JP2007187583A - Optical path length measuring device and specific component measuring device using it - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To precisely measure optical path length that is easily varied in a living body and is difficult to be measured depending on the part of the living body. <P>SOLUTION: A magnetic field is applied to the living body, the optical path length L is calculated based on the rotation angle θ of the rotation in the polarization direction by the Faraday effect of the living body itself, the intensity H of the magnetic field, and the Verdet constant V of the living body. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a technique for obtaining an optical path length of light propagating through a biological sample or measuring a concentration of a specific component in the biological sample.

Conventionally, the concentration of a specific component in a test sample has been measured by irradiating the test sample with light and detecting the intensity of the transmitted light having a specific wavelength. In this case, the following formula (2):
I = I ₀ × exp (−A × C × L) (2)
(In the formula (2), I ₀ : intensity of irradiated light
I: Intensity of transmitted light
L: Distance (light path length) that light propagates through the test sample
C: Specific component concentration
A: Absorption coefficient of a specific component for a specific wavelength)
Was used to calculate the concentration. That is, I is measured, and the concentration C of the specific component is calculated from I ₀ , L, and A. Therefore, in order to calculate the concentration, it is necessary to know the optical path length L in advance.

Here, for example, a quantitative analysis apparatus capable of so-called non-invasive measurement is proposed that calculates the concentration of glucose or the like from the outside of a human body by irradiating a biological sample such as an earlobe and measuring transmitted light. (For example, refer to Patent Document 1).
Here, it is disclosed that a mechanical member that clamps a biological sample with a constant thickness is used in order to determine the optical path length and make it constant.
JP 2001-356089 A

However, when the test sample is a living body, if it is clamped at a certain thickness, the original state of the biological sample may not be maintained due to the pinching pressure, and the concentration of the specific component may not be accurately measured. . More specifically, the blood flow and pressure change due to the pinching pressure, and the component concentration in the living tissue changes, so that there is a possibility that the component concentration cannot be measured accurately. For example, when the blood glucose level in the vein changes, the glucose concentration in the cell interstitial fluid also changes with a slight delay, but this may affect the degree of this delay.
Further, when the clamp is performed for a long time, the subject feels uncomfortable, and it may be difficult to perform continuous measurement at all times. Furthermore, there are cases where it is desired to perform measurement at a site that is difficult to clamp, such as the eyeball and its surroundings, but the technique described in Patent Document 1 cannot be measured accurately.
Therefore, it is preferable to measure the optical path length of the biological sample without applying a pinching pressure having such a size that the thickness of the biological sample is constant.

  However, when the optical path length is measured with a biological sample sandwiched between calipers or the like without applying a pinching pressure of a size that keeps the thickness of the biological sample constant, the thickness of the biological sample changes due to the pressure pinching the biological sample. Therefore, it is difficult to accurately measure the optical path length.

  Therefore, in view of the above-described conventional problems, the present invention can accurately calculate the optical path length of a biological sample without applying a pinching pressure of a size that makes the thickness of the biological sample constant. An object is to provide an optical path length measuring device. Another object of the present invention is to provide a specific component measuring apparatus capable of accurately calculating the concentration of a specific component in a biological sample using the obtained optical path length of the biological sample.

In order to solve the above problems, the present invention controls a light source that projects linearly polarized light onto a biological sample, a magnetic field application unit that applies a magnetic field to the biological sample, a magnetic field control unit that controls the magnetic field, and a magnetic field control unit. A magnetic field control signal generating unit that generates a magnetic field control signal to be detected; an analyzer that transmits a component in a specific polarization direction among the light transmitted through the biological sample; and the component that is transmitted through the analyzer is detected, and the detection is performed. An optical path length measuring device comprising: an optical sensor that outputs a signal corresponding to the signal; and an arithmetic unit that calculates an optical path length of linearly polarized light propagating through the biological sample based on the magnetic field control signal and the output signal of the optical sensor. I will provide a.
Furthermore, the present invention also provides a specific component measuring apparatus provided with the optical path length measuring apparatus of the present invention described above.

  According to the optical path length measuring device of the present invention, the optical path length of a biological sample can be accurately calculated without applying a pinching pressure of a size that makes the thickness of the biological sample constant. Moreover, according to the specific component measuring apparatus of the present invention, the concentration of the specific component in the biological sample can be accurately calculated using the obtained optical path length of the biological sample.

The optical path length measurement apparatus of the present invention irradiates a biological sample with light, simultaneously applies a magnetic field to the biological sample, rotates the polarization direction of the light by a predetermined angle by the Faraday effect, and calculates the optical path length from the applied magnetic field strength. Moreover, the specific component measuring apparatus of the present invention calculates the concentration of the specific component in the biological sample using the obtained optical path length of the biological sample.
That is, according to the present invention, by applying light to a biological sample and simultaneously applying a magnetic field to the biological sample, the optical path length of the biological sample and the concentration of a specific component can be adjusted in a non-contact manner without restraining the biological sample by clamping or the like. It can be measured.

In the present invention, examples of the part of the living body that emits light include an arm, a finger, an ear, and an eye.
Examples of the specific component contained in the biological sample and to be measured by the present invention include glucose, hemoglobin, and albumin.

  The optical path length measurement device of the present invention includes a light source that projects linearly polarized light onto a biological sample, a magnetic field application unit that applies a magnetic field to the biological sample, a magnetic field control unit that controls the magnetic field, and a magnetic field that controls the magnetic field control unit. A magnetic field control signal generation unit that generates a control signal, an analyzer that transmits a component of a specific polarization direction among light transmitted through a biological sample, and the component that transmits the analyzer, and detects the component according to the detection An optical sensor that outputs a signal; and an arithmetic unit that calculates an optical path length of the linearly polarized light propagating through the biological sample based on the magnetic field control signal and the output signal of the optical sensor.

Here, the magnetic field control unit sweeps the magnetic field until the output signal of the optical sensor shows a local maximum value and a local minimum value, and the arithmetic unit calculates a magnetic field control signal when the output signal of the optical sensor shows a local maximum value. It is preferable to calculate the optical path length based on the difference between the intensity and the intensity of the magnetic field control signal when the output signal of the optical sensor shows a minimum value.
In addition, the arithmetic unit selects n discrete magnetic field control signals Xi (i is an integer) from among the magnetic field control signals, and further outputs n optical sensor output signals corresponding to the magnetic field control signals Xi. Yi (i is an integer) is selected, and the n Xi and the n Yi are represented by the formula (1):
Y = α + β × (Sin ((X / γ) −δ)) ² (1)
(Equation (1) where Y is a variable indicating the output signal of the optical sensor, α, β, γ and δ are calculated constants, and X is a variable corresponding to the magnetic field control signal). It is preferable to calculate α, β, γ, and δ by regression processing based on the principle of the square method, and to calculate the optical path length of the linearly polarized light propagating in the biological sample from the γ.
The optical path length measuring device of the present invention also includes a signal generator for generating and outputting a signal for modulating the intensity of light emitted from the light source, and an output signal of the optical sensor as a reference signal. It is preferable to further include a lock-in amplifier that performs phase-sensitive detection and outputs a signal corresponding to the detection, and the output signal of the lock-in amplifier is used as the output signal of the optical sensor.
The specific component measuring apparatus of the present invention calculates the absorbance in the biological sample based on the above optical path length measuring apparatus and α or β, and the absorbance, the extinction coefficient of the specific component contained in the biological sample, and γ It is preferable to include a concentration calculation unit that calculates the concentration of the specific component in the biological sample from the calculated optical path length of the biological sample.

The principle used by the optical path length measuring device and the specific component measuring device of the present invention will be described below.
When light is propagated in a substance and a magnetic field is applied in the propagation direction, the polarization direction of the light is rotated according to the propagation by so-called magnetic rotation. This phenomenon is called the optical Faraday effect. This optical Faraday effect is expressed by the following equation (3):
Θ = V × H × L (3)
(In the formula (3), Θ: rotation angle of polarization direction [minute],
V: Verde constant of matter [min / A]
H: Magnetic field [A / m]
L: Optical path length [m])
It is represented by
V in this formula (3) varies depending on the substance, the wavelength of light, and the temperature. An example of V of various substances is shown in Table 1 below.

An optical Faraday modulator used in the prior art is one that uses this optical Faraday effect. In this method, a solenoid coil is wound around a rod-shaped flint glass to apply a magnetic field by passing a current through the solenoid coil, thereby modulating the polarization direction of light propagating in the magnetic field direction. The polarization direction can be freely controlled by controlling the current flowing through the solenoid coil.
Thus, the polarization direction can be controlled by applying a magnetic field to a substance by the optical Faraday effect. As can be seen from Table 1, this is the same for water, chloroform, acetone and the like. The same applies to a living body mainly composed of water.

Examples of the magnetic field application unit include a solenoid coil and a magnet that apply a magnetic field in the light propagation direction. This magnetic field can be modulated by modulating the current flowing through the solenoid coil or by modulating the distance between the magnet and the test sample.
As described above, for example, Japanese Patent No. 3072040 discloses that the polarization direction can be controlled by applying a magnetic field to a substance and controlling the magnetic field.

Here, the above equation (3) is converted into the following equation (4):
L = Θ / (V × H) (4)
Can be converted to
As is clear from Equation (4), L can be calculated from H at that time and V of the substance by rotating Θ by a predetermined angle.
In this way, the optical path length L can be calculated from the rotation angle Θ of the polarization direction rotated by the Faraday effect of the living body itself, the intensity H of the magnetic field, and the constant V of the Verde of the living body by applying a magnetic field to a test sample such as a living body. .

Hereinafter, embodiments of the present invention will be described with reference to the drawings. More specifically, first, the optical path length measurement principle of the present invention will be described using pure water as a test sample instead of a biological sample, and then the present invention will be described using an aqueous glucose solution as the test sample instead of the biological sample. The principle of measuring the concentration of specific components will be described.
A configuration for carrying out the optical path length measuring device and the specific component measuring device of the present embodiment is shown in FIG. As shown in FIG. 1, the optical path length measurement device and the specific component measurement device according to the present embodiment are configured to convert a substantially parallel light 2 from a light source 1 that emits light having an absorption wavelength of a specific component into a biological sample (or test sample). Irradiate.

The light source 1 is, for example, a white light emitting device such as a lamp, a spectroscopic device such as a diffraction grating or an optical filter that extracts only light of a specific wavelength, a lens system that makes substantially parallel light, and intermittently intensifies light to modulate the intensity of the substantially parallel light Consists of choppers.
Further, as the light source 1, a projection module including a light emitting device such as a semiconductor laser or an LED, a lens, and a driving circuit may be used.

A sample cell 20 for holding a test sample is composed of a cylindrical member 3 and polaroid plates 4 and 5 having dichroism and transmitting linearly polarized light. The optical path length of the substantially parallel light 2 in the test sample is L.
The polaroid plate 4 constitutes an incident surface on which the substantially parallel light 2 enters the test sample, and the polaroid plate 5 constitutes an exit surface on which the substantially parallel light 2 exits from the test sample.
Further, the polaroid plate 4 functions as a polarizer that transmits light whose polarization direction is parallel to the paper surface, and the polaroid plate 5 functions as a polarizer that transmits light whose polarization direction is perpendicular to the paper surface. Here, the relative angle D of the polarization direction of the light transmitted through the entrance surface and the exit surface is π / 2.

The material constituting the cylindrical member 3 is not particularly limited, and may or may not have light transmittance.
Note that the propagation distances at the entrance surface and the exit surface are sufficiently smaller than the propagation distance (optical path length) of the substantially parallel light 2 in the test sample.
A magnetic field is applied to the test sample in the sample cell by the solenoid coil 6 wound around the substantially parallel light 2 with the sample cell 20 interposed therebetween. This magnetic field is applied in the propagation direction of the substantially parallel light 2 and its intensity is substantially uniform in the optical path of the substantially parallel light 2 in the test sample. Further, the strength of the magnetic field is proportional to the current flowing through the solenoid coil 6.

In addition, the optical path length measuring device of the present embodiment controls the intensity of the parallel light 2 by controlling the driver 7 for passing the current J through the solenoid coil 6, the optical sensor 8 for detecting the light emitted from the emission surface, and the light source 1. A signal generator (that is, a signal generator that generates and outputs a signal for modulating the intensity of light emitted from the light source) 9 and an output signal of the optical sensor 8 are output from the signal generator 9. A lock-in amplifier 10 that performs phase-sensitive detection using the signal as a reference signal, and a computer (including a calculation unit and a control unit) 11 that issues a command signal to the driver 7 and records and analyzes the output signal of the lock-in amplifier 10 are provided.
Here, the solenoid coil 6 is the magnetic field application unit of the present invention, the driver 7 is the magnetic field control unit of the present invention, the polaroid plate 5 is the analyzer of the present invention, and the computer 11 is the arithmetic unit and the magnetic field control signal generation unit of the present invention. It corresponds to.

According to the above configuration, the polarization direction of the substantially parallel light 2 in the test sample rotates Θ in proportion to the current J flowing through the solenoid coil. The intensity of the substantially parallel light 2 reaching the optical sensor 8 at that time, that is, the output signal S of the lock-in amplifier 10 is expressed by the following equation (5):
S = E + F × (Sin (Θ−δ)) ²
= E + F × (Sin ((V × k × J × L) −δ)) ² (5)
(In the formula (5), the output signal of the lock-in amplifier 10 when E: Θ = 0 (J = 0)
F: Value obtained by subtracting E from the output signal of the lock-in amplifier 10 when Θ = π / 2
k: Proportional constant
δ: Polarization direction rotation in the test sample independent of the magnetic field)
It is represented by

Note that E is zero when the polaroid plates 4 and 5 are ideal and depolarization does not occur in the test sample, and F corresponds to the transmittance of the test sample.
In this embodiment, since the intensity of the substantially parallel light 2 is modulated, the intensity of the substantially parallel light 2 reaching the optical sensor 8 is indicated by an output signal of the lock-in amplifier. However, in the present invention, the intensity of the substantially parallel light 2 need not be modulated. When the intensity of the substantially parallel light 2 is not modulated, the output signal of the optical sensor 8 may be used to indicate the intensity of the substantially parallel light 2 that reaches the optical sensor 8.

The operation of the optical path length measurement device and the specific component measurement device according to the present embodiment will be described in the case where pure water or an aqueous glucose solution is used as a test sample and the optical path length L is 5 cm.
The light source 1 emits light having a wavelength that is absorbed by glucose in the aqueous glucose solution. The computer 11 issues a command signal to the driver 7 to sweep the current flowing through the solenoid coil 6 from -10A to + 10A. The output signal of the lock-in amplifier 10 at this time is shown in FIG.
In FIG. 2, the horizontal axis indicates the current J (A) flowing through the solenoid coil 6, and the vertical axis indicates the output signal (arbitrary value) of the lock-in amplifier 10. FIG. 2 plots the results of measurement at 21 measurement points for pure water as the test sample.

Here, each measurement point is assigned as a measurement point Pi (Xi, Yi) (in this case, i is an integer of 1 to 21). Xi represents the current J at each point, and Yi represents the output signal of the lock-in amplifier at each point. Then, Xi and Yi of these 21 measurement points Pi (Xi, Yi) are subjected to regression processing based on the principle of the least squares method with the regression equation shown in the above formula (1), and α, β, γ and δ is calculated. As a result, the following values are obtained.
α = 8.9 × 10 ⁻⁵
β = 2.2
γ = 586 / π
δ = 0
FIG. 3 shows a diagram in which a regression curve obtained by substituting these numerical values into the above equation (1) is drawn in the range of X = −600 to 600.

Here, when the above formula (1) is compared with the above formula (5), the following formula:
L = 1 / (γ × V × k) = (1 / γ) × (1 / (V × k))
Is obtained.
V can be determined by the substance contained in the test sample. Since pure water is used here, V is 1.645 as shown in Table 1 above. However, V of the biological sample takes a slightly large value (approximately within 10%) close to 1.645 because the main component of the biological sample is water.

Such a V value can also be determined by the following method, for example.
(A) A method in which an animal (eyeball or the like) or a simulated living body (phantom) using water, protein, and fat is created and placed in a sample cell having a known optical path length and measured.
(B) A method in which the optical path length is determined at a part (such as an arm or a finger) where the optical path length can be easily measured by another method and V is measured (for example, the sample cell 20 is not used in the apparatus shown in FIG. 1). , How to place a finger etc. and measure).
(C) A method in which the glucose concentration in the living body is separately measured (invasive type is acceptable), and the optical path length is obtained from the light absorption coefficient and transmittance using the above equation (2) to measure V.

Further, k can be determined based on the characteristics of the solenoid coil 6. More specifically, it can be determined by, for example, calculating electromagnetically (known) using the number of turns, the length, or the like of the solenoid coil 6 or using a magnetic field measuring machine.
Therefore, the optical path length L can be calculated using the above formula (1) and the above formula (5).

Moreover, when measuring the same measurement site | part (for example, finger | toe) of the same biological body (the same person) using a certain apparatus, ie, measuring the biological sample (test sample) of the same composition, V is It can be regarded as a constant, and V × k can also be regarded as a constant. Therefore, the optical path length L can be regarded as being proportional to 1 / γ.
Therefore, if γ is obtained in advance using a biological sample whose optical path length is known, the actual optical path length can be calculated from the ratio with γ calculated for the test sample whose optical path length is unknown.

The optical path length in the “biological sample whose optical path length is known” can be measured by another method. For example, when measuring by another method, measurement based on the present invention is simultaneously performed to obtain γ (however, at this time, the optical path length of the biological sample is considered constant).
As another method, for example, a method of mechanically measuring with a caliper or the like can be considered.

Embodiment 1
In the present embodiment, the optical path length measuring device and the specific component measuring device shown in FIG. 1 described above are used by using a glucose aqueous solution (pseudo biological sample) as a test sample instead of the biological sample.

1. Measurement of optical path length The optical path length L was set to 2.5 cm, 1 cm, or 0.5 cm, the current passed through the solenoid coil 6 was swept from −10 to +10 A, and γ was calculated using 21 measurement points. The result is shown in FIG. In FIG. 4, the horizontal axis indicates the optical path length (cm), and the vertical axis indicates 1 / γ. From FIG. 4, it can be confirmed that the optical path length L is proportional to 1 / γ.
Therefore, using FIG. 4 as a calibration curve, the optical path length can be determined based on γ.

2. Measurement of Specific Component Next, the optical path length L is set to 5 cm, and glucose coils having a glucose concentration of 100 mg / dl, 250 mg / dl, and 500 mg / dl are used as a pseudo biological sample, and the solenoid coil 6 is used in the same manner as described above. The current passed through was swept from −10 to +10 A to obtain 21 measurement points. Then, similarly to the above, a regression curve equation was calculated using the measurement point Pi (Xi, Yi) and the above equation (1).
Β obtained at this time is normalized by β (= 2.2) in the case of pure water (that is, when β = 2.2, it is normalized so that it becomes 1 (= 100) on the vertical axis in FIG. ) And displayed on the vertical axis of FIG. From FIG. 5, it can be confirmed that β depends on the concentration.
Therefore, using FIG. 5 as a calibration curve, the specific component (glucose) concentration can be obtained based on the calculated β.

Further, since the optical path length can be calculated using the above formula (5), the concentration of the specific component (glucose) may be calculated based on the absorption coefficient of glucose and β using the Lambert-Bear formula. .
This concentration calculation may be performed as follows. This case corresponds to the case where the optical path length L and glucose extinction coefficient A are known in the Lambert-Bear equation shown in the above equation (2). Therefore, the glucose concentration (Cy) of the simulated biological sample is measured in advance by another method, and at the same time, α and β (αy, βy) at that time are obtained by the method of the present invention.

Thereafter, when the concentration Cx of the pseudo biological sample is measured, the pseudo biological sample is measured by the above-described method of the present invention to obtain αx and βx. These are respectively expressed by the following formulas (6) and (7). However, Q is a constant.
I ₀ × exp (−A × Cy × L) = Q × (αy + βy) (6)
I ₀ × exp (−A × Cx × L) = Q × (αx + βx) (7)
By dividing both sides of the above equation (7) by both sides of the above equation (6), the following equation (8) is obtained, and the concentration Cx can be calculated from the above equation (8).
Cx = Cy− (1 / (A × L)) × Ln ((αx + βx) / (αy + βy))
... (8)

Here, α and β satisfy the relationship of the following formula (9).
α = s × β (9)
Here, s is a constant regardless of the concentration C if it is the same part of the same living body. Substituting equation (9) into (8) yields the following equation (10).
Cx = Cy− (1 / (A × L)) × Ln (((s + 1) × βx) / ((s + 1) × βy))
= Cy- (1 / (A * L)) * Ln ([beta] x / [beta] y) (10)
As shown in the above equation (10), the concentration Cx can be calculated from only β.

  As described above, according to the present embodiment, the optical path length and the specific component are determined from the relationship between the current flowing through the solenoid coil corresponding to the magnetic field strength and the output signal of the lock-in amplifier, by sweeping the magnetic field applied to the test sample. Concentration can be measured.

In the present embodiment, the magnetic field is swept only in the vicinity where the output signal of the lock-in amplifier exhibits a minimum value, but the range in which the output signal of the lock-in amplifier exhibits a minimum value to a maximum value (in FIG. 3, current J = 0A to In the range of 293A, the magnetic field may be swept, the optical path length may be calculated from the difference between the current values indicating the respective values, and the concentration may be calculated from the difference between the minimum value and the maximum value.
However, in this embodiment, the regression curve equation is calculated based on the above equation (1) by sweeping the magnetic field only around the periphery where the output signal of the lock-in amplifier shows the minimum value, and performing the regression process. The value of the current that flows can be reduced, which is particularly advantageous for downsizing.

Further, the sweep range of the magnetic field is not particularly limited, and for example, it is possible to perform measurement using the optical path length measuring device and the specific component measuring device of the present invention even if sweeping is performed in a range not including the extreme value.
However, sweeping in a range including the extreme value is preferable from the viewpoint of obtaining the effect of the present invention more reliably. In particular, in the case of the minimum value, compared with the change in the output signal of the optical sensor due to the sweeping of the magnetic field (the second term in the above formula (1)), the offset of the output signal (the first in the above formula (1)) ) Is small, it is possible to increase the gain of the lock-in amplifier and increase the S / N, which is advantageous because more accurate measurement is possible.

<< Embodiment 2 >>
In the present embodiment, a finger is used as a biological sample, and an optical path length measuring device and a specific component measuring device shown in FIG. 6 to be described later are used.
A configuration for carrying out the optical path length measuring device and the specific component measuring device of the present embodiment is shown in FIG. The components indicated by reference numerals 1, 2 and 6-11 in FIG. 6 are the same as the constituent elements indicated by reference numerals 1, 2 and 6-11 in FIG. 1, and have similar functions. Reference numeral 12 denotes a biological sample.

In the case of this embodiment, since the test sample is a biological sample, it has dichroism. Here, “dichroism” means a phenomenon in which the absorbance varies when the polarization direction is different even with linearly polarized light of the same wavelength (see, for example, “Biochemical Dictionary 3rd edition”). This refers to a phenomenon exhibited by a substance drawn from a polymer. Even isotropic materials may exhibit dichroism when pressure is applied.
Skin on the surface of a living body exhibits dichroism, and the size of the dichroism changes depending on the stretched state of the skin. The surface of the biological sample 12, that is, the skin, corresponds to the portions indicated by reference numerals 4 and 5 in FIG.

1. Measurement of optical path length As in the first embodiment, the light source 1 emits light having a wavelength that glucose absorbs, the computer 11 issues a command signal to the driver 7, and the current flowing through the solenoid coil 13 ranges from -20 to 20A. Sweep.
FIG. 7 is a prediction diagram showing the current dependency of the output signal of the lock-in amplifier 10. In FIG. 7, the horizontal axis indicates the current J (A) flowing through the solenoid coil 7, and the vertical axis indicates the output signal (arbitrary value) of the lock-in amplifier 10. In FIG. 7, the results of measurement performed on 41 measurement points are plotted.

Here, each measurement point is assigned as a measurement point Pi (Xi, Yi) (i is an integer from 1 to 41). Xi represents the current J at each point, and Yi represents the output signal of the lock-in amplifier at each point.
Then, Xi and Yi of these 41 measurement points Pi (Xi, Yi) are subjected to regression processing based on the principle of the least squares method with the regression equation shown in the above formula (1), and α, β, γ and δ is calculated. As a result, the following values are obtained.
α = 0.2
β = 0.8
γ = 3000 / π
δ = 0

FIG. 8 is a diagram obtained by enlarging the horizontal axis of FIG. 7 using the above α, β, and γ. From this γ, the optical path length L in the biological sample 12 can be calculated in the same manner as in the first embodiment.
Further, the glucose concentration in the biological sample 12 can be calculated from the optical path lengths L and β in the same manner as in the first embodiment.

Note that the thickness (= optical path length) L ₀ of the biological sample is mechanically measured in advance, and γ at this time is γ ₀ . For example, in the case of a finger or the like, the optical path length L ₀ may be measured by a mechanical method such as calipers. When measuring by this method, γ ₀ is obtained by simultaneously measuring according to the present invention.
Thereafter, when measuring the glucose concentration, the optical path length L _x may be obtained by the following equation (10) by comparing with the calculated γ = γ _x .
L _x = (γ ₀ / γ _x ) × L ₀ (10)
This eliminates the need for mechanical measurement each time the thickness changes for a biological sample.

Here, the thickness of a part having a different biological sample thickness (= optical path length) may be mechanically measured, and each γ may be measured in the same manner as described above to create a calibration curve similar to FIG. At the same time, the glucose concentration in the living body is separately measured (invasive type is possible), β at that time is obtained, and β is similarly obtained even when glucose in the living body is different. A calibration curve similar to 5 may be created.
Similarly, the glucose concentration C ₀ in the biological sample is measured, and at this time, γ is γ ₀ , and β is = β ₀ . Thereafter, when measuring the glucose concentration, the calculated γ _x and β _x are compared with γ ₀ and β _0, and from this result, the glucose concentration C _x can be calculated based on C _0. Good.

Here, FIG. 9 shows a modification of the optical path length measurement device and the specific component measurement device according to the second embodiment of the present invention. As shown in FIG. 9, the signal generator and the lock-in amplifier are not necessarily used, the output signal of the optical sensor 8 is used as the output signal of the lock-in amplifier 10, and the optical path length measuring device and the specific component measuring device are used as described above. It is also possible to operate and measure the optical path length and specific components.
However, it is preferable to use the signal generator and the lock-in amplifier as described above from the viewpoint of securing a higher S / N and measuring the optical path length and the specific component more accurately.

As described above, according to the present embodiment, the optical path length and the concentration of the specific component are determined from the relationship between the current flowing through the solenoid coil corresponding to the magnetic field strength and the output signal of the lock-in amplifier, by sweeping the magnetic field applied to the biological sample. Can be measured.
In the case of this embodiment, it is not necessary to apply pressure to the biological sample with a clamp or the like, which is advantageous for continuous measurement. Moreover, since it can respond also to the change of optical path length, the practical effect is very large.

In the first and second embodiments, an example is shown in which the concentration is calculated from β. As in the first and second embodiments, when β is larger than α (s <1), it is advantageous to increase the accuracy by calculating the concentration using β.
However, when β is smaller than α (s> 1), it is advantageous to calculate the concentration in the same manner as described above from α instead of β. Examples of the case where β is smaller than α include a case where depolarization in the test sample is large and a case where the dichroism of the biological sample is small.

  The optical path length measurement device and the specific component measurement device according to the present invention are useful when obtaining the optical path length of a biological sample or measuring the concentration of a specific component in a biological sample.

It is a figure which shows the structure of the optical path length measuring apparatus of Embodiment 1 of this invention, and a specific component measuring apparatus. It is a graph which shows the relationship between the electric current sent through a solenoid coil in Embodiment 1 of this invention, and the output signal of a lock-in amplifier. It is a graph which shows the relationship between the electric current sent through a solenoid coil in Embodiment 1 of this invention, and the output signal of a lock-in amplifier. In Embodiment 1 of this invention, it is a graph which shows the relationship between optical path length and 1 / gamma. It is a graph which shows the relationship between the glucose level and the logarithm of an output signal (arbitrary value) in Embodiment 1 of this invention. It is a figure which shows the structure of the specific component measuring apparatus of Embodiment 2 of this invention. It is a graph which shows the relationship between the electric current sent through a solenoid coil in Embodiment 2 of this invention, and the output signal of lock-in amplifier. It is a graph which shows the relationship between the electric current sent through a solenoid coil in Embodiment 2 of this invention, and the output signal of lock-in amplifier. It is a figure which shows the structure of the modification of the specific component measuring apparatus of Embodiment 2 of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Light source 2 Parallel light 3 Cylindrical member 4 Polaroid plate 5 Polaroid plate 6 Solenoid coil 7 Driver 8 Optical sensor 9 Computer

Claims (5)

A light source that projects linearly polarized light onto a biological sample;
A magnetic field application unit for applying a magnetic field to the biological sample;
A magnetic field controller for controlling the magnetic field;
A magnetic field control signal generator for generating a magnetic field control signal for controlling the magnetic field controller;
Of the light transmitted through the biological sample, an analyzer that transmits a component in a specific polarization direction;
An optical sensor that detects the component transmitted through the analyzer and outputs a signal according to the detection;
An arithmetic unit that calculates an optical path length of the linearly polarized light propagating through the biological sample based on the magnetic field control signal and the output signal of the optical sensor;
An optical path length measuring device. The magnetic field controller sweeps the magnetic field until the output signal of the optical sensor shows a maximum value and a minimum value,
The arithmetic unit is configured to determine an optical path based on a difference between an intensity of the magnetic field control signal when the output signal of the optical sensor shows a maximum value and an intensity of the magnetic field control signal when the output signal of the optical sensor shows a minimum value. Calculate the length,
The optical path length measuring device according to claim 1. The arithmetic unit selects n discrete magnetic field control signals Xi (i is an integer) from the magnetic field control signals, and further outputs n output signals Yi (n) corresponding to the magnetic field control signals Xi. i is an integer),
The n pieces of Xi and the n pieces of Yi are represented by the formula (1):
Y = α + β × (Sin ((X / γ) −δ)) ² (1)
(Where, Y is a variable indicating the output signal of the optical sensor, α, β, γ, and δ are calculated constants, and X is a variable corresponding to the magnetic field control signal). To calculate α, β, γ and δ by regression based on the principle of least squares method,
Calculating an optical path length of the linearly polarized light propagating in the biological sample from the γ,
The optical path length measuring device according to claim 1. A signal generator for generating and outputting a signal for modulating the intensity of the light emitted from the light source;
A phase-insensitive detection of the output signal of the optical sensor using the output signal of the signal generator as a reference signal, and a lock-in amplifier that outputs a signal corresponding to the detection; and
The output signal of the lock-in amplifier is the output signal of the photosensor,
The optical path length measuring device according to claim 1. An optical path length measuring device according to claim 3,
Based on the α or β, the absorbance in the biological sample is calculated, from the absorbance, the extinction coefficient of the specific component contained in the biological sample, and the optical path length of the biological sample calculated from the γ A concentration calculator that calculates the concentration of the specific component in the biological sample;
A specific component measuring apparatus.

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