JPH04332535A - Instrument for measuring concentration of bilirubin in blood - Google Patents

Abstract

PURPOSE:To measure the concn. of the bilirubin in blood without collecting blood. CONSTITUTION:Light emitting means 11 to 14 which emit light having a suitable wavelength respectively toward sections to be measured, a light receiving means 16 which receives the light transmitted through the sections to be measured and converts this light to signals, signal forming means 28, 30, 40 which form the signals corresponding to the transmitted quantities of the respective light rays in accordance with the output signals of this light receiving means, and an arithmetic means 42 which calculates the concn. of the bilirubin in the blood in accordance with the respective signals formed at the 1st time and the 2nd time in these signal forming means are provided.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a device for measuring the concentration of bilirubin contained in blood.

0002

[Prior Art] Generally, jaundice, especially severe jaundice in newborns, leads to death, and even if death is avoided, there is a risk of progressing to kernicterus, which leaves aftereffects such as cerebral palsy, so early detection is extremely important. This has become a major issue.

[0003] Conventionally, as a means of accurately measuring the intensity of jaundice, blood was collected from the above-mentioned newborn (25
There is generally known an apparatus that determines the bilirubin concentration in blood by measuring the transmittance of a plurality of types of light having different wavelengths, for example, by an optical method. This blood bilirubin concentration is directly linked to the intensity of jaundice in a patient, and therefore, by measuring this concentration, accurate diagnosis of jaundice can be made.

However, such conventional devices require blood sampling, which causes pain to the patient and poses a risk of infection. Especially for premature babies,
It is difficult to frequently collect blood, making it difficult to use this device.

[0005] Therefore, Japanese Unexamined Patent Publication No. 54-148586 proposes a jaundice meter for diagnosing jaundice in a patient without blood sampling, that is, in a non-invasive manner. This jaundice meter responds to at least two wavelength ranges of light that are different in absorption by the bilirubin deposited in the subcutaneous fat from the light source that enters the light into the skin of the human body, and the reflected light of the above-mentioned light. It is equipped with two light-receiving elements and measures the degree of jaundice from the output of each light-receiving element, and is configured to indirectly measure the intensity of jaundice without measuring the blood bilirubin concentration. There is. Therefore, it has the advantage of not requiring blood sampling and being easy to handle.

[0006]

[Problems to be Solved by the Invention] Since the above-mentioned jaundice meter measures jaundice based on light reflected from the skin, the measurement result is based on the patient's natural skin color (i.e., skin color that differs depending on race). ), making it difficult to always accurately measure jaundice. In addition, the degree of jaundice in the skin decreases during or after phototherapy, so if you measure it with the jaundice meter mentioned above at this time, you will be able to accurately measure the intensity of jaundice corresponding to the actual blood bilirubin concentration. There is a disadvantage that it is not possible to measure the

[0007] In view of the above circumstances, an object of the present invention is to provide an apparatus that can accurately measure blood bilirubin concentration without requiring blood sampling.

[0008]

[Means for Solving the Problems] The present invention provides a first light emitting means for emitting a first light having a wavelength absorbed by deoxyhemoglobin, oxyhemoglobin and bilirubin in blood toward a measurement site; a second light emitting means that emits, toward a measurement site, second light having a wavelength that is different from the wavelength of the light and that is absorbed by at least deoxyhemoglobin among deoxyhemoglobin, oxidized hemoglobin, and bilirubin in the blood; and the wavelength of the second light,
and a third light beam having a wavelength that is absorbed by at least oxygenated hemoglobin among deoxyhemoglobin, oxyhemoglobin, and bilirubin in the blood, and emits toward the measurement site.
a fourth light emitting means that emits a fourth light having a wavelength that is not absorbed by deoxyhemoglobin, oxyhemoglobin, and bilirubin in blood but is absorbed only by water, toward the measurement site; A light receiving means receives the light emitted from the light emitting means and passes through the measurement site and converts it into an electrical signal, and based on the output signal of the light receiving means, the first light,
a signal generating means for generating signals respectively corresponding to the transmitted amounts of the second light, the third light, and the fourth light; each signal generated at a first time in the signal generating means;
and calculation means for calculating the blood bilirubin concentration based on each signal created at a second time different from the time (Claim 1).

Here, the setting of the wavelength λi (i=1, 2, 3, 4) of each light from the first light to the fourth light is, for example, as shown in FIGS. 4(a) and 4(b). This may be done by utilizing the relationship between the light wavelength and the light absorption coefficient of each substance. That is, the wavelength λ1 of the first light is the deoxyhemoglobin in the blood,
It may be set in a region where the absorption coefficients of oxyhemoglobin and bilirubin are not 0, for example, in a region of about 500 nm or less. Further, the wavelength λ2 of the second light is set to a region where the absorption coefficient of at least reduced hemoglobin among deoxyhemoglobin, oxyhemoglobin, and bilirubin is not 0, for example, a region of about 1000 nm or less, and the wavelength λ2 of the third light
3 may be set to a region where the absorption coefficient of at least oxyhemoglobin among deoxyhemoglobin, oxyhemoglobin, and bilirubin is not 0, for example, a region of about 1100 nm or less. On the other hand, at the wavelength λ4 of the fourth light, the absorption coefficient of water is 0.
For example, a region near 1200 nm or a region around 1450 nm.
It may be set in a region around nm or the like.

Further, the light receiving means may be a single element that receives all of the transmitted light, or may be composed of a plurality of elements provided corresponding to each of the transmitted light. In the former case, the signal generating means may be configured to separate the output signal of the light receiving means into signals corresponding to transmitted light of each wavelength (claim 2).

[0011]

[Operation] According to the above device, the first to fourth lights are incident on a predetermined measurement site from each light emitting means, the transmitted light is received by the light receiving means, and a signal is generated based on the output signal of the light receiving means. A signal corresponding to the amount of transmission of each light from the first light to the fourth light is created by the creation means. Then, the blood bilirubin concentration is calculated based on each signal obtained at the first time and each signal obtained at a second time different from the first time.

[0012] The principle underlying the calculation of the blood bilirubin concentration described above is as explained below.

[0013] Now, the first light L1, the second light L2, and the third light L1
The wavelengths of the light L3 and the fourth light L4 are λi (i=1
, 2, 3, 4). The transmitted light intensity when these lights L1 to L4 are irradiated onto the measurement site is related to the thickness of the arterial blood at that time, but since the thickness of the arterial blood changes over time in synchronization with the heartbeat, this When d(t) (t is time), the intensity of transmitted light at the first time t1 can be expressed by the following equation (Equation 1) according to Lambert Bear's law.

[0014]

[Math 1]

Similarly, at a second time t1 different from the first time t1,
The transmitted light intensity at time t2 is expressed by the following equation (Math. 2).

[0016]

[Math 2]

In proceeding with the calculation, a value Pi (i=1, 2, 3, 4) shown by the following equation (3) is introduced.

[0018]

[Math 3]

Substituting the above two equations (Equation 1) and (Equation 2) into this equation and setting d(t2)=d(t1)+Δd, we get
The above value Pi is as shown in the following equation (Equation 4).

[0020]

[Math 4]

Here, the wavelength λ4 of the fourth light L4 includes deoxyhemoglobin (Hb), oxidized hemoglobin (HbO2
) and bilirubin, so when i=4 in the above equation (4), the absorption coefficient εi(Hb) of deoxyhemoglobin and the absorption coefficient εi(Hb) of oxidized hemoglobin are selected. HbO2) and bilirubin absorption coefficient εi(Bil) are both 0,
Substituting these into the above formula (Equation 4) (for Xi, (
(See Equation 1)) By squaring both sides, the following equation (Equation 5) can be obtained.

[0022]

[Math 5]

Therefore, (Δd)2 is expressed by the following equation (Equation 6).

[0024]

[Math 6]

On the other hand, regarding the wavelengths λi (i=1 to 3) of the first light L1, second light L2, and third light L3, the first light is deoxyhemoglobin, oxidized hemoglobin, Since the second light is selected to be absorbed by at least deoxyhemoglobin and the third light is absorbed by at least oxidized hemoglobin, in the above (Equation 4), at least the absorption coefficient ε1 (
Bil) is not necessarily 0, and in all cases of i=1, 2, and 3, the absorption coefficients εi(Hb) and εi(HbO
2) never becomes 0. In these cases, the following equation (Equation 7) is obtained from the above equation (Equation 4).

[0026]

[Math 7]

In this (Equation 7), each absorption coefficient εj(
Hb), εj(HbO2), εj(Bil) are known values, each value P12, P22, P32 is a measured value obtained by the apparatus of the present invention, and (Δd)2 is calculated from the above formula (Equation 6).
), this formula (Math. 7) is expressed as the following formula (Math. 8):
The blood concentration of each substance C(Hb), C(
This is a three-dimensional simultaneous linear equation with unknowns being HbO2) and C(Bil).

[0028]

[Math. 8]

[0029] Therefore, by solving these simultaneous equations, the blood bilirubin concentration C (Bil) can be calculated.

In addition, in the case where the light receiving means is constituted by a single light receiving element (claim 2), the output signal thereof is
By separating the signals into signals corresponding to the amount of light transmitted with each wavelength, a signal that is the basis of calculation is created.

[0031]

DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 shows a blood bilirubin concentration measuring device according to an embodiment of the present invention.

[0032] This device includes a measurement probe 10 and an arithmetic control system 20. The measurement probe 10 has a shape that is fitted onto the measurement site of the subject (for example, the top of the foot) so as to cover it from the outside,
In this attached state, a first light emitting element 11, a second light emitting element 12, and a third light emitting element 1 are placed at predetermined positions on one side sandwiching the measurement site.
The third and fourth light emitting elements 14 are disposed close to each other, and a single light receiving element 16 is disposed at a position corresponding to the light emitting elements 11 to 14 on the other side.

Among the four light-emitting elements 11 to 14, the first light-emitting element 11 is one that emits light having a wavelength that is absorbed by deoxyhemoglobin, oxyhemoglobin, and bilirubin in the blood, and the second The light-emitting element 12 uses a device that emits light with a wavelength that is absorbed by at least deoxyhemoglobin among deoxyhemoglobin, oxyhemoglobin, and bilirubin in the blood, and the third light-emitting element 13 emits light with a wavelength that is absorbed by at least deoxyhemoglobin in the blood. Among oxyhemoglobin and bilirubin, one that emits light with a wavelength that is absorbed by at least oxyhemoglobin is used. On the other hand, the fourth light emitting element 14 includes the reduced hemoglobin,
What is used is one that emits light with a wavelength that is not absorbed by either oxyhemoglobin or bilirubin and is absorbed only by water.

The light receiving element 16 is connected to the light emitting elements 11 to 16.
It is configured to receive the light emitted from 14 and transmitted through the measurement site, and to convert it into an electrical signal and output it.

The calculation control system 20 includes a power supply section 22, a light emitting element drive section 24, a timing generation section 26, an I/V conversion section 28, a signal separation circuit 30, an A/D conversion section 40, a calculation control section 42, and a display. (output means) 44.

The light emitting element driving section 24 outputs a drive signal to the four light emitting elements 11 to 14 to cause them to emit light. The timing generating section 26 outputs a timing signal to the light emitting element driving section 24 and each sample hold section 31 to 34 described below, and more specifically, it outputs a timing signal to the light emitting element driving section 24 at a predetermined timing. By outputting a signal, each light emitting element 11 to 14 is turned on in a time-divisional manner, and in synchronization with this, each light emitting element 11 is turned on.
A timing signal is outputted to operate the sample hold units 31 to 34 corresponding to 14.

Note that the lighting period of each of the light emitting elements 11 to 14 is set to be sufficiently shorter than a heartbeat, so that lighting is performed many times per one heartbeat period.

The I/V converter 28 converts the photocurrent output from the light receiving element 16 into an analog voltage. The signal separation circuit 30 separates the output signal of the I/V converter 28 into four signals corresponding to the wavelengths λ1 to λ4 of the transmitted light of the light emitting elements 11 to 14, respectively. 4 sample hold sections 31 to 34 and low pass filter sections 35 to 14 respectively corresponding to
It is equipped with 38. Each of the sample and hold sections 31 to 34 samples and holds the output of the I/V conversion section 28 while the corresponding light emitting elements 11 to 14 are turned on, based on the output timing signal of the timing generation section 26, The low-pass filter sections 35 to 38 create photoplethysmogram signals for each wavelength based on the outputs of the corresponding sample and hold sections 31 to 34, respectively.

The A/D converter 40 receives the output control signal from the arithmetic control section 42 and performs analog-to-digital conversion on the outputs of each of the low-pass filter sections 35 to 38. The arithmetic control section 42 includes the timing generation section 26
It outputs a control signal to the A/D converter 40 to control the same, and calculates the blood bilirubin concentration based on the output signal of the A/D converter 40. More specifically, the A/D converter 40 performs analog-to-digital conversion on the outputs of each of the low-pass filter sections 35 to 38 at a first time t1 and a second time t2 different from this.
Based on the converted value, the blood bilirubin concentration is calculated based on the calculation formula described in the section of the above-mentioned operation, and the calculation result is displayed on the display section 44.

Note that the first time t1 and the second time t2 are set, for example, when a predetermined time Δt has elapsed from the first time t1 when the analog-to-digital conversion was first performed. The next analog-to-digital conversion may be performed at the second time t2, or
Alternatively, after the first time t1, the second time t2 is a point in time when the output of one channel of the low-pass filter sections 35 to 38 increases or decreases by more than a predetermined value due to a change in the thickness of arterial blood. You may also do so. In the latter method, it is possible to ensure a sufficient output difference between times t1 and t2.

Next, the operation of this device will be explained.

First, with the measurement probe 10 attached to the test subject's measurement site (for example, the top of the foot), the timing generator 26 moves the light emitting element drive unit 24 as shown in the upper half of FIG. A light emission timing signal is output, and based on this signal, first light, second light, and third light having different wavelengths are emitted from each of the light emitting elements 11 to 14 intermittently and out of phase with each other toward the measurement site. and the fourth light are respectively incident. The transmitted light is received by the light receiving element 16 all at once, converted into an electric signal, and then sent to the I/V converter 2.
8 to the signal separation circuit 30. The input signal at this time is, for example, as shown in FIG. 3(a).

In this signal separation circuit 30, as shown in FIG.
Since the sample-and-hold timing signal is output to , each sample-and-hold unit 31 to 34 samples and holds only a portion of the input signal that corresponds to the transmitted light emitted by each light emitting element 11 to 14 . Therefore, for example, the output signal of the sample hold section 31 becomes as shown in FIG. 3(b). Each output signal is sent to the low-pass filter sections 35 to 38.
As shown in Fig. 3(c), A/
The signal is input to the D converter 40. Therefore, the waveforms of these signals correspond to the wavelengths λ1 to λ4 of each light.

[0044] These signals are A/D converted at a preset first time t1 and a second time t2, and are taken into the arithmetic control section 42. Based on these signals, the calculation control unit 42 calculates the blood bilirubin concentration C (Bil) by solving the above-mentioned simultaneous equations (Equation 8),
This is displayed on the display section 44.

[0045] According to such a device, the blood bilirubin concentration can be measured non-invasively without drawing blood from the subject, and accurate diagnosis can be made based on the measurement results. Moreover, with this device, by solving the above simultaneous equations, the blood reduced hemoglobin concentration C(H
b) and blood oxygenated hemoglobin concentration C (HbO2)
Based on these values, blood total hemoglobin concentration C(Hb+HbO2) and arterial blood oxygen saturation (C(HbO2)/C(Hb+HbO2)
)) has the advantage of being easy to calculate.

In this embodiment, a single light-receiving element 16 receives all the transmitted light from the first light to the fourth light, but a plurality of light-receiving elements each receiving each light individually are used. It is also possible to include a light receiving element and calculate the blood bilirubin concentration based on the output signal of each light receiving element. In this case, there is no need for means for separating signals as in the above embodiment. However, as in the above embodiment, a single light receiving element 1
If all of the light is received at 6, there is an effect that the structure can be simplified and the cost can be reduced.

[0047]

As described above, the present invention emits light having appropriate wavelengths toward the measurement site, receives the transmitted light, and creates a signal corresponding to the amount of transmitted light for each wavelength. Since the blood bilirubin concentration is calculated based on each signal obtained at the first time and the second time, the blood bilirubin concentration can be measured non-invasively without drawing blood from the subject. Can be done. Therefore, it is possible to accurately diagnose jaundice by directly measuring the blood bilirubin concentration without causing pain or disability to the subject.

Furthermore, according to the device according to claim 2, the light receiving means is constituted by a single light receiving element, which receives all the transmitted light, so that the structure of the device can be simplified and the cost can be reduced. This has the effect of reducing costs.

[Brief explanation of the drawing]

FIG. 1 is an overall configuration diagram of a blood bilirubin concentration measuring device in one embodiment of the present invention.

FIG. 2 is a waveform diagram showing a light emission timing signal and a sample hold timing signal output from a timing generation section in the above device.

FIG. 3 (a) is a waveform diagram showing the output signal of the I/V conversion section in the above device, (b) is a waveform diagram showing the output signal of the sample hold section corresponding to the first light emitting element in the same device; c) is a waveform diagram showing an output signal of the low-pass filter section corresponding to the first light emitting element.

[Figure 4] (a) is a graph showing the relationship between light wavelength and the light absorption coefficient of each substance in the short wavelength region, and (b) is a graph showing the relationship between light wavelength and the light absorption coefficient of each substance in the long wavelength region. This is a graph showing.

[Explanation of symbols]

10 Measurement probe 11 First light emitting element (first light emitting means) 12 Second light emitting element (second light emitting means) 13 Third light emitting element (third light emitting means) 14 Fourth light emitting element (fourth light emitting means) 16
Light-receiving element (light-receiving means) 20 Arithmetic control system 24 Light-emitting element drive section (light-emitting means) 26 Timing generation section 28 I/V conversion section (signal generation means) 30 Signal separation circuit (signal generation means) 40 A/D converter ( Signal creation means) 42 Arithmetic control section (arithmetic means)

Claims (2)

[Claims] 1. A first light emitting means for emitting a first light having a wavelength absorbed by deoxyhemoglobin, oxyhemoglobin and bilirubin in blood toward a measurement site;
different from the wavelength of light, and reduced hemoglobin in the blood,
a second light emitting means that emits a second light having a wavelength that is absorbed by at least deoxyhemoglobin of oxyhemoglobin and bilirubin toward the measurement site, and the wavelength of the first light and the second light are different from each other; and third light emitting means for emitting third light having a wavelength absorbed by at least oxyhemoglobin among deoxyhemoglobin, oxidized hemoglobin and bilirubin in the blood toward the measurement site; a fourth light emitting means for emitting fourth light having a wavelength that is not absorbed by bilirubin but absorbed only by water, toward the measurement site; and a fourth light emitting means for receiving light emitted from these light emission means and transmitted through the measurement site. a light-receiving means for converting into an electrical signal, and based on the output signal of the light-receiving means, create signals corresponding to the transmitted amounts of the first light, the second light, the third light, and the fourth light, respectively. and a calculation for calculating the blood bilirubin concentration based on each signal created at a first time in the signal creation means and each signal created at a second time different from the first time. A blood bilirubin concentration measuring device characterized by comprising: means. 2. The blood bilirubin concentration measuring device according to claim 1, wherein the light receiving means is composed of a single light receiving element that receives all of the transmitted light, and the output signal of the light receiving means is transmitted to the first light receiving element. A blood bilirubin concentration measuring device characterized in that the signal generating means is configured to separate the signals into signals corresponding to the transmitted amounts of the light, the second light, the third light, and the fourth light, respectively.