PORTABLE DEVICE AND METHOD FOR NON-INVASIVE GLUCOSE BLOOD-CHOLE ESTIMATION - Patent application

Abstract

The present invention relates to a device (1) comprising a measuring unit (2) with a measuring module (4) for measuring glucose levels, a first computer module (5) for processing data relating to a first part of the process for measuring glucose levels, a first communication module (6), a first data storage module (7), and a push button (8). The device also comprises a personal monitoring unit (3) with a second communication module (17) and a third communication module (20), a second computer module (18) for processing data relating to a second part of the process for measuring blood glucose levels, an interface module (19), and a second data storage module (22). A method for non-invasive blood glucose level estimation is also described.

Description

Detailed Description of the Invention

[0001] [Subject of the present invention] The subject matter of the invention described herein is in the field of Information and Communication Technologies (ICT).

[0002] More specifically, the subject matter of the present invention is situated in the context of biomedical engineering and medical technology, since it encompasses the development of portable electronic devices for monitoring people's physiological variables and general health conditions, particularly blood glucose levels.

[0003] [Background of the invention] There are 425 million people with diabetes in the world, and this number is estimated to increase to 629 million in 2045 as a result of population growth and aging, as well as urbanization, the prevalence of obesity, sedentary lifestyles, and other unhealthy lifestyles. One in 11 adults suffers from diabetes, and one in seven pregnant women is affected by gestational diabetes. Efficient control of the disease requires blood glucose tracking. Glucometers, which measure blood glucose levels based on blood samples, are the most widely used device for measuring blood glucose levels due to their accuracy. This method is painful and cumbersome, especially when blood glucose tracking is required. To prevent these problems, many methods for non-invasive blood glucose measurement have been proposed in recent years.

[0004] Reverse iontophoresis is based on the flow of a small electric current through the skin located between an anode and a cathode placed on the surface of the skin. When a potential is applied between the anode and the cathode, sodium and chloride ions under the skin migrate toward the cathode and anode, respectively. Uncharged molecules such as glucose are carried along with the ions by convection. This flow causes glucose in the tissue to be transported through the skin and thus collected at the cathode, where it is measured by a conventional sensor. The main drawback of this technology is that it requires a long exposure time to the electric potential, which often tends to cause irritation to the skin. Two examples of patents based on this technology are US6885882 and WO2008 / 120936.

[0005] Impedance spectroscopy is based on injecting electrical current at multiple frequencies and measuring the resulting voltage in the measured body area. Glucose measurement is indirectly performed from the analysis of its effect on the impedance spectrum. Some examples of patents based on this technology are ES2445700, ES2582185, WO2007 / 053963, US2005 / 0192488, US2016 / 0007891 and US2015 / 0164387.

[0006] Optical coherence tomography is a non-invasive imaging technique based on low-coherence optical interferometry. The resulting interference pattern contains information about the optical properties of the sample, more specifically about the changes in refractive index, which can be used to estimate glucose levels. The main drawback of the method is its complexity and the need for expensive and bulky devices. Furthermore, the method is sensitive to device movement, tissue inhomogeneity, and interference with other analytes. Patents US2007 / 0027372 and US2016 / 0058347 utilize this method.

[0007] Polarimetry is a technique based on the measurement of the optical rotation that occurs on a polarized beam when it passes through an optically active substance. Most researchers focus on the aqueous humor of the eye due to the fact that the high scattering coefficient of the skin causes beam depolarization. Some of the limitations of the method are errors due to eye movements, safety limits for light exposure to avoid damage, and discomfort when performing measurements inside the eye. Polarimetry is used in patents ES2313140, US4014321, EP0534166, US6704588 and US6442410.

[0008] Thermal infrared spectroscopy measures the thermal radiation emitted by the human body as a result of changes in glucose concentration. This method has many error factors, such as the movement of the measuring device, the ambient temperature, and fluctuations in body and tissue temperature. US2005 / 0043630 is an example of a patent based on this method.

[0009] Raman spectroscopy is based on the use of a laser beam to induce rotation and vibration of molecules in a solution. The resulting emission of scattered light is affected by said vibrations of the molecules, which depends on the concentration of the solute in the solution. The main drawback of this technique is that biological tissues can be damaged by the powerful laser of the Raman system. This technique is used in ES2093243, ES2206610, ES2314906, US5448992, US8355767 and US2016 / 0100777.

[0010] Photoacoustic spectroscopy is based on using a laser beam to excite a fluid, resulting in an acoustic response. The photoacoustic signal depends on the specific heat of the tissue, which in turn depends on the glucose concentration. The technique is limited by its sensitivity to chemical (other biological compounds) and physical (changes in temperature and pressure) interferences. EP1346684 utilises this method.

[0011] Infrared spectroscopy is based on the absorption of infrared radiation by vibrating molecules. Molecules absorb energy from a light beam if their vibration frequency matches the light wavelength. In this way, the glucose concentration can be estimated from the change in the intensity of the light across the tissue. The basic advantages are that it is a completely non-invasive technique, the system is simple to build, and the cost is relatively low. Near-infrared spectroscopy (NIR) ranges from 700 nm to 2500 nm, and mid-infrared spectroscopy (MIR) ranges from 2500 nm to 10 μm. Assuming that the invention is based on infrared spectroscopy techniques, a state-of-the-art overview of the application of said techniques for the estimation of glucose concentration and other analytes is as follows:

[0012] Many publications involving the use of infrared spectroscopy techniques (eg, CN204318765) do not pursue the manner in which the techniques are performed and are therefore excluded from the state of the art overview.

[0013] Patent CN104970802 uses near-infrared spectroscopy in the spectral range of 1500nm to 3000nm. However, the patent does not show how to obtain glucose values. The device is integrated into a wristwatch that contains a microprocessor and a Bluetooth transmission module. In addition, it includes a gravity sensor and a skin temperature sensor for gait estimation during walking.

[0014] Patent CN105232055 uses a 1610 nm infrared light source on the earlobe. The device is based on optical spectroscopic measurement on two tracks, one of which is a track according to a light beam that acts as a reference, and the other is a track influenced by reflection on the body measurement area.

[0015] Document US2009 / 004682 describes a procedure for the estimation of glucose in liquid blood samples. A method based on the absorption spectrum of infrared light in the wavelength range of 9615-9804 nm is used. For the estimation of glucose, the integral of the absorption intensity and the integral of the second derivative of the absorption intensity are used, but no mention is made of how to obtain the absorption spectrum. In patent ES2101728 the second derivative of the absorption intensity is also used, but in the range comprised between 1100 nm and 1900 nm. The document shows a procedure for the estimation of the absorption spectrum.

[0016] In US2008 / 171925, multiple wavelengths from different light sources are used simultaneously and the delay between the incident and reflected signals is measured to estimate glucose levels. Patent ES2133643 also uses two wavelengths for glucose level estimation. The device in patent US2017 / 105663 performs two spectroscopic measurements in the near infrared region and fits the data using a convolution function and Monte Carlo simulation.

[0017] The device described in EP0869348 irradiates a measurement area with three wavelengths: a first wavelength (typically between 1550nm and 1650nm) associated with the absorption peak of the OH group of the glucose molecule, a second wavelength (typically between 1480nm and 1550nm) associated with the absorption peak of the NH group, and a third wavelength (typically between 1650nm and 1880nm) associated with the absorption peak of the CH group of the glucose molecule. The glucose value is estimated based on the received radiation by multivariate analysis.

[0018] According to the procedure given in EP 0 807 812, a low-coherence light beam is irradiated onto the eye. The beam reflected from different depths of the eye interferes with another reference light beam, reflected from a movable mirror. The method used makes it possible to separate the light coming from the interface between the cornea and the anterior chamber (aqueous humor) from the light coming from the interface between the anterior chamber and the crystalline lens. The absorbance of the aqueous humor is calculated from the captured intensities of the two light beams. The process is repeated at different wavelengths to obtain the glucose concentration in the aqueous humor.

[0019] In patents US2005 / 0107676 and WO2006 / 047273, a broadband infrared light source and different optical filters are used to estimate the absorption spectrum of infrared light from 1100 to 1900 nm. An active temperature control system is included in the sensor area to avoid temperature effects. Patents US2005 / 020892 and US7299080 have a similar configuration, but for the range included in 1150 to 1850 nm. Furthermore, in these documents, different optical fibers are used for access to different detection areas. The use of multiple probes minimizes interference of the sample spectrum due to placement errors.

[0020] In CN102198004, a halogen light bulb is used as an infrared source and a digital signal processor (DSP) is used for glucose estimation. Such a light source emits wavelengths in the range of 600-2500 nm, which covers the absorption wavelength bands of glucose and water. In this document, a spectrum and neural network are used to estimate glucose levels.

[0021] Patents GB2531956 and WO2015 / 097190 describe devices for characterizing an analyte. The analyte can be glucose in the superficial layer of the skin. A reflector embedded under the superficial layer of the skin receives the incident radiation that has passed through the body measurement area and reflects the incident radiation through the body measurement area towards a sensor located outside the body. The documents also use the analysis method of Raman spectroscopy. Furthermore, the possibility of applying growth factors to stimulate hair growth in the measurement area is shown.

[0022] Invention CN103344597 describes a method for estimating sugar and salt concentrations in lotus roots, using mid-infrared spectroscopy techniques and a model calibrated by least squares method based on measurements made on a set of samples with salt and sugar concentrations of 5%, 10%, 15%, 20%. WO2012 / 048897 shows a method for classifying sugar beet seeds according to the absorption spectrum of the sample in the infrared range.

[0023] Patent ES2102259 describes a procedure for analytical determination of glucose concentration in a biological matrix based on calculation of the propagation time of light in the biological matrix under study. The method described in US2011 / 0184260 directs two light sources with different optical rotations at the sample and estimates glucose from a comparison of the light captured at each optical rotation. In contrast, ES2086969 characterizes the concentration of glucose value in a biological matrix based on the light received by two detectors placed at different distances relative to the emitter.

[0024] Patent GB2482378 describes an optical device and method for non-invasively measuring analyte concentration in a tissue sample. The device has two optical interfaces from which incident light is reflected, with the second optical interface located above the sample. The two interfaces are arranged to produce an interference pattern as a result of the phase difference between the light reflected from the first interface and the light reflected from the second interface. In US6043492, two Fabry-Perot interferometers are utilized to obtain the absorption spectrum of glucose in the near infrared region.

[0025] The method described in patent US8629399 makes it possible to analyze the progress of biological processes such as fermentation. According to this procedure, an initial absorption spectrum in the mid-infrared region is combined with a reference pattern, which makes it possible to predict the expected spectrum when the biological process is finished. By comparing the current spectrum with the expected spectrum, the progress of said process is analyzed.

[0026] WO2001 / 007894 protects a procedure for determining the concentration of analytes (albumin, cholesterol, glucose, total protein, triglycerides and urea) in biological fluids, comprising the following steps: (i) firstly, a sample of the liquid is dried on a glass plate to produce a membrane on the plate; (ii) then, an infrared beam is directed through the plate and the membrane at infrared wavelengths between 2500 and 5000 nm; (iii) finally, the spectrum thus obtained is analysed to determine the concentration of the analytes in the membrane.

[0027] In infrared spectroscopy analysis, absorption spectroscopy is an analytical technique used to determine the concentration of one or more substances in a sample. Absorption spectroscopy is performed with a device called a spectrophotometer. In its most basic form, a spectrophotometer is formed by a light source, a sample holder, and a detector. Documents WO2003076883 and US7133710 are based on a spectrophotometer that measures different wavelengths in the range of 1180 to 2320 nm. Light originating from the light source (incident light) passes through the sample to a detector that measures the amount of light transmitted. For non-dispersive samples, the absorbance of the sample is proportional to the logarithm of the amount of incident light that illuminates the sample divided by the amount of light transmitted through the sample. The incident light is obtained by measuring the amount of light that would reach the detector in the absence of a sample. However, it is common that in order for light to be transmitted through a sample, the intensity of the incident light must be significantly greater than the amount of light required to saturate the detector.

[0028] One way to compensate for detector saturation is to use a smaller integration time (the time the detector is exposed to light before a measurement) for the reference measurement. However, using different integration times for the sample and reference measurements can introduce errors into the measurement of the analyte.

[0029] Another way to compensate for detector saturation is to attenuate the reference beam by a photometric filter. A photometric filter makes it possible to reduce the intensity of the incident light reaching the detector. Patent WO2001 / 015596 describes an artificial filter made of polytetrafluoroethylene (PTFE) and glass fibers, which mimics the absorption spectrum of a part of the body and contains the spectral components of blood. Other similar patents are US6015610 and US5596450. However, any variations in the filter as a result of temperature fluctuations may affect the accuracy of the estimation. Patent US2003 / 0174321 describes an artificial filter for wavelengths between 600 nm and 1650 nm, which is robust against temperature changes.

[0030] Another commonly used method is attenuated total reflection (ATR) infrared spectroscopy. In this method, a crystal is bombarded with a light beam. Depending on the size and shape of the crystal, a series of internal reflections may be promoted, after which the beam may exit the crystal carrying information with it. The top surface of the crystal is located on the surface of the sample, which may be skin. When the infrared beam strikes the top surface of the crystal at an angle greater than the critical angle, the beam is totally reflected within the crystal. Each reflection off the top surface provides a little more information about the sample composition.

[0031] The reflected beam contains evanescent waves that penetrate a short distance into the sample over a wide range of wavelengths. In those regions of the infrared spectrum where the sample absorbs the emitted light, some of the light does not return to the crystal. The amount of light absorbed provides the information needed to quantify the glucose level.

[0032] Patents WO2001 / 079818, WO2000 / 021437, EP1137364, US2005 / 0137469, US2004 / 225206, US2003 / 176775, US2005 / 0171413 and US6362144 are based on the ATR method. In these documents, the measurement of glucose levels is based on comparative analysis in two specific regions of the infrared spectrum, one of which is used as a reference with a wavelength in the range of 8250-8750 nm, and the other is used as a measurement result with a wavelength of 9500-10000 nm. JP2001174405 is an invention similar to the aforementioned invention. However, a single wavelength generated by a laser and a total reflection prism as a crystal are used. Another example is JPH11188009, in which an ATR prism or optical fiber is used.

[0033] WO2006 / 079797 describes a device for measuring an analyte such as glucose with an electrically heated ribbon as an infrared light source, an ATR waveguide, a waveguide collimator and a photodetector. The collimator and the detector are positioned with respect to the waveguide by an adjustable angle. The glucose value is obtained by applying a predictive algorithm to measurements taken at different time intervals. The temperature effect is compensated with the measurement of a temperature sensor and the pressure is controlled by a pressure sensor. Patent WO2016 / 086448 also includes as an innovative element a pressure sensor for normalizing the glucose estimate.

[0034] Document JP2010217097 describes a spectrometer that includes a light source in the mid-infrared region, an ATR unit, and a set of optical bandpass filters to detect different wavelengths, each of which is actuated by the rotation of a prism driven by a motor.

[0035] Patents CN103919560 and CN103919561 are also based on ATR technology, but in said documents, the reflective member is the end of an optical fiber implanted under the skin. The sensitivity of the measurement is enhanced by metal nanoparticles located at the end of the optical fiber. Another document based on ATR is JPH0856565, where different wavelengths from 8333 to 11111 nm are used to estimate the degree of fermentation in the liquid. Further other documents based on ATR include US2003 / 031597 and US7438855B2, where an ATR prism and a customized calibration curve are used to estimate the glucose concentration. Other documents based on ATR include US2004 / 0097796.

[0036] CN101947115 describes an implantable system for measuring glucose concentration in human blood based on ATR on optical fiber, in which light is split into two different optical paths: in one path, the light is coupled into the optical fiber by the ATR sensor, and in the other path, the received light is directly used as a reference signal.

[0037] Patent WO2002 / 082990 uses infrared spectroscopy based on Fourier transform. Instead of projecting a monochromatic light beam onto the sample, a light beam containing multiple wavelengths is generated at once and the amount absorbed by the sample is measured. The process is repeated many times, modifying the beam to contain different combinations of wavelengths. Finally, a computer estimates the absorption at each wavelength based on all the measurements. Other documents using infrared spectroscopy based on Fourier transform include JP2008 / 256398, which incorporates a procedure to remove noise caused by water. Alternatively, KR2015 / 0122381 applies it to the estimation of galactose and anhydrogalactose in liquid media. US6865408 integrates a diffuse reflectance accessory that creates an interferogram from which the computer system estimates glucose levels. WO2013 / 135249 uses a commercial Fourier transform-based infrared spectrometer (Shimadzu IRPrestige-21 / 8400S, Japan) and an ATR crystal prism mounted on a PIKE Technologies accessory (ATR-8200 HA) as a basis, while CN1194133 uses another commercially available spectrometer (Nicolet Magna-IR 750SeriesII).

[0038] [Description of the Invention] The present invention relates to a device for non-invasive blood glucose estimation and to a method used by said device, said device being preferably formed by two devices, a measuring unit and a personal monitoring unit, communicating with each other wirelessly.

[0039] The measuring unit is a portable device that is placed on the skin of the area of ​​the human body irrigated by the vascular bed and emits light at two different wavelengths, one of which corresponds to the maximum absorbance of the absorption spectrum of glucose molecules in the near infrared range. The measuring unit also captures the light that crosses the measuring area, and the personal monitoring unit estimates the blood glucose level based on the information obtained by the measuring unit and displays the result of the estimation to the user.

[0040] The main advantage of glucometers, which are common devices for measuring glucose values, is that they are harmless and painless to use, so they do not cause any kind of discomfort or bother to the user. Moreover, the measurements can be repeated as many times as desired. Another advantage of the proposed device is its low cost, since it uses off-the-shelf electronic components and does not require reactive strips, which increases the cost of using the device. As for commercially available clinical systems for automatic / semi-automatic monitoring of glucose in interstitial fluid, their main advantages are again their low cost (no auxiliary equipment is required, which increases the cost of using), their safety (no insertion of electrodes under the skin, which may cause irritation, in addition to the risk of infection), and their accuracy, since they analyze the glucose component in the blood itself, and not that of the interstitial fluid, which may induce errors.

[0041] In addition, the device has other innovative configurations and technical advantages, including:

[0042] The measurement principle is based on the photoelectric effect, so that the measurement is harmless and can be repeated as many times as desired without causing discomfort to the user.

[0043] -A portable system capable of communicating with the outside world via two-way wireless communication, integrating measurements in the e-Health system in the upstream direction and remote configuration and customization of the device in the downstream direction.

[0044] The device that is the subject of the present invention is based on the technology of infrared spectroscopy. Compared to other proposals based on the technology, the device and method described in the present invention have the following novelties and innovations: 1) absolute normalization consisting of a comparative analysis on a second wavelength that is not affected by the presence of glucose molecules; 2) access to the arterial component of blood, identification of pulsatile components in the captured signal; 3) relative normalization to variations in light level, movement and other condition factors consisting of a comparative analysis on the continuous level of the captured signal; 4) customization of the glucose estimation model depending on the specific characteristics of the person and on the context in which the measurement is performed. The novelty of the subject of the present invention is shown in the claims attached hereto.

[0045] [Brief description of the drawings] As a supplement to the description provided herein, and for the purpose of aiding in making the configuration of the present invention more readily comprehensible, in accordance with preferred practical exemplary embodiments, the description of each embodiment is accompanied by a series of drawings, which are shown below, by way of example and not by way of limitation:

[0046] FIG. 1 shows a basic architectural diagram of the device that is the subject of this patent and the devices that compose it.

[0047] FIG. 2 shows a diagram of the basic architecture of the measurement unit.

[0048] FIG. 3 shows a diagram of the basic architecture of the measurement module.

[0049] FIG. 4 shows a diagram of the basic architecture of a personal monitoring unit.

[0050] FIG. 5 shows a diagram of a single device combining the measurement unit and the personal monitoring unit.

[0051] FIG. 6 shows a method for non-invasive blood glucose estimation.

[0052] [Preferred embodiment of the present invention] A possible embodiment of the first aspect of the invention shown in figure 1 comprises a device (1) for non-invasive blood glucose estimation, which in a preferred embodiment is formed by two units: a measuring unit (2) and a personal monitoring unit (3). The device (1) is capable of wireless and bidirectional communication with an external service provider (21).

[0053] The measurement unit (2) is a portable device that is placed on the skin of the area of ​​the human body irrigated by the vascular bed and emits light at two different wavelengths, one of which corresponds to the maximum absorbance of the absorption spectrum of glucose molecules in the near infrared range. The measurement unit (2) captures the light that crosses the measurement area and, in cooperation with the personal monitoring unit (3), performs a blood glucose level estimation by a computerized model based on the following conditions: 1) Isolate the effect of glucose from the relationship that exists in the amount of light received at each of the multiple wavelengths; 2) Normalize the estimation with respect to the effect of ambient light and with respect to stationary characteristics of the measurement, such as the level of light emitted, the characteristics of the tissue, the arrangement and configuration of the light emitter and the light detector, or the effect of the measurement area, as well as motion artifacts and other low-frequency noise sources; 3) Isolate the effect of arterial blood, taking into account the pulsatile component of the received light signal. In a preferred embodiment, the measurement unit (2) comprises the following modules, referred to in FIG. 2:

[0054] a) A measurement module (4) containing several components for the non-invasive measurement of glucose levels.

[0055] b) a first computer module (5) responsible for activating certain components of the measurement module (4) and a first part of the processing related to the estimation of glucose values ​​based on the data provided by the measurement module (4).

[0056] c) a first communications module (6) responsible for receiving configuration commands and for transmitting relevant data to the first computer module (5).

[0057] d) A first data storage module (7) for temporarily storing information in case of a communication failure or for permanently recording information from the measuring unit (2).

[0058] e) A push button (8) for activating the measuring unit (2).

[0059] The measurement module (4) then comprises the following components shown in FIG.

[0060] a) a first light emitter E1 (9) activatable from the first computer module (5), said first light emitter having a wavelength corresponding to the maximum absorbance of the absorption spectrum of glucose molecules in the near infrared range and intended to impinge on the skin of a body area (10) irrigated by a vascular bed. In one embodiment of the invention a wavelength corresponding to 950 nm is used, although other wavelengths are possible.

[0061] b) A second light emitter E2 (11), also activatable from the first computer module (5), having a wavelength corresponding to an absorbance minimum in the absorption spectrum of glucose molecules, located close to the first light emitter E1 (9) and affecting the same area of ​​the skin (10). In one embodiment of the invention, a wavelength corresponding to 660 nm is used, although other wavelengths are possible.

[0062] c) a photodetector (12) sensitive to the wavelengths of the first and second emitters (9, 11), said photodetector generating a current signal S1 having an amplitude that depends on the intensity of light received in the sensitivity spectrum of the photodetector (12). In a preferred embodiment, the sensitivity spectrum of the photodetector integrates wavelengths corresponding to 660 nm and 950 nm.

[0063] d) If the signal S1 is too weak, a first amplification step (13) produces from said signal S1 an amplified voltage signal S2.

[0064] e) A first filtering step (14) of extracting the components of signal S2 that vary as a result of the arterial blood flow in the vascular bed, generating signal S3. In a preferred embodiment, said step is performed by a high-pass filter, having a cut-off frequency making it possible to pass the pulsatile components associated with the cardiac activity.

[0065] f) a second amplification step (15) for generating an amplified signal S4 from the signal S3 if the signal S3 is too weak.

[0066] g), a second filtering step (16) to extract components of signal S2 related to stationary characteristics of the measurement (influence of the emission level, stationary characteristics of the tissue, the arrangement and configuration of the light emitter and light detector (12), or the measurement area (10) (which may vary from measurement to measurement, as well as giving rise to possible motion artifacts and other low-frequency error sources), generating signal S5. In a preferred embodiment, this step is performed by a low-pass filter with a cut-off frequency that makes it possible not to pass pulsating components related to cardiac activity.

[0067] The information generated by the measuring unit (2) is transmitted wirelessly to the personal monitoring device (3), thus maintaining a two-way communication link. The start time of the measurement can be activated locally by a push button (8) on the measuring unit (2) or remotely by sending a command from the personal monitoring unit (3). Also, by another command the moment (time point) at which the automatic glucose estimation is performed can be preset.

[0068] In the personal monitoring unit (3), which has greater capabilities compared to the measuring unit (2), both in terms of hardware and software, part of the processing with the highest computational load related to the method for glucose value estimation is deployed. A multi-level distribution of the processing favors energy saving and reduces the computational load. The personal monitoring unit (3) may also be responsible for processing and managing information coming from other portable sensors connected to it, which may relate to other physiological variables (such as respiratory rhythm, heart rate, ECG, heart rate variability, body temperature, physical activity, falls, body composition, skin impedance and pulse oximetry). In a preferred embodiment, and with reference to FIG. 4, the personal monitoring unit (3) comprises the following modules:

[0069] a) A second communication module (17) intended to establish a two-way wireless communication with at least the measuring unit (2).

[0070] b) A second computer module (18) responsible for a second part of the processing related to the estimation of glucose values. Algorithms for detecting alarm or attention situations also run in the second computer module (18).

[0071] c) An interface module (19) that displays the information from the measurement unit (2) and the results from the second computer module (18) and allows the user to interact in a coordinated manner, i.e. tactile (19.a), visual (19.b), auditory (19.c) or voice control (19.d). If an alarm event is detected, the interface (19) reacts with coordinated warning means (light, sound, vibration, etc.). The user can then deactivate or silence the alarm while managing and reviewing the information provided. The interface (19) can be used by two types of users: a monitored user, which may occur in a home environment, or a professional user, which may occur in a clinical environment.

[0072] d) a third communication module (20) intended to establish a two-way wireless communication with an external service provider (21).

[0073] e) A second data storage module (22) responsible for temporarily storing information from the personal monitoring unit (3) in case of a communication failure or for permanently recording such information, allowing future access to the information without the need for a remote connection to an external database.

[0074] The personal monitoring unit (3) is portable in a preferred embodiment of the invention, but may be a fixed installation in other possible embodiments. Such a device may be physically embodied by a smartphone or a tablet.

[0075] The measuring unit (2) and the personal monitoring unit (3) maintain a real-time timing system to manage the measurement moments and durations of operation. The timing system is also responsible for assigning to each estimation the time moment at which they are executed. The personal monitoring unit (3) is responsible for coordinating the realization of the glucose estimation according to a pre-set plan, which may be set by an expert user locally via the device's interface (19) or remotely via the telematic services of the e-Health system. Such estimations are activated in the measuring unit (2) by sending a command. Based on the sending of a command for the synchronization of the timing system, a hierarchical procedure is established from the personal monitoring unit (3) to the measuring unit (2). Different users, both expert and monitored users, can also activate the instantaneous execution of the estimation. This instantaneous activation can be done from the push button (8) of the measuring unit (2) or from the interface (19) of the personal monitoring unit (3).

[0076] The personal monitoring unit (3) is capable of autonomously managing information, including alarm management, and establishing seamless communication to the user together with the measurement unit (2) and external service providers (21) in order to integrate information and alarms into the e-Health system.

[0077] The structural and functional modularization of the device for non-invasive blood glucose estimation allows two possible configurations: (i) a distributed type (1), where the measuring unit (2) is physically isolated from the personal monitoring unit (3), and (ii) another single type (monolithic type) (1), shown in FIG. 5, where the measuring unit (2) is integrated with the personal monitoring unit (3) in a single device (23). In this second case, the communication between both units can be performed directly or by wires (rather than wirelessly). Furthermore, the measuring unit (2) and the personal monitoring unit (3) can share physical components in a single configuration (device (23)), such as a single computer module.

[0078] In a preferred embodiment of the invention, a first light emitter E1 and a second light emitter EE2 (9, 11) are positioned such that a light beam crosses a relatively translucent body area (10) (e.g. a finger) and is captured by a light detector (12) located on the opposite side of the body area. The first embodiment focuses on incorporating the measurement unit (2) in a casing that is opaque to the spectrum of light to which the light detector (12) is sensitive. The opaque casing is configured to maintain a constant pressure on the measurement area (10).

[0079] In another embodiment, also shown in FIG. 1, the measuring unit (2) includes a temperature module (24). The temperature module (24) is responsible for measuring the temperature of the measuring area (10). This allows the glucose estimation model to incorporate this data in order to adjust the coefficients as a function of temperature. In addition to the components and elements that make up the device (1) covered by the present patent, the device is also characterized by the method used for non-invasive blood glucose estimation. The method is carried out in a distributed manner at two levels, namely a first level of processing at the measuring unit (2) and a second level of processing at the personal monitoring unit (3). Thus, a distributed processing architecture and method is established that is advantageous in terms of computation and energy saving. In terms of computation, this is because such a multi-level structure allows the processing load between the two devices to be compensated to prevent computation overload. In terms of energy, this is because the highest energy consumption in portable devices is related to transmitting data wirelessly. The multi-level processing reduces and extracts the wireless information transmitted, thus promoting energy saving.

[0080] The method, with reference to FIG. 6, includes the following operations:

[0081] a) During a preset period P1 (25), during which the first light emitter E1 and the second light emitter E2 (9, 11) are switched off, an estimation (28) of the parameter D1 as the average value of the signal S5 is performed.

[0082] b) During a second preset period P2 (26), during which the first emitter E1 (9) is activated and the second emitter E2 (11) is deactivated, an estimation (29) of the parameter D2 as the average value of the signal S5 is performed.

[0083] c) During this period P2 (26), an estimation (30) of the parameter D3 is performed as the average value of the differences between successive maximum and minimum values ​​identified in the pulsatile signal S4 related to the cardiac activity.

[0084] d) During a third preset period P3 (27), during which the second emitter E2 (11) is activated and the first emitter E1 (9) is deactivated, an estimation (31) of the parameter D4 as the average value of the signal S5 is performed.

[0085] e) During this period P3 (27), an estimation (32) of the parameter D5 is performed as the average value of the differences between successive maximum and minimum values ​​identified in the pulsatile signal S4 related to the cardiac activity.

[0086] f) Estimation of blood glucose level (33) based on a model depending on parameters D1, D2, D3, D4 and D5. The model separates the influence of glucose by weighting the dependence on the parameters according to two conditions: (i) glucose molecules exposed to light associated with a maximum absorbance in parameters D2 and D3, or (ii) glucose molecules exposed to light associated with a minimum absorbance in parameters D4 and D5. The influence of ambient light on the measurement of the photodetector (12) is weighted in the dependence with respect to parameter D1. The influence of signal components related to stationary characteristics of the measurement (emission level, stationary characteristics of the tissue, placement and configuration of the emitter and photodetector (12) or influence of the measurement area (10)) as well as possible motion artifacts and other error sources generated by low frequency signals are weighted in the dependence with respect to parameters D2 and D4. The model separates the influence of arterial blood on the estimation, excludes the influence of other tissues, and weights the dependence with respect to parameters D3 and D5.

[0087] The dependency of the model for blood glucose value estimation on parameters D1, D2, D3, D4, and D5 is based on coefficients that can be remotely set by sending commands. The values of the coefficients are fixed by a quantitative method (least squares method, genetic algorithm, swarm intelligence, or neural network). The quantitative method is used as a calibration method to minimize the mean square error of the estimated values in the reference study. There are three possible models for glucose value estimation as a function of the coefficients. 1) A generalized model in which the values of the coefficients are adjusted for use of the model in multiple users. 2) A customized model in which the values of the coefficients are adjusted to optimize glucose estimation for a given user. 3) A generalized and customizable model. The model includes dependencies on other parameters related to the specific characteristics of the user, such as age, gender, type of diabetes, or measurement situation.

[0088] It is also possible to select a method for representing the glucose value estimation in the user interface (19), that is, text, graphic, auditory stimulus, etc., or a combination of multiple of them. Furthermore, the proposal gives the possibility to select a classification method for the user based on the result of the estimation. The selected classification method establishes a threshold based on the blood glucose value. This makes it possible to classify the user into different levels, such as very high, high, normal, low, or very low, for example. The threshold, level, and classification result are shown by a method related to the representation method (text, graphic, auditory stimulus, etc., or a multiple selection of them) selected for the estimation. The classification method estimates prior clinical knowledge and classification criteria to provide direct information about the user's condition. This facilitates their evaluation and diagnosis.

[0089] The possibility of performing a history tracking of the glucose estimated values in different measurements of the user is further considered. Such a history is shown by a method related to the representation method (text, graphic, auditory stimulus, etc., or a multiple selection of them) selected. In each measurement, the date and time when the estimation is performed can be identified.

[0090] The subject matter of the present invention may include additional processing of the measurement records with the goal of automatically establishing trends, patterns, and predictions in the measurement records, which may be communicated to the user.

[0091] The second computer module (18) also executes a system for detecting undesirable situations. In case of detection, the system triggers a series of local and remote alarms enabling preventive measures for the user. The system uses a library of locally or remotely configurable indicators and a table with critical values ​​for triggering alarms associated with said indicators. The indicators can be associated with specific glucose estimates, but also with analysis of trends, patterns and forecasts of the estimate history. The logic and decision rules governing the activation of alarms can also be set to associate one or more indicators. [Brief description of the drawings]

[0092] [Figure 1] A diagram of the basic architecture of the device that is the subject of this patent and the devices that make it up is shown. [Diagram 2] 1 shows a diagram of the basic architecture of a measurement unit. [Diagram 3] 1 shows a diagram of the basic architecture of the measurement module. [Figure 4] 1 shows a diagram of the basic architecture of a personal monitoring unit. [Diagram 5] FIG. 1 shows a diagram of a single device combining a measurement unit and a personal monitoring unit. [Figure 6] A method for non-invasive blood glucose estimation is presented.

Claims

1. A device (1) for non-invasive blood glucose level estimation, comprising: A measuring unit (2); a personal monitoring unit (3) physically isolated from the measurement unit (2), The measuring unit (2) a measurement module (4) for measuring blood glucose levels, the measurement module including a number of elements for carrying out a process for non-invasive blood glucose measurement; a first computer module (5) for controlling said measuring module (4) and for processing data related to a first part of said process for measuring the blood glucose level on the basis of data provided by said measuring module (4); a first communication module (6) for receiving configuration commands and transmitting data related to said commands to said first computer module (5); a first data storage module (7) for storing information from said measurement unit (2); a push button (8) for activating the measuring unit (2), The personal monitoring unit (3) comprises: a second communication module (17) for establishing a bidirectional wireless communication with at least said measurement unit (2); a second computer module (18) for processing data relating to a second part of the process for measuring the blood glucose level; an interface module (19) that displays information from the measurement unit (2) and data provided by the second computer module (18) and allows a user to interact with it; a third communication module (20) for establishing two-way wireless communication with an external service provider (21); a second data storage module (22) for storing data from said personal monitoring unit (3); The measuring module (4) a first light emitter E1 (9) capable of being activated by said first computer module (5) and emitting light at a wavelength near 950 nm, which is aimed at the skin of a body area (10) irrigated by a vascular bed; a second light emitter E2 (11) capable of being activated by the first computer module (5), emitting light at a wavelength near 660 nm and located close to the light emitter E1 (9); a photodetector (12) sensitive to the wavelengths of the first light emitter E1 and the second light emitter E2 (9, 11), generating a current signal (S1) having an amplitude that depends on the intensity of light received in the sensitivity spectrum of the photodetector (12); a first signal amplifier (13) for generating an amplified voltage signal (S2) from the current signal (S1) when the current signal (S1) is weak; a first high-pass filter (14) having a cutoff frequency for passing pulsating components related to cardiac activity so as to extract components of the voltage signal (S2) that vary with arterial blood flow and generate a third signal (S3); a second signal amplifier (15) for generating an amplified signal (S4), hereinafter called pulsating signal, from said third signal (S3); a second low-pass filter (16) having a cut-off frequency that does not pass pulsatile components related to cardiac activity, so as to extract components of the voltage signal (S2) related to stationary characteristics in the measurement and low-frequency noise, and generate a fifth signal (S5), The device, wherein the first and second light emitters E1 and E2 (9, 11) are positioned such that a light beam traverses the relatively translucent body area (10), such as a finger or earlobe, and is captured by the light detector (12) located on the opposite side of the body area (10).

2. A method for non-invasive blood glucose estimation using a device according to claim 1, comprising: the method being executed in a distributed manner by the first computer module (5) and the second computer module (18), The method comprises: - performing a first estimation (28) of a first parameter (D1) as the average value of said fifth signal (S5 according to claim 1) during a preset period P1 (25) during which said light emitters E1 (9) and E2 (11) are switched off; performing a second estimation (29) of a second parameter (D2) as the average value of said fifth signal (S5 according to claim 1) during a second preset period P2 (26) during which said emitter E1 (9) is activated and said emitter E2 (11) is deactivated; performing, during said second preset period P2 (26), a third estimation (30) of a third parameter (D3) corresponding to the average value of the differences between successive maximum and minimum values ​​identified in the pulsation signal (S4 of claim 1); performing a fourth estimation (31) of a fourth parameter (D4) as the average value of said fifth signal (S5 according to claim 1) during a third preset period P3 (27) during which said light emitter E2 (11) is activated and said light emitter E1 (9) is deactivated; performing, during said third preset period P3 (27), a fifth estimation (32) of a fifth parameter (D5) corresponding to the average value of the differences between successive maximum and minimum values ​​identified in said pulsation signal (S4 according to claim 1); and an operation of estimating a blood glucose level (33) based on a model that depends on the first parameter to the fifth parameter (D1, D2, D3, D4, D5), the model isolates the effect of glucose by weighting the dependences on the first through fifth parameters (D1, D2, D3, D4, D5) according to two conditions: whether the glucose molecule is exposed to light associated with a maximum absorbance in the second parameter (D2) and the third parameter (D3), or whether the glucose molecule is exposed to light associated with a minimum absorbance in the fourth parameter and the fifth parameter; the influence of ambient light on the measurement of the light detector (12) is weighted in dependence on the first parameter (D1); the influence of signal components related to the stationary characteristics and low frequency noise in the measurement is weighted in dependence on the second and fourth parameters (D2, D4); The method of claim 1, wherein the model weights the dependencies associated with the third and fifth parameters (D3, D5) to isolate the effect of arterial blood in the estimation and to eliminate the effects of other tissues.

3. the dependency of said model for estimating glucose values ​​on said first to fifth parameters (D1, D2, D3, D4, D5) is realized on the basis of coefficients that can be remotely set by sending a command; 3. The method of claim 2, wherein the values ​​of the coefficients generate (i) a generalized model for use with different users, (ii) a model customized for personal use, or (iii) a generalized and customizable model that includes dependencies on other parameters related to specific characteristics of a user.

4. 3. The method of claim 2, further comprising the operation of locally and remotely activating an alarm if the glucose estimate records a value considered to be inadequate.

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