JP2009128099A - Method and apparatus for concentration measurement - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a measuring method and apparatus capable of measuring the concentration of substances at any depth of a scattered object having no interface. <P>SOLUTION: Low-coherent light emitted from a prescribed light source is divided into measuring light for making the low-coherent light incident onto an object to be measured to generate backscattered light and reference light to interfere with the backscattered light. The concentration of the object to be measured in computed on the basis of the intensity of interference light acquired by the interference between the backscattered light and the reference light in the concentration measuring method. The concentration measuring method includes the measuring position determination process for measuring the intensity of the interference light as changing an optical path length and determining a plurality of measuring positions from among a region in which a rate of change in the intensity of the interference light is small to changes in the optical path length and the concentration computation process for computing the concentration of the object to be measured on the basis of the intensity of the interference light at the plurality of measuring positions. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a concentration measurement method and a concentration measurement device, and more particularly to a concentration measurement method and a concentration measurement device for measuring a substance concentration at an arbitrary depth of a scattering object.

  As a method for obtaining a tomographic image of a measurement object such as a living body, a method called OCT (Optical Coherence Tomography) has been proposed and has been put to practical use mainly in the ophthalmic field. Since OCT uses interference of low-coherence light, it has the feature that the measurement object can be identified in the depth direction with the resolution of the coherence length, and non-invasively measures the measurement object. This technology has been attracting attention in recent years.

  A measuring method and a measuring apparatus for measuring the concentration of glucose in a living body using such characteristics of OCT have been proposed (for example, see Patent Documents 1 and 2).

  Patent Document 1 describes a method of measuring the intensity of backscattered light from two boundary surfaces of the eyeball and determining the glucose concentration in the aqueous humor component based on the intensity of the two backscattered lights. Yes.

Patent Document 2 describes a method of obtaining a phase gradient from an interference signal by reflected light from two reflection points, and obtaining a refractive index as a measure of glucose concentration from the difference therebetween.
JP 9-299333 A JP 9-512722 A

  However, the methods described in Patent Documents 1 and 2 can be applied only when the measurement object has two boundary surfaces, and the concentration of a scattering object having no boundary surface is determined. It was difficult to measure.

  Moreover, what can be measured by the methods described in Patent Documents 1 and 2 is only an average concentration in a region sandwiched between two boundary surfaces, and the concentration at an arbitrary depth of the measurement object cannot be measured. There was a problem.

  Furthermore, the method described in Patent Document 2 has a problem that the amount of calculation required for obtaining the concentration, such as Fourier transform, is very large, which increases the size of the measuring device and lengthens the measuring time.

  The present invention has been made in view of the above technical problems, and an object of the present invention is to provide a measurement method and a measurement apparatus capable of measuring a substance concentration at an arbitrary depth of a scattering object having no boundary surface. Is to provide.

  In order to solve the above problems, the present invention has the following features.

  1. The low-coherent light emitted from a predetermined light source is divided into measurement light for entering a measurement object and generating backscattered light, and reference light for causing interference with the backscattered light, and the backscattered light A concentration measurement method for calculating a substance concentration of an object to be measured from the intensity of interference light obtained by interference with the reference light, measuring the intensity of the interference light while changing the optical path length, From the region where the change rate of the intensity of the interference light with respect to the change is small, a measurement position determining step for determining a plurality of measurement positions, and from the intensities of the interference light at the plurality of measurement positions, And a concentration calculating step for calculating a substance concentration.

  2. The measurement position determining step is a step of calculating a second derivative value of the intensity of the measured interference light and determining the plurality of measurement positions from a region where the second derivative value is substantially zero. 2. The concentration measuring method according to 1 above, wherein

  3. The concentration calculation step is a step of calculating a substance concentration of a measurement object based on a ratio of the intensity of the interference light at the plurality of measurement positions and a distance between the plurality of measurement positions. 3. The concentration measuring method according to 1 or 2 above.

  4). A light source that emits low-coherent light, light emitted from the light source is divided into measurement light that is incident on a measurement object and generates backscattered light, and reference light that is interfered with the backscattered light Splitting means for performing measurement, intensity measuring means for measuring the intensity of interference light obtained by interference between the backscattered light and the reference light, and concentration calculation for calculating the substance concentration of the measurement object from the intensity of the interference light An optical path length changing means for changing an optical path length of the reference light to change a measurement position in a measurement object, and for calculating a substance concentration by the concentration calculating means. Measuring position determining means for determining a plurality of measurement positions for measuring the intensity of the interference light to be used, wherein the measurement position determining means changes the optical path length by the optical path length changing means, and the intensity of the interference light The Determining the plurality of measurement positions from a region where the change rate of the intensity of the interference light is small in a fixed case, and the concentration calculation means is configured to determine the plurality of measurement positions determined by the measurement position determination means. A concentration measuring apparatus that calculates a substance concentration of an object to be measured from the intensity of the interference light at a measurement position.

  5). The measurement position determining means determines the plurality of measurement positions from a region where the second derivative of the intensity of the interference light is approximately 0 when the intensity of the interference light is measured while changing the optical path length. 5. The concentration measuring apparatus according to 4 above, wherein:

  6). The concentration calculation means calculates the substance concentration of the measurement object based on the ratio of the intensity of the interference light at the plurality of measurement positions and the distance between the plurality of measurement positions. 5. The concentration measuring apparatus according to 5.

  In the present invention, a plurality of measurement positions are determined from a region where the change rate of the intensity of the interference light with respect to the change in the optical path length is small, and the substance of the measurement object is determined from the intensity of the interference light at the plurality of measurement positions. In order to calculate the concentration, it is possible to measure the substance concentration at any depth of a scattering object having no interface.

  Hereinafter, embodiments of the present invention will be described in detail with reference to FIGS.

FIG. 1 is a diagram showing a concentration measuring apparatus 10 which is an example of an embodiment of the present invention. FIG. 2 is a flowchart showing an example of the concentration measuring method of the present invention. FIG. 3 is a diagram illustrating measurement light and backscattered light incident on a measurement object, and FIG. 4 is a diagram illustrating an intensity profile of interference light measured by the concentration measurement apparatus 10. Moreover, FIG. 5 is a figure which shows the density | concentration measuring apparatus 20 which is another embodiment of this invention.
(Concentration measuring device 10)
First, the configuration of the concentration measuring apparatus 10 shown in FIG. 1 will be described.

  The concentration measuring apparatus 10 has a light source 11 that emits low-coherent light. As the light source 11, for example, an LED (light emitting diode), an SLD (super luminescence diode), a halogen lamp, or the like can be used.

  In the concentration measuring apparatus 10, the resolution in the depth direction of the measurement object can be increased as the coherent length (coherence distance) of the light emitted from the light source 11 is shorter. Therefore, among the above, the SLD can be preferably used as the light source 11 because the coherent length of the emitted light is as short as about several tens of μm. In addition, a short pulse laser such as a femtosecond laser, or a laser whose emission light wavelength changes with time can be used as the light source 11.

  The emitted light 31 from the light source 11 is split into measurement light 32 and reference light 33 by the half mirror 12 that functions as the splitting means of the present invention. The measurement light 32 is a light beam for entering the measurement object 40 and generating backscattered light 34, and the reference light 33 is caused to interfere with the backscattered light 34 generated at a predetermined depth of the measurement object 40. This is a light beam for generating the interference light 35.

  In FIG. 1, the light beam that has passed through the half mirror 12 is the measurement light 32, and the light beam that has been reflected by the half mirror 12 is the reference light 33. However, the present invention is not limited to this. The light beam may be configured as the reference light 33 and the light beam reflected by the half mirror 12 as the measurement light 32.

  There is no particular limitation on the intensity ratio between the measurement light 32 and the reference light 33. Usually, the ratio may be about 1: 1, but the division ratio may be changed according to the properties of the measurement object 40 and the like.

  The reference light 33 is reflected by the reference mirror 13 and returns to the half mirror 12 again. The reference mirror 13 can move in the optical axis direction of the reference light 33 (the arrow direction in FIG. 1) to change the optical path length of the reference light 33, and the optical path for changing the measurement position in the measurement object 40. Functions as a length changing means.

  On the other hand, the measurement light 32 is incident on the measurement object 40. Since the measurement object 40 is a scattering object, the measurement light 32 incident on the measurement object 40 generates scattered light 36 at any depth and proceeds while decreasing the intensity. Of the scattered light 36, the light that has returned almost linearly with respect to the measuring light 32 reaches the half mirror 12 as backscattered light 34.

  The intensity of the interference light 35 obtained by the interference between the back scattered light 34 reflected by the half mirror 12 and the reference light 33 reflected by the reference mirror 13 and then transmitted through the half mirror 12 is measured by the detector 14. To do. Here, the reference light 33 and the backscattered light 34 interfere with each other only when the difference in optical path length between them is equal to or less than the coherent length of the emitted light 31 from the light source 11. In this embodiment, since the emitted light 31 from the light source 11 is a low-coherent light having a short coherent length, only the backscattered light 34 from a specific depth at which the optical path length is substantially equal to the reference light 33 contributes to interference. It will be. Therefore, by moving the reference mirror 13 and adjusting the optical path length of the reference light 33, the intensity of the interference light 35 due to the backscattered light 34 from the predetermined depth of the measurement object 40 can be measured.

  When a laser whose emission light wavelength changes with time is used as the light source 11, the intensity measurement of the interference light 35 by the detector 14 is preferably performed by integrating the interference light intensity over time.

The concentration measuring apparatus 10 further includes a measurement position determining unit 15 and a concentration calculating unit 16 configured by a computer having a CPU, a memory, and the like. The measurement position determination means 15 determines a plurality of measurement positions for measuring the intensity of the interference light 35 used for the calculation of the substance concentration by the concentration calculation means 16. The plurality of measurement positions are determined from an area where the change in the intensity change rate of the interference light 35 is small when the intensity of the interference light 35 is measured while changing the optical path length by the reference mirror 13. Further, the concentration calculation means 16 calculates the substance concentration of the measurement object 40 from the intensities of the interference light 35 at the plurality of measurement positions determined by the measurement position determination means 15.
(Concentration measurement method)
Next, an example of an embodiment of the concentration measuring method of the present invention using the concentration measuring apparatus 10 will be described with reference to the flowchart of FIG.

  In the flowchart of FIG. 2, in steps S11 to S14, the intensity of the interference light 35 is measured while changing the optical path length. From the region where the change in the rate of change of the intensity of the interference light 35 with respect to the change in the optical path length is small, It is a measurement position determination step for determining a plurality of measurement positions. The step S15 is a concentration calculation step for calculating the substance concentration of the measurement object 40 from the intensities of the interference light 35 at the determined plurality of measurement positions.

  In order to facilitate understanding, the concentration calculation step S15 will be described first. FIG. 3 is a schematic diagram showing the measurement light 32 incident on the measurement object 40 and the backscattered light 34 (d1) and 34 (d2) generated at the two measurement positions (depths) d1 and d2. Here, the distance from the position d0 on the surface of the measurement object 40 to the measurement position d1 is D1, and the distance from the position d0 on the surface of the measurement object 40 to the measurement position d2 is D2. The concentration measurement target region is a region between d1 and d2, and the concentration of the substance in this region is constant at C.

  The intensity of the measurement light 32 incident on the surface of the measurement object 40 is I0. Further, the intensity of the interference light 35 due to the backscattered light 34 (d1) generated at the measurement position d1 is I1, and the intensity of the interference light 35 due to the backscattered light 34 (d2) generated at the measurement position d2 is I2.

  In an object with strong forward scattering, backscattered light that is almost linear light can be obtained by interference of low-coherence light. Therefore, from Lambert-Beer law (Beer-Lambert law), the following formulas (1) and (2) ) Holds.

-Log (I1 / I0) = 2 · ε · C · D1 (1)
-Log (I2 / I0) = 2 · ε · C · D2 Equation (2)
Here, ε is an intrinsic extinction coefficient.

  From the expressions (1) and (2), the concentration C in the target region is obtained by the expression (3).

  By using Expression (3), the predetermined measurement object is determined based on the ratio of the intensity of the interference light 35 (I2 / I1) at a plurality of measurement positions and the distance (D2-D1) between the plurality of measurement positions. The density C in the target area can be obtained. As a result, the substance concentration at an arbitrary depth of the scattering object having no boundary surface can be measured. Further, as apparent from the equation (3), the concentration C in a predetermined region can be obtained without being affected by a region shallower or deeper than the measurement target region.

  In the case of obtaining the concentration C by the equation (3), in order to obtain high measurement accuracy, the substance is homogeneous in the target region between the plurality of measurement positions, that is, the change in the refractive index is small, and the interference light The change in the intensity change rate of 35 is required to be small. Therefore, in the present embodiment, prior to the concentration calculation, in the measurement position determination step (S11 to S14), a plurality of regions are selected from regions where the change rate of the intensity of the interference light 35 with respect to the change in the optical path length is small. Determine the measurement position.

  Next, returning to the flowchart of FIG. 2, the measurement position determining step (S11 to S14) will be described.

  First, the intensity of the interference light 35 is measured while changing the optical path length, and the intensity profile of the interference light 35 is acquired (step S11). The optical path length is changed by moving the reference mirror 13. FIG. 4A is a graph showing an example of the intensity profile 41 obtained in this step. The horizontal axis indicates the optical path length of the reference light 33, and the vertical axis indicates the intensity of the interference light 35. In this step, it is preferable to move the reference mirror 13 in a sufficiently wide range so that the intensity of the interference light corresponding to the depth to be measured is surely included. Note that when the refractive index of the measurement object 40 is n, it is necessary to move the position of the reference mirror 13 by n × D in order to ensure the depth width D of the measurement object 40.

  Next, the optical path length d0 corresponding to the surface of the measuring object 40 is determined (step S12). Here, the optical path length d0 corresponding to the surface of the measurement object 40 is the optical path length d0 of the reference light 33 when the backscattered light 34 from the surface of the measurement object 40 interferes with the reference light 33. is there. In the present embodiment, as shown in FIG. 4A, the position where the intensity of the interference light 35 rapidly increases first may be set as d0.

  Next, using the optical path length d0 as the surface (depth 0) of the measuring object 40, the second derivative of the intensity of the interference light 35 is obtained in the vicinity of the optical path length d corresponding to the depth to be measured (step S13). . 4B shows the first derivative 42 of the intensity of the interference light 35 obtained in the vicinity of the optical path length d, and FIG. 4C shows the second derivative 43 of the intensity of the interference light 35 obtained in the same region. Show.

  Then, two measurement positions d1 and d2 used for calculation of the substance concentration in the next concentration calculation step S15 are determined from the region where the second derivative 43 of the intensity of the interference light 35 is substantially 0 (step S14). In this way, by determining two measurement positions from the region where the second derivative 43 of the intensity of the interference light 35 is substantially zero, a region where the change in the rate of change of the intensity of the interference light 35 is small, that is, the substance It is possible to set two measurement positions in a homogeneous region.

  Here, the region where the secondary derivative 43 is substantially zero does not require the secondary derivative 43 to be completely zero in all the regions, and various factors (for example, vibration, temperature change, etc.) that affect the measured value. Etc.) is allowed as long as it does not cause a problem in measurement accuracy.

  There is no restriction | limiting in particular in the space | interval of two measurement position d1 and d2, What is necessary is just to determine suitably according to the property etc. of the measuring object 40. FIG. In general, when the product (ε · C) of the extinction coefficient ε and the concentration C of the measurement object 40 is large, if the distance between d1 and d2 is too wide, the intensity of the interference light 35 is reduced and the accuracy is improved. Since there is a risk of lowering, it is preferable to narrow the interval. Conversely, when the product of the extinction coefficient ε and the concentration C of the measurement object 40 is small, it is preferable to widen the distance between d1 and d2 in order to obtain high accuracy.

In addition, the number of measurement positions determined in the measurement position determination step for use in the calculation of the concentration is not limited to two if it is plural, and more measurement positions such as three and four are determined. May be. In this case, the concentration C can be obtained by a method such as calculating the equation (3) in a plurality of regions and obtaining an average value.
(Concentration measuring device 20)
Next, the concentration measuring apparatus 20 which is another embodiment of the present invention shown in FIG. 5 will be described. The same components as those in the concentration measuring apparatus 10 described above with reference to FIG.

  The light source 11 emits low coherent light in the same manner as the concentration measuring apparatus 10. The light emitted from the light source 11 is shaped by the beam shaping element 21 so that the beam profile (beam cross-sectional shape) is circular. When the light source 11 is a semiconductor light source such as an SLD, the beam profile may be elliptical. In that case, by using the beam shaping element 21 to shape the beam profile into a circle, the light utilization efficiency can be improved and the measurement accuracy can be improved.

  The light shaped by the beam shaping element 21 is converted into parallel light by the collimator lens 22 and enters the polarization beam splitter 23. The polarization beam splitter 23 is configured to transmit the P-polarized component of the light from the light source 11. The P-polarized light (linearly polarized light) transmitted through the polarizing beam splitter 23 is converted into circularly polarized light by the λ / 4 wavelength plate 24 and then reaches the optical path length changing means 25.

  The optical path length changing means 25 has a condensing optical element 26, a half mirror 12 and a reference mirror 13, and changes the optical path length by moving in the direction of the arrow as a whole while keeping their relative positions constant. It is configured to be able to.

  The parallel light that has reached the optical path length changing means 25 is converted into convergent light by the condensing optical element 26. The half mirror 12 is disposed in the optical path of the convergent light, and divides the incident convergent light into measurement light (transmitted light) and reference light (reflected light).

  The reference light reflected by the half mirror 12 is reflected by the reference mirror 13 disposed at the condensing position by the condensing optical element 26 and returns to the half mirror 12 again. Then, the light reflected again by the half mirror 12 becomes parallel light by the condensing optical element 26.

  On the other hand, the measurement light transmitted through the half mirror 12 is incident on the measurement object 40, the generated backscattered light reaches the half mirror 12, a part thereof is transmitted through the half mirror, and is collimated by the converging optical element 26. It becomes.

  At this time, of the returned backscattered light, only the backscattered light from a predetermined position where the optical path length is equal to the reference light interferes with the reference light and becomes interference light. The interference light that has passed through the λ / 4 wavelength plate 24 is converted from circularly polarized light to S polarized light, reflected by the polarizing beam splitter 23, and condensed by the sensor lens 27.

  A confocal point 28 is disposed at the focal position of the sensor lens 27. As a result, only the backscattered light, which is emitted in a narrow angle range and is close to the straight light, out of the scattered light generated from the measurement object 40 passes through the confocal 28, so that unnecessary scattered light components are removed. Measurement accuracy can be further improved.

  The interference light that has passed through the confocal 28 is detected by the detector 14 and the intensity is measured. The signal detected by the detector 14 is amplified by the signal amplification means 29 and sent to the measurement position determination means 15 and the concentration calculation means 16. The signal amplifying means 29 can be constituted by a lock-in amplifier or the like, and contributes to improvement in measurement accuracy when the interference light is weak.

  The method for measuring the substance concentration when using the concentration measuring device 20 is the same as that when using the above-described concentration measuring device 10, and can be performed according to the flowchart shown in FIG.

It is a figure showing concentration measuring device 10 which is an example of an embodiment of the present invention. It is a flowchart which shows one example of the density | concentration measuring method of this invention. It is a figure which shows the measurement light and backscattered light which injected into the measuring object. It is a figure which shows the intensity profile of interference light. It is a figure which shows the density | concentration measuring apparatus 20 which is another embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10, 20 Density measuring apparatus 11 Light source 12 Half mirror 13 Reference mirror 14 Detector 15 Measurement position determining means 16 Concentration calculating means 21 Beam shaping element 22 Collimating lens 23 Polarizing beam splitter 24 λ / 4 wavelength plate 25 Optical path length changing means 26 Condensing Optical element 27 Sensor lens 28 Confocal 29 Signal amplification means 31 Emission light 32 Measurement light 33 Reference light 34 Back scattered light 35 Interference light 36 Scattered light 40 Measurement object 41 Intensity profile 42 First derivative 43 Second derivative d1, d2 Measurement position

Claims (6)

Dividing the low-coherent light emitted from a predetermined light source into measurement light for entering the measurement object and generating backscattered light, and reference light for interfering with the backscattered light,
A concentration measurement method for calculating a substance concentration of an object to be measured from the intensity of interference light obtained by interference between the backscattered light and the reference light,
A measurement position determining step of measuring the intensity of the interference light while changing the optical path length, and determining a plurality of measurement positions from a region where a change in the change rate of the intensity of the interference light with respect to the change in the optical path length is small;
And a concentration calculation step of calculating a substance concentration of the measurement object from the intensity of the interference light at the plurality of measurement positions.   The measurement position determining step is a step of calculating a second derivative value of the intensity of the measured interference light and determining the plurality of measurement positions from a region where the second derivative value is substantially zero. The concentration measuring method according to claim 1.   The concentration calculation step is a step of calculating a substance concentration of a measurement object based on a ratio of the intensity of the interference light at the plurality of measurement positions and a distance between the plurality of measurement positions. The concentration measuring method according to claim 1 or 2. A light source that emits low coherent light;
Splitting means for splitting light emitted from the light source into measurement light for entering the measurement object and generating backscattered light, and reference light for causing interference with the backscattered light,
Intensity measuring means for measuring the intensity of interference light obtained by interference between the backscattered light and the reference light;
A concentration measuring device having a concentration calculating means for calculating a substance concentration of an object to be measured from the intensity of the interference light,
An optical path length changing means for changing an optical path length of the reference light to change a measurement position in the measurement object;
Measuring position determining means for determining a plurality of measuring positions for measuring the intensity of the interference light used for calculation of the substance concentration by the concentration calculating means,
The measurement position determining unit is configured to measure the plurality of measurement positions from a region where the change rate of the interference light intensity is small when the intensity of the interference light is measured while changing the optical path length by the optical path length changing unit. Is to determine
The concentration measuring device calculates a substance concentration of a measurement object from the intensity of the interference light at the plurality of measurement positions determined by the measurement position determining unit.   The measurement position determining means determines the plurality of measurement positions from a region where the second derivative of the intensity of the interference light is approximately 0 when the intensity of the interference light is measured while changing the optical path length. The concentration measuring apparatus according to claim 4, wherein:   5. The concentration calculation unit calculates a substance concentration of a measurement object based on a ratio of the intensity of the interference light at the plurality of measurement positions and a distance between the plurality of measurement positions. Or the concentration measuring apparatus according to 5;

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