DE102007014583B3 - Blood components concentration determination device for diagnosing micro-vascular damages, has computing device computing absorption of emitted measuring radiation based on measured reflected and transmitted radiation portions - Google Patents

Abstract

The device (10) has a radiation source (12) e.g. LED, for emitting a measuring radiation (14) towards body parts (16) i.e. finger, to be examined. A receiver (18) receives radiation (20) reflected through the body parts, and another receiver (22) receives radiation (24) transmitted through the body parts. A computing device (26) connected with the two receivers computes absorption of the emitted measuring radiation based on the measured reflected and transmitted radiation portions. An independent claim is also included for a method for operating a device for determining concentrations of different blood components in a bloodstream.

Description

• – sauerstoffungesättigtes Hämoglobin (RHb)
• – sauerstoffgesättigtes Hämoglobin (O₂Hb)
• – Carboxy-Hämoglobin (COHb)
• – Methämoglobin (MetHb)

The invention relates to a device for determining concentrations of various blood constituents, and to methods of operating such a device. For medical purposes, it is often necessary to determine the concentration of hemoglobin in the blood. For example, 38.5% of human blood consists of hemoglobin in the dry matter (ie, all unbound water is withdrawn) and about 15% in wet mass (ie, normal physiological state). Hemoglobin again has four other constituents:

• Oxygenated hemoglobin (RHb)
• Oxygen-saturated hemoglobin (O ₂ Hb)
• - carboxy-hemoglobin (COHb)
• - Methaemoglobin (MetHb)

The However, the invention can also be used to determine the concentration of others Blood components are used. All related to hemoglobin mentioned features thus also for measuring the concentration of further blood components be used.

It is known to determine the hemoglobin content in the blood a Hb-Fotometer to use. The Hb photometer has a capillary gap, the filled with a chemical reagent is. A small amount of blood, for example a drop of blood, is fed to this capillary gap and changes its translucency due to the chemical decomposition. The change the translucency can be detected photometrically.

A Such device has the disadvantage that the patient to review the Hb value blood must be taken.

US 5,297,548 describes a device for the noninvasive examination of blood parameters, wherein a measuring radiation with different wavelengths is emitted in the direction of a body part to be examined. On the side of the body part opposite the radiation source, two radiation receivers arranged one above the other are provided, which measure the radiation transmitted through the body part to be examined.

CA 2 221 968 describes a device for the non-invasive determination of blood components in a bloodstream, wherein two are provided at a small distance juxtaposed radiation sources. Coaxially disposed around these radiation sources are a plurality of radiation receivers. For example, to determine the blood oxygen content, the radiation reflected from a body part to be examined is measured.

task The invention is an apparatus for non-invasive detection the concentrations of various blood components as well as a procedure to provide for operating such a device.

The solution The object is achieved according to the invention by the features of the device claim 1 and the method claim 22.

A Apparatus for continuous noninvasive determination of concentrations Different blood components have a radiation source for emitting a measuring radiation in the direction of a body part to be examined, such as a human finger. In the measuring radiation it can be electromagnetic radiation, such as Light in the visible range, and / or near infrared radiation Act infrared range. The device further has a first one Radiation receiver for Receiving radiation reflected by the body part to be examined on. Furthermore, a second radiation receiver for receiving by the body part to be examined provided transmitted radiation. The device also has a calculation device connected to the first and the second radiation receiver for the calculation of the absorption by the body part to be examined the emitted radiation based on the measured reflected and transmitted radiation component. At the calculation facility For example, it could be a computer. The calculation the part of the body to be examined in particular, absorption of the emitted radiation can take place take place in the computing device such that an interaction the calculation device with the body part to be examined is not required. For example, the calculation device as a device be trained on which runs a specific software program.

Of the Invention is based on the idea that the various components of the blood, for example the hemoglobin and the water, absorbing radiation to varying degrees. In particular, certain wavelengths of radiation exist, for example of light, where the absorption of the different Blood components particularly significantly different. A selection the radiation source emitting such a wavelength, can improve the results of the device according to the invention. When using a single wavelength, instead of the concentrations different blood components only a volume pulse course be determined.

• 1. Absorption
• 2. Transmission
• 3. Reflexion

The emitted measuring light enters the tissue in which different interactions take place:

• 1. absorption
• 2. Transmission
• 3. Reflection

The sum of the three optical gradients is always 100% or 1, according to the following formula: 1 = τ + α + φ (1) in which

wobei:

E

= Extinktion

I

= austretende/durchgelassene Intensität

I₀

= einfallende Intensität

ε

= molarer Extinktionskoeffizient

c

= Konzentration

d

= Schichtdicke

The theoretical basis of the invention is the Lambert-Beer law:

in which:

e

= Absorbance

I

= leaking / transmitted intensity

I ₀

= incident intensity

ε

= molar extinction coefficient

c

= Concentration

d

= Layer thickness

The Lambert-Beer's law describes how the radiation intensity in the passage through an absorbent depending on the concentration the substance behaves. The extinction results from the ratio of the transmitted to the incident light.

Thus, according to the invention through the first radiation receiver Radiation measured by the body part to be examined is reflected. Furthermore, by the second radiation receiver radiation measured, which is transmitted through the body part to be examined. Subsequently is calculated with the help of the calculation device that works with the first and the second radiation receiver connected, based on the absorption of the emitted radiation the measured reflected and transmitted radiation component calculated.

Since the various blood components, as mentioned above, absorb different wavelengths of radiation different degrees, with appropriate choice of the wavelength used on the basis of the measured absorbance with the help of further calculations, the concentration of different Blutbe components are determined. Preference is given to the use of a radiation source through which radiations of different wavelengths can be emitted.

Especially it is preferred that the radiation source and the first radiation receiver for Receiving radiation reflected by the body part to be examined on the same side of the body part to be examined. The second radiation receiver for receiving the transmitted radiation can then the first radiation receiver across from lying on a second side of the body part to be examined be arranged.

Around a more accurate measurement of hemoglobin concentration to allow in the blood and / or to allow a measurement of the concentration of hemoglobin derivatives, it is further preferred that the radiation source several individual radiation sources different wavelength having. The individual radiation sources can be used, for example, as LEDs, Laser diodes or white light LEDs with filter, be formed. This feature is particularly advantageous because different hemoglobin derivatives at certain wavelengths particularly striking differences in the degree of absorption having the emitted radiation. It is particularly advantageous to measure these wavelengths to use in which the difference in the degree of absorption of different Hemoglobin derivatives or other blood components, such as water, especially is great.

• • 540 nm ± 5 nm, 562 nm ± 5 nm, 573 ± 5 nm zur Unterscheidung von Carboxyhämoglobin von oxygeniertem Hämoglobin
• • 623 ± 5 nm zur Unterscheidung von Methämoglobin von oxygeniertem Hämoglobin
• • 660 nm ± 10 nm zur Unterscheidung aller Hämoglobinderivate voneinander, da bei dieser Wellenlänge alle Bestandteile unterschiedliche Absorptionsgrade aufweisen
• • 805 nm ± 10 nm zur Unterscheidung von Gesamthämoglobin von Wasser, da bei dieser Wellenlänge nur Hämoglobin absorbiert, nicht aber Wasser
• • 950 nm ± 10 nm als Referenzpunkt, da hier alle Bestandteile einen gleichen Absorptionsgrad aufweisen (isosbestischer Punkt)
• • 1200 nm ± 50 nm zur Unterscheidung von Wasser von Gesamthämoglobin, da bei dieser Wellenlänge nur Wasser absorbiert, nicht aber Hämoglobin Zur Berechnung der Konzentrationen der fünf Blutbestandteile (vier Hämoglobinderivate, Wasser) wären eigentlich nur fünf Wellenlängen notwendig. Es ist jedoch bevorzugt, die oben genannten acht Wellenlängen zu verwenden.

The use of single radiation sources to emit different wavelengths enables a particularly accurate measurement of the concentration of various blood components, since a measurement can be made precisely at those wavelengths in which particularly striking differences in absorption occur. For example, the following wavelengths have proven to be particularly advantageous for measuring the hemoglobin derivatives:

• • 540 nm ± 5 nm, 562 nm ± 5 nm, 573 ± 5 nm to distinguish carboxyhemoglobin from oxygenated hemoglobin
• • 623 ± 5 nm for distinguishing methemoglobin from oxygenated hemoglobin
• • 660 nm ± 10 nm to distinguish all hemoglobin derivatives from each other, since at this wavelength all components have different degrees of absorption
• • 805 nm ± 10 nm to distinguish total hemoglobin from water, as only hemoglobin absorbs at this wavelength, but not water
• • 950 nm ± 10 nm as reference point, since all components have the same absorption coefficient (isosbestic point)
• • 1200 nm ± 50 nm to differentiate water from total hemoglobin since only water absorbs at this wavelength, but not hemoglobin. To calculate the concentrations of the five blood components (four hemoglobin derivatives, water), only five wavelengths would actually be needed. However, it is preferable to use the above-mentioned eight wavelengths.

• 1. Absorptionseigenschaften der Hämoglobin-Derivate
• 2. Absorptionseigenschaften des Wassers
• 3. Eindringtiefe bzw. Durchlässigkeit der Haut für bestimmte Wellenlängen
• 4. Isosbestische(r) Punkt(e) im Absorptionsspektrum der unterschiedlichen Derivate

In order to be able to determine various parameters of the blood composition with respect to hemoglobin, several discrete wavelengths must be irradiated quasi-parallel into the tissue. The choice of the wavelengths is based, as already partially described, by the following dependencies:

• 1. Absorption properties of hemoglobin derivatives
• 2. Absorption properties of water
• 3. Penetration depth or permeability of the skin for specific wavelengths
• 4. Isosbestic point (s) in the absorption spectrum of the different derivatives

5. Technical possibilities the radiation sources

Especially the selection of the wavelengths used is preferred optical windows for the Skin considered. This is due to human skin in a wavelength range from about 350 nm to 1650 nm.

in the Below are further preferred features of the device according to the invention described.

Especially Preferably, the device is designed such that the first and the second radiation receiver opposite each other are arranged, so that between the first and the second radiation receiver, a receiving space is designed for receiving the body part to be examined. The Radiation source and the first radiation receiver can be arranged in a plane be.

Especially it is preferred that the radiation source as a light source, for example formed by LEDs and the first and second radiation receiver as Light receiver, for example, form as photodiodes.

The LEDs can, in particular circular around the first light receiver be arranged on the first side of the receiving space.

A particularly uniform illumination of the body part to be examined can be achieved in that the radiation source at least each having two individual light sources of the same wavelength, which are arranged diametrically. If due to a large number used wavelengths design-wise not the possibility consists of two single light sources of the same wavelength diametrically to arrange can also work with a single light source per wavelength become. It is particularly preferred in this context, the of the first light receiver away-facing side of the individual light sources in particular by one Raise angle of 15 °, so that the emitted radiation of the individual light sources a point at which the body part to be examined, such as a human finger, is located.

Around To avoid detection differences are the first and the second light receiver in particular of the same type and can, for example, as photodetectors be educated. To the relatively broad wavelength range of, for example 400 nm to cover 1650 nm, a two-color detector is preferably used. This includes, for example, a silicon receiver surface a wavelength range of 400 nm to 1100 nm, and, for example, an indium gallium arsenide receiver surface with a wavelength range from 1000 nm to 1700 nm. But it can also be a detector with For example, three receiver surfaces different Materials are used. It is important that the total area from 350 nm to 1650 nm.

Around to prevent direct stray light (shunt light) at first light receiver meets, the light source from the first light receiver through a separating device, in particular by an opaque inner and outer sleeve, separated. The inner wall of the outer sleeve is with a white one Coating provided to homogenize the light to be emitted. The sleeve can be conically shaped so that the radiation is at a defined level area (corresponds approximately to the area a finger berry) can be irradiated. It is still conceivable that in particular the reflection sensor two close together lying receiver so as to confound, which can be derived from the difference between the two signals obtained (Tissue, scattering, etc.).

Out hygiene, and for better handling the pods be glued firmly to the light source and the first light receiver. Farther can between the pods lying cavities with a, in particular transparent, scratch-resistant, hard and / or biocompatible adhesive filled be. The adhesive can be slightly curved inwards (concave) with the sleeve. This Opposite arrangement the transmittive radiation receiver is arranged.

The Device may have a first and a second receiving element, the recording room on its first and second page respectively limit. It can the first and the second receiving element by a clamping mechanism be connected to each other such that attaching the device on the body part to be examined, as on a finger, can be done.

Especially it is preferred to float the first and the second radiation receiver store so that optimal contact with the to be examined body part guaranteed and a consistent reproducible contact pressure can be achieved can. In particular, it should be noted that the first and the second radiation receiver directly on the body part to be examined or on the coupling medium issue.

Especially it is preferred to use a fiber optic cable for optical coupling between to use the LEDs and the skin or between the skin and the recipient surfaces, to get the light on as possible to focus on a small measuring area.

To improve the signal quality, the device according to the invention can be designed such that an automatic continuous tracking of the radiation intensity of the radiation sources, for example the transmission LEDs, takes place per channel used. If the output signal is too small or too large, the transmission power is automatically amplified or attenuated. This factor must quantitatively reproduce be able to be included in the evaluation of the signal can. The same principle can also be applied to the intensity of the radiation receiver, in particular the two-color detectors. Thus, for example, eight readings for the eight LEDs used (eight wavelengths) and four readjustments for the detectors used (transmittive and reflective, in each case for two receiver surfaces) can take place.

All Features described in the present application with respect to the inventive methods can also be the device of the invention and have vice versa.

The inventive device can for a variety of applications are used. For example a use of the described device for continuous noninvasive determination of hemoglobin concentration possible. Furthermore, a use of the device for the diagnosis of microvascular damage possible. Another possible Use concerns continuous non-invasive detection of blood pressure. Details regarding the possible Uses of the device according to the invention in the application also filed by the Applicant "Continuous non-invasive method Determination of the concentration of blood components "as well as in the application" Procedure for the determination of microvascular Damage " can the device of the invention for further in particular also uses diagnostic or medical procedures become.

Especially is the device according to the invention suitable for a volume pulse course of one or more blood components to investigate. From the determined volume pulse progressions and in particular from the form of a volume pulse curve can further medical findings, such as the blood pressure of a Patient or information about a presence of microvascular damage, be derived. The volume pulse course of a single blood component can for example be determined using a single wavelength become. The measured course corresponds to the absorption at the wavelength used the volume pulse course of the blood component to be determined. Around to allow accurate detection of the volume pulse waveform The choice of the wavelength used must be as shown above Criteria are made.

A independent The invention relates to a method for operating a device for determining concentrations of various blood components. In this case, a device can be used, as in the present Registration is described. Essential feature is that the Device has at least one radiation source for emitting several measuring radiations of different wavelengths suitable is. In the method according to the invention the radiation source is used to emit a measuring radiation each one wavelength in particular switched on sequentially. This means that the Radiation source is driven such that they each successively emits a measuring radiation with a specific wavelength. Especially In this context, the radiation source can consist of several individual radiation sources. such as LEDs, for emitting a measuring radiation with each one wavelength be educated. Alternatively to a sequential emission of a Measuring radiation, each with a wavelength, can be a radiation source be provided for the simultaneous emission of measuring radiation different wavelengths suitable is. The first and second radiation receiver used here must be designed such that they are for separately receiving the measuring radiation the individual emitted wavelengths are suitable. This can be realized for example by providing a plurality of individual radiation receiver are where everyone, for example with the help of a frequency filter on certain frequency band of the emitted radiation receives. Prefers However, it is that every wavelength is broadcast sequentially.

Farther takes place in the inventive method receiving the measuring radiation reflected by a body part to be examined every wavelength by a first radiation receiver. Furthermore, a reception takes place the part of the body to be examined transmitted measuring radiation of each wavelength by a second radiation receiver. Subsequently, will the part of the body to be examined absorption of the emitted radiation for each wavelength determined. This determination is based on the measurement of the reflected Radiation through the first radiation receiver and the measurement of the transmitted Radiation through the second radiation receiver.

Incidentally, can the inventive method all Features associated with the device of the invention have been described.

In particular, the method preferably comprises storing the determined absorption values of each wavelength and repeating the previously mentioned method steps, wherein the determined absorption values of each wavelength for each repetition cycle. Subsequently, the individual absorption values of the emitted radiation for each wavelength are summarized to show a time profile of the absorption at each wavelength. This representation can take place, for example, in the form of a curve or in the form of a table and is referred to as a volume pulse profile.

The Storing the determined absorbance values of each wavelength for each Repeat cycle, summarizing the absorbance values for each wavelength Representation of a temporal course of the absorption and the representation This course is preferably carried out in a calculation device such that the computing device does not interact with the body part to be examined or with the body a patient stands.

Prefers is that at least as many wavelengths as the number of too determining blood components are used. For example the concentration of the four mentioned Hemoglobinderivate and the Water in the blood to be determined, it is necessary at least five different wavelength to use. Possible Methods for the determination of the concentration ratios of the constituents of the For example, blood is the determination by linear systems of equations, the determination with the help of the heuristic deluge algorithm, as well as the determination by correlation. These methods will be in the embodiments closer to the present application explained. Common to all is the use of various characteristic ones Wavelengths, so finally a volume pulse course for a variety of individual blood components can be determined. In practice, to determine the concentration of individual blood components not the entire volume pulse course is determined for each blood component, but only different absorption values at prominent points the volume pulse curves the wavelengths used.

• a. sequentielles Ausstrahlen mehrerer Messstrahlungen mit jeweils verschiedenen Wellenlängen,
• b. Empfangen der durch ein zu untersuchendes Körperteil reflektierten Messstrahlung jeder Wellenlänge durch ein ersten Lichtempfänger,
• c. Empfangen der durch das zu untersuchende Körperteil transmittierten Messstrahlung jeder Wellenlänge durch einen zweiten Lichtempfänger,
• d. Ermitteln der durch das zu untersuchende Körperteil erfolgten Absorption der Strahlung auf Basis der Messung der reflektierten Strahlung durch den ersten Strahlungsempfänger und der Messung der transmittierten Strahlung durch den zweiten Strahlungsempfänger
• e. Mehrmaliges Wiederholen der Verfahrensschritte a bis d, wobei die jeweiligen Absorptionswerte für jede Wellenlänge der Messstrahlung für jeden Wiederholungszyklus gespeichert werden,
• f. Zusammenfassen der gespeicherten Absorptionswerte zu einer Darstellung des zeitlichen Verlaufs der Absorption (Volumenpulsverlauf) für jede verwendete Wellenlänge der Messstrahlung.

In summary, the method according to the invention can comprise the following steps:

• a. sequentially emitting a plurality of measuring radiations, each having different wavelengths,
• b. Receiving the reflected by a body part to be examined measuring radiation of each wavelength by a first light receiver,
• c. Receiving the transmitted by the body part to be examined measuring radiation of each wavelength by a second light receiver,
• d. Determining the absorption of the radiation by the body part to be examined on the basis of the measurement of the reflected radiation by the first radiation receiver and the measurement of the transmitted radiation by the second radiation receiver
• e. Repeating steps a through d several times, storing the respective absorbance values for each wavelength of the measuring radiation for each repetition cycle,
• f. Combining the stored absorption values to a representation of the time course of the absorption (volume pulse profile) for each wavelength of the measuring radiation used.

Especially the method steps d and f take place in a calculation device such that the computing device does not interact to the body part to be examined stands.

in the The following are preferred embodiments the inventions explained with reference to figures.

It demonstrate:

1 a schematic representation of a reflection measurement,

2 a schematic representation of a transmission measurement,

3 a schematic representation of the device according to the invention for determining concentrations of various blood components,

4 a graphic representation of the penetration depth of optical radiation into human skin,

5 a schematic representation of the first receiving element of the device according to the invention,

6 a sectional view of the first radiation receiver,

7 and 8th a graphical representation of the detector areas of the radiation receiver,

9 a schematic representation of the control of the individual radiation sources and the radiation receiver,

10 a schematic representation of the readout behavior of the radiation receiver,

11 a graphic representation of volume pulse progressions at different wavelengths,

12 a schematic representation of a calibration device for the reflexive receiver,

13 a schematic representation of a calibration device for the transmittive receiver,

14 a graphical representation of the light intensities to calculate the factors for the normalization of the volume pulse curves, and

15 a graphical representation of the calculated factors for the normalization of the volume pulse curves.

A device for the continuous determination of volume pulse curves in different blood components has a radiation source 12 for emitting a measuring radiation 14 in the direction of a body part to be examined 16 on ( 3 ). The body part to be examined is particularly preferably 16 around a human finger. Alternatively, however, for example, the earlobe of a person, as well as other suitable body parts can be used for measurement.

Furthermore, the device 10 a first radiation receiver 18 for receiving by the body part to be examined 16 reflected radiation 20 on. The first radiation receiver is in the illustrated embodiment in the first receiving element 28 arranged. In this first receiving element 28 is also the radiation source 12 arranged.

The device 10 also has a second radiation receiver 22 for receiving by the body part to be examined 16 transmitted radiation 24 on. The second radiation receiver 22 is in the illustrated embodiment in the second receiving element 30 that the first receiving element 28 opposite, arranged. Opposite in this context means that the two receiving elements 28 . 30 , as well as the first 18 and the second 22 Radiation receiver are arranged such that, for example, a finger 16 can be positioned between them.

In 1 the reflection measurement carried out with the aid of the device according to the invention is shown schematically. In this case emits the radiation source 12 a measuring radiation 14 , The radiation source 12 may preferably be a plurality of LEDs 12a to 12h be educated. The emitted measuring radiation 14 becomes through the body part to be examined 16 at least partially reflected, so that a portion of the measuring radiation 14 as reflected radiation 20 in the direction of the first radiation receiver 18 is reflected.

The measurement of the part of the body to be examined 16 transmitted radiation 24 is in 2 shown schematically. This is also due to the radiation source 12 a measuring radiation 14 in the direction of the body part to be examined 16 emitted. At least a portion of the radiation 14 happens to be examined body part 16 and hits as transmitted radiation 24 on the second radiation receiver 22 , The first 18 and the second 22 Radiation receivers are preferably designed as photodiodes.

The device also according to 3 a calculation device 26 on that with the first one 18 and the second 22 Radiation receiver is connected. The measured reflected 20 and intermittent 24 Radiation component is the calculation device 26 supplied, so that these on the basis of the measured radiation components through the body part to be examined 16 followed absorption of the emitted radiation 14 can determine. This determination is preferably based on the Lambert-Beerschen law (formula 2).

The calculation device 26 For example, it may be embodied as a PC running a specific software program for performing the above calculations. In particular, these calculations can also be made on a PC at a different time than the measurement of the transmitted and reflected radiation. Thus, the calculation steps essential to the invention take place independently of the physical detection of the patient features described so far.

Particularly preferred is the device 10 according to 5 formed such that the radiation source 12 several individual radiation sources 12a to 12h having. These individual radiation sources can be designed as LEDs and around the first radiation receiver 18 be arranged circularly around.

According to the 5 and 6 is the first light receiver 18 within a particular circular separation device 32 arranged, which has an inner opaque sleeve 32a and an outer opaque sleeve provided with a white coated inner wall 32b , may have. The LEDs 12a to 12h are in a gap 33 between the inner sleeve 32a and the outer sleeve 32b arranged. The LEDs are at their from the first light receiver 18 turned away side by an angle of 15 °. As a result, the emitted measuring radiation is bundled on a point on which the body part to be examined is located 16 located.

In particular, the inner run 32a and the outer sleeve 32b in a lower section 34 , starting from a base plate 36 , such as a board, vertically upwards and continue to run in an upper section 35 bent inwardly at an angle β, ie in the direction of the first radiation receiver 18 , This arrangement in conjunction with the raising of the LEDs, for example, by an angle of 15 ° ensures that only a narrow gap 37 is available, through which the emitted measuring radiation 14 in the direction of the body part to be examined 16 can radiate. This can be effectively avoided that stray light (shunt light) directly from the light source 12 in the direction of the first radiation receiver 18 shine. The aim of this measure is that the first radiation receiver 18 only the radiation 20 receives through the body part to be examined 16 is reflected.

Between the inner sleeve 32a and the outer sleeve 32b is a cavity 33 formed in which the LEDs 12a to 12h for example, on the board 36 are attached. This cavity 33 For example, it can be filled with a transparent adhesive.

• • 540 nm ± 5 nm, 562 nm ± 5 nm, 573 ± 5 nm
• • 623 ± 5 nm
• • 660 nm ± 10 nm
• • 805 nm ± 10 nm
• • 950 nm ± 10 nm
• • 1200 nm ± 50 nm

Based on the fact that different hemoglobin derivatives as well as the water in the blood can absorb different wavelengths differently the single light sources 12a to 12h be designed so that they emit the following wavelengths:

• 540 nm ± 5 nm, 562 nm ± 5 nm, 573 ± 5 nm
• • 623 ± 5 nm
• • 660 nm ± 10 nm
• • 805 nm ± 10 nm
• • 950 nm ± 10 nm
• • 1200 nm ± 50 nm

The emitted wavelengths are in the range in which, for example, human skin is radiolucent. This area is called an optical window and lies in a wave range from approx. 350 nm to 1650 nm (see 4 ). Outside of this range, the absorption of the skin is so high that hardly any radiation can penetrate into the underlying tissue.

In order to cover the said wavelength range of about 400 nm to 1650 nm, are preferred as the first 18 and second 22 Radiation receiver so-called two-color detectors used. These are photodetectors with two wavelength ranges, each of which is designed as a receiver surface. The first receiver surface is designed as a silicon receiver surface, for example, and covers the wavelength range from 400 nm to 1100 nm. The second receiver surface is formed, for example, as an indium-gallium-arsenide receiver surface and covers the wavelength range from 1000 nm to 1700 nm. The two receiver surfaces are each in the first radiation receiver 18 and in the second radiation receiver 22 united.

A graphical representation of the detectable wavelength ranges of the receiver surfaces used is shown in FIGS 7 and 8th to find. In the 8th shown characteristics show two different indium gallium arsenide detectors. Particularly preferred is the use of the left detector (L 1713-05 / -09).

seven the eight wavelengths are detected by the silicon detector. Wavelengths over 1100 nm are accordingly detected by the indium gallium arsenide photodiode.

According to 3 it is preferred that the body part to be examined 16 in a recording room 38 is taken, which is between the first receiving element 28 and the second receiving element 30 located.

Furthermore, the device can be a clamping mechanism 40 , such as having a spring mechanism through which the first 28 and the second 30 Receiving element are connected to each other such that attaching the device 10 on the body part to be examined 16 can be done. For easier attachment of the device 10 , for example on a finger 16 , can be two actuation approaches 42 be provided.

Particularly preferred, the device 10 a control device 41 for sequentially switching on the individual light sources 12a to 12h on.

The following describes a method of operating a device for continuous non-invasive determination of blood component concentrations. In particular, this method is suitable for operating the device described so far 10 , It is essential that the device 10 at least one radiation source 12 for emitting a measuring radiation 14 having different wavelengths. As in 9 shown, there is a sequential switching on the individual radiation sources, such as the LEDs 12a to 12h for emitting a measuring radiation 14 each with a wavelength. These may, for example, be the wavelengths 540 nm, 562 nm, 573 nm, 623 nm, 660 nm, 805 nm, 950 nm and 1200 nm.

For example have hemoglobin derivatives as well as the water in human blood at these distinctive wavelengths in part particularly significant differences in their degree of absorption on.

According to the invention, receiving is carried out by a body part to be examined, such as a finger 16 , reflected measuring radiation 20 each using wavelength through the reflexive photodiode 18 that on the first page 15 of the finger 16 is arranged. The by the finger 16 transmitted radiation 24 each wavelength used is transmitted through the transmittive photodiode 22 received, the opposite of the reflective photodiode on the second side 17 of the finger 16 is arranged.

The driving of the LEDs 12a to 12h may be such that the wavelengths are switched on and off successively at a frequency of 1.2 KHz, so that no two different wavelengths light up at the same time. A selection of other suitable frequencies is also possible.

The Representation of the signals obtained can be either in the so-called Normal operation or in lock-in operation. The lock-in operation creates an improvement of the signal quality. To the lock-in procedure to be able to apply must be the lock-in amplifier once the signal is detected when the respective LED is turned on is and once when it is off. The clock numbers of the LEDs can Therefore, they differ from normal operation to lock-in operation. In lock-in operation, the drive frequency for the LEDs to the needed Adjusted frequency of the lock-in amplifier become.

The Lock-in principle is a method of filtering and amplification very much small signals. In this case, the reference signal becomes a reference signal known frequency and phase modulates, so that DC, AC voltages other frequencies and noise are eliminated.

Either in normal operation as well as in lock-in operation become a DC component (DC component / offset) and a pulse-shaped AC component (AC component) determined. The DC content is due to the physiological properties of the irradiated tissue. He is influenced by various causes, such as tissue properties, blood vessels without pulsatile portion (venules etc.). At this offset lies the pulse-shaped AC component (alternating component), which is due to the volume change of the blood.

Of the DC component can be taken into account as a correction component. An additional Option is the use of analog or digital filters for separation of the AC and DC components. In principle, this should be possible in both modes but at least in normal operation done to a sufficient signal quality to gain, because otherwise all disturbances are amplified.

In 9 is the clock behavior of the LEDs 12a to 12h and the tactics of the reflexive 18 as well as the transmittive 22 Photodiode shown.

It is a so-called sample-and-hold operation shown, wherein in the lower half of the figure, two detector signals of the two detector surfaces used for each wavelength range imaged are. The silicon receiver surface covers the wavelength range from 400 nm to 1100 nm, while the indium-gallium arsenide receiver surface covers the wavelength range from 1000 to 1700 nm. When the LEDs are turned on at 540, 562, 573, 623, 660, 805, and 950 nm, respectively, the reflected 20 and the transmitted 24 Measuring radiation detected by the silicon receiver surface. The value of the signal present at each time at the detector is recorded for each wavelength (sample), held (hold) and stored until the wavelength is addressed again. The same is done by incorporating the LED with 1250 nm, and the indium gallium arsenide sensor in the same clock regime. This procedure is repeated so that the individual samples (values) can be further processed. This happens as in 10 shown, one after the other for each wavelength, where in 10 only five wavelengths are shown. According to the embodiment described so far eight wavelengths or more or less wavelengths can be used. However, the absorption of the wavelengths used is read out analogously to the five wavelengths in 10 , Furthermore, according to 10 other suitable detector ranges are selected.

Thus, in the first cycle, for example, eight wavelengths are emitted, their more reflexive 20 and transmissive 24 Measured light content and then stored. With the aid of the further read-out values from the following repetition cycles, the individual absorption values of the emitted radiation are summarized 14 for each wavelength representing a time course of absorption at each wavelength (volume pulse curve).

It is not necessary a separate volume pulse curve for each the five to determine the blood components to be determined. At most wavelengths you get one Mixed signal (sum volume pulse) from the absorption of all blood components. Based on the recorded absorption-amplitude ratios to each other can Using the discrete substance- and wavelength-specific extinction coefficients the concentration ratios the blood components to each other in several ways. The extinction coefficients can depending on the amount of substance per volume, as well as on mass per volume Respectively. As a result, the ratios to be calculated correspond either the mass ratios or the volume ratios the individual blood components per volume.

A_g

= Gesamtabsorption

A_b1

= Absorption von Blutbestandteil 1

A_b2

= Absorption von Blutbestandteil 2

A_bn

= Absorption von Blutbestandteil n

A first possibility for determining the concentration ratios is provided by linear systems of equations. Assuming that the total absorption corresponds to the sum of the individual absorbances, the following equation can be established: Ag = A b1 + A b2 + ... + Abn (3)

A _g

= Total absorption

A _b1

= Absorption of blood component 1

A _b2

= Absorption of blood component 2

A _bn

= Absorption of blood component n

A_bn

= Absorption des Blutbestandteils n

E(λ, bn)

= Absorptionskoeffizient des Blutbestandteils n bei der Lichtwellenlänge λ

C_bn

= Konzentration des Blutbestandteils n

The intensity of the absorption of a particular wavelength of light is directly proportional to the concentration of the constituent blood component and proportional to the absorption coefficient of the constituent blood at the given wavelength, that is, the higher the concentration of substance per given volume or the higher the value of the absorption coefficient, the greater the absorption , A bn = E (λ, bn) · C bn

A _bn

= Absorption of the blood component n

E (λ, bn)

= Absorption coefficient of the blood component n at the light wavelength λ

C _bn

= Concentration of blood component n

The proportional absorptions of the initial equation (3) can be replaced accordingly and equation (3) can also be expressed in the following form: Ag = E (λ, b1) · C b1 + E (λ, b2) · C b2 + ... + E (λ, bn) (4) · C _bn

In each case, the measured total absorption at each wavelength of light used and the respective absorption coefficient associated with the blood constituent at the wavelength of light used are known. U.N known and to be determined are the respective proportions of the substance concentrations.

Corresponding the equation (4) can now set up a n · n system of equations be to the individual proportions of the blood components in the total volume to determine.

If 5 different concentrations are to be determined, at least 5 different wavelengths of light must be measured in order to be able to solve the equation uniquely. This results in a linear 5 × 5 equation system, which is clearly solvable. Ag (λ1) = E (λ 1 , b 1 ) · C b1 + E (λ 1 , b 2 ) · C b2 + E (λ 1 , b 3 ) · C b3 + E (λ 1 , b 4 ) · C b4 + E (λ1, b 5 ) · C b5 Ag (λ2) = E (λ 2 , b 1 ) · C b1 + E (λ 2 , b 2 ) · C b2 + E (λ 2 , b 3 ) · C b3 + E (λ 2 , b 4 ) · C b4 + E (λ 2 , b 5 ) · C b5 Ag (λ3) = E (λ 3 , b 1 ) · C b1 + E (λ 3 , b 2 ) · C b2 + E (λ 3 , b 3 ) · C b3 + E (λ 3 , b 4 ) · C b4 + E (λ 3 , b 5 ) · C b5 Ag (λ4) = E (λ 4 , b 1 ) · C b1 + E (λ 4 , b 2 ) · C b2 + E (λ 4 , b 3 ) · C b3 + E (λ 4 , b 4 ) · C b4 + E (λ 4 , b 5 ) · C b5 Ag (λ5) = E (λ 5 , b 1 ) · C b1 + E (λ 5 , b 2 ) · C b2 + E (λ 5 , b 3 ) · C b3 + E (λ 5 , b 4 ) · C b4 + E (λ 5 , b 5 ) · C b5 (5)

Solving the system of equations via matrices or substitution and employing the corresponding coefficients and the results of the absorption measurement gives directly the discrete substance concentrations C _b1 to C _b5 .

One second option to determine the concentration ratios offers the heuristic Flood algorithm.

It become eight different wavelengths used, in each case the associated total absorption measured becomes. Important here are not the absolute measured values, but the relations of the measured values to each other, which in the deluge algorithm be used. The readings are scaled to the highest absorption 100% corresponds. Each additional absorption has the remaining 7 wavelengths therefore a value less than 100%.

It now becomes a first random, theoretically possible Blood composition accepted.

Under Knowledge of substance-specific and wavelength-specific absorption coefficients the involved blood components becomes theoretically expected Total absorption calculated at each wavelength. Just like In the real measurement, the theoretical absorptions also become 100% scaled. This first calculated absorption spectrum becomes correlated with the real measured absorption spectrum. The result The resulting correlation coefficient forms the starting point of the algorithm.

Now In each round, the previous theoretically assumed blood composition becomes slightly changed and the resulting absorption spectrum again with the correlated measured absorption spectrum. This new correlation coefficient is compared to a slightly rising threshold per round.

exceeds the threshold value is the current correlation coefficient, so will discarded the newly determined theoretical blood composition and determined from the previous a new blood composition.

exceeds the threshold is not the current correlation coefficient, so the threshold is slightly raised, and the newly determined blood composition will be the starting point of the next Round used.

is no change the blood composition more possible, which not to exceed of the current threshold can, the algorithm is terminated.

It can be assumed that the current blood composition a good approximation the real measured blood composition corresponds.

Of the Algorithm can work multiple times with different border parameters and different ones Starting points executed to better verify the heuristically determined outcome to be able to.

The concentration ratios can continue to be determined by correlation.

Under Knowledge of substance- and wavelength-specific Absorption coefficient can be calculated assuming a theoretically possible Blood composition a corresponding expected total absorption at the individual wavelengths of light be calculated. Here again is the ratio of the absorptions to each other decisive.

• • Wasser 44–54%
• • Oxygeniertes Hämoglobin 50–100%
• • Nichtoxygeniertes Hämoglobin 1–50%
• • Carboxyhämoglobin 1–60%
• • Methämoglobin 1–70%

A set of such theoretically conceivable absorption spectra is calculated, each substance concentration to be determined being represented in each case from the minimum possible proportion up to the maximum possible proportion in small steps. These are in our case:

• • water 44-54%
• • oxygenated hemoglobin 50-100%
• • Non-oxygenated hemoglobin 1-50%
• • Carboxyhemoglobin 1-60%
• • Methemoglobin 1-70%

The Measured absorption spectrum will now be calculated with all that precalculated Spectra correlates. The theoretically determined concentration ratios the blood components of the spectrum in the set, which is best with correlated to the measured spectrum, correspond to a good approximation of the real concentration ratios.

The Accuracy of this method depends especially from the available computing power of the hardware. The more computing power to disposal stands, the finer you can the concentration gradations are chosen and the more accurate is the expected result.

Of the Advantage of this method the deluge algorithm is that the result is unique and not heuristic nature is, that is, there are under consideration a certain blur of the result, which is greater than Zero in the parameter distribution is unavoidable, certainly no possible better result than the specific.

At the Flood algorithm can not be assumed with certainty that the result obtained corresponds to the best result. This is compensated by the fact that the algorithm uses several different ones Is traversed starting points.

Of the The advantage of this method is that the result obtained by reducing the step size of the parameters just before the Provide a comparatively more accurate result at the end of the algorithm can be considered the method of correlation.

The starting point for the calculation methods explained are the volume pulse curves which were determined for each wavelength ( 11 ). The curves are divided into individual heart periods and for each period the maximum at each wavelength is determined. For each wavelength then an average of the maxima is formed. Thus, depending on the number of wavelengths used, there are five or more average absorption values, which are to be regarded as ratios to one another. With the aid of the aforementioned calculation methods, the proportionate concentration of the blood constituents can be calculated. From these concentrations, further parameters such as, for example, oxygen saturation, total hemoglobin concentration or the hematocrit value can be determined.

A more possible Application of the device according to the invention lies in a method for the diagnosis of microvascular damage.

In order to achieve a fundamental improvement of the measurement results, it is possible to calibrate the device at different time intervals. This can according to 12 a first calibration device 48 used, for example, is designed as a calibration sleeve for the reflexive receiver. The calibration of the device takes place to determine the actual light intensities of the LEDs initially without the body part to be examined.

For calibration of the reflexive radiation receiver 18 can be a hemispherical gauge sleeve 48 on the reflexive sensor 18 be positioned so that the emitting surface is included. The calibration sleeve 48 has a white inner surface 50 on, by which a diffuse reflection of the light is simulated, so that the light intensity of the individual LEDs 12a to 12h can be determined.

According to 13 can continue to calibrate the transmissive sensor 22 a particular cone truncated calibration sleeve 52 between the transmissive 22 and the reflexive 18 Receiver be positioned. The calibration sleeve also has a white inner surface 54 and further, a white membrane centrally placed between the two detector surfaces 56 on. The white membrane 56 prevents direct irradiation of the LEDs 12a to 12h on the transmittive receiver and simultaneously generates a non-directional diffuse light radiation. With the help of this measurement, the light intensities of the respective LEDs 12a to 12h in relation to the transmittive recipient 22 detected.

In 14c is the total measured light intensity of each LED 12a to 12h shown. This measurement is referred to as zero measurement and can be performed with the calibration sleeves shown above. In order to assume uniform radiation for further calculations, the intensities are normalized to 100%. This results in a normalization factor for the light intensity for each LED ( 15c ). This calibration measurement is done once for each sensor head and is performed again at defined time intervals, for example every two to three years. This method is due to the decrease in the light output of the light sources used, for example the LEDs.

To The calibration described may be the measurement on a body part respectively. In this case, a DC and a AC component is preferred detected. To compare the recorded pulsatile light absorptions can, have to they are dependent from the DC share for every wavelength be normalized. This is done at least once per measurement a determination of the DC component for each wavelength.

In 14b For example, the transmitted light component is shown. As can be seen, the vast majority of light has been absorbed by the tissue (bone, skin and its constituents, eg melanin degradation products of hemoglobin eg bilirubin, venules, etc.).

At the light intensities without fingers ( 14c ) will be like in 15 , light intensity factors (1.33, 1.25, 1.00, etc.) are determined. Furthermore, factors for the normalization of the DC component to 100% are determined (in 15 : 20.00; 33.33; 12.5; etc.).

The calculation takes place as shown in the following table: wavelength 542 nm 560 nm 577 nm 660 nm 805 nm 950 nm 1200nm Measurement of the AC component by peak detection from the pulse curve in percent 3 2 5 7 4 11 10 Multiplication with light intensity factor 4.00 2.50 5.00 5.83 3.81 12.22 6.67 Multiplication by DC component factor 80,00 83.33 62.50 58.33 54.42 81.48 55.56 Division by analog amplification 80,00 83.33 62.50 5.83 10.88 4.07 2.78 absolute intensity of the pulsatile AC component 80,00 83.33 62.50 5.83 10.88 4.07 2.78

At a wavelength of 542 nm, for example, a peak value of 3 AU (arbitrary unit) is measured. This peak value is multiplied by the light intensity factor (here 1.33) so that the result is 4 AU. Then this result is calculated with the DC component factor (here 20 multiplied). The obtained 80 AU are then divided by the analog gain of 1, each wavelength being characterized by its own gain (acc. 15 : 542 nm: 1; 560 nm: 1; 577 nm: 1; 660 nm: 10; 805 nm: 5; 950 nm: 20; 1200 nm: 20).

The absolute intensity of the pulsatile alternating component at 542 nm is thus 80.00 AU. For the rest wavelength the calculation of bills takes place according to the same principle, so that the normalized values can be compared with each other. By this procedure will remove the DCs and become them considered only the pulsatile fluctuating proportions. The DC component ownership for each person an individual value based on his skin color, Skin texture (keratinization), its bone structure and others location-related properties.

As explained above, however, other methods can also be used in the method according to the invention application methods.

Claims (26)

Apparatus for the noninvasive determination of concentrations of various blood components in the bloodstream, comprising a radiation source ( 12 ) for emitting a measuring radiation ( 14 ) in the direction of a body part to be examined ( 16 ), a first radiation receiver ( 18 ) for receiving by the body part to be examined ( 16 ) reflected radiation ( 20 ), with a second radiation receiver ( 22 ) for receiving by the body part to be examined ( 16 ) transmitted radiation ( 24 ), and one with the first ( 18 ) and the second ( 22 ) Radiation receiver associated calculation device ( 26 ) for calculating the part of the body to be examined ( 16 ) absorption of the emitted radiation ( 14 ) based on the measured reflected ( 20 ) and transmitted ( 24 ) Radiation component. Apparatus according to claim 1, characterized in that by the radiation source ( 12 ) Radiations ( 14 ) of different wavelengths are emitted. Apparatus according to claim 1 or 2, characterized in that the radiation source ( 12 ) and the first radiation receiver ( 18 ) on a first page ( 15 ) of the body part to be examined ( 16 ) are arranged. Apparatus according to claim 3, characterized in that the second radiation receiver ( 22 ) on a second page ( 17 ) of the body part to be examined ( 16 ), in particular the first page ( 15 ) is arranged opposite one another. Device according to one of claims 1 to 4, characterized in that between the first ( 18 ) and the second ( 22 ) Radiation receiver a receiving space ( 38 ) for receiving the body part to be examined ( 16 ) is trained. Device according to one of claims 1 to 5, characterized in that the radiation source ( 12 ) several individual radiation sources ( 12a - 12h ) of different wavelengths. Device according to one of claims 1 to 6, characterized in that the radiation source ( 12 ) as the light source and the first ( 18 ) and second ( 22 ) Radiation receiver are designed as a light receiver. Apparatus according to claim 6, characterized in that the individual light sources ( 12a - 12h ) are formed as LEDs. Apparatus according to claim 6 and 7, characterized in that the individual light sources ( 12a - 12h ), in particular arranged in a circle around the first light receiver. Device according to one of claims 6 to 9, characterized in that the light source ( 12 ) at least two individual light sources ( 12a - 12h ) of the same wavelength. Device according to claims 9 and 10, characterized in that the individual light sources ( 12a - 12h ) are arranged diametrically with the same wavelength. Apparatus according to claim 1 to 11, characterized in that the first ( 18 ) and the second ( 22 ) Light receiver each have two photodetectors for each wavelength range per photodetector. Apparatus according to claim 1 to 12, characterized in that at the first light receiver ( 18 ) a separating device ( 32 ) for preventing the arrival of stray light from the light source ( 12 ) to the first light receiver ( 18 ) is trained. Apparatus according to claim 13, characterized in that the separating device ( 32 ) by an inner ( 32a ) and an outer ( 32b ) Sleeve is formed. Device according to one of claims 1 to 14, characterized in that between the light source ( 12 ) and the first light receiver ( 18 ) lying cavity ( 33 ) is filled by a, in particular transparent, adhesive. Device according to one of claims 6 to 15, characterized in that the individual light sources ( 12a - 12h ) at its from the first light receiver ( 18 ) away side by an angle β, in particular by an angle β of 15 °, are raised. Device according to one of claims 1 to 16, characterized in that the receiving space ( 38 ) on the first page ( 15 ) of the body part to be examined ( 16 ) by a first receiving element ( 28 ) and on the second page ( 17 ) of the body part to be examined ( 16 ) by a second receiving element ( 30 ) is limited. Apparatus according to claim 17, characterized in that the first and the second ( 30 ) Receiving element by a clamping mechanism ( 40 ) are connected to one another such that an attachment of the device ( 10 ) on the body part to be examined ( 16 ). Device according to one of claims 1 to 18, characterized by a control device ( 41 ) for sequentially switching on the individual light sources ( 12a - 12h ). Use of a device according to one of claims 1 to 19, for non-invasive, especially continuous determination the concentration of blood components. Use of a device according to one of claims 1 to 19, for the diagnosis of microvascular damage. Use of a device according to one of claims 1 to 19, for determining a volume pulse course of one or more Blood components in a bloodstream. Method for operating a device for the non-invasive determination of concentrations of various blood components in a bloodstream, in particular for operating a device ( 10 ) according to one of claims 1 to 19, wherein the device ( 10 ) at least one radiation source ( 12 ) for emitting a measuring radiation ( 14 ) having different wavelengths, comprising the following steps: - sequentially radiating a plurality of measuring radiations ( 14 ) each having different wavelengths, - receiving the part of the body to be examined ( 16 ) reflected measuring radiation ( 20 ) of each wavelength by a first radiation receiver ( 18 ) and the part of the body to be examined ( 16 ) transmitted measuring radiation ( 24 ) of each wavelength by a second radiation receiver ( 22 ), and - determining the part of the body to be examined ( 16 ) absorption of the emitted radiation ( 14 ) based on the measurement of the reflected radiation ( 20 ) by the first radiation receiver ( 18 ) and the measurement of the transmitted radiation ( 24 ) by the second radiation receiver ( 22 ). A method according to claim 23, characterized in that for emitting measuring radiation ( 14 ) with different wavelengths several individual radiation sources ( 12a - 12h ) be used. A method according to claim 23 or 24, characterized through the following steps: - To save the determined absorption values of each wavelength - Repeat the process steps of claim 22 wherein the determined absorbance values of each wavelength are for each Be stored repetition cycle, - Combining the individual Absorption values of the emitted radiation for each wavelength Representation of a time course of the absorption at each wavelength. Method according to claim 25, comprising the step: - Determine the concentration of individual blood constituents using the temporal courses the stored absorbance values for each wavelength.