DE102009034467A1 - Portable hand device for non-invasive measuring of blood glucose level for treating diabetes mellitus of patient, has receiver coils with windings, where change of flux penetrating coil effects voltage at connection of windings of coils - Google Patents

Abstract

The device has a magnetic field unit for producing a static base field (B0) and another magnetic field unit for producing a time variable magnetic field (B1) aligned perpendicular to the base field. Multiple of receiver coils are provided with coil surface that extends perpendicular to alignment of the base field. Multiple of receiver coils e.g. ring coils, are arranged on a semiconductor chip and provided with windings, where change of magnetic flux penetrating the coil effects induction voltage at a connection of windings of the coils.

Description

State of the art

From particular benefit in terms of a non-invasive measurement of Body fluid ratios is the provision of blood sugar levels. The monitoring of blood sugar concentrations is particularly important in the treatment of a variety of diseases, z. As the diabetes mellitus and the metabolism during z. B. a physical operation of a person understand to be able to.

diabetes Mellitus is one of the leading causes of death in developed countries. It is estimated that the number of those who participate in it suffer from over 100 million people in the year 2000 300 million people in 2030 will increase. Uncontrolled or poorly controlled diabetes leads to or hypoglycaemia, causing long-term damage in the form of Blindness, kidney failure, coronary heart disease and the like has more. These damages can avoided or slowed their progress significantly Strict control of blood sugar concentration.

Therefore monitoring blood glucose levels is an essential Part of a diabetes treatment that attempts to to achieve the setting of a normal blood sugar level.

For this For example, blood is taken from a puncture of a finger. The amount of blood is applied to a test strip containing blood sugar responding. Subsequently, an analysis by UV / VIS spectroscopy carried out. In this type of spectroscopy is both used ultraviolet as well as visible light. Based on the energy absorption you get information about the composition the sample, especially the blood sugar concentration.

Indeed Such tests are not painless and uncomfortable. That's why they are for frequent or even regular monitoring the blood sugar level, especially at work or during physical activities or in sleep essentially not suitable.

Therefore is the development of non-invasive methods for continuous monitoring the blood sugar level prioritized for the future Diabetes care.

Currently available devices for the not invasive in vivo monitoring of blood sugar levels are based essentially on optical processes. Are known z. B. the Infrared spectroscopy, Raman spectroscopy, photoacoustic Spectroscopy, just to name a few.

Due to the complexity of human tissue and the low optical feedback of glucose, such methods are unsuitable for clinical applications due to insufficient accuracy. Another approach to non-invasive measurement of sugar levels is based on nuclear magnetic resonance spectroscopy. in the U.S. Patent 4,875,486 describes an apparatus for non-invasive in vivo measurement for body fluid fractions based on proton nuclear magnetic resonance.

Another device for determining a sugar value is from the U.S. Patent 6,163,154 and the U.S. Patent 6,404,197 known. Due to the size and the fact that the resonance signal of water limits the sensitivity for determining the sugar value, no clinical use has taken place so far.

In order to make a distinction between a nuclear magnetic resonance signal of water and sugar, a homogeneity of the magnetic field in nuclear spin spectroscopy in the range of 10 ^{-6 is} required. As a result, complex shielding and homogenizing the magnetic field are necessary. This leads to high costs and thus to a limited distribution of such devices.

Purpose and advantages of the invention

Of the Invention is based on the object, a device for not invasive measurement of body fluid levels, especially the blood sugar level in humans, provide which allows a simple clinical use.

These The object is solved by the features of claim 1.

In the dependent claims are advantageous and expedient developments of the invention called.

The invention is based on a device for the non-invasive measurement of body fluid fractions with the aid of nuclear magnetic resonance spectroscopy (NMR spectroscopy), which comprises first magnetic field means to provide a static basic magnetic field B0 and second magnetic field means for generating a transverse, in particular having perpendicular to the basic magnetic field B0 aligned, time-varying magnetic field B1. In addition, receiver coils are provided, the spanned coil surface is transverse, in particular perpendicular to the orientation of the basic field B0 he stretches. The core of the invention lies in the fact that a plurality of receiver coils on a substrate, in particular semiconductor chip are arranged, and that the receiver coils are toroidal coils with at least one turn, wherein a change of the receiver coils penetrating magnetic flux an induction voltage to each case in particular two terminals causes at least one turn of the receiver coils. The substrate used may be semiconductor substrates, ceramic substrates or glass substrates. This opens up the possibility of forming receiver coils small enough so that in the magnetically active surface of the receiver coils the basic field B0 has a homogeneity which lies in the abovementioned range of 10 ^-6 and smaller. In addition, the exact position of individual receiver coils to the basic field can be determined exactly by the arrangement on a substrate or chip. It is Z. B. conceivable, on an area of z. B. 1 × 1 mm 100 coils field-like or matrix-shaped. It is also conceivable to integrate separate amplifier circuits on a semiconductor chip for individual or all receiver coils which are arranged on the chip.

to Preparation of the basic field B0 can z. B. a permanent magnet used come.

Under the term "body fluid" is according to the invention both an intracellular as well as extracellular fluid Understood. In particular, it is possible with the present device the ability to continuously monitor the blood sugar levels of patients, who suffer from diabetes mellitus and to measure other people, whose blood sugar levels need to be monitored, eg. During heavy physical stress.

The Basic field B0 can z. B. by an arrangement of two permanent magnets, which are opposite, be provided. Also Magnetic coils are conceivable to form the basic field B0. The time-varying magnetic field B1 can be replaced by one or more additional coils are generated, which are aligned in the Ideally, the resulting field is perpendicular to the basic field B0. The measurement of the nuclear magnetic resonance response is carried out by the plurality the coils arranged on the substrate.

If z. For example, given a basic field B0 of 1.4 Tesla, the center frequency of the nuclear spin response is about 60 MHz for the ¹ H resonance, 15 MHz for the ¹³ C resonance, or 24 MHz for the ³¹ P resonance. From the spectrum obtained can be derived the concentrations of water ( ¹ H spectrum), sugar ( ¹ H and / or ¹³ C spectrum), cholesterol ( ¹ H and / or ¹³ C spectrum), ATP (adenosine triphosphate ³¹ P spectrum) and other blood components become. The concentration of water is used for calibration for the individual measurement of relevant blood components.

Provided inexpensive permanent magnets or coils for use come to create the basic field B0, is the homogeneity limited to the basic field, which, where appropriate, the required resolution the signals can not be reached. To solve this problem, may be the magnetically effective area of the receiver coils be reduced. Preferably, a plurality of receiver coils a maximum magnetically effective geometric dimension in the basic field less than 100 microns, preferably 50 microns. The geometric dimension relates z. B. on one side or a diameter. If necessary, the size the coils also be one or two 10 powers smaller. In A preferred embodiment of the invention is the magnetic effective area of the receiver coils by at least 4, preferably 5 or 6 or more orders of magnitude smaller than one from the main field of the first magnetic field means flooded surface.

In a particularly preferred embodiment of the invention, the device is designed as a portable hand-held device. Preferably, the handset has a volume of <1000 cm ³ .

In order to it is possible, the inventive Use device in a variety of places, eg. For example a running measurement in a diabetic during a physical effort.

in the Further, it is preferred if control means are provided which using the position of the receiver coils in the Basic field B0 by superposition of single signals of Receiver coils generate a total signal. Depending on the position the respective receiver coil in the basic field must have the signal the receiver coils when superimposed to a total signal be weighted. Because about the area of all receiver coils may the basic field B0 change, which is only possible when using a coil on the same area a lot too Great inaccuracy would cause to mess with sufficient precision to meet measurement specifications can. For a weighted single receiver coil However, a required homogeneity can be maintained.

In a further particularly preferred embodiment, control means are provided and designed to generate a pulsed time-variant field B1 on a sample and to measure the nuclear magnetic resonance response with the receiver coils. In this connection, it is preferable that the control means carry out the nuclear magnetic resonance response for each of a plurality of receiver coils in the frequency domain by a fast filter rier transformation for the preservation of the spectrum. The individual spectra are then preferably weighted with respect to the position in the basic field B0 combined into an overall spectrum.

In A preferred embodiment of the invention is the device designed as a portable handset to take measurements on extremities like a finger, an earlobe or any other suitable part of a human body to be able to.

Around even larger inhomogeneities in a basic field To allow B0 are preferably the dimensions the receiver coils in the lower micrometer range up to the nanometer range settled.

To determine an absolute concentration of a body fluid fraction, the measurement of the ¹ H NMR intensity of water can be used as a reference.

The Generation of the time-varying field B1 can with several Coils take place. One or more of these coils can also be used as a receiver.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• US 4875486 [0008]
• - US 6163154 [0009]
• US 6404197 [0009]

Claims (8)

A device for the non-invasive measurement of body fluid fractions using nuclear magnetic resonance spectroscopy comprising: first magnetic field means to provide a basic static field B0, second magnetic field means for generating a transversely, in particular perpendicularly to the basic magnetic field B0 aligned time-varying magnetic field B1 and receiver coils whose spanned coil surface transversely , In particular perpendicular to the orientation of the basic field B0 extends, characterized in that a plurality of receiver coils on a substrate, in particular semiconductor chip are arranged, and that the receiver coils are toroidal coils with at least one turn, wherein a change of the receiver coil penetrating magnetic flux to an induction voltage respective terminals of the at least one turn of the receiver coils causes. Device according to claim 1, characterized in that that a large number of receiver coils maximum magnetic effective geometric dimensions of <100 microns, preferably 50 microns exhibit. Device according to one of the preceding claims, characterized in that the magnetically active surface the receiver coils by at least 4, preferably 5 or 6 powers of ten is smaller than one of the main field of the first magnetic field means flooded area. Device according to one of the preceding claims, characterized in that the device is a portable hand-held device is designed. Device according to one of the preceding claims, characterized in that control means are provided under Using the position of the receiver coils in the basic field B0 by superposition of individual signals of the receiver coils generate a total signal. Device according to one of the preceding claims, characterized in that control means provided and designed are a pulsed time-varying field B1 at one To generate sample and the nuclear spin response with the receiver coils to eat. Device according to one of the preceding claims, characterized in that control means present and designed are at known positions of the receiver coils in the basic field B0, although of inhomogeneities of the Basic field B0, individual signals of the receiver coils to one To be able to combine the total signal. Device according to one of the preceding claims, characterized in that control means are provided which in are able to measure the measured nuclear magnetic resonance response for each of a plurality of receiver coils in the frequency domain through a fast Fourier transform for obtaining a Evaluate spectrum.