Non-invasive blood glucose monitoring system

Abstract

System for non-invasive measurement of blood glucose levels, characterized in that the measurement is supported by a control loop, in which the control loop evaluates the absorption and transmission data measured at discrete wavelengths, e.g., to determine the glucose concentration and / or the volume of the tissue under investigation and / or its content of blood and / or interstitial fluid.

Description

[0001] The invention relates to a system for non-invasive measurement of blood glucose levels, in which absorption, reflection and / or transmission can be investigated over a discrete spectrum of several wavelengths, from the visible to the deep infrared range; in one embodiment, the measurement is supported by measuring and / or changing the volume of the tissue or blood under investigation.

[0002] Diabetes mellitus is one of the most common serious diseases. Worldwide, over 500 million people aged 20-79 had diabetes in 2023; of these, approximately 60 million were in Europe. The number of affected individuals will continue to rise due to demographic changes. The costs are estimated at almost US$1 trillion (10th edition of the International Diabetes Federation's (IDF) Diabetes Atlas). Medically, a distinction is made between two types of the disease: the less common type 1 diabetes, which begins in adolescence and is caused by the destruction of insulin-producing cells, and the more common type 2 diabetes, which tends to affect older patients and is caused by a relative insulin deficiency.

[0003] Regardless of whether it is type I or type II diabetes, the patient should regularly check their blood sugar levels. (Aresteh, K. et al.: Internal Medicine. Thieme, Stuttgart 2028).

[0004] Currently, there are three different measurement methods: either the doctor takes a venous blood sample from the patient and has the blood glucose level determined in a laboratory; this is the most accurate method, but can only be used in a hospital or doctor's office. The second option is for the patient to have a small amount of blood drawn invasively and measured with a portable device. Thirdly, a wire inserted under the skin can be used to determine the glucose level in the tissue, which roughly corresponds to the level in the blood.

[0005] Multiple daily blood draws or measurements using wires are associated with considerable pain and also pose a risk of infection. Tissue glucose measurement is not ideal because it only approximates blood glucose levels. Therefore, a device that allows for non-invasive blood glucose measurement would significantly improve patients' quality of life.

[0006] For another parameter in the blood, namely the proportion of oxygenated hemoglobin, such a method has existed for many years: pulse oximetry. It is based on sending a light beam through the patient's finger and measuring how much of the light was absorbed on the other side. Since oxygen-depleted and oxygen-saturated hemoglobin have different absorption spectra, their concentrations can be determined. (A detailed description can be found, for example, in: Webster, JG: Design of Pulse Oximeters. Bristol 1997). This measurement does not necessarily have to be performed using transmitted light; reflection can also be measured.

[0007] Pulse oximetry uses a method that, in principle, can also be applied to blood glucose measurement, in addition to measuring light absorption: it measures absorption at different points in a pulse wave. Since blood vessels are filled with more blood during the systolic phase than during the diastolic phase, it's possible to determine how much light absorption is due to the tissue and how much to the blood. Instead of passively recording the pulse wave, one can, of course, also influence blood flow, for example, by inflating a cuff to a supersystolic pressure, as in blood pressure measurement, which temporarily stops blood flow.

[0008] For many years, laboratory experiments have successfully measured the sugar concentration of a solution using light absorption methods (e.g., Müller, A.: Blood glucose measurements without injury. Vallendar 1994). This method utilizes glucose's property of absorbing light of different wavelengths to varying degrees; the procedure is therefore very similar to pulse oximetry. In addition to its specific light absorption, glucose possesses other physical and chemical properties that differ from those of other substances and are, in principle, suitable for measuring its concentration. Therefore, in addition to optical methods, infrared absorption methods, photoacoustic, Raman, and other spectroscopic methods, etc., are now available. (For an introductory overview, see, for example, Kondepati, VR and Heise, HM: Recent progress in analytical instrumentation for glycemic control in diabetic and critically ill patients.)Anal Bioanal Chem (2007) 388:545-563.).

[0009] Therefore, it is tempting to apply the principles of pulse oximetry—namely, the measurement of absorption or another specific property and the behavior of a pulse wave—to glucose measurement. Such projects are described, for example, in Tuchin, V.: Handbook of optical sensing of glucose in biological fluids and tissues. Taylor & Francis, Boca Raton 2009. Many have also been patented, for example, as early as 1997 as US Patent 5638816, and later, for example, in 2006 as US Patent 6993372.

[0010] However, it has not yet been possible to translate these laboratory experiments into medical practice. The main problem, which has remained unsolved until now and is solved by the present invention, is that the signal from glucose, e.g., its specific absorption, is very low compared to all other substances, tissues, etc., that also absorb light. This is primarily due to the very low light absorption of glucose compared to hemoglobin. Despite sophisticated statistical methods, it has not yet been possible to calculate the glucose concentration from the background noise of the other light absorbers with sufficient accuracy.

[0011] In laboratory experiments conducted in 2021 by the applicant and his colleagues (funded, among other sources, by the ZIM program of the Federal Ministry for Economic Affairs and Energy), it was possible to determine glucose concentrations in cuvettes by measuring light absorption and, for the first time, to measure blood flow-dependent, purely blood-related transmissions (article in the Journal of Health & Technology, submitted). A combination of these results for blood glucose measurement failed due to the unreliability of the light source used – otherwise, the problem would have been solved at that time.

[0012] The invention solves the problem by using a lighting source that provides discrete wavelengths at adjustable intensities. This lighting source can consist of several laser light sources that are coupled via fiber optics and can act on a single volume element. The laser light sources can be, for example, individual laser diode modules or a single multimode module.

[0013] In its simplest form, the system consists of a measuring device that utilizes a physicochemical property of glucose, such as its absorption, as well as a light source as described above, electronics, and a computer that controls and coordinates the measurements to achieve optimal results. Additionally, the volume of light passing through the tissue (and blood) can be measured, for example, by sensors that track the path of the light. An actuator can also be included to influence the blood flow to the tissue under investigation. During measurement, the computer controls the actuator according to the recorded signals. For example, a sensor measures absorption until a sufficiently accurate value is determined using statistical methods. Only then does the actuator alter the blood flow, for example, by applying pressure to the tissue. The actuator's activity is controlled based on the respective results.For example, the actuator can first be gradually adjusted to diastolic pressure, with continuous measurements taken, then to systolic pressure, and so on, up to hypersystolic pressure, at which point tissue fluid, along with blood, is displaced from the measuring area. The pressure adjustment is controlled by a system. In particular, this makes it possible, for example, to maintain the diastolic blood pressure until a sufficient number of measurements have been taken, and only then to increase the pressure further. (It goes without saying that the actuator is controlled in such a way that the applied pressure remains harmless to the patient.) The result is a curve of the applied pressure and a simultaneous curve of the blood flow, as well as a simultaneous curve of absorption or glucose content. From the applied pressure curve and the geometry, especially the size of the measuring probe or actuator, the volume of the measured blood or glucose can also be determined.The tissue's volume can be estimated and also included in the calculation of the concentration from absorption or another physicochemical measurement. In total, one obtains (1) exactly as many measurements as are actually required, and (2) measurements at pressure and volume values ​​that are determined by the measuring system itself and can be adjusted to values ​​that are particularly favorable for the measurement. Finally, it should be noted that the pressure profile can be determined from the glucose concentration itself, since the arterial blood glucose level is higher than the venous level, and the measured glucose concentration changes accordingly with a change in pressure. Nevertheless, the measurements are more accurate and the measurement logic easier to implement if a design such as the one described in the following advanced training courses is used.

[0014] In the first stage of the advanced training, not only is the pressure applied by the actuator recorded, but also the spatial position of system elements is measured, for example, the distance between the light source and the light receiver. This makes it possible to precisely define the volume under investigation and thus accurately determine the amount of blood and interstitial fluid. This reduces measurement fluctuations caused by absorption differences resulting from varying measurement volumes.

[0015] In a further development, the actuator and / or the physicochemical measuring device, e.g., a light transmitter and receiver, can be equipped with a touch sensor, which facilitates precise placement on the tissue and thus the setting of a precise measuring volume at a specific pressure. Additionally or instead, a mechanism can be incorporated that generates a minimum tension, e.g., a spring that clamps the tissue under investigation.

[0016] In a further development, the actuator and / or other elements of the system have a built-in pressure gauge.

[0017] In a further embodiment, the measuring device is connected to a device for measuring blood pressure, which can be taken, for example, at the wrist of the same or the other hand, and whose values ​​are used for controlling the control loop, e.g., to adjust the applied pressure in hypertensive patients and / or to calculate the glucose concentration, e.g., to calculate the measured blood volume.

[0018] All measurement methods can be performed reflectively as well as using transmitted light. In this case, the reflection behavior is altered by changes in pressure or volume.

[0019] The following illustrations show one possible embodiment of the invention. In Fig. Figure 1 shows a possible anatomical setting for the measurement. Here, the measurement is taken at a skin fold between the thumb and forefinger. In cross-section, the non-vascularized skin layers (1a) and the vascularized layers of the skin and the deeper tissue layers are visible on the outside. Their blood vessels are partially cut longitudinally and partially transversely. Arrow 1b points to one of the blood vessels. In Fig. Figure 2 explains the actual measuring principle using this skin fold as an example. The measuring device has two stamp-shaped extensions, 2a and 2b. At the end of the upper stamp, i.e., where it touches the skin, are a light source as well as a touch and a pressure sensor. Stamp 2b contains a receiver, a touch sensor, and a pressure sensor. Both stamps also have a connection (not shown) to the measuring device's control unit, through which the collected data is transmitted and evaluated and can be used to control the motor.

[0020] A motor (not shown) can be used to change and simultaneously measure the distance between the pistons. This is shown in Figure 2d: by reducing the distance between the pistons, the blood vessels are compressed. This is indicated by arrow 2e.

[0021] According to the invention, the motor is controlled by means of a control loop that calculates the data collected by the pistons and thus controls the motor. This makes it possible to measure the light absorption very precisely at precisely known pressures and volumes of the tissue under investigation or of the affected blood flow, and for exactly as long as is required to measure the glucose concentration. Fig. Figure 3 shows that a ring-shaped design is also possible. Here, pressure is exerted on the tissue of the finger by a ring-shaped element, e.g., an inflatable ring. The light source with the pressure sensor is labeled 3b, the receiver 3c. All three are connected via cables to the rest of the measuring device, which in turn controls the ring-shaped element. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] US 5638816

[0009] US 6993372

[0009] Cited non-patent literature

[0000] Webster, JG: Design of Pulse Oximeters. Bristol 1997

[0006] Heise, HM: Recent progress in analytical instrumentation for glycemic control in diabetic and critically ill patients. Anal Bioanal Chem (2007) 388:545-563

[0008]

Claims

[1] System for non-invasive measurement of blood glucose levels, characterized by , that the measurement is supported by a control loop, in which the control loop evaluates the absorption and transmission data measured at discrete wavelengths, e.g., to determine the glucose concentration and / or the volume of the tissue under investigation and / or its content of blood and / or interstitial fluid. [2] System according to claim 1, additionally characterized by that it actively controls the volume under investigation by applying pressure. [3] System according to claim 1, additionally characterized by , that the system determines the position in space of some or all of its elements, e.g. the distance between measuring probe and sensor. [4] System according to claim 1, additionally characterized by that a touch sensor is built in. [5] System according to claim 1, additionally characterized by that a pressure gauge is built in. [6] System according to claim 1, additionally characterized by that a blood pressure monitor is linked to the glucose meter. [7] System according to claim 1, further characterized by combinations of the measurement of the spatial position, the touch sensor, the pressure gauge and / or the blood pressure measuring device.

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