Portable device and method for non-invasive blood glucose level estimation

Abstract

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

Description

[0001] Purpose of the Invention

[0002] The object of the invention described herein falls within the field of Information and Communication Technologies (ICT).

[0003] More specifically, the object of the invention lies in the context of biomedical engineering and medical technology, since it covers the development of portable electronic devices for monitoring a person's physiological variables and his health status in general and his blood glucose level in particular. Background of the Invention

[0005] 425 million people in the world suffer from diabetes, and it is estimated that this number will increase to 629 million by 2045 due to population growth and aging, increasing urbanization, the prevalence of obesity, sedentary lifestyles and other unhealthy lifestyle habits. One in eleven adults suffer from diabetes, and one in seven pregnant women suffer from gestational diabetes. Effective management of this disease requires tracking blood glucose levels. Glucose meters that measure blood glucose levels from a blood sample are the most commonly used devices for measuring blood glucose due to their accuracy. This method is both painful and annoying, especially in cases where tracking blood glucose levels is necessary. To prevent this problem, many methods for non-invasive blood glucose measurement have been proposed in recent years. Reverse iontophoresis is based on the flow of a small current through the skin between an anode and a cathode placed on the surface of the skin. Applying an electric potential between the anode and the cathode causes sodium and chloride ions under the skin to migrate toward the cathode and anode, respectively. Uncharged molecules, such as glucose, are convected along with the ions. This flow causes interstitial glucose to be transported through the skin and collected at the cathode, where it is measured by a conventional sensor. The main disadvantage of this technique is that it requires long exposure to the electric potential, which often leads to irritation in the skin. Two examples of patents based on this technique are US6885882 and WO2008 / 120936. Impedance spectroscopy is based on the measurement of current injection at multiple frequencies and measuring the voltage generated in the body area. Starting from the analysis of the effect of glucose on the impedance spectrum, the measurement of glucose is performed indirectly. Some examples of patents based on this technique are ES2445700, ES2582185, WO2007 / 053963, US2005 / 0192488, US2016 / 0007891 and US2015 / 0164387.

[0006] Optical coherence tomography is a non-invasive imaging test based on low-coherence light interferometry. The interferogram obtained contains information about the optical properties of the sample, and more specifically, about changes in the refractive index that can be used for glucose level estimation. The main disadvantages of this method are its complexity and the need for expensive and large equipment. In addition, it is sensitive to movement of the equipment, heterogeneity of the tissue, and interference with other analytes. Patents US2007 / 0027372 and US2016 / 0058347 use this method.

[0007] Polarimetry is a technique based on measuring the optical rotation produced on a polarized light beam when it passes through an optically active substance. Most researchers have focused on the aqueous humor of the eye due to the fact that the high scattering coefficient of the skin causes depolarization of the light beam. Some limitations of the method are errors due to eye movements, safety standards for light exposure (so that no damage occurs), and discomfort when the measurements are performed in the eye. Polarimetry is used in patents ES2313140, US4014321, EP0534166, US6704588 and US6442410.

[0008] Infrared thermal spectroscopy measures the thermal radiation emitted by the human body due to changes in glucose concentration. This method has many sources of error, such as movement of the measuring device, ambient temperature, and changes 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 that induces rotation and oscillation of molecules in a solution. The subsequent emission of scattered light is affected by this vibration of the molecules, which depends on the concentration of the solute in the solution. Its main disadvantage is that biological tissues can be damaged by the strong laser light of the Raman system. This technology is used in ES2093243, ES2206610, ES2314906, US5448992, US8355767 and US2016 / 0100777.

[0010] Photoacoustic spectroscopy is based on the use of a laser beam to excite a fluid and thereby generate an acoustic response. The photoacoustic signal depends on the specific heat of the tissue, which in turn depends on the glucose concentration. The main limitation of this technique is its sensitivity to chemical (other biological compounds) and physical (changes in temperature and pressure) interferences. EP1346684 makes use of this approach.

[0011] Infrared spectroscopy is based on the absorption of infrared radiation by vibrating molecules. If the vibration frequency of a molecule matches the wavelength of light, it absorbs energy from the light beam. In this way, the glucose concentration can be estimated based on the changes in the intensity of the light passing through the tissue. As a fundamental advantage, it can be emphasized that it is a completely non-invasive technique with simple system assembly and relatively low cost. The near infrared (NIR) spectrum ranges from 700nm to 2500nm, while the mid-infrared (MIR) spectrum ranges from 2500nm to 10μm. Given that the present invention is based on infrared spectroscopy technology, the following is a review of the prior art of the application of this technology in the estimation of glucose concentration and other analytes.

[0012] Many documents that include the use of infrared spectroscopy techniques do not delve into the manner in which this technique is implemented, such as CN204318765, and for this reason are omitted from the overview of the prior art.

[0013] Patent CN104970802 uses near infrared spectrum in the spectral range of 1500nm to 3000nm, but does not indicate how to obtain glucose values. The device is integrated in a watch, which includes a microprocessor and a Bluetooth transmission module. In addition, it includes a gravity sensor and a skin temperature sensor for estimating the number of steps while walking.

[0014] Patent CN105232055 uses a 1610 nm infrared light source on the earlobe. The device is based on spectral measurement with two tracks: one for the beam as a reference and the other track affected by the reflection on the measurement area of ​​the body.

[0015] The procedure for the estimation of glucose in a liquid blood sample is described in the document US2009 / 004682. They use a method based on the absorption spectrum of infrared light in the wavelength range of 9615 to 9804 nm. For glucose estimation, it uses the integral of the absorption intensity and the integral of the second derivative of the absorption intensity, but it does not mention how to obtain the absorption spectrum. Patent ES2101728 also uses the second derivative of the absorption intensity, but in the range included from 1100 to 1900 nm. This document shows a procedure for the estimation of the absorption spectrum.

[0016] In US2008 / 171925, multiple wavelengths obtained from different sources are used simultaneously, and the delay between the incident signal and the reflected signal is measured to provide a glucose level estimate. Patent ES2133643 also uses two wavelengths for glucose estimation. The device of patent US2017 / 105663 performs two spectral measurements in the near-infrared region and uses convolution functions and Monte Carlo simulations to fit the data.

[0017] The device described in EP0869348 irradiates the measurement area with three wavelengths: a first wavelength associated with the absorption peak of the OH group of the glucose molecule (usually 1550nm to 1650nm), a second wavelength associated with the absorption peak of the NH group (usually 1480nm to 1550nm) and a third wavelength associated with the absorption peak of the CH group (usually 1650nm to 1880nm). It estimates the glucose level starting from the received radiation by means of multivariate analysis.

[0018] According to the protocol shown in EP0807812, a low coherence beam is irradiated to the eyeball. The beams reflected from different depths of the eyeball interfere with another reference beam reflected from a movable mirror. The method used enables the light from the interface between the cornea and the anterior aqueous chamber (aqueous humor) to be separated from the light from the interface between the anterior aqueous chamber and the lens. The light absorption of the aqueous humor is calculated based on the captured intensity of the two beams. The process is repeated at different wavelengths to obtain the glucose concentration in the aqueous humor.

[0019] Patents US2005 / 0107676 and WO2006 / 047273 use a broadband infrared light source and different optical filters in order to estimate the absorption spectrum of infrared light between 1100 and 1900 nm. To avoid the influence of temperature, they include an active temperature control system in the sensor area. Patents US2005 / 020892 and US7299080 have similar features, but the range is between 1150 and 1850 nm. In addition, they use different optical fibers for access to different detection areas. The use of multiple probes can minimize the interference with the sample spectrum caused by placement errors.

[0020] CN102198004 uses a halogen bulb as an infrared source and a digital signal processor (DSP) for glucose estimation. This light source emits a wavelength range from 600 to 2500nm, covering the absorption wavelength band of glucose and water. It uses spectroscopy and neural networks to estimate glucose levels.

[0021] Patents GB2531956 and WO2015 / 097190 describe a device for characterizing an analyte (which may be glucose) in the surface layer of the skin. A reflector implanted below the surface layer of the skin receives incident radiation that passes through a measurement area of ​​the body and reflects it through it to a sensor located outside the body. It also uses an analysis method of Raman spectroscopy. In addition, in order to promote hair growth in the measurement area, the possibility of applying growth factors is indicated.

[0022] Invention CN103344597 describes a method for estimating the concentration of sugar and salt in lotus roots. It uses mid-infrared spectroscopy and a model calibrated by the least squares method starting from measurements of a set of samples with salt and sugar concentrations of 5%, 10%, 15%, 20%. Patent WO2012 / 048897 shows a method for classifying beet seeds by means of the absorption spectrum of the samples in the infrared region.

[0023] Patent ES2102259 describes a procedure for determining the analysis of glucose concentration in a biological matrix based on the calculation of the propagation time of light in the biological matrix under study. The method described in US2011 / 0184260 causes two light sources with different polarizations to hit the sample, estimating glucose based on the comparison of the light captured in each polarization. In contrast, ES2086969 starts with the light received in two detectors located at different distances relative to the emitter to characterize the concentration of glucose levels in the biological matrix.

[0024] Patent GB2482378 describes an optical device and method for non-invasive determination of analyte concentration in a tissue sample. The device has two optical interfaces, on which the incident light is reflected and the second one is located on the sample. These interfaces are arranged so as to generate an interference pattern due to the phase difference between the light reflected from the first interface and the light reflected from the second interface. US6043492 uses two Fabry-Perot interferometers to obtain the absorption spectrum of glucose in the near infrared region.

[0025] The method described in patent US8629399 enables the analysis of the evolution of biological processes such as fermentation. According to this procedure, the initial absorption spectrum in the mid-infrared region is combined with a reference pattern, which enables the prediction of the expected spectrum at the end of the biological process. The evolution of the process is analyzed by comparing the current spectrum with the expected spectrum.

[0026] WO2001 / 007894 protects a procedure for determining the concentration of analytes (albumin, cholesterol, glucose, total protein, triglycerides and urea) in a biological fluid, the procedure comprising the following steps: drying a sample of the fluid on a glass plate so as to produce a film on the plate; directing an infrared beam at an infrared wavelength between 2500 and 5000 nm through the plate and the film; and analyzing the spectrum thus obtained in order to determine the concentration of the analyte in the film. In analysis by means of infrared spectroscopy, absorption spectroscopy is an analytical technique for determining the concentration of one or more substances in a sample. Absorption spectroscopy is performed using a device called a spectrophotometer, which in its most basic form is formed by a light source, a sample holder and a detector. Documents WO2003076883 and US7133710 are based on a spectrophotometer, which measures different wavelengths in the range from 1180 to 2320 nm. The light generated from the light source (incident light) passes through the sample to the detector, which 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 illuminating 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 the sample. However, it is common that for the light to be transmitted through the sample, the intensity of the incident light must be significantly greater than the amount required to saturate the detector.

[0027] 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 may lead to errors in the analyte determination.

[0028] Another way to compensate for the saturation of the detector is to use a photometric filter to attenuate the reference beam, which reduces the intensity of the incident light reaching the detector. Patent WO2001 / 015596 describes an artificial filter made of polytetrafluoroethylene (PTFE) and glass fiber that simulates the absorption spectrum of a part of the body and includes the spectral component of blood. Other similar patents are US6015610 and US5596450. However, any changes in the filter due to temperature fluctuations may affect the accuracy of the estimate. Patent US2003 / 0174321 describes an artificial filter for wavelengths included between 600nm and 1650nm, which is robust to temperature changes.

[0029] Another common method is attenuated total reflectance (ATR) infrared spectroscopy. In this method, a beam of light hits a crystal. The size and shape of the crystal favor a series of internal reflections before the beam leaves the crystal with information. The top surface of the crystal sits on the surface of a sample, which could be skin. When the infrared beam hits the top surface of the crystal at an angle exceeding the critical angle, the beam is completely reflected inside the crystal. Each reflection off the top surface provides more information about the composition of the sample.

[0030] The reflected beam consists of an evanescent wave, which penetrates the sample a short distance over a wide range of wavelengths. In those regions of the infrared spectrum where the sample absorbs radiation, a portion of the light does not return to the crystal. The amount of light absorbed provides the information needed for quantification of glucose levels.

[0031] 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 determination of glucose levels starts from the comparative analysis of two specific regions of the infrared spectrum, one used as a reference in the range between 8250 and 8750 nm, and the other used as a measurement in the range between 9500 and 10000 nm. P2001174405 is an invention similar to the previous invention, but it uses a single wavelength generated by a laser and uses a total reflection prism as a crystal. Another example is JPH11188009, in which an ATR prism or optical fiber is used.

[0032] WO2006 / 079797 describes a device for measuring an analyte (such as glucose) by means of an electric heating tape as an infrared light source, an ATR waveguide, a waveguide collimator and a light detector. The collimator and the detector are positioned at an adjustable angle relative to the waveguide. Glucose values ​​can be obtained by applying a prediction algorithm to measurements taken at different time intervals. The influence of temperature is compensated by measurement with a temperature sensor, and the pressure is controlled by a pressure sensor. Patent WO2016 / 086448 also includes a pressure sensor as an innovative element to normalize the glucose estimate. Document JP2010217097 describes a spectrometer comprising a light source in the mid-infrared region, an ATR unit and a set of optical bandpass filters to detect different wavelengths. Each filter is activated by means of the rotation of a motor-actuated prism. Patents CN103919560 and CN103919561 are also based on ATR technology, but in this case, the reflective element is the end of an optical fiber that is implanted under the skin. Metal nanoparticles at the end of the optical fiber enhance the sensitivity of the measurement. Other documents based on ATR are JPH0856565, which uses different wavelengths included between 8333 and 11111 nm to estimate the degree of fermentation in a fluid; US2003 / 031597 and US7438855B2, which use an ATR prism and a custom calibration curve to estimate glucose concentration; or US2004 / 0097796.

[0033] CN101947115 describes an implantable system for measuring glucose concentration in human blood based on fiber optic ATR. In this case, the light is split into two different optical paths: in one optical path, the light is coupled to the optical fiber with the aid of an ATR sensor, and in the other optical path, the received light is used directly as a reference signal.

[0034] Patent WO2002 / 082990 uses an infrared spectroscopy technique based on Fourier transforms. Instead of projecting a monochromatic beam of light onto a sample, this technique generates a beam containing multiple wavelengths at once and measures the amount absorbed by the sample. The process is repeated multiple times, modifying the beam to contain a combination of different wavelengths. Finally, a computer infers the absorption at each wavelength from all the measurements. Other documents using infrared spectroscopy techniques with the aid of Fourier transform are JP2008 / 256398, which includes a procedure for eliminating the noise generated by water; KR2015 / 0122381, which is suitable for the estimation of galactose and anhydrous galactose in liquid media; US6865408, which integrates a diffuse reflectance accessory that creates an interference pattern, from which a computer system estimates the glucose level; WO2013 / 135249, which uses a commercial infrared spectrometer based on Fourier transform (Shimadzu IRPrestige-21 / 8400S) and an ATR crystal prism mounted on a Parker Technology accessory (ATR-8200HA) as a basis, or CN1194133, in which another commercial spectrometer is used (Nicolet Magna IR 750 Series II).

[0035] Description of the invention

[0036] The invention relates to a device for non-invasive blood glucose level estimation and a method used by such a device. The device is preferably formed of two devices: a measuring unit and a personal monitoring unit, which communicate with each other wirelessly.

[0037] The measuring unit is a portable device that is placed on the skin of a human body area irrigated by a vascular bed and emits light of two different wavelengths, one of which corresponds to the maximum absorbance in the absorption spectrum of glucose molecules in the near-infrared range. The measuring unit also captures the light that passes through the measuring area, and the personal monitoring unit estimates the blood sugar level based on this information, thereby displaying the estimated result to the user.

[0038] With regard to the commonly used devices for measuring blood glucose levels, the main advantage of a blood glucose meter is that its harmless and painless use prevents the user from experiencing any type of discomfort or annoyance. In addition, the measurement can be repeated as many times as needed. Another advantage of the proposed device is its low cost, since it uses readily available electronic components and does not require reaction strips that would increase the ongoing cost of the device. With regard to commercial clinical systems for automatic / semi-automatic monitoring of glucose in interstitial fluid, its main advantages also lie in its low cost (no supplements are required that would increase the ongoing cost), its safety (no elements that could cause irritation need to be inserted under the skin, besides the risk of infection that this implies) and its accuracy, since it analyzes the glucose component in the blood and not in the interstitial fluid that could lead to errors.

[0039] In addition, the device has other innovative features and technical advantages:

[0040] - The measuring 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.

[0041] - It is a portable system capable of communicating with the outside world by means of bidirectional wireless communication, for integration of measurements into electronic health systems in the upstream direction, and for remote configuration and customization of devices in the downstream direction.

[0042] The device object of the invention is based on the technology of infrared spectroscopy. Compared with other proposals based on this technology, the device and method described in the present invention have a series of novelties and innovations: 1) Absolute normalization including comparative analysis on a second wavelength that is not affected by the presence of glucose molecules. 2) Acquisition of the arterial component of the blood, identification of the pulsating component in the captured signal. 3) Relative normalization for fluctuations in light levels, movement and other regulatory factors, including comparative analysis of continuous levels in the captured signal. 4) Customization of the glucose estimation model depending on the specific characteristics of the person and the environment in which the measurement is performed. The novelty of the object of the invention is expressed in the set of claims attached to this description. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] As a supplement to the description provided herein, and for the purpose of helping to make the features of the invention more easily understood, this description is accompanied by a set of drawings, which, by way of illustration and not limitation, represent the following, according to a preferred practical exemplary embodiment of the invention:

[0044] Figure 1 The basic architecture diagram of the device object of this patent and its constituent devices is shown.

[0045] Figure 2 The basic architecture diagram of the measurement unit is shown.

[0046] Figure 3 The basic architecture diagram of the measurement module is shown.

[0047] Figure 4 The basic architecture diagram of a personal monitoring unit is shown.

[0048] Figure 5 A diagram of a single-chip device combining a measurement unit and a personal monitoring unit is shown.

[0049] Figure 6 A method for non-invasive blood glucose level estimation is explained.

[0050] Preferred embodiments of the present invention

[0051] Here, the Figure 1In a possible embodiment of the first aspect of the invention shown in , it has a device (1) for non-invasive blood glucose level estimation, which in a preferred embodiment comprises a device 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).

[0052] The measuring unit (2) is a portable device that is placed on the skin of an area of ​​the human body irrigated by a vascular bed and emits light of two different wavelengths, one of which corresponds to the maximum absorbance in the absorption spectrum of glucose molecules in the near-infrared range. The measuring unit (2) together with the personal monitoring unit (3) captures the light that passes through the measuring area and performs blood glucose level estimation with the help of a computational model based on the following conditions: 1) isolating the influence of glucose from the relationship existing in the amount of light received at each wavelength; 2) normalizing the estimate with respect to the influence of ambient light and with respect to static characteristics of the measurement (such as the level of emitted light, characteristics of the tissue, arrangement and characteristics of the light emitter and photodetector), or the influence of the measuring area, as well as motion artifacts and other low-frequency noise sources; 3) isolating the influence of arterial blood taking into account the pulsating component of the received signal. In a preferred embodiment, the measuring unit (2) comprises the following modules, such as Figure 2 As shown in:

[0053] a) a measurement module (4) comprising components for non-invasive measurement of blood glucose levels;

[0054] b) a first computer module (5) responsible for activating some components of the measurement module (4) and for a first part of the processing associated with glucose level estimation, starting from the data provided by the measurement module (4);

[0055] c) a first communication module (6), which is responsible for receiving configuration commands and sending data associated with the first computer module (5);

[0056] d) a first data storage module (7) for temporarily storing information in the event of a communication failure or for permanently recording information from the measuring unit (2);

[0057] e) a button (8) for activating the measuring unit (2);

[0058] Furthermore, the measuring module (4) comprises the following components, such as Figure 3 As shown in:

[0059] a) A first light emitter E1 (9), activatable from the first computer module (5), with a wavelength corresponding to the maximum absorbance in the absorption spectrum of glucose molecules in the near infrared range, which light impinges on the skin of a human body area (10) irrigated by a vascular bed. In one embodiment of the invention, a wavelength corresponding to 950 nm is used, but other wavelengths may be used.

[0060] b) a second light emitter E2 (11) located close to the first emitter E1 (9) and affecting the same area of ​​the skin (10), which can also be activated from the first computer module (5) and has a wavelength corresponding to the minimum absorbance in the absorption spectrum of the glucose molecule. In one embodiment of the invention, a wavelength corresponding to 660 nm is used, but other wavelengths may be used.

[0061] c) a photodetector (12) sensitive to the wavelength of the first and second emitters (9, 11), generating a current signal S1, the amplitude of which depends on the intensity of the 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.

[0062] d) When the signal S1 is very weak, the first amplification step (13) generates a voltage signal S2 amplified from the signal S1.

[0063] e) A first filtering step (14) of extracting the component of signal S2 that varies with the arterial blood flow in the vascular bed, thereby generating signal S3. In a preferred embodiment, this step is performed with the aid of a high-pass filter having a cut-off frequency that allows the pulsatile component associated with cardiac activity to pass.

[0064] f) When the signal S3 is very weak, a second amplification step (15) which generates an amplified signal S4 starting from the signal S3.

[0065] g) a second filtering step (16) which extracts components of the signal S2 related to the stationary properties of the measurement (emitted light level, stationary properties of the tissue, arrangement and characteristics of the light emitter and photodetector (12), or the influence of the measurement area (10)), which may vary from measurement to measurement, as well as possible motion artifacts and other low-frequency error sources, thereby generating a signal S5. In a preferred embodiment, this step is performed with the aid of a low-pass filter with a cut-off frequency that does not allow the pulsating components related to cardiac activity to pass. The information generated by the measuring unit (2) is transmitted wirelessly to the personal monitoring device (3), with which it maintains a bidirectional communication link. The start time of the measurement can be activated locally by means of a button (8) on the measuring device (2) or remotely by means of a command sent from the personal monitoring unit (3). Also by means of another command, the moment at which the automatic glucose estimation will be performed can be preconfigured.

[0066] In the personal monitoring unit (3), which has greater capabilities in terms of hardware and software than the measuring unit (2), the processing part with the greatest computational load associated with the glucose level estimation method is developed. The multi-level distribution of processing is advantageous for energy saving and reducing the amount of computation. The personal monitoring unit (3) may also be responsible for processing and managing information from other portable sensors connected to it, which may be related to other physiological variables (respiratory rhythm, heart rate, ECG, heart rate variability, body temperature, physical activity, falls, body composition, skin impedance and pulse oximetry, etc.). In a preferred embodiment, the personal monitoring unit (3) comprises the following modules, such as Figure 4 As shown in:

[0067] a) A second communication module (17) intended to establish a two-way wireless communication with at least the measuring unit (2).

[0068] b) A second computer module (18) responsible for the second part of the processing associated with glucose level estimation. Also executed therein is an algorithm for detecting alarm situations or situations that should be considered as worthy of attention.

[0069] c) an interface module (19) for displaying the information from the measuring unit (2) and the results from the second computer module (18), enabling the user to interact in an adapted manner: touch (19.a), vision (19.b), hearing (19.c) or voice control (19.d), etc. If an alarm event is detected, the interface (19) comprises adapted warning means (light, sound, vibration, etc.). The user can then deactivate or turn off the alarm while managing and viewing 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.

[0070] d) A third communication module (20) is intended to establish two-way wireless communication with an external service provider (21).

[0071] e) A second data storage module (22) responsible for temporarily storing information from the personal monitoring unit (3) in the event of a communication failure, or for permanently recording such information, which enables future access to it without requiring a remote connection to an external database.

[0072] In a preferred embodiment of the present invention, the personal monitoring unit (3) is portable, but in other possible embodiments, it can also be a fixed device. Such a device can be physically implemented with the help of a smartphone or a tablet computer.

[0073] The measuring unit (2) and the personal monitoring unit (3) maintain a real-time timing system to manage the measurement moments and the operating time periods. The timing system is also responsible for allocating the moments for executing each estimate. The personal monitoring unit (3) is responsible for coordinating the implementation of the glucose estimation according to a pre-established plan, which can be configured locally by an expert user through the interface (19) of the device, or remotely through the telematics service of the electronic health system. Such an estimate will be activated in the measuring unit (2) by sending a command. A hierarchical procedure is established from the personal monitoring unit (3) to the measuring unit (2) based on sending a command for synchronization of the timing system. Different users, including both experts and monitored users, can also activate the immediate execution of the estimate. This immediate activation can be performed by a button (8) of the measuring unit (2) or an interface (19) of the personal monitoring unit (3).

[0074] The personal monitoring unit (3) can manage information in an autonomous manner, including alarm management, establishing communications with the measurement unit (2) and external service providers (21) in a manner seamless to the user in order to integrate information and alarms in the electronic health system.

[0075] The structural and functional modularity of the device for non-invasive blood glucose level estimation enables two possible configurations: a distributed configuration (1), in which the measurement unit (2) is physically separated from the personal monitoring unit (3); Figure 5 , where the measuring unit (2) and the personal monitoring unit (3) are integrated in a single device (23). In the second case, the communication between the two units can be performed directly or wired (not wireless). In addition, the measuring unit (2) and the personal monitoring unit (3) can share physical components in a monolithic configuration (device (23)), such as a single computer module.

[0076] In a preferred embodiment of the invention, the first and second light emitters E1 and E2 (9, 11) are arranged so that the light beam passes through a relatively translucent body region (10) (e.g. a finger) and is captured by a photodetector (12) located on the opposite side of the body region. The first embodiment focuses on incorporating the measurement unit (2) into a housing that is opaque to the spectrum to which the photodetector (12) is sensitive, the housing being configured to maintain a constant pressure on the measurement region (10).

[0077] In another embodiment, Figure 1 As shown in , the measuring unit ( 2 ) comprises a temperature module ( 24 ) which is responsible for measuring the temperature of the measuring area ( 10 ) so that the glucose estimation model includes this data in order to adjust the coefficients which are dependent on temperature.

[0078] In addition to the components and elements constituting the device object of the present patent (1), it is also characterized in that in the method for non-invasive blood glucose level estimation, it is performed in a distributed manner in two stages: a first stage of processing in the measuring unit (2) and a second stage of processing in the personal monitoring unit (3). Thus, a distributed processing architecture and method system are established, which is advantageous in terms of computing and energy saving. In terms of computing, because this multi-stage structure is able to compensate for the processing load between the two devices in order to prevent computing overload. In terms of energy, because the highest energy consumption of portable devices is related to wirelessly sending data. Since the multi-stage processing reduces and extracts the wireless information to be transmitted, it is beneficial to energy saving.

[0079] The method comprises the following operations, such as Figure 6 As shown:

[0080] a) During a preconfigured time period P1 (25) in which the first and second optical emitters E1 and E2 (9, 11) are deactivated, the parameter D1 is estimated (28) as an average value of the signal S5.

[0081] b) During a second preconfigured time period P2 (26) in which the first light emitter E1 (9) is activated and the second light emitter E2 (11) is deactivated, the parameter D2 is estimated (29) as an average value of the signal S5.

[0082] c) During the same time period P2 (26), the parameter D3 is estimated (30) as the average of the differences between consecutive maximum and minimum values ​​identified in the pulsation signal S4 associated with the cardiac activity.

[0083] d) During a third preconfigured time period P3 (27) in which the second optical emitter E2 (11) is activated and the first optical emitter E1 (9) is deactivated, the parameter D4 is estimated (31) as an average value of the signal S5.

[0084] e) During the same time period P3 (27), the parameter D5 is estimated (32) as the average of the differences between consecutive maximum and minimum values ​​identified in the pulsation signal S4 associated with the cardiac activity.

[0085] f) Estimation of blood glucose level (33) starting from a model depending on parameters D1, D2, D3, D4 and D5. The model isolates the influence of glucose by weighting the dependencies with respect to the parameters according to the following two conditions: the glucose molecules are subjected to light associated with a maximum absorbance in parameters D2 and D3, or 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 dependency with respect to parameter D1. The influence of signal components related to stationary characteristics in the measurement (emitted light level, stationary characteristics of the tissue, arrangement and characteristics of the light emitter and the photodetector (12), or the 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 dependency with respect to parameters D2 and D4. The model isolates the influence of arterial blood on the estimate and eliminates the influence of other tissues, thereby weighting the dependencies with respect to parameters D3 and D5. The model of blood glucose level estimation with respect to the dependence of the parameters D1, D2, D3, D4 and D5 is based on coefficients that can be remotely configured by sending commands. The values ​​of the coefficients are fixed by means of quantitative methods (least squares, genetic algorithms, swarm intelligence or neural networks), which minimize the mean square error of the estimation in the reference study, which is used as a calibration method. As a function of the coefficients, there are three possible models of glucose level estimation: 1) a general model, in which the values ​​of the coefficients are adapted to use the model in multiple users; 2) a customized model, in which the values ​​of the coefficients are adjusted in order to optimize the glucose estimation for a given user; 3) a general and customizable model, which includes the dependence on other parameters related to user-specific characteristics (such as age, sex, type of diabetes) or the measurement environment.

[0086] It is also possible to select a method for representing the estimation of the blood glucose level in the user interface (19): text, graphic, auditory, etc., or multiple selections thereof. In addition, the proposal adds the possibility of selecting a classification method for the user based on the result of the estimation. The selected classification method will establish thresholds based on the blood glucose level, which will enable the user to be classified into different levels, such as: very high, high, normal, low or very low. The thresholds, levels and results of the classification will be displayed in a manner related to the representation method (text, graphic, auditory, etc. or multiple selections thereof) selected for the estimation. The classification method assumes previous clinical knowledge and classification criteria in order to provide direct information about the user's state and thus facilitate its estimation and diagnosis. The possibility of historical tracking of glucose estimates in different measurements of the user is further considered. Such historical records will be displayed in a manner related to the selected representation method (text, graphic, auditory, etc. or multiple selections thereof). In each measurement, the date and time when the estimation was performed can be identified.

[0087] Objects of the present invention may include additional processing of measurement records with the aim of automatically establishing trends, patterns and predictions in the measurement history, which trends, patterns and predictions can be communicated to the user.

[0088] The second computer module (18) also implements a system for detecting undesirable conditions and, if detected, generating a series of local and remote alarms to enable preventive measures to be taken by the user. The system uses a library of local or remote configurable indicators and tables with thresholds for generating alarms related to the indicators. These indicators can be associated with specific blood glucose estimates, but can also be associated with analysis of trends, patterns and predictions of the estimate history. The logic and decision rules controlling the activation of the alarms can also be configured to be related to one or more indicators.

Claims

1. A device (1) for non-invasive blood glucose level estimation, comprising: - A measuring unit (2), comprising the following modules: - a measuring module (4) for measuring the blood sugar level, comprising a plurality of elements configured to perform non-invasive blood sugar level measurement; - a first computer module (5) configured to control the measurement module (4) and to process the data provided by the measurement module (4); - a first communication module (6) configured to receive configuration commands and to send data associated with such commands to said first computer module (5); - a first data storage module (7) configured to store information from the measurement unit (2); - a button (8) configured to activate the measuring unit (2); - a personal monitoring unit (3) physically separated from said measuring unit (2), comprising: - a second communication module (17) intended to establish a two-way wireless communication with at least the measuring unit (2); - a second computer module (18) configured to process the data received from the measurement unit (2); - an interface module (19) configured to display information from said measuring unit (2) and data provided by said second computer module (18) and to enable user interaction; - a third communication module (20) configured to establish a two-way wireless communication with an external service provider (21); - a second data storage module (22) configured to store data from the personal monitoring unit (3); And wherein the measuring module (4) comprises: - a first light emitter E1 (9) capable of activating light from said first computer module (5) to impinge on the skin of a body area (10) irrigated by a vascular bed; a second light emitter E2 (11) which can be activated from said first computer module (5) and which is arranged close to said first light emitter E1 (9); a photodetector (12) sensitive to the wavelength of said first light emitter E1 (9) and said second light emitter E2 (11), configured to generate a current signal (S1) the amplitude of which depends on the intensity of the light received in the sensitivity spectrum of said photodetector (12); - a first signal amplifier (13) which generates a voltage signal (S2) amplified from the current signal (S1) when the current signal (S1) is weak; - a first high pass filter (14) generating a third signal (S3); - a second signal amplifier (15) which generates an amplified signal (S4) from said third signal (S3); - a second low pass filter (16) generating a fifth signal (S5); The invention is characterized in that: the first light emitter E1 is configured to emit light at a wavelength corresponding to the maximum absorbance in the absorption spectrum of glucose molecules in the near-infrared range, the second light emitter E2 is configured to emit light at a wavelength corresponding to the minimum absorbance in the absorption spectrum of the glucose molecules, the first light emitter E1 (9) and the second light emitter E2 (11) are arranged so that the light beam passes through a relatively translucent body region (10) and is detected by the photodetector located on the opposite side of the body region (10) where the light emitter is located. The device (12) captures; the photodetector is sensitive to the wavelengths of the first light emitter E1 (9) and the second light emitter E2 (11); the first high-pass filter (14) has a cutoff frequency that allows the pulsating component related to cardiac activity to pass, so that it extracts the component of the voltage signal (S2) that changes due to arterial blood flow; and the second low-pass filter (16) has a cutoff frequency that prevents the pulsating component related to cardiac activity from passing, so that it extracts the component of the voltage signal (S2) related to the stable characteristics and low-frequency noise in the measurement.

2. The device according to claim 1, characterized in that The first light emitter E1 (9) and the second light emitter E2 (11) are arranged so that the light beam passes through a finger or an earlobe.

3. A method for non-invasive blood glucose level estimation using the device according to any one of claims 1 and 2, executed by the first computer module (5) and the second computer module (18) in a distributed manner, and comprising the following operations: - during a preconfigured time period P1 (25) in which said first optical transmitter E1 (9) and said second optical transmitter E2 (11) are deactivated, performing a first estimation (28) of a first parameter (D1) as an average value of said fifth signal (S5); - during a second preconfigured time period P2 (26) in which the first optical emitter E1 (9) is activated and the second optical emitter E2 (11) is deactivated, performing a second estimation (29) of a second parameter (D2) as an average value of the fifth signal (S5); - performing a third estimation (30) of a third parameter (D3) during said second preconfigured time period P2 (26), wherein said third parameter corresponds to an average value of differences between consecutive maximum and minimum values ​​identified in the pulsatile signal; - during a third preconfigured time period P3 (27) in which the second optical emitter E2 (11) is activated and the first optical emitter E1 (9) is deactivated, performing a fourth estimation (31) of a fourth parameter (D4) as an average value of the fifth signal (S5); - performing a fifth estimation (32) of a fifth parameter (D5) during said third preconfigured time period P3 (27), wherein said fifth parameter corresponds to an average value of differences between consecutive maximum and minimum values ​​identified in the pulsatile signal; - estimating the blood glucose level (33) starting from a model depending on a first parameter to a fifth parameter (D1, D2, D3, D4, D5), wherein the model weights the dependencies with respect to these parameters (D1, D2, D3, D4, D5) so as to isolate the influence of glucose according to the following two conditions: subjecting the glucose molecules to light associated with a maximum absorbance in the second parameter (D2) and the third parameter (D3), or to light associated with a minimum absorbance in the fourth parameter (D4) and the fifth parameter (D5), and wherein the influence of ambient light in the measurement of the photodetector (12) is weighted in the dependency with respect to the first parameter (D1), and wherein the influence of signal components related to stationary characteristics in the measurement and low-frequency noise are weighted in the dependency with respect to the second and fourth parameters (D2, D4), and the model weights the dependencies with respect to the third and fifth parameters (D3, D5) so as to isolate the influence of arterial blood in the estimation and eliminate the influence of other tissues.

4. The method according to claim 3, characterized in that Dependence of a model for glucose level estimation relative to said first to fifth parameters (D1, D2, D3, D4, D5) is performed based on coefficients that can be remotely configured by sending commands, and wherein the values ​​of said coefficients generate a generic model for different users, or a customized model for individual uses, or a generic and customizable model including dependencies on other parameters related to specific characteristics of said users.

5. The method according to claim 3, characterized in that Included is the operation of activating an alarm locally and remotely when the glucose estimate records a value deemed inappropriate.

6. A method as claimed in any one of claims 3 to 5, wherein the automatic estimation of blood glucose level is performed at preconfigured moments according to a pre-established schedule.

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