end, said device comprises a fixed element which is placed on the user's skin by means of a suitable adhesive means, mechanical means, etc, and comprising an intelligent core or processor and a disposable exchangeable element which is coupled to the fixed element and which incorporates the system performing the samplings.
Said system for sampling consists of an automated mechanical multi-puncturing system comprising micro-needles, the means for driving said micro-needles, the samples of reagent for mixing with the analyte, the electrodes for the reading and the electric contacts necessary for the operation of the driving means and the suction system, and wherein each of the puncturing units is susceptible to be programmed for its activation in a determined time instant and at the depth necessary according to the type of sample to be obtained, i.e., if the measurement is made in blood or in interstitial fluid. Likewise, the system will also decide, depending on the type of measurement to be made or on other pre-established criterion, the start and stop of the sample suction system operation.
Thus, once said measurements are made, these are sent at the first instance to the processor to obtain the data of the blood glucose level or interstitial fluid, performing the transfer of these data in a second instance to the database and to the communications system inside the device of the invention which in turn will communicate and send the data to the external reading and management device.
More specifically, the fixed element of the device of the invention comprises the electronic part for controlling the disposable element which in turn comprises:
To complement the description and for the purpose of aiding to better understand the features of the invention according to a preferred embodiment thereof, a set of drawings is attached as an integral part of said description in which the following has been depicted with an illustrative and non-limiting character:
As can be seen in the drawings, the device for continuous measuring of an analyte of the present invention is structured, according to a preferred embodiment of the invention, from a fixed element (1) which is placed on the user's skin by an adhesive or mechanical means of the elastic band or watch-strap type or others and comprising an intelligent core or processor and a disposable exchangeable element (2) which is coupled to the fixed element (1) and which incorporates the system performing the sampling or automated mechanical multi-puncturing system comprising a plurality of puncturing units.
Said puncturing units, susceptible of being programmed for the activation thereof in a determined time instant in turn comprise the micro-needles (3), means for driving said micro-needles (3) allowing them to reach different depths, the biosensors with the samples of reagent for mixing with the analyte and the electrodes (13) for the reading and the electric contacts (20) necessary for the operation of said driving means.
Specifically, and according to a possible practical embodiment of the invention shown in the drawings, the fixed element (1) has a central area of preferably rigid or semi-rigid insulating material to facilitate attaching the disposable element (2) and an exterior of semi-elastic insulating material to allow a correct placement on and adhesion to the skin, the electronic part for controlling the disposable element (2) being in the central area, which central part comprises a processing and control unit of the mechanisms for activating and deactivating the driving means and the suction system (19), a data processing unit which allows capturing analog readings coming from an interstitial or blood glucose measurement system, an intelligent core having a base for gathering, translating, interpreting and transmitting data (RDTIT) to the exterior device for reading and active two-directional interaction (DELIBA).
Thus, the central area has a hole in its center to house the disposable element (2) which will be fixed by means of clipping, gripping or another suitable method and will have a preferably rectangular shape, there being according to a possible preferred embodiment in its longer sides the contacts of connection to the disposable element (2) and in the shorter sides the clipping or gripping system for the attachment between the fixed element (1) and the disposable element (2).
As can be seen in the drawings, especially in the
As has been said, the disposable element (2) incorporates the automated mechanical multi-puncturing system comprising the puncturing units, which are in turn structured from three compartments:
According to a possible embodiment of the invention and in order to save energy, the puncturing units comprise at least one magnet (not depicted) located bottom wise, for example, in the lower area of the central compartment (4) and/or the outer compartment (14) which would allow maintaining the micro-needle (3) in its lowest position as a result of the magnetic attraction thereof while the sampling is performed without the need of inducing a magnetic field in the winding (15), it therefore involves energy saving.
Likewise, the puncturing unit is susceptible of having, together with the above, a second magnet (not depicted) located top wise serving to maintain the micro-needle (3) in resting position, i.e., in an upper position, at the ready for the induction of magnetic field in the winding (15) which commands the puncturing.
As the result of using these magnets, it can even do without an elastic spring (10) which allows recovering the micro-needle (3) or, according to another possible embodiment, coexists with the latter for the purpose of reinforcing the function thereof, the objective of said magnets always being to reduce the amount of magnetic flow used, i.e., the amount of magnetic field induced which will lead to energy saving and therefore to a longer duration of the electric power supply system.
In both cases said magnets could have, for example, a toroidal shape and be housed inside the central compartment (4) and/or the outer compartment (14), although their location and dimensions will generally be those which allow them to carry out the function for which they are designed.
On the other hand, in a manner independent from the puncturing units there is the suction system supplied by means of windings or electromagnetic induction systems, and which is responsible for aiding the sample extraction when this is performed at interstitial level or when it is required, which will be programmable from the control system. More specifically, said suction system comprises on one hand suction pistons (21) outside said puncturing units but connected to them through suction channels (19), which will be responsible for sucking of the sample itself.
According to another possible practical embodiment of the invention, the suction system can also be individual for any of the puncturing units. In such a case, a micro pump (not depicted) makes the sample pass through micro channels to the biosensor of the upper compartment (11), while an anti return micro valve prevents that the sample returns to the puncturing unit.
Also, according to a further practical embodiment of the invention and irrespective of the means of suction, pistons (21) outside the puncturing units or micro pumps in each puncturing unit, a waste reservoir (not depicted) can be implemented in order to collect and store the samples already analyzed.
According to the above, a possible practical embodiment of the disposable element (2) of the invention wherein the puncturing elements are arranged in a matrix of 10×10, it could comprise the following elements:
Wherein each side or edge of the disposable element (2) has 10 electric contacts (20) (
In another not depicted embodiment, a thin membrane of a shape memorizing material could be placed between the lower layer and the lower base of the central compartment (4) of the disposable element (2) which is passed through by the micro-needles (3) in its actuation. This would have, on one hand, the function of sealing the communications of the micro-needle with the outside and maintaining the sterilization of the same until its activation and on the other hand allows isolating the space (8) of the central compartment (4) after the micro-needle returns to its resting position, once aseptic contamination is made with the biological means and the analyte is extracted.
b) A central part (17) like the one shown in
This central layer which forms the main element will be made, according to a preferred embodiment, of a non-ferromagnetic material such as for example aluminium or epoxy resin.
Likewise, it will have openings for placing the windings (15) of actuation. Said windings (15) will not be at the same level with the block, but they will protrude for a few hundredths of a millimeter so that once upper and lower covers are placed, they exert certain pressure on the latter to assure the correct electric power supply contact which will be located in said covers.
c) an upper cover (18) like the one shown in
Therefore, the upper cover (18) similar to the lower cover (16) in terms of the constructive material will contain the biosensors comprising the substances which, together and mixed with the blood or interstitial fluid, will facilitate a characteristic measurement current to the incorporated sensors, made of specific materials, also in said cover, for the measurement by the processor of the fixed electronic part. The upper cover (18) will also be formed by more than one superimposed surface, multilayer electronic board, for the purpose of allowing the crossing of electrical connections at different levels, to contain all the buses necessary.
On the other hand, the electric interconnections which will reach the vertexes of the upper and lower covers (16, 18) must be elongated to the profile of the respective edges so that the electric contacts (20) are at the 4 sides of the disposable device, with the purpose of facilitating the electric contact with the fixed part of the apparatus.
Furthermore, said upper and lower covers (16, 18) will have the ducts suitable for transmitting pressure by the 3 suction devices of the suction system (19).
Therefore, in a normal operation of the device of the invention, the control means will send the appropriate activation signals of one or several of the puncturing units with the desired and/or established frequency, puncturing units will obtain the sample either at interstitial level or vessel level as required, said means controlling the induced current which reaches the micro-needles (13) and therefore the depth at which the puncture will be performed, as well as the activation or non-activation of the suction system (19).
Thus, as has been seen in the preferred embodiment described and shown in the drawings, the disposable element (2) will have several dimensions in plan views of (20×20 mm), and in elevational views of 6.4 mm in height, 40 electric contacts 10 distributed at each side of the square being needed, although another arrangement could also be possible, such as for example that which arrange 20 contacts in the opposite faces, and the other free faces can be used for anchoring to the fixed element (1).
On the other hand, in terms of the electronics of the fixed element (1) and according to a possible embodiment of the invention in accordance with the aforementioned preferred embodiment for the disposable element (2), the same has to comprise the following non depicted parts:
For the aforementioned possible practical embodiment in which the micro-needles (3) are arranged in a matrix of 10×10 this electronics will at least be made up of a 4 multiplexer system supplied and controlled by an address bus of at least 4 bits from a processor, two of which will allow a routing towards a determined pair of metal sensors (x, y) of the matrix of the disposable element (2) for reading the data. Likewise, it will also serve to direct the power supply to a determined winding (15) responsible for the actuation of the corresponding micro-needle inside the matrix, not ruling out the need of using any other element for supplying additional power to said windings.
It is therefore deduce that the address bus of the (x) multiplexer of the sensors will have the same information as that of the (x) windings (15), and thus with the (y) multiplexers, being able to use the same address bus. Therefore, if 4 bits are needed for the (x) and 4 more for the (y), using a bus of 1 byte (8 bits) of the processor for addressing the matrix of the disposable will be sufficient.
The processor will maintain the addressing status of the byte throughout the process from the start to finish, being able to use an extra “hold” bit where appropriate. Said extra bit known as “hold” is used so that the multiplexers maintain their addressing while said bit is activated, allowing the processor to change the status of the address bus for other operations without affecting the addressing status of the multiplexers of the matrix.
Said processor will further direct and exchange data with a memory having a sufficient capacity for storing data of the samples, with the related metadata thereof such as the day and time, coordinates of the micro-needle (3), batch, user, license, and those considered appropriate.
Said memory will be a flash type memory, in a preferred embodiment given its capacity for storing data after it is disconnected from the power supply, other types are not ruled out if they are considered as more appropriate.
On the other hand, and if the measurements allow it, instead of it being welded to the board said electronics will have a connector for extracting the memory. And if the same is desired for the processor, a base which allows the extraction thereof for its possible reprogramming and adjustment by the technical staff. Instead of the fastening socket for the processor, a system of connectors which allows connecting the fixed device, for example through mini USB, with a computer for said tasks is not ruled out.
Said fixed electronic part will contain, as has been said, a device for connecting with the outside in a wireless manner, preferably with Bluetooth technology which will be communicated with the processor by means of a data bus. Said Bluetooth® device must allow typical safety characteristics, such as the terminal presentation and the linking between them.
Finally, the power supply system of the device for continuous measurement of the invention could be formed according to a possible embodiment by 3V coin cell batteries, not ruling out other energy generation systems such as for example, peltier cells in reverse which convert the body heat into a potential difference capable of being stored in condensers or rechargeable batteries of the fixed electronic part.
Another advantage of the present invention is its versatility when being used for obtaining and analyzing other type of samples given its capacity to select the moment over time and/or frequency of the analysis and to control parameters such as the depth of the puncture and the possibility of extracting the sample by means of suction if necessary. Thus, it will be sufficient to intercalate specific puncturing units to perform other type of measurements, such as for example that of fructosamine for the purpose of combining measurements from different indicators and thus obtaining a more complete and efficient tracking of the diabetes.
| Number | Date | Country | Kind |
|---|---|---|---|
| P201031309 | Sep 2010 | ES | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP11/65076 | 9/1/2011 | WO | 00 | 5/17/2013 |
