JPH07508426A - Blood sample measuring device and method - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Blood sample measuring device and method The present invention relates to the measurement of blood samples by a method that does not invade healthy tissue. The method It is a general product and can be used for various constituents present in blood. However, glucose and glycated hemoglobin It is of particular interest in measuring substances associated with diabetes, such as Robin, without affecting healthy tissue. It's something deep in the heart.

Testing the glucose level in the blood is generally helpful in controlling diabetes. , is considered to be among the front lines. Normally, glucose in the blood of diabetics It is recommended to monitor the level several times a day. Current glucose level in the blood The most common way to test blood samples is to use a test strip that is attached to a blood sample. This is a method of adding a pull. This test involves a small hole, usually obtained by making a small hole in the finger. A large amount of blood sample is required. The band-shaped fragment is a porter that quantitatively deciphers this. Typically tested using a pull-back battery-powered glucose meter. suffered many times It is clearly undesirable to take blood samples from people who In recent years, attention has been focused on blood measurements that are not performed.

Examples of the technologies investigated are: ・Near-infrared spectroscopy and mid-infrared spectroscopy ・Photoacoustic spectroscopy ・Measurement of eyepiece focal characteristics ・Optical rotation in the aqueous humor of the eye ・Analysis of gingival exudate ・Roman spectroscopy etc.

One of the most promising technologies to date is near-infrared (NIR) rcd I? eglon).

European Patent Application Publication Box EP-0160768 does not attack healthy tissue Infrared technology determines ΔP1 of glucose and detects transmitted or reflected radiation The technology is disclosed. The infrared technology used here can be used to target fingers) with infrared light of one or more wavelengths in the range of 1000 to 2700 nm. There is. A broadband light source is filtered to sequentially create the desired wavelengths. at least The intensity of the focused light at one wavelength λg depends on the glucose concentration present and the intensity of the focused light at at least one other wavelength is The wavelength is chosen so that it is largely independent of the glucose concentration. Measurement of light intensity 71-1 to determine glucose concentration using the common technique of NIR spectroscopy. can be replaced with.

The wavelength λg is l575±15nm, 1765±15r+m, 2100±15n m and 2270±150m.

The absorption peak attributable to glucose in the NIR is similar to that of other four (e.g. water) Since it substantially overlaps with 4t4, the concentration of glucose normally present in the blood. , that is, in the range of 2 to 10 mIIol/liter, it is not particularly disclosed. It is extremely difficult to obtain an accurate 1lpj constant value using the method described above.

WO/90107905 describes the relationship between blood glucose δ and constant using NIR. It is something to do. According to the disclosure document, a photodiode is placed on a body part (usually a finger). Irradiation is performed using NIR at a number of different frequencies using an array of codes.

Interference filters are used to determine the response of each detector and/or the specific NIR band of each LIED. The glucose level is detected using a calibration algorithm that controls the injection into associated with a linear combination of bands. Sensitivity is increased by using a larger number of wavelengths. improved and described in European Patent Application Publication No. EP-A-0160768. The accuracy can be improved over other devices.

Many traditional NIR methods use sites such as fingers, ear lobes, and skin to measure NIR. It is recommended that There are many drawbacks to using all of these body parts. be. especially, 1. In all these cases, there is a large temperature variation, for example of the order of 5 degrees, It has a great influence on the light absorption power and absorption wavelength of water present in tissues.

2. These pigments vary greatly from person to person.

3.The fat level in the body varies greatly from person to person.

This also has a significant impact on glucose levels determined by DI.

Here, the anterior surface of the eye is found that it is significantly better than other body surfaces.

According to a first aspect of the invention, the presence and/or concentration of an animal blood sample can be detected in a healthy population. A method for measuring without damaging the animal's tissue, which includes: a) irradiating the surface of the animal's body with infrared light; b, detecting the infrared light reflected by the surface, and calculating the spectral vector of the reflected light; A method for measuring a blood sample, comprising: analyzing the sample and determining the concentration of the sample. The method is characterized in that the surface is the surface of the eye.

As mentioned above, the anterior surface of the eye contains a healthy organ for measuring blood samples (especially glucose). more than other surfaces that have been previously proposed for noninvasive NIR spectroscopy. There are many advantages.

especially: 1. The temperature of the eyes tends to be extremely stable compared to many other parts of the body. be.

2. The pigment level of the eyes is relatively low, and the differences between individuals are not large and are similar. Similarly, the difference in fat levels is not that big.

Additionally, the eye has many other benefits for such 111-1 measurements.

In particular, the anterior surface of the eye (the white part of the eye) and adjacent tissues (e.g. the rim of the eye) ) blood vessels are concentrated on the surface. Using the surface of the blood vessels of the eye, other parts of the body Reflection spectra from the eye can be measured at wavelengths that are unsuitable for the eye. this This is because blood vessels in other parts of the body are well below the tissue surface. This means that a large amount of infrared light does not pass through other parts.

The ocular surface tissue is relatively simple in structure and can cause high levels of scattering. It is also advantageous that there is no difference. Yet another advantage of performing an eye δpj determination is that the table Because the surface is relatively smooth and kept moist, specular reflection is relatively limited. , and therefore it is relatively easy to separate specular reflections from diffuse reflections. This is possible.

Diffuse reflection accounts for most of the spectral information indicating blood analyte levels.

In order to be able to measure the reflected light from the anterior surface of the eye, the anterior surface is illuminated. means for diffusely reflected (backscattered) light from said illuminated surface; It is necessary to provide means for detecting the Furthermore, it is related to the characteristic parts of the individual's face. Therefore, it is also necessary to provide one or both of the irradiation means and the detection means.

Accordingly, in accordance with another aspect of the invention, the presence and/or concentration of an animal's blood specimen is An apparatus for determining δpI without invading healthy tissues, which includes: a) infrared light applied to the surface of the animal's body; irradiation means for irradiating; b. detecting infrared light reflected by the surface; a detection means for analyzing the spectrum of the analyte and measuring the presence and/or concentration of the analyte; 11, wherein the surface is the front surface of the eye; The irradiation means and/or the It is characterized in that it is provided with a placement means for arranging the detection means.

Said positioning means may be arranged to locate specific contours of an individual's face, such as the eye sockets and/or the eye sockets of an individual animal. Preferably, it includes a mold shaped to match the nose. Particularly suitable example In this case, a "standard" assembly supporting the irradiation means and the detection means is provided, and the assembly is is placed in a specific position of a mold molded to the facial contours of the particular individual in question. It is configured so that it can be fixed, and after creating a mold for the individual, the irradiation means and This makes it possible to return the detection means to the same location. Furthermore, in the pond example, Either or both of the irradiation means and the detection means is connected to a site where blood vessels are extremely concentrated. can be configured to focus on the rim region of the eye, particularly the medial and lateral rims of the eye. Wear.

In another preferred embodiment of the invention, the illumination means and the detection means are provided with minimal specular reflection. have the means to do so. - As an example, this means that specular reflections are virtually eliminated. The irradiating means and the detecting means can be positioned so that the irradiating means and the detecting means are illuminated. example For example, the irradiation means and the detection means are such that the specularly reflected light does not reach the detector. It is possible to point in a direction that can guarantee the following. In other examples, the detector is The system is configured to detect spatial changes in the signal. For example, the detector , a CDD array. By providing such an array , the position of the specular reflection can be easily determined, and once determined (for example, the specular reflection (by totally ignoring the spatial region where the specular reflection occurs) The noise can be minimized.

In yet another example of the invention, the polarization of the diffusely reflected light and the specularly reflected light is Discrimination means for distinguishing between diffuse and specular reflections from the ocular surface based on the differences between It is equipped with This means pointing in the direction that minimizes the signal obtained from specular reflections. A polarizer associated with one or both of the irradiating means and/or the detecting means can be realized. I can do it.

For example, insert a polarizer into the light beam to direct the incident light to the eye perpendicular to the plane of incidence. It can be linearly polarized. The polarizer, which also consists of a polarizer, is It can be inserted into the beam after irradiation.

The second polarizer is oriented to block surface-reflected light from the eye.

For example, the analyzer can be crossed to a polarizer. Using circularly polarized light It comes with me. A wavelength plate can also be used as a polarizing element.

Still other aspects of the invention are based on the characteristics of the equipment itself and the characteristics of the NIR band being detected. It is related. In the device disclosed in WO90107905, NIR It is desirable to measure the absorption at multiple points in the spectrum, and In order to obtain quantitative results that more accurately indicate the presence of endogenous analytes, these It is desirable to combine the results obtained from the points. However, this , depending on the particular LED and/or detector used. As a result, the device It is mechanically extremely complex and extremely expensive to manufacture.

Additionally, W090107905 can be detected using low-cost silicon detectors. It is carried out in the spectral region, wavelengths up to about 1l100nr: It is described as follows. However, the absorption rate of glucose in this region is extremely low. This absorption rate overlaps considerably with the absorption rate of water. many places In some cases, operating at longer wavelengths reduces the overlap between absorption bands. It can be made smaller.

However, detectors for use at longer wavelengths are more expensive and therefore more expensive. If longer wavelengths are to be detected, separate detectors can be used for each absorption band. That is extremely expensive.

At frequencies that depend on the wavelength of light over a relatively wide band, various NI+? modulate wavelength By doing, various Nll? It is known that wavelengths can be encoded. example I wish it was written by Lawrence Herts. So-called l’1fiftJ (mock) interferometer” (“Transformation in optics”, Low Rence Melf, John Wiley & Sons, Inc., New York; 1965 (Lawrence Herts, John Wylle & 5o ns, lnc, + New York, 1965)) is the grid image different wavelengths are encoded at different modulation frequencies using a rotating grating formed by Describes the equipment. This device is extremely useful in measuring astronomical spectra. It is said to be useful.

The device in question was considered remarkable when it was proposed in the mid-1960s. , to the best of our knowledge, has never been commercially produced.

To obtain a NIR spectrum, light is emitted at a frequency that depends on the wavelength of the light beam. Modulating the beam and then demodulating the signal obtained from the reflected light It is particularly useful as a method of measuring NIR spectra of body parts for 1F+ determination. It is effective. Using such equipment means that each frequency you wish to investigate has an independent 1. IEI), there is no need to install a filter, and despite this, it is mechanically extremely A very large number of frequencies, e.g. 20 or more, using simple equipment. This is extremely advantageous in that it can be investigated independently. Obtained at various frequencies Discrimination between signals can be achieved, for example, by a discrete RC circuit set to the desired frequency, or suitable electronic frequency filters such as lock-in amplifiers and frequency synthesizers. can be used and done. This filter filters the frequencies present in the detected signal. Analyze component strength.

Accordingly, in another aspect of the invention, the presence and/or concentration of an animal blood analyte may be determined in a healthy population. A device for determining JFI without damaging fabrics, which includes: (a) a beam that generates a polychromatic light beam; generating means; b. a polychromatic light beam such that the modulation frequency depends on the wavelength of the light beam; a modulation means for modulating the C8 The modulated light beam is irradiated onto the surface of the animal's body, and the blood sample is irradiated with the modulated light beam. means for interacting with the beam and perturbing the spectral dispersion of the light beam; d, from the final optical beam by detecting the beam at multiple modulation frequencies. means for extracting spectral information and determining the presence and/or concentration of said analyte; and, It is equipped with

This device is used for measurements of the anterior part of the eye according to the first aspect of the invention. Although it is suitable for use on other body surfaces, it can also be used on other body surfaces.

The modulation means includes a rotatable grating, a means for rotating the grating, and an image. the grating plane of said grating separated from the position of the grating by an amount that depends on the wavelength of the light being formed; Preferably, in the upper position, means for generating an image of the grating are provided. . The means for producing an image of the grating on the grating is a dispersive element, e.g. a prism. It is preferable to have the following.

By using such equipment, when using equipment with a discrete interference filter Easily measure absorption or reflection spectra of blood samples at a larger number of wavelengths than Can be done.

When measuring the concentration of blood analytes, especially in small volumes of blood, spectral measurements are It is desirable to use many wavelengths. Using normal analytical techniques, e.g. multilinear Determine concentration data from spectral measurements made by regression, partial least squares or principal component regression. data can be obtained.

According to another aspect of the invention, infrared radiation obtained from an animal for measuring blood specimens is provided. The signal is increased by measuring changes in said spectrum that are synchronized with the animal's pulse. It was determined that ΔP1 was strengthened. A similar technique optically measures blood oxygen content at A1. It is commonly used for so-called "pulse oximetry", which is used to determine the

However, as far as we know, no proposals have been made so far, and no Blood by infrared spectroscopy by using similar technology related to RonaPulse The sensitivity of liquid sample measurement can be increased. Therefore, according to another aspect of the invention: Apparatus for determining the presence and/or concentration of an animal blood sample by Δp1 without invading healthy tissue a. irradiation means for irradiating infrared light onto the surface of the animal's body; and b. the surface. detect the infrared light reflected by the specimen, analyze the spectrum of the reflected light, and determine the presence of the specimen. detection means for measuring the presence and/or concentration; In the blood sample 11-1 determination device equipped with the components of the spectrum that change with the pulse rate at 1lNF1 constant. The apparatus further includes a means for measuring the blood sample, thereby making it possible to improve the measurement accuracy of the blood sample.

In still other embodiments of the invention, the presence and/or concentration of an animal blood analyte is determined in healthy tissue. A method for measuring the animal's body without damaging it, which includes: (a) irradiating the surface of the animal's body with infrared light; and b, detecting infrared light reflected by the surface and analyzing the spectrum of the reflected light. and determining the presence and/or concentration of the analyte. In the body measurement method, the animal's pulse is detected and changes in the spectrum that are synchronized with the pulse are detected. The method further includes a step for measuring the change in temperature.

This aspect of the invention provides that the NIR spectral measurements are performed on a high area, such as a finger or an earlobe. When the NIR spectrum n1 is determined in a body part that is supplied with blood by pulsation, Most advantageous. The blood supply to the anterior surface of the eye is relatively pulsatile and therefore Therefore, this method is effective only when applied to the anterior surface of the eye. But long This aspect of the invention relates to modulating the light used according to the wavelength of the light. It is advantageous to use the embodiments in conjunction with the previously described embodiments of the invention.

The technology related to pulse oximetry is well known and detailed description thereof will be omitted.

Various aspects of the present invention used alone or in combination will be described below with reference to the drawings. A number of preferred embodiments are described.

FIG. 1 is a schematic diagram illustrating a blood glucose level 1111 determination device according to the present invention. .

FIG. 2 is a schematic plan view of the device according to the invention.

FIG. 3 is a sectional view taken along section AA in FIG.

FIG. 4 is a side view of the device shown in FIG. 2.

FIG. 5 is a schematic diagram showing the instrument in use.

Figure 6 shows an arrangement for reducing specular reflection in the apparatus shown in Figures 1 and 2. This is a diagram.

FIG. 7 is a schematic diagram illustrating another embodiment for minimizing specular reflection.

FIG. 8 is a diagram for explaining still another method.

Figure 9 shows the so-called FIG. 2 is a schematic diagram showing “simulated interference=1”.

FIG. 10 shows an ocular blood analyte measurement device according to the present invention, comprising a one-week device. It is a schematic diagram.

FIG. 11 shows a schematic diagram in more detail of the device according to the invention comprising light beam modulation means. This is the essential diagram.

Referring to Drawing Detail 1, FIG. 1 shows a preferred embodiment of the invention, showing the anterior surface of the eye. FIG. 2 is a schematic diagram showing the main components for determining glucose δ-1 in . The apparatus of Figure 1 uses light [1, typically a tungsten/halogen lamp or lament lamp), reflector 2, and collimating lens 3 that creates a parallel light beam. and has. The parallel light beam passes through a light modulator 4. The optical modulator 4 is a light beam is modulated at a modulation frequency corresponding to the wavelength. The details of the optical modulator 4 will be described later. .

The modulated light beam 7 passes through a beam splitter 8 and a focus lens 9. Ru. The focus lens 9 uses a modulated optical beam to measure the concentration of the blood sample. The camera is focused on the anterior surface 10 of the eye.

Its arrangement allows the focused light beam to cover superficial blood vessels particularly well. It is designed to irradiate the area at the edge of the eye.

The light diffusely reflected by the surface 10 is focused by the lens 9 and sent to the beam splitter. 8, the image is focused onto the detector 12 by the lens 11.

A processing section 5 connected to a detector 12 and an optical modulator 4 is provided. The processing unit 5 has a large number of It has an electrical filter circuit and can handle multiple modulation frequencies (and therefore multiple infrared wavelengths). ), the reflected light intensity is detected.

Detector] 2 is a condenser that does not create an image (non-Imaging C0nC Ontrator) is preferred. The processing unit 5 includes a microprocessor and appropriate software. It can be configured by software.

The processing unit 5 uses, for example, multiple linear regression, partial least squares, principal component regression, etc. , it also has means for analyzing the absorption band as a detection result.

The device may further comprise a pulse detector 6 allowing pulse detection of the individual. . This is schematically shown in Figure 1, but in reality, the specimen 4 is When performing -1 constants, the use of a pulse detector is not very important. This is this part This is because there is relatively little variation in pulse rate due to blood supply at this position. But long However, if the 5g1 test is performed using other parts of the body, such as the fingers or earlobes, a pulse check should be performed. The output device is very important. Pulse detector 6 is used for conventional pulse oximetry It may be of any type.

Pulse oxygen, il? + The standard method is to determine the optical absorption at a body part as aP1, This is a method to measure blood oxidation. Typically red or infrared absorption of body parts is measured by two wavelengths. One of these two wavelengths is oxyhemoglycerin. Robin (oxidized hemoglobin) and deoxyhemoglobin (deoxygenated hemoglobin) Select a wavelength that is uniformly absorbed by moglobin), and on the other hand, select a wavelength that is uniformly absorbed by - It is strongly absorbed by hemoglobin, but only weakly by other types. Select the wavelength to be used. The amount of blood present in tissues, as well as the pulsation of blood within the body increases and decreases cyclically. Pulse oxygen is produced by changes in the amount of blood present in tissues. The absorption of the light beam at the two wavelengths by the tissue is then monitored. Pulsatile formation of absorption depends primarily on blood within the tissue rather than on surrounding tissue It is something. JFI determination of tissue oxidation is possible based on the amplitude ratio of two pulsating signals. can.

The processing unit 5 has a phase sensitive detector coupled to an input from a pulse detector 6. , only the component of the detection signal that changes in synchronization with the detected pulse is supplied to the detection circuit. be done.

In this way, the processing unit 5 separates the static component and the fluctuating (pulsating) component of the optical spectrum. It is possible to separate. The pulsating component of the spectrum is strong in the blood absorption spectrum are correlated and therefore provide a suitable basis for calculating the concentration of blood samples. be.

It is useful to correlate spectral measurements with blood pulses. It is continuous Although the measured spectra generally contain a great deal of information about other tissue components, This is because the pulsating component of the spectrum very clearly indicates blood.

Relating a spectral measurement + constant to a pulse is, for example, sufficiently shorter than a pulsation. Record multiple complete spectra with a period of roughly 1/10th of a second, Then absorb for each wavelength for further analysis, 'I11 constant pulsation. This can be achieved by extracting the components.

2 to 5 show the external appearance of a portable device that is an embodiment of the present invention. Figures 2 to 4 The device shown in Figure 1 has a body 20 that houses optical components and detection circuitry.

The components within the main body 20 are such that the focused beam directed onto the anterior surface of the eye is It is configured to pass through the opening 21. A screw thread is provided around the opening 21. An adapter 22 is disposed, and the adapter 22 has a threaded thread. u23 is installed. The adapter 22 is shaped to match the contour of the user's face, and is It has a flexible nose and eyes. The shape of the mold 23 is such that the device can be Positioned precisely according to the contours of the face, the light beam enters the desired position in front of the eye It is formed like this. Shaped hand grip 24 for user convenience is provided. On the top surface of the main unit, there is a start button operated by the user. 25 and a liquid crystal screen 26 for displaying measurement results. General information about the device Figure 5 shows how to use it.

The general setup 51 shown in FIGS. Particularly suitable, but for example, using a Fourier transform spectrometer, It is also possible to use other detection systems that can obtain infrared spectra of be.

Specularly reflected light contains spectral information about blood that is transmitted through diffuse reflection (backscattered light). ) to reduce the effect of specular reflection, since the light has less It is desirable to provide some kind of mechanism.

One midline configuration is shown in FIG. In the configuration of this embodiment, the combined light beam is It is arranged so as to be incident on the ocular surface at a point 10. This point 10th place The position has a curvature such that specular reflections do not enter the detection system. Optical modulator and The processing section is omitted for simplicity.

Alternatively, in the embodiment shown in FIG. A CCD imaging device with arrayed detection points is used.

In the configuration of this embodiment, a beam blocking section 13 is provided to limit the width of the parallel beam. This allows the detector to capture a wider angle than the light occupied by specular reflection. It becomes possible to focus light within a range. The optical modulator and processing section are omitted because they are inside the cylinder. ing. The processing unit 5 is programmed to receive the specular reflection on the detector 12. It is placed in the area where it is located. Specular reflections are usually relatively sharp and produce strong signals, so It is easy to determine the location where specular reflection occurs, and It is also easy to give a low weight (or set the weight to zero) to the signal.

FIG. 8 shows another means for suppressing the influence of m-plane reflection based on polarization. ing. In FIG. 8, for the sake of simplicity, this aspect of the system configuration is shown. Only things are shown.

A polarizer 33 is inserted between the lens 3 and the lens 9 to polarize the light that enters the eye. has been done. As a polarizer, for example, it polarizes light perpendicular to the plane of incidence. A directed linear polarizer or a circular polarizer can be used. In the path of the detection beam , an analyzer 30 is provided between the lens 31 and the lens 32. This blocks the specularly reflected light from the eye. Using wave plates with polarizing elements is also possible.

Figure 9 shows the so-called “model” mentioned in Lawrence Merz’s literature, which was introduced earlier. "pseudo-interferometer" is used to modulate a light beam to a frequency corresponding to its wavelength. It is shown that a simple mechanical configuration can be used. Figure 10 shows such a device 1 schematically shows a simple mechanical configuration applied to an analyzer according to the present invention.

An optical diffraction grating with a spacing of approximately 10 lines per millimeter, as shown in Figure 9. The lens 40 is mounted on a rotary base, and the light passes through the rotation M'r grating and enters the lens 42. is focused on. A dispersing prism 44 with a mirror-like back surface passes through the lens 42. The light beam is reflected to form an image of the grating on the grating surface. The position of the image on the grid is the wave of light length, the degree of correspondence between the lines of the grating and the lines of the image, and hence the chopping frequency or modulation. Depends on frequency.

Therefore, this also depends on the wavelength.

Figure 10 schematically shows how such a device can be incorporated into a device according to the invention. It shows. The same reference numbers as in FIG. 1 are used. Figure 11 shows the FIG. 2 is a schematic diagram showing such a device in more detail. Again, reference numbers are the same as in Figure 1. I'm using one.

The device includes a polychromatic light source 1 (tungsten halogen filament lamp), It has a reflector 2 and a collimating lens 3 similar to those shown in FIG. A parallel light beam is The light passes through an optical modulator having a disk 40 whose surface is a diffraction grating. Diffraction grating is either a phase grating or an amplitude grating, and has a large spacing compared to the wavelength of the light. (typically spacing on the order of 10 lines per millimeter). Dis The engine 40 is rotated at a constant speed by an electric motor 41.

The optical system includes a lens 42, a mirror 43 and a scattering element 44, and includes a rotating scale. The diffraction grating is arranged to form an image of the child on the surface of the diffraction grating itself. As shown in Figure 11 The lenses 42 are spaced apart from each other by the sum of the individual focal pressures Mf, so that the grating is It is placed so that it is in the focal plane of a nearby lens. Due to the presence of the scattering element 44 Therefore, the position of the image on disk 40 depends on the amount of light dispersed by element 44; It depends on the wavelength of the light in question. As a result, the light transmitted by the grating is It is cut off or modulated at a frequency that varies circularly, but parallel to one quadrant with respect to the grating. It depends on the moving object and therefore on the wavelength of the light.

The modulated light passes through beam splitter 8 and lens 9 and is directed to the anterior surface of the eye (or is reflected by another suitable part of the body) and detected by a detector.

The electrical signal detected by the detector is, for example, a Electrical filters such as Cree-1-RCu paths, lock amplifiers, frequency synthesizers, etc. are separated into frequency "containers" and analyzed using known methods.

Instead, the eye's reflection spectrum is a non-uniform sample of time-varying signals. It can also be obtained by Fourier transform at ring intervals (Lawren ce Merz Goran Srormat+ons in 0ptics”, J ohn Wylie & 5ons, Inc., New York, 19 135). A particularly useful feature of this kind of configuration is that it allows light to pass through the slit. Since this is not necessary, the optical throughput of the device is high. The throughput is The higher the battery power supply, the lower the power consumption of the device. This is a significant advantage in equipment. It also measures the analyte concentration with a certain accuracy. This will also shorten the time required to do so.

The modulation methods described so far have been used in devices that scan the anterior surface of the eye. For example, the retina, choroid, optic nerve head (optic disc), finger , earlobes, lips, or other parts of the body that have a good blood supply. It is also useful when performing sample measurements at the same location. Using the optic nerve head is This is useful in environments where That is, the optic nerve head is well supplied with blood and has a pulse. movement, adequate contact with blood-filled tissue, and a stable temperature. There is no pigmentation, and the configuration of the optical system can be simplified by using the optical system of the eye. This is because it is possible. However, the level of glucose in the aqueous fluid of the eye and The difficulty of obtaining sufficient light levels limits the usefulness of the back of the eye in this connection. Reduce.

In addition, certain eye diseases, such as cataracts, cannot be treated using the retina, choroid, or optic nerve head. and make it difficult.

As already pointed out, the wavelength and intensity of water absorption in the near-infrared region of the spectrum varies with temperature. This phenomenon makes reliable measurements of blood analyte concentrations Makes it difficult to develop calibration algorithms. Some calibration algorithms Therefore, when developing the algorithm, measure the body temperature and use the temperature as a variable. It is beneficial to use Temperature can be simply monitored by the position of the moisture absorption peak It can be measured by (“Po5sible Medical＾ppl 1catlonsor NIR-, K, 11. Norris, Making Light Work: Advanced in NIR5pcctros copy, Aberdecn 1991), edited lan Hur Ray and fan Love.

(See VCI+, 1992). Therefore, in a preferred embodiment of the invention, the investigation The temperature of the affected body part is measured by NIR absorption measurement of water in the area in question. determined. Alternatively, the temperature can be measured using a thermistor, thermocouple, or other conventional means. It can also be measured by

Another aspect of the present invention is to increase the temperature of a body part to a constant temperature, or It is desirable to suppress fluctuations in spectral characteristics. heating power or The cooling mechanism may be composed of an electrical resistance or a thermoelectric conversion element, respectively. These can be coupled via a feedback loop to temperature sensors such as those described above. It will be done. It is preferable to increase body temperature rather than cool it. The reason is , body temperature may drop considerably but rarely rise significantly? and also “Non1nvasive Pu1se Oxisetry Itilizing 5kin Relectance Photople L hysmography'', Y, Mendelsonandrl, D, 0ch s, IEEETransactionsonBlomcdlcalEngin earing.

Vol, 35. No, 10. pp, 798-805.0ctober As shown in 1998, increasing the temperature of a body region increases the This is because it increases the amount of fluid and increases the intensity of the pulsating component of blood flow. Particularly of the present invention In a preferred embodiment, heating of the body part is provided for spectral measurements. This can be done by applying infrared radiation to heat the body part being investigated. Ru.

The simplicity of the instrument means that it can be used at many wavelengths through the use of appropriate calibration algorithms. Is it okay? This means that I can be determined. Different wavelengths to different populations , or can be used in different individuals to more accurately determine blood glucose or This will enhance the ability of the instrument to measure the concentration of other blood analytes.

The above-described embodiments of the invention do not use separate interference filters and do not use any It is also configured to test the wavelength, so the measurement instrument itself can be used for calibration purposes. can be used.

Deriving appropriate calibration algorithms for various blood samples means properly extracted a lot of data about the fluctuations in the blood sample concentration of Proper phasing of absorption and blood analyte concentration at multiple frequencies using any of the techniques It is about gaining a relationship.

The methods described herein may be performed using, for example, alcohols, in particular ethanol, urea, total/ HD cholesterol, hemoglobin, oxyhemoglobin, low/high density sebum protein , triglycerides, total protein, albumin, serum globulin, etc. of other blood samples. It is also possible to apply the avj constant.

ig 5 Figure 7 international search report 1. l++I11. . ++, 115m'. 11. PCT/GO921018 94 International Search Report Continuation of front page (31) Priority claim number 9207149.7 (32) Priority mill April 1992 1 day (33) Priority claim country: United Kingdom (GB) (81) Designated country: EP (AT, BE, CH, DE.

DK, ES, FR, GB, GR, IE, IT, LU, MC, NL, SE), JP , U.S. (72) Inventor: Pettigrew, Robert, Martin, United Kingdom, CP -26 Earl Peken Bridgeshire, Foxton.

High Street 51. Pond Cottage (no address)

Claims (15)

[Claims] 1. Device for measuring the presence and/or concentration of animal blood specimens without invading healthy tissue And, a. irradiation means for irradiating infrared light onto the surface of the animal's body; b. reflected from the surface detect the infrared light of the analyte, analyze the spectrum of the reflected light, and determine the presence and/or is a detection means for measuring the concentration; A blood sample measuring device comprising: the surface being the front surface of the eye, and The irradiation means and/or the detection device are placed at a fixed position relative to a characteristic part of the animal's face. A blood sample measuring device characterized by comprising a positioning means for arranging the output means. Place. 2. 2. The blood sample measuring device according to claim 1, wherein the placement means blood characterized by having a mold shaped to match the contours of the face of Specimen measurement device. 3. 3. The blood sample measuring device according to claim 2, wherein the placement means is placed in the eye socket of the animal. and/or having a mold shaped to match the nose. Liquid sample measuring device. 4. The blood sample measuring device according to claim 2 or 3, wherein the arrangement means A mounting member for the irradiation means and the detection means, and the mold molded to the outline of the animal's face. and a fixing means for fixing the attachment member to the blood. Specimen measurement device. 5. The blood sample measuring device according to any one of claims 1 to 4, Either or both of the irradiation means and the detection means is connected to a site where blood vessels are extremely concentrated. A blood sample measuring device characterized by focusing on the limbal region of the eye. 6. The blood sample measuring device according to any one of claims 1 to 5, The illumination means and the detection means are positioned such that specular reflection is substantially eliminated. A blood sample measuring device characterized by: 7. The blood sample measuring device according to any one of claims 1 to 6, The detection means detects a spatial change in the reflected light and compensates for the influence of specular reflection. A blood sample measuring device characterized in that it is capable of: 8. The blood sample measuring device according to any one of claims 1 to 7, The irradiating means and/or the detecting means can generate diffusely reflected light and specularly reflected light. Distinguish between diffuse and specular reflections from the ocular surface based on the difference in polarization between A blood sample measuring device characterized in that it is equipped with an identification means for. 9. Device for measuring the presence and/or concentration of animal blood specimens without invading healthy tissue And, a. beam generating means for generating a polychromatic light beam; b. The modulation frequency of the light beam modulation means for modulating the polychromatic light beam in a wavelength dependent manner; c. The modulated light beam is irradiated onto the surface of the animal's body, and the blood sample is exposed to the light beam. means for interacting with the beam and perturbing the spectral dispersion of the light beam; d. from the final light beam by detecting the beam at multiple modulation frequencies. means for extracting spectral information and determining the presence and/or concentration of said analyte; and, A blood sample measuring device comprising: 10. The blood sample measuring device according to claim 9, wherein the modulating means comprises: A rotatable grid and means for rotating the grid; a grating of said grating spaced apart from the position of the grating by an amount that depends on the wavelength of the light forming the image; means for generating an image of the grating at a position on the plane; A blood sample measuring device comprising: 11. A device for measuring the presence and/or concentration of an animal blood sample without invading healthy tissue. The location is a. irradiation means for irradiating infrared light onto the surface of the animal's body; b. reflected from the surface detect the infrared light that is reflected, separate the spectrum of the reflected light, and determine the presence of the analyte and/or is a detection means for measuring the concentration; Detects the animal's pulse and synchronizes with the pulse of the animal. the analyte present in the blood; A blood sample measuring device characterized by improving detection accuracy. 12. A device for measuring the presence and/or concentration of an animal blood sample without invading healthy tissue. The location is a. irradiation means for irradiating infrared light onto the surface of the animal's body; b. reflected from the surface detect the infrared light that is reflected, separate the spectrum of the reflected light, and determine the presence of the analyte and/or is a detection means for measuring the concentration; In a blood sample measuring device equipped with and means for measuring the components of said spectrum that vary with said pulse rate. A blood sample measuring device further comprising: Place. 13. Measuring the presence and/or concentration of animal blood samples without invading healthy tissue The law is a. irradiating the surface of the animal's body with infrared light; b. red reflected by said surface A line that detects external light, analyzes the spectrum of the reflected light, and measures the concentration of the analyte. In the method for measuring a blood sample, the surface is the anterior surface of the eye. A blood sample measurement method characterized by the following. 14. Measuring the presence and/or concentration of animal blood samples without invading healthy tissue The law is a. irradiating the surface of the animal's body with infrared light; b. red reflected by said surface Detect external light, analyze the spectrum of the reflected light, and determine the presence and/or concentration of the analyte. In a blood sample measurement method that includes a step of measuring the animal's pulse rate, and further comprising a step for measuring a change in the spectrum synchronized with the pulse. A blood sample measuring device characterized by: 15. Measuring the presence and/or concentration of animal blood samples without invading healthy tissue The law is a. Modulating a polychromatic light beam such that the modulating wavenumber depends on the wavelength of the light beam The journey and b. The modulated light beam is irradiated onto the surface of the animal's body, and the blood sample is exposed to the light beam. a process that interacts with the beam and disrupts the spectral dispersion of the light beam; c. from the final light beam by detecting the beam at multiple modulation frequencies. extracting spectral information and determining the presence and/or concentration of the analyte; A blood sample measuring method characterized by comprising: