Method for measuring concentration of optically active substance and apparatus for measuring concentration of optically active substance

Abstract

Provided is a method for measuring the concentration of an optically active substance in aqueous humor and an apparatus for measuring the concentration of an optically active substance, which can measure the concentration of an optically active substance in aqueous humor simply and with high accuracy. The method for measuring the concentration of an optically active substance includes a first step of irradiating incident light, which is polarized light, to the aqueous humor of an eye and measuring the polarization state of reflected light obtained by reflection at the interface between the aqueous humor and the lens, wherein the first incident light is irradiated so that the angle between the normal at the point where the incident light intersects the surface of the lens and the incident light is smaller than the Brewster angle, and the polarization state of the first reflected light is measured; a second step of irradiating second incident light so that the angle of the incident light is equal to or greater than the Brewster angle, and the polarization state of the second reflected light is measured; a third step of calculating the optical rotation of the aqueous humor using the information on the polarization state of the first reflected light and the information on the polarization state of the second reflected light; and a fourth step of calculating the concentration of the optically active substance in the aqueous humor based on the optical rotation of the aqueous humor.

Description

Technical Field

[0001] The present invention relates to a method for measuring the concentration of an optically active substance and a device for measuring the concentration of an optically active substance. Background Art

[0002] As a non-invasive method for measuring blood sugar levels, the following method has been proposed: utilizing optical properties that depend on glucose concentration, irradiating polarized light into the aqueous humor of the eye, and measuring the optical rotation of the polarized light that passes through the aqueous humor and is reflected at the interface with the lens, thereby measuring the glucose concentration.

[0003] For example, in patent document 1, the following device is described, which includes: a light source mechanism for irradiating light into the anterior chamber along a primary side optical path having a central light ray; a detection mechanism for detecting light emitted from the light source mechanism and light emitted from the anterior chamber along a secondary side optical path having a central light ray, and generating a measurement signal representing the detected light; and a signal processing mechanism connected to the detection mechanism, for measuring optical properties based on the measurement signal, wherein the device is a device for measuring the optical properties of aqueous humor in the anterior chamber of a patient's eye in vivo, wherein the device is arranged to be located in front of the patient's eye, and the central light rays of the primary side optical path and the secondary side optical path are arranged to be equidistant from a perpendicular line relative to the anterior interface of the lens of the eye and to be at opposite angles, wherein mirror reflection from the interface is detected by the detection mechanism.

[0004] Previous technical literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Laid-Open No. 6-237898 Summary of the Invention

[0007] Technical issues to be solved by the invention

[0008] In the method of measuring glucose concentration by irradiating polarized light into the aqueous humor of the eye and measuring the optical rotation of the polarized light that has passed through the aqueous humor, the polarized light passes through the cornea of ​​the eye when it enters the aqueous humor and when it is reflected by the lens and emitted. The cornea has optical properties that easily cause polarization to vary compared to the aqueous humor. Therefore, for example, due to the influence of individual patient variations in optical rotation based on the cornea, it is difficult to accurately measure the optical rotation based on the aqueous humor, resulting in a problem of low accuracy in measuring glucose concentration in the aqueous humor.

[0009] An object of the present invention is to provide a method for measuring the concentration of an optically active substance and an optically active substance concentration measuring device capable of measuring the concentration of an optically active substance in aqueous humor simply and with high accuracy.

[0010] Means for solving technical problems

[0011] In order to solve the problem, the present invention has the following configuration.

[0012] [1] A method for measuring the concentration of an optically active substance, comprising:

[0013] A first step is a step of irradiating first incident light, which is polarized light, into the aqueous humor of the eye and measuring the polarization state of first reflected light obtained by reflecting the first incident light at the interface between the aqueous humor and the crystalline lens, wherein the first incident light is irradiated so that an angle θ1 formed by the first incident light and a normal to a tangential plane at a point where the first incident light intersects the surface of the crystalline lens is smaller than a Brewster angle, thereby measuring the polarization state of the first reflected light;

[0014] A second step is a step of irradiating the aqueous humor of the eye with second incident light as polarized light and measuring the polarization state of second reflected light obtained by reflecting the second incident light at the interface between the aqueous humor and the crystalline lens, wherein the second incident light is irradiated so that an angle θ2 formed between the normal to the tangential plane at a point where the second incident light intersects the surface of the crystalline lens and the second incident light is equal to or greater than Brewster's angle, thereby measuring the polarization state of the second reflected light;

[0015] a third step of calculating the optical rotation of aqueous humor using the information on the polarization state of the first reflected light obtained in the first step and the information on the polarization state of the second reflected light obtained in the second step; and

[0016] The fourth step is to calculate the concentration of the optically active substance in the aqueous humor based on the optical rotation of the aqueous humor.

[0017] [2] The method for measuring the concentration of an optically active substance according to [1], wherein:

[0018] The first step is performed multiple times under the condition that the angle θ1 formed between the normal line and the first incident light is different to obtain information on the polarization states of the first reflected light in the multiple first steps, and the third step is performed using the obtained information.

[0019] [3] The method for measuring the concentration of an optically active substance according to [1] or [2], wherein:

[0020] The second step is performed multiple times under the condition that the angle θ2 formed between the normal line and the second incident light is different to obtain information on the polarization state of the second reflected light in multiple second steps, and the third step is performed using the obtained multiple pieces of information.

[0021] [4] The method for measuring the concentration of an optically active substance according to any one of [1] to [3], wherein:

[0022] The first step is performed a plurality of times while changing the wavelength of the first incident light, thereby acquiring information on the polarization states of the first reflected light in the plurality of first steps, and the third step is performed using the acquired information.

[0023] [5] The method for measuring the concentration of an optically active substance according to any one of [1] to [4], wherein:

[0024] The second step is performed a plurality of times while changing the wavelength of the second incident light, thereby acquiring information on the polarization states of the second reflected light in the plurality of second steps, and the third step is performed using the acquired information.

[0025] [6] The method for measuring the concentration of an optically active substance according to any one of [1] to [5], wherein:

[0026] The angle θ2 formed between the normal line and the second incident light in the second step is larger than the Brewster angle.

[0027] [7] The method for measuring the concentration of an optically active substance according to any one of [1] to [6], wherein:

[0028] The optically active substance is glucose.

[0029] [8] The method for measuring the concentration of an optically active substance according to any one of [1] to [7], wherein:

[0030] In at least one of the first step and the second step, a two-dimensional sensor is used in which light receiving parts that receive reflected light are two-dimensionally arranged.

[0031] [9] The method for measuring the concentration of an optically active substance according to any one of [1] to [8], wherein:

[0032] The third step uses the information on the polarization state of the first reflected light obtained in the first step to obtain information on the optical properties of the cornea of ​​the eye.

[0033] The optical rotation of the aqueous humor is calculated using information on the optical characteristics of the cornea and information on the polarization state of the second reflected light obtained in the second step.

[0034]

[10] An optically active substance concentration measuring device for carrying out the optically active substance concentration measuring method described in any one of [1] to [9], the optically active substance concentration measuring device comprising:

[0035] a light source that irradiates incident light as polarized light into the aqueous humor of the eye;

[0036] a measuring unit for measuring a polarization state of reflected light obtained by reflecting incident light at an interface between aqueous humor and the lens;

[0037] a control unit that controls the incident angle of the incident light; and

[0038] The calculation unit calculates the optical rotation of the aqueous humor using information on the polarization state of the reflected light measured by the measurement unit.

[0039]

[11] The optically active substance concentration measuring device according to

[10] , wherein:

[0040] The light source comprises a light emitting element and a polarizing plate.

[0041] The measuring unit has a polarizing plate and a light receiving element.

[0042] At least one of the light source and the measuring unit includes a phase difference plate.

[0043]

[12] The optically active substance concentration measuring device according to

[11] , wherein:

[0044] The light receiving element is a two-dimensional sensor in which light receiving portions that receive reflected light are two-dimensionally arranged.

[0045] Effects of the Invention

[0046] According to the present invention, a method for measuring the concentration of an optically active substance and an optically active substance concentration measuring device capable of simply and accurately measuring the concentration of an optically active substance in aqueous humor can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 This is a conceptual diagram for explaining the first step of the method for measuring the concentration of an optically active substance of the present invention.

[0048] Figure 2 This is a conceptual diagram for explaining the calculation model in the first step.

[0049] Figure 3 It is a diagram for explaining the angle θ.

[0050] Figure 4 This is a conceptual diagram for explaining the second step of the method for measuring the concentration of an optically active substance of the present invention.

[0051] Figure 5 This is a conceptual diagram for explaining the calculation model in the second step.

[0052] Figure 6 This is a conceptual diagram used to explain the change in polarized light from air to the cornea.

[0053] Figure 7 is a graph showing intensity changes at the air-cornea interface.

[0054] Figure 8 This is a conceptual diagram used to explain the changes in polarized light between the cornea and aqueous humor.

[0055] Figure 9 It is a graph showing the intensity change at the cornea-aqueous humor interface.

[0056] Figure 10 This is a conceptual diagram used to explain the changes in polarized light between the aqueous humor and the lens.

[0057] Figure 11 This is a conceptual diagram used to explain the changes in polarized light between aqueous humor, cornea, and air.

[0058] Figure 12 This is a diagram conceptually showing an example of the optically active substance concentration measuring device of the present invention.

[0059] Figure 13 It is a schematic diagram for explaining another example of the measuring unit.

[0060] Figure 14 This is a graph showing the relationship between the rotation angle and the light intensity.

[0061] Figure 15 It is a schematic diagram for explaining another example of the measuring unit.

[0062] Figure 16 It is a diagram showing the relationship between the polarization state and the light reception pattern.

[0063] Figure 17 It is a schematic diagram for explaining another example of the measuring unit.

[0064] Figure 18 It is a schematic diagram for explaining another example of a light receiving element.

[0065] Figure 19 This is a perspective view for explaining the arrangement of polarizing plates in a measurement unit.

[0066] Figure 20 Observing from the other direction Figure 19 When the picture. DETAILED DESCRIPTION

[0067] Hereinafter, the optically active substance concentration measuring method and the optically active substance concentration measuring device of the present invention will be described in detail based on the preferred embodiments shown in the accompanying drawings.

[0068] In this specification, the numerical range expressed with "to" means a range including the numerical values ​​described before and after "to" as the lower limit and the upper limit.

[0069] In this specification, “same”, “equal”, etc. include an error range generally allowed in the technical field.

[0070] [Measurement method of concentration of optically active substances]

[0071] The method for measuring the concentration of an optically active substance of the present invention comprises:

[0072] A first step is a step of irradiating first incident light, which is polarized light, into the aqueous humor of the eye and measuring the polarization state of first reflected light obtained by reflecting the first incident light at the interface between the aqueous humor and the crystalline lens, wherein the first incident light is irradiated so that an angle θ1 formed by the first incident light and a normal to a tangential plane at a point where the first incident light intersects the surface of the crystalline lens is smaller than a Brewster angle, thereby measuring the polarization state of the first reflected light;

[0073] A second step is a step of irradiating the aqueous humor of the eye with second incident light as polarized light and measuring the polarization state of second reflected light obtained by reflecting the second incident light at the interface between the aqueous humor and the crystalline lens, wherein the second incident light is irradiated so that an angle θ2 formed between the normal to the tangential plane at a point where the second incident light intersects the surface of the crystalline lens and the second incident light is equal to or greater than Brewster's angle, thereby measuring the polarization state of the second reflected light;

[0074] a third step of calculating the optical rotation of aqueous humor using the information on the polarization state of the first reflected light obtained in the first step and the information on the polarization state of the second reflected light obtained in the second step; and

[0075] The fourth step is to calculate the concentration of the optically active substance in the aqueous humor based on the optical rotation of the aqueous humor.

[0076] <First Step>

[0077] Figure 1 This is a conceptual diagram showing the first step for explaining the method for measuring the concentration of an optically active substance of the present invention.

[0078] The first step is a step in which first incident light Sin1 as polarized light is incident on the aqueous humor 14 of the eye 10 from a light source (not shown), and a measuring unit (not shown) measures the polarization state of reflected light Sout1 reflected at the interface between the aqueous humor 14 and the lens 16 and emitted from the eye 10.

[0079] Specifically, first, as indicated by arrow I1, first incident light Sin1 emitted from a light source passes through air and enters cornea 12. As indicated by arrow I2, the light that entered cornea 12 passes through cornea 12 and enters aqueous humor 14. As indicated by arrow I3, the light that entered aqueous humor 14 passes through aqueous humor 14 and reaches lens 16, where it is reflected at the interface between aqueous humor 14 and lens 16. As indicated by arrow I4, the reflected light passes through aqueous humor 14 and enters cornea 12. As indicated by arrow I5, the light that entered cornea 12 passes through cornea 12 and exits eye 10. The emitted light (arrow I6) enters the measurement unit. The measurement unit measures the polarization state of first reflected light Sout1.

[0080] The measurement unit for measuring the polarization state of the reflected light will be described in detail later. The polarization state is preferably measured using a two-dimensional sensor having light receiving units for receiving the reflected light arranged two-dimensionally.

[0081] In this first step, as light travels, it is affected by the cornea 12, aqueous humor 14, and reflections, causing the polarization state to change. Figure 2 2 shows a model for calculating the change in the polarization state of light in the first step. Figure 2 The diagram shows incident light Sin1 sequentially passing through the incident cornea 12a, the incident aqueous humor 14a, the reflecting aqueous humor 14b, and the reflecting cornea 12b from the left side to be emitted as reflected light Sout1.

[0082] The cornea 12 and aqueous humor 14 each have optical properties that change the polarization state of light, specifically, optical rotation. Optical rotation is an optical property that causes the plane of polarization of incident linearly polarized light to rotate. Therefore, as the first incident light Sin1 passes through the incident cornea 12a, the incident aqueous humor 14a, the reflected aqueous humor 14b, and the reflected cornea 12b, its plane of polarization rotates at various locations and is emitted as the first reflected light Sout1.

[0083] Therefore, in the first step, the angle θ1 of the first incident light Sin1 when it is reflected at the interface between the aqueous humor 14 and the lens 16 is smaller than the Brewster angle. Figure 3 As shown, the angle θ of the incident light is the angle formed by the normal line N and the direction of travel of the incident light (arrow I3), and the normal line N is the normal line relative to the cut surface H when defining the cut surface H at the point where the incident light intersects the surface (interface) of the crystal 16. In the following description, the angle of the first incident light Sin1 in the first step is referred to as θ1, and the angle of the second incident light Sin2 in the second step is referred to as θ2. And, the so-called Brewster angle θ B , is to make the medium on the incident side ( Figure 3The refractive index of the aqueous humor 14 is set to ni, and the medium on the reflecting side ( Figure 3 The refractive index of the crystal 16 is set to nt, and tanθ B =The angle represented by nt / ni.

[0084] When the angle θ1 of the first incident light Sin1 is less than the Brewster angle, if it is incident on the interface between the aqueous humor 14 and the crystalline lens 16, the crystalline lens has a higher refractive index than the aqueous humor, so the phase of the s-polarized light is shifted by π, while the phase of the p-polarized light is not shifted. The plane of incidence is a plane perpendicular to the plane of reflection that includes both the incident light and the reflected light.

[0085] Therefore, the angle (optical rotation) by which the plane of polarization is rotated due to the optical rotation of the aqueous humor 14 when the light passes through the aqueous humor 14 before being reflected at the interface between the aqueous humor 14 and the lens 16 (arrow I3) and the optical rotation based on the optical rotation of the aqueous humor 14 when the light passes through the aqueous humor 14 after being reflected (arrow I4) cancel each other out, so that the optical rotation caused by passing through the aqueous humor 14 becomes approximately 0.

[0086] On the other hand, the polarization change of light due to the birefringence of the cornea 12 when the light passes through the cornea 12 before being reflected at the interface between the aqueous humor 14 and the lens 16 (arrow I2) and the polarization change of light due to the birefringence of the cornea 12 when the light passes through the cornea 12 after being reflected (arrow I5) cannot be completely offset, and the optical rotation caused by passing through the cornea 12 cannot become 0.

[0087] This is because, with respect to the oblique incident polarized light, the axis angle is different between the incident side and the reflected side.

[0088] Typically, optically active optical elements, such as aqueous humor 14, exhibit an optical effect (also known as circular retardation) in which light is rotated by an amount corresponding to the retardation amount, with the North Pole or South Pole of the Poincare sphere as the center of rotation. Because the position of the rotation center is fixed, there is no concept of an axis, and light is rotated by an amount corresponding to the retardation amount in the same rotation direction, regardless of the incident direction.

[0089] On the other hand, birefringent optical elements, such as the cornea 12, exhibit an optical effect (also known as linear retardance) of rotating about the equator of the Poincare sphere by an amount corresponding to the retardation. The point on the equator that serves as the rotation center depends on the direction of the slow axis. Thus, in optical elements with birefringent axis, axis shift occurs depending on the direction of incident light.

[0090] Therefore, as described above, in the first step, the optical rotation caused by passing through the aqueous humor 14 is canceled out on the incident side and the reflected side, but the polarization change caused by passing through the cornea 12 is not canceled out on the incident side and the reflected side.

[0091] Therefore, the polarization state of the first reflected light measured in the first step can ignore the influence of the optical rotation of the aqueous humor 14 and can be considered to be substantially affected only by the optical properties of the cornea 12. Therefore, the optical properties of the cornea 12 can be calculated based on the information on the polarization state of the first incident light Sin1 and the information on the polarization state of the first reflected light Sout1 in the first step.

[0092] <Second step>

[0093] Next, use Figure 4 The second step will be described. Figure 4 This is a conceptual diagram showing the second step for explaining the method for measuring the concentration of an optically active substance of the present invention.

[0094] The second step is as follows: second incident light Sin2 as polarized light is incident on the aqueous humor 14 of the eye 10 from a light source (not shown), and the polarization state of reflected light Sout2 reflected at the interface between the aqueous humor 14 and the lens 16 and emitted from the eye 10 is measured by a measuring unit (not shown).

[0095] Specifically, first, as shown by arrow I7, the second incident light Sin2 emitted from the light source passes through the air and is incident on the cornea 12. As shown by arrow I8, the light incident on the cornea 12 passes through the cornea 12 and is incident on the aqueous humor 14. As shown by arrow I9, the light incident on the aqueous humor 14 passes through the aqueous humor 14 and reaches the lens 16, and is reflected at the interface between the aqueous humor 14 and the lens 16. As shown by arrow I 10 As shown, the reflected light passes through the aqueous humor 14 and enters the cornea 12. As shown by arrow I 11 As shown, the light incident on the cornea 12 passes through the cornea 12 and is emitted from the eye 10. The emitted light (arrow I 12 The polarization state of the second reflected light Sout2 is measured by the measuring unit.

[0096] In this second step, as the light travels, it is affected by the cornea 12, aqueous humor 14, and reflections, causing the polarization state to change. Figure 5 2 shows a model for calculating the change in the polarization state of light in the second step. Figure 5 The figure shows that the second incident light Sin2 passes through the cornea 12a on the incident side, the aqueous humor 14a on the incident side, the reflection of the lens 16, the aqueous humor 14b on the reflecting side, and the cornea 12b on the reflecting side in sequence and is emitted as the second reflected light Sout2.

[0097] The second incident light Sin2 has its polarization plane rotated at each portion when passing through the incident-side cornea 12a, the incident-side aqueous humor 14a, the reflecting-side aqueous humor 14b, and the reflecting-side cornea 12b, and is emitted as the second reflected light Sout2.

[0098] Therefore, in the second step, the angle θ2 of the second incident light Sin2 when the incident light Sin2 is reflected at the interface between the aqueous humor 14 and the lens 16 is equal to or greater than the Brewster angle.

[0099] When the angle θ2 of the second incident light Sin2 is greater than the Brewster angle, if it is incident on the interface between the aqueous humor 14 and the lens 16, the refractive index of the lens is higher than that of the aqueous humor, so the phase of the s-polarized light is shifted by π, and the phase of the p-polarized light is also shifted by π. Therefore, the polarization state of the reflected light does not substantially change.

[0100] Therefore, the angle (degree of polarization rotation) by which the plane of polarization of light is rotated due to the optical rotation of the aqueous humor 14 when light passes through the aqueous humor 14 before being reflected at the interface between the aqueous humor 14 and the lens 16 (arrow I9) is the same as the angle (degree of polarization rotation) by which the plane of polarization of light is rotated due to the optical rotation of the aqueous humor 14 when light passes through the aqueous humor 14 after being reflected (arrow I9). 10 ) based on the optical rotation of the aqueous humor 14 do not cancel each other, and light is affected by the optical rotation caused by passing through the aqueous humor 14.

[0101] Furthermore, the optical rotation of the light passing through the cornea 12 (arrow I8) before being reflected at the interface between the aqueous humor 14 and the lens 16 is based on the birefringence of the cornea 12, and the optical rotation of the light passing through the cornea 12 (arrow I8) after being reflected is based on the birefringence of the cornea 12. 11 )'s optical rotation based on the birefringence of the cornea 12 will not be canceled out, and will be affected by the optical properties caused by passing through the cornea 12.

[0102] Therefore, the polarization state of the second reflected light measured in the second step is affected by the optical rotation of the aqueous humor 14 and the optical characteristics (birefringence) of the cornea 12 .

[0103] <Third step>

[0104] Next, the third step will be described.

[0105] The third step is a step of calculating the optical rotation of the aqueous humor 14 using the information on the polarization state of the first reflected light Sout1 obtained in the first step and the information on the polarization state of the second reflected light Sout2 obtained in the second step.

[0106] For example, in the third step, first, information about the optical properties of the cornea 12 of the eye 10 is calculated using information about the first incident light Sin1 and information about the polarization state of the first reflected light Sout1 obtained in the first step. Next, the optical rotation of the aqueous humor 14 is calculated using the calculated information about the optical properties of the cornea, information about the second incident light Sin2, and information about the polarization state of the second reflected light Sout2 obtained in the second step.

[0107] The method for calculating the optical rotation in the third step will be described in detail later.

[0108] <Fourth step>

[0109] Next, the fourth step is a step of calculating the concentration of an optically active substance such as glucose in the aqueous humor 14 based on the optical rotation of the aqueous humor 14 calculated in the third step.

[0110] Aqueous humor has almost the same composition as serum, containing proteins, glucose, ascorbic acid, and the like. Furthermore, it is known that there is a correlation between the glucose concentration in blood and the glucose concentration in the aqueous humor. Furthermore, the aqueous humor does not contain the cellular material found in blood, so the influence of light scattering is minimal. Furthermore, the proteins, glucose, ascorbic acid, and the like contained in the aqueous humor are optically active substances and exhibit optical rotation. Therefore, the aqueous humor is advantageous as a site for optically measuring the concentration of glucose and the like using optical rotation. Furthermore, if the concentration of glucose and the like in the aqueous humor can be optically measured, blood sugar levels can be measured non-invasively.

[0111] As a method for calculating the sugar concentration from the optical rotation, various known methods can be used, such as a method using the optical rotation of a glucose aqueous solution or a method of performing correction using the blood sugar level measured only in the initial blood collection.

[0112] As described above, in the method of measuring glucose concentration by irradiating polarized light into the aqueous humor of the eye and measuring the optical rotation of the polarized light that passes through the aqueous humor, the polarized light passes through the cornea of ​​the eye when it enters the aqueous humor and when it is reflected by the lens and emitted. The cornea has optical properties that easily cause changes in polarized light compared to the aqueous humor. Therefore, it is impossible to accurately measure the optical rotation based on the aqueous humor, resulting in a problem of low accuracy in measuring glucose concentration in the aqueous humor.

[0113] In contrast, the method for measuring the concentration of an optically active substance of the present invention comprises: a first step of irradiating the aqueous humor with first incident light in such a manner that the angle θ of the incident light is less than the Brewster's angle, thereby measuring the polarization state of the first reflected light; and a second step of irradiating the aqueous humor with second incident light in such a manner that the angle θ of the incident light is greater than the Brewster's angle, thereby measuring the polarization state of the second reflected light, and using information on the polarization state of the first reflected light measured at a temperature less than the Brewster's angle and information on the polarization state of the second reflected light measured at a temperature greater than the Brewster's angle, calculating the optical rotation based on the aqueous humor, and calculating the concentration of the optically active substance in the aqueous humor based on the optical rotation.

[0114] As described above, the polarization state of the first reflected light measured in the first step can ignore the influence of the optical rotation of the aqueous humor 14 and can be considered to be substantially affected only by the optical properties of the cornea 12. Therefore, the optical properties of the cornea 12 can be calculated based on the information on the polarization state of the first reflected light Sout1 measured in the first step. Based on this information on the optical properties of the cornea 12 and the information on the polarization state of the second reflected light Sout2 measured in the second step, the optical rotation based on the aqueous humor 14 can be calculated with high accuracy. Therefore, the concentration of optically active substances in the aqueous humor can be measured with high accuracy.

[0115] Hereinafter, the polarization changes occurring in each of the first step and the second step will be described.

[0116] First, when light enters the cornea 12 from the air (arrow I1), the intensity changes at the interface between the air and the cornea 12 (referred to as process A). This intensity change depends on the incident angle θ on the cornea 12. i (refer to Figure 6 ), and different changes occur in p-polarized light and s-polarized light. Figure 7 The incident angle θ is shown in i Graph showing the relationship between θ and transmittance.

[0117] Light incident on the cornea 12 from air travels through the cornea 12 (denoted by arrow I2, process B). The cornea 12 has birefringence as an optical characteristic. Therefore, the light traveling through the cornea 12 undergoes a phase change depending on the birefringence of the cornea 12. As described above, the birefringence of the cornea 12 can be calculated based on information on the polarization state of the first reflected light measured in the first step.

[0118] Then, if Figure 8 As shown in FIG, light enters the aqueous humor 14 from the cornea 12 (arrows I2 to I3, process C). The refractive indexes of the cornea 12 and the aqueous humor 14 are close. Figure 9As shown in the graph in FIG, the incident angle of light relative to the interface between the cornea 12 and the aqueous humor 14 is approximately 0° to 65°, and the intensity hardly changes. Figure 9 As shown, there is no difference between p-polarized light and s-polarized light.

[0119] Light incident on the aqueous humor 14 from the cornea 12 travels through the aqueous humor 14 (denoted by arrow I3, process D). The aqueous humor 14 has optical rotation. Therefore, the light traveling through the aqueous humor 14 undergoes a phase change depending on the optical rotation of the aqueous humor 14. As described above, the optical rotation of the aqueous humor 14 can be calculated based on information on the polarization state of the first reflected light measured in the first step and information on the polarization state of the second reflected light measured in the second step.

[0120] like Figure 10 As shown, light traveling through the aqueous humor 14 reaches the lens 16 and is reflected at the interface between the aqueous humor 14 and the lens 16 (denoted by arrows I3 and I4, process E). Therefore, as described above, when the angle θ of light incident on the interface between the aqueous humor 14 and the lens 16 is less than the Brewster's angle, the refractive index of the lens is higher than that of the aqueous humor, so the phase of s-polarized light shifts by π, while the phase of p-polarized light does not shift. On the other hand, when the angle θ of light incident on the interface between the aqueous humor 14 and the lens 16 is greater than the Brewster's angle, the phase of s-polarized light shifts by π, and the phase of p-polarized light also shifts by π.

[0121] Light reflected at the interface between the aqueous humor 14 and the lens 16 travels through the aqueous humor 14 (denoted by arrow I4, process F). As described above, the aqueous humor 14 has optical rotation. Therefore, the light traveling through the aqueous humor 14 undergoes a phase change depending on the optical rotation of the aqueous humor 14. As described above, as shown in the first step, when the angle θ of light reflected at the interface between the aqueous humor 14 and the lens 16 is less than the Brewster angle, the influence of the optical rotation from the aqueous humor 14 before reflection (arrow I3) and the influence of the optical rotation from the aqueous humor 14 after reflection (arrow I4) cancel each other out.

[0122] In the case where the reflecting surface is flat, total reflection occurs when the angle is greater than the Brewster angle. However, since the surface (interface) of the crystal is curved, reflected light is emitted.

[0123] like Figure 11 As shown, light traveling through the aqueous humor 14 enters the cornea 12 from the aqueous humor 14 (arrows I4 to I5, process G). As described above, since the refractive indexes of the cornea 12 and the aqueous humor 14 are close, there is little change in intensity.

[0124] Light incident on the cornea 12 from the aqueous humor 14 travels in the cornea 12 (set as arrow I5, process H). As described above, the cornea 12 has birefringence as an optical property, and thus light traveling in the cornea 12 undergoes a phase change according to the birefringence of the cornea 12.

[0125] Light traveling in the cornea 12 is emitted into the air (set as arrow I5 ~ arrow I6, process I). As described above, an intensity change occurs at the interface between the air and the cornea 12.

[0126] If each of these processes is modeled, it can be expressed by the formula of Sout = M IHG • M F • M E • M D • M CBA • Sin. Thus, Sin is the Stokes vector of incident light, Sout is the Stokes vector of reflected light, and M is a Mueller matrix representing each process. That is, M CBA is the Mueller matrix of process A ~ process C, M D is the Mueller matrix of process D, M E is the Mueller matrix of process E, M F is the Mueller matrix of process F, and M IHG is the Mueller matrix of process G ~ process I.

[0127] For the Mueller matrix, it is described in

[10] S.-Y. Lu and R. A. Chipman, "Interpretation of Mueller matrices based on polar decomposition", J. Opt. Soc. Am. A, 13, (1996), 1106-1113.

[0128] In the third process, the optical rotation of the aqueous humor is calculated using such a model formula. Hereinafter, such a model formula is described in detail.

[0129] First, the Mueller matrix Mref of the change in polarized light due to general reflection is described.

[0130] The Mueller matrix Mref of the change in polarized light due to reflection can be expressed by the following formula (for example, refer to Yuji Fujihara, Spectroscopic Elliptical Polarimetry, p. 65, Table 3.2).

[0131] [Formula 1]

[0132]

[0133] A, Ψ, Δ are expressed by the following formula.

[0134] [Formula 2]

[0135]

[0136] [Formula 3]

[0137]

[0138] Therefore, r p 、r s are the amplitude reflection coefficients of the reflected light associated with the p-wave and s-wave, respectively, derived from the Fresnel formula. And, r p * With r s * is their complex conjugate (at r p When r is a real number, p * =r p ), δrp and δrs represent the phases of the p-wave and s-wave of the reflected light respectively, and Δ represents the phase difference.

[0139] As mentioned above, Brewster's angle θ B is the value obtained by tanθ B = nt / ni. When the medium on the reflecting side does not absorb and nt>ni, δrp and δrs when the angle of incidence on the medium on the reflecting side is less than the Brewster angle and when it is greater than the Brewster angle are expressed as follows (for example, see Hecht, Optics I, p. 182, Figure 4 .44(a), (b) for reference).

[0140] In the case of less than Brewster's angle:

[0141] δrp=0[deg], δrs=180[deg], Δ=-180[deg]

[0142] Above Brewster's angle:

[0143] δrp=180[deg], δrs=180[deg], Δ=0[deg]

[0144] Next, the formula expressing incident light as polarized light using a combination of natural light, a polarizer, and a phase difference element will be described.

[0145] The incident polarized light, Spolin, can be set in various ways by combining the natural light source with the polarizer and retardation element. Specifically, if the Stokes vectors of the incident polarized light and natural light are Spolin and Sin, respectively, the value can be determined using the following equation. Therefore, Mpol(θpol) is the Mueller matrix of a polarizer with the transmission axis oriented in the θpol direction, and Mret(θret, φ) is the Mueller matrix of a retardation element with the slow axis oriented in the θret direction and a phase difference φ between the slow and fast directions.

[0146] [Formula 4]

[0147]

[0148] [Formula 5]

[0149] S polin =M ret (θ ret ,φ)M pol (θ pol )S in

[0150] [Formula 6]

[0151]

[0152] [Formula 7]

[0153]

[0154] Next, the formula representing the polarization state of the reflected light measured in the first step and the second step will be described.

[0155] As described above, the polarization state of the reflected light measured in the first step and the second step can be expressed as Sout=M IHG ·M F ·M E ·M D ·M CBA ·Sin can be expressed by the above-mentioned Spolin formula. E is the Mueller matrix of the reflection, which can be expressed by the same formula as the above Mref. IHG With M CBA is the Mueller matrix of the cornea, which can be expressed by the same formula as Mret above. IHG Set to M c2 (θ c2 ,φ c2 ), M CBA Set to M c1 (θ c1 ,φ c1 ). M FWith M D is the Mueller matrix of aqueous humor, which can be expressed by the same formula as the Mueller matrix Mrot of a photorotor with optical rotation ε. F Set to M h2 (ε h2 ), M D Set to M h1 (ε h1 ).

[0156] [Formula 8]

[0157]

[0158] As described above, the polarization state of the reflected light Sout measured in the first step and the second step is expressed by the following equation.

[0159] [Formula 9]

[0160] S out =M c2 (θ c2 ,φ c2 )M h2 (∈ h2 )M ref (Ψ, Δ)M h1 (∈ h1 )M c1 (θ c1 ,φ c1 )S polin

[0161] Formula (1)

[0162] Next, a method for calculating the optical rotation of aqueous humor using the above-mentioned formula in the third step will be described.

[0163] The incident polarization Spolin is known from the settings during incident light irradiation, and the reflected polarization Sout is known from measurement. Meanwhile, the Mueller matrices of the cornea and aqueous humor of the eye are unknown. In the third step, the Mueller matrices of the cornea and aqueous humor are calculated using the information on the polarization state of the reflected light measured in the first and second steps.

[0164] As described above, in the first step, polarized light is incident from the air layer so that the angle θ of the incident light from the aqueous humor to the lens is smaller than the Brewster angle, and the reflected polarized light is measured. Since the optical path length of the light passing through the aqueous humor before and after reflection is almost the same, ε h1 With ε h2 is substantially equal, and by setting the angle θ to be smaller than the Brewster angle, the phase difference is shifted by 180 degrees. h1 (ε h1)) and the optical rotation of aqueous humor based on the reflection side (M h2 (ε h2 )) is almost canceled out (i.e., M h2 (ε h2 )Mref(Ψ、Δ)M h1 (ε h1 ) is close to the unit matrix). Therefore, the above formula (1) in the first step can be regarded as almost the Mueller matrix of the cornea.

[0165] Taking this into consideration, by fitting the relationship between Sout and Spolin using the above formula (1), the phase difference of the cornea and the axis (θ c1 、φ c1 ,θ c2 、φ c2 ).

[0166] Alternatively, the least squares method can be used as a fitting method. In the nonlinear least squares method, the function R(λ) is substituted while varying the unknown number (variable) to minimize the sum of the squares of the differences between the function R(λ) and the normalized polarization state change R, which is the measured value. This method uses algorithms such as the Levenberg-Marquardt method, the quasi-Newton method, and the conjugate gradient method.

[0167] Next, by using the measurement results of the second step of measuring the reflected light so that the angle θ of the incident light from the aqueous humor to the lens becomes greater than the Brewster angle (information on the polarization state of the second reflected light), the phase difference of the cornea and the axis (θ) obtained above, the c1 、φ c1 ,θ c2 、φ c2 ), and by fitting the relationship between Sout and Spolin using the above formula (1), the optical rotation of aqueous humor can be obtained.

[0168] If the angle θ is set to be greater than the Brewster angle, there is no phase change, so the optical rotation of the aqueous humor on the incident side (M h1 (ε h1 )) and the optical rotation of aqueous humor based on the reflection side (M h2 (ε h2 )) is added, the optical rotation is almost doubled. According to this situation, the phase difference of the cornea and the axis (θ c1 、φ c1 ,θ c2 、φ c2 ) information, the optical rotation of aqueous humor can be determined with high precision.

[0169] Thus, by measuring at two angles, one above the Brewster angle and one below the Brewster angle, the birefringence of the cornea and the optical rotation of the aqueous humor can be distinguished and calculated with high precision.

[0170] In addition, the order in which the first process and the second process are performed is not particularly limited, and the second process can be performed after the first process, or the first process can be performed after the second process. Also, in the third process, the timing at which the optical properties of the cornea are calculated is not particularly limited. That is, a part of the third process (the process of calculating the optical properties of the cornea) can be performed before the second process, and then the remaining processes of the third process (the process of calculating the optical rotation of the aqueous humor) can be performed after the second process.

[0171] Here, preferably, the first process is performed multiple times under conditions in which the angle θ1 between the normal to the surface of the cut surface and the first incident light at the point where the first incident light intersects the surface of the lens is different, and the polarization state information of the first reflected light of the first process is obtained, and the third process is performed using the obtained multiple pieces of information.

[0172] By performing the first process multiple times under conditions in which the angle θ1 is different, and calculating the optical properties of the cornea by fitting using the polarization state information of the multiple reflected lights, the optical information of the cornea can be obtained with higher precision.

[0173] Also, as described above, the optical properties (birefringence) of the cornea can be calculated from the results of the first process. Therefore, the phase difference of the cornea calculated in the above equation (1) corresponds to the in-plane retardation Re when viewed from the direction of incidence of light, but the cornea also has a thickness-direction retardation Rth. This thickness-direction retardation Rth can be calculated by one measurement, but by performing the first process multiple times under conditions in which the angle θ1 is different, obtaining the polarization state information of the multiple first reflected lights, and performing fitting using the above equation (1) for each of the polarization states of the first reflected lights, the in-plane retardation Re and the thickness-direction retardation Rth of the cornea can be calculated.

[0174] Also, preferably, the second process is performed multiple times under conditions in which the angle θ2 between the normal to the surface of the cut surface and the second incident light at the point where the second incident light intersects the surface of the lens is different, and the polarization state information of the second reflected light of the second process is obtained, and the third process is performed using the obtained multiple pieces of information.

[0175] By performing the second process multiple times under conditions in which the angle θ2 is different, and calculating the optical rotation of the aqueous humor by fitting using the polarization state information of the multiple reflected lights, the optical rotation of the aqueous humor can be obtained with higher precision.

[0176] Furthermore, it is preferable to perform the first step a plurality of times while changing the wavelength of the first incident light, thereby acquiring information on the polarization states of the first reflected light in the plurality of first steps, and perform the third step using the acquired plurality of information.

[0177] Furthermore, it is preferable to perform the second step a plurality of times while changing the wavelength of the second incident light, thereby acquiring information on the polarization states of the second reflected light in the plurality of second steps, and perform the third step using the acquired plurality of information.

[0178] It is known that aqueous humor contains, in addition to glucose, albumin or ascorbic acid as optically active components. The wavelength dependence of the optical rotation of an optically active substance varies depending on the type of optically active substance. Therefore, by performing the first step and / or the second step multiple times while varying the wavelength of the incident light, information on the polarization states of multiple pieces of reflected light can be obtained. Based on the wavelength dependence of each optically active substance, the proportion of glucose in the optically active substance in the aqueous humor can be determined.

[0179] Specifically, in a certain object to be measured containing a single optically active substance, the optical rotation φ relative to the wavelength λ is represented by the product of the optical path length L and the concentration C. The optical rotation φ is represented by a Drude monomial, a nonlinear function that becomes monotonically decreasing or monotonically increasing in a wavelength region longer than the maximum point and / or minimum point. The Drude monomial is an example of a function that represents the optical rotation dispersion of an optically active substance. In the case where the object to be measured contains multiple optically active substances, the optical rotation φ of each optically active substance represented by the Drude monomial is expressed. j In other words, the optical rotation φ of each optically active substance is expressed by j The observed optical rotation φ is represented by the sum of the wavelength-dependent functions of . In addition, j is an integer greater than 1.

[0180] As an example, the optical rotation φ of aqueous humor AH It is represented by the sum of two Drude monomials shown in the following formula (2). When the optically active substance to be obtained is glucose, the first term on the right is the term contributed by glucose. The second term on the right is the term contributed by other optically active substances other than glucose. Let the concentration of glucose be the glucose concentration C g . A g ,λ g A is a constant inherent in the optically active substance (glucose) (an inherent value that specifies the optical dispersion characteristics of the optically active substance (glucose)). x ,λ x is the inherent value when other optically active substances are combined. Also, L is the optical path length. Therefore, the optical rotation φ of aqueous humor is AHA representing an eigenvalue when the glucose concentration C g and other optically active substances is summarized x , λ x .

[0181] [Formula 10]

[0182]

[0183] In addition, in the formula (2), other optically active substances than glucose contained in the aqueous humor can be represented by a plurality of terms with respect to the other optically active substances. For example, terms of albumin and globulin, etc. can be provided in addition to the term of glucose. At this time, terms of other optically active substances than the optically active substances (glucose, albumin, globulin, etc.) provided as the terms can be provided. Further, in the case where the contribution of the other optically active substances is small, etc., the terms of the other optically active substances can not be provided. Only the terms of the optically active substances desired to be obtained and the aqueous humor with respect to the degree of influence on the optical rotation degree Φ AH can be provided.

[0184] By performing the first process and / or the second process a plurality of times with the wavelength of the incident light changed, information of the polarization state of the reflected light is obtained, and after the optical rotation degree of the aqueous humor is found for each wavelength using the above formula (1), the concentration of glucose in the aqueous humor can be more accurately found using the above formula (2).

[0185] In the present application, it is preferable that the optically active substance whose concentration is measured is glucose.

[0186] Further, it is more preferable that the first process and the second process are performed with incident light of different wavelengths respectively. By performing the first process and the second process for each wavelength, the wavelength dispersion of the optical rotation of the aqueous humor as a whole (Φmeasure) is calculated, and the mixing ratio is determined so that Φ of the above formula (2) coincides with Φmeasure, whereby the concentration of glucose in the aqueous humor can be more accurately found.

[0187] Further, if the angle θ1 formed by the normal to the cleavage surface at the point where the first incident light in the first process intersects the surface of the lens and the first incident light is less than the Brewster angle, there is no particular limitation, and it is preferable to be 2° to 45°, more preferably 3° to 35°, and further preferably 4° to 25°.

[0188] Further, if the angle θ2 formed by the normal to the cleavage surface at the point where the second incident light in the second process intersects the surface of the lens and the second incident light is the Brewster angle or more, there is no particular limitation, and it is preferable to be greater than the Brewster angle, more preferably 50° to 65°, and further preferably 50° to 60°.

[0189] [Optically active substance concentration measuring device]

[0190] The optically active substance concentration measuring device of the present invention is an optically active substance concentration measuring device for carrying out the above-mentioned optically active substance concentration measuring method, and comprises:

[0191] a light source that irradiates incident light as polarized light into the aqueous humor of the eye;

[0192] a measuring unit for measuring a polarization state of reflected light obtained by reflecting incident light at an interface between aqueous humor and the lens;

[0193] a control unit that controls the incident angle of the incident light; and

[0194] The calculation unit calculates the optical rotation of the aqueous humor using information on the polarization state of the reflected light measured by the measurement unit.

[0195] Figure 12 A diagram conceptually showing an example of the optically active substance concentration measuring device of the present invention is shown.

[0196] Figure 12 The optically active substance concentration measuring device 100 shown includes a light source 110 , a measuring unit 120 , a control unit 130 , and a calculation unit 140 .

[0197] Light Source

[0198] The light source 110 irradiates polarized light toward the aqueous humor of the eye 10 .

[0199] exist Figure 12 In the illustrated example, light source 110 includes, as an example, a light emitting element 112; a polarizer 114 for converting light emitted from light emitting element 112 into polarized light; and a phase difference plate 116 for converting the polarization state of the polarized light converted by polarizer 114. Light source 110 can emit light of a desired polarization state by including polarizer 114 and phase difference plate 116.

[0200] The structure of the light source 110 is not particularly limited. For example, the light source 110 may include the light emitting element 112 and the polarizing plate 114 , may include only the light emitting element 112 that emits polarized light, or may include the light emitting element 112 and the phase difference plate 116 .

[0201] (Light-emitting element)

[0202] Examples of the light emitting element 112 include a mercury lamp or other light bulb, a fluorescent lamp, a halogen lamp, an LED (Light Emitting Diode), and a laser such as a semiconductor laser. Preferably, the light emitting element 112 is an LED or a laser such as a semiconductor laser that can emit light in a narrow band.

[0203] The wavelength of light emitted by the light emitting element 112 is not limited and may be visible light or non-visible light such as infrared light and ultraviolet light. However, visible light and near-infrared light are preferably used as the light emitted by the light emitting element 112 .

[0204] Furthermore, the light emitted by the light emitting element 112 may be unpolarized light or polarized light. In the case where the light emitting element 112 emits polarized light, the emitted light may be linearly polarized light or circularly polarized light.

[0205] (Polarizing Plate)

[0206] The polarizing plate is not particularly limited, and various known polarizing plates can be appropriately used.

[0207] As an absorbing linear polarizer, an iodine-based polarizer, a dye-based polarizer using a dichroic dye, or a polyene-based polarizer can be used. Iodine-based polarizers and dye-based polarizers include coated polarizers and stretched polarizers, both of which are applicable. Of these, polarizers made by adsorbing iodine or a dichroic dye onto polyvinyl alcohol and then stretching it are preferred.

[0208] Furthermore, as methods for obtaining a polarizer by stretching and dyeing a laminated film having a polyvinyl alcohol layer formed on a substrate, Japanese Patent No. 5048120, Japanese Patent No. 5143918, Japanese Patent No. 4691205, Japanese Patent No. 4751481, and Japanese Patent No. 4751486 can be cited, and known technologies related to these polarizers can also be preferably utilized.

[0209] Absorption-type polarizers are particularly preferred, as they utilize the orientation properties of liquid crystals to orient the dichroic dye without stretching. These polarizers offer several advantages: They can be made very thin with a thickness of approximately 0.1 μm to 5 μm; they are less prone to cracking and thermal deformation when bent, as described in Japanese Patent Application Publication No. 2019-194685; they exhibit excellent durability even for polarizers with a transmittance exceeding 50%, as described in Japanese Patent Application No. 6483486; and they exhibit excellent heat moldability. Furthermore, the support can be peeled off and the polarizer transferred for use.

[0210] As a reflective linear polarizer, a film obtained by stretching a layer containing two polymers or a metal wire grid polarizer, as described in Japanese Patent Application Laid-Open No. 2011-053705, can be used. From the perspective of brightness, a film obtained by stretching a layer containing a polymer is preferred. As commercially available products, a reflective polarizer (trade name APF) manufactured by 3M Company or a metal wire grid polarizer (trade name WGF) manufactured by Asahi Kasei Corporation can be preferably used.

[0211] (Phase difference plate)

[0212] The phase difference plate converts the phase of incident polarized light and is arranged to adjust the direction of the slow axis relative to the transmission axis of the polarizer so that the polarized light emitted from the light source 110 has a desired polarization state.

[0213] The phase difference plate used in the present invention can be a single-layer type consisting of 1 layer of optically anisotropic layer, or a multilayer type consisting of a stack of more than 2 optically anisotropic layers having a plurality of different slow axes. As an example of a multilayer phase difference plate, WO13 / 137464, WO2016 / 158300, Japanese Patent Application Publication No. 2014-209219, Japanese Patent Application Publication No. 2014-209220, WO14 / 157079, Japanese Patent Application Publication No. 2019-215416, WO2019 / 160044 can be cited, but it is not limited thereto.

[0214] <Control Department>

[0215] The control unit 130 controls the direction and position of the light irradiated by the light source 110 so as to adjust the light irradiated by the light source 110 to be directed toward the position where the eyes of the test subject are located.

[0216] The control unit 130 may include a mechanism for moving the position of the light source 110 and a mechanism for rotating the light source 110. As such a mechanism, a well-known mechanism can be preferably used.

[0217] Specifically, in order to change the incident angle of light incident on the eye, the control unit 130 changes the position and angle of the light source 110 with the position of the eye as the origin to change the polar angle.

[0218] Furthermore, the control unit 130 may include a rotation mechanism that rotates the polarizing plate 114 of the light source 110 about an axis perpendicular to the main surface of the polarizing plate 114 .

[0219] Furthermore, the control unit 130 may include a rotation mechanism that rotates the phase difference plate 116 of the light source 110 about an axis perpendicular to the main surface of the phase difference plate 116 .

[0220] By having a rotation mechanism that rotates the polarizing plate 114 and / or the phase difference plate 116, it is possible to change the polarization state of the polarized light emitted from the light source 110.

[0221] Measurement section

[0222] The measurement section 120 is a section that receives the reflected light obtained by the light source 110 irradiating and reflecting at the interface of the aqueous humor and the crystalline lens, and measures the polarization state. If the measurement section 120 can detect the polarization state of the received light, it is possible to use various publicly known measurement devices.

[0223] In the example shown in FIG. 1, the measurement section 120 has, for example, a light receiving element 122, a polarizing plate 124, and a phase difference plate 126. Figure 12 Such a measurement section can measure the polarization state of the reflected light with the same principle as the rotating compensator type ellipsometry. In this case, it is sufficient to rotate the phase difference plate 126 in principle. Also, as the phase difference plate 126, it is sufficient to use a λ / 4 plate that becomes λ / 4 with respect to the wavelength λ of the incident light. Also, as shown in FIG. 2, the polarizing plate 124 can be configured so that the horizontal direction DA of the section H when the section H is observed from the main surface of the polarizing plate 124 is set to 0°, and the transmission axis becomes 45° or 135°.

[0224] Figure 19 Figure 20

[0225] In order to receive the reflected light, the measurement section 120 is controlled by a control section not shown in the drawing in the orientation and position, and the like. Specifically, the position and the angle of the measurement section 120 are changed so as to change the polar angle with the position of the eye as the origin, so that the reflected light is perpendicularly incident on the measurement section 120. Also, the measurement section 120 can be controlled in the orientation and the position, and the like in conjunction with the control of the orientation and the position of the light source 110 based on the control section 130.

[0226] Hereinafter, an example of the measurement section will be described.

[0227] Figure 13 is a conceptual diagram that conceptually shows an example of the measurement section.

[0228] Figure 13 The measurement section 120a shown in FIG. 3 has a light receiving element 122 and a polarizing plate 124.

[0229] In the example shown in FIG. 3, the measurement section 120a has a phase difference plate 126. Figure 13 ​​​In the measuring section 120a shown, the polarizing plate 124 is rotated around an axis perpendicular to the main surface of the polarizing plate 124, and the reflected light passing through the polarizing plate 124 is received by the light receiving element 122. For example, in the case where the light incident on the measuring section 120a is linearly polarized light, if the transmission axis of the polarizing plate 124 is the same as the vibration direction of the linearly polarized light, the linearly polarized light is almost transmitted and received by the light receiving element 122, so the light receiving element 122 detects light of high light quantity (intensity). On the other hand, in the case where the transmission axis of the polarizing plate 124 is orthogonal to the vibration direction of the linearly polarized light, the linearly polarized light is almost blocked, so light of low light quantity (intensity) is detected in the light receiving element 122. Therefore, as Figure 14 As shown, by rotating the polarizing plate 124, the amount (intensity) of light detected by the light receiving element 122 changes according to the rotation angle of the polarizing plate. Therefore, the polarization state of light incident on the measuring unit 120a can be detected based on this change in light amount.

[0230] (Light receiving element)

[0231] The light receiving element 122 is a well-known photodetector such as a silicon diode, and outputs an electrical signal corresponding to the intensity of incident light.

[0232] Figure 15 This is a diagram conceptually showing another example of the measuring unit.

[0233] Figure 15 The measuring section 120b shown includes a light receiving element 122b and a polarizing plate 124b.

[0234] (2D sensor)

[0235] The light receiving element 122b is a two-dimensional sensor in which light receiving sections 123 for receiving light are arranged two-dimensionally in one direction along the surface and in a direction orthogonal to the one direction. Each light receiving section 123 outputs an electrical signal corresponding to the intensity of the incident light. Suitable two-dimensional sensors include well-known image sensors such as CMOS (Complementary Metal Oxide Semiconductor) and CCD (Charge Coupled Device). Furthermore, a two-dimensional sensor can be constructed by two-dimensionally arranging well-known photodetectors such as silicon diodes as the light receiving sections 123.

[0236] (Patterned Polarizer)

[0237] The polarizing plate 124b has regions with different transmission axis directions arranged in a predetermined pattern (hereinafter also referred to as a patterned polarizing plate). Figure 15In the example shown, four regions with different transmission axis directions are grouped as one, and a plurality of such groups are arranged two-dimensionally. The patterned polarizing plate 124b is arranged so that each region corresponds to each light receiving unit 123 of the two-dimensional sensor 122b.

[0238] As an example, in Figure 15 In the figure, the first area with the transmission axis in the up-down direction, the second area located on the right side of the first area and with the transmission axis in the direction from the upper right to the lower left, the third area located on the upper side of the second area and with the transmission axis in the left-right direction, and the fourth area located on the left side of the third area and with the transmission axis in the direction from the upper left to the lower right are grouped as one group, and there are multiple such groups.

[0239] use Figure 16 , the function of the measuring unit 120b including the two-dimensional sensor 122b and the patterned polarizing plate 124b will be described.

[0240] like Figure 16 As shown in the figure on the left side of the figure, when linearly polarized light vibrating in the left-right direction is incident on the measuring unit 120b, in the first area of ​​the patterned polarizer 124b, the direction of its transmission axis is orthogonal to the vibration direction of the linearly polarized light, so it is almost blocked. Therefore, almost no light is detected in the light receiving unit corresponding to the first area. In the second and fourth areas, the direction of the transmission axis is approximately 45° to the vibration direction of the linearly polarized light, so a portion of the linearly polarized light is transmitted. Therefore, an intermediate amount of light is detected in the light receiving units corresponding to the second and fourth areas. In the third area, the direction of the transmission axis is parallel to the vibration direction of the linearly polarized light, so the linearly polarized light is almost transmitted. Therefore, a high amount of light is detected in the light receiving unit corresponding to the third area.

[0241] If Figure 16 As shown in the lower left figure, different light amounts are detected in the light receiving units corresponding to the first to fourth areas. In the figure, white represents a high light amount detected by the light receiving unit, gray represents an intermediate light amount, and black represents a low light amount.

[0242] On the other hand, Figure 16As shown in the figure in the middle of the left and right directions, when linearly polarized light vibrating from the upper right to the lower left is incident, in the first and third regions of the patterned polarizer 124b, the direction of its transmission axis is approximately 45° to the vibration direction of the linearly polarized light, so a portion of the linearly polarized light is transmitted. Therefore, an intermediate amount of light is detected in the light receiving units corresponding to the first and third regions. In the second region, the direction of the transmission axis is parallel to the vibration direction of the linearly polarized light, so the linearly polarized light is almost transmitted. Therefore, a high amount of light is detected in the light receiving unit corresponding to the second region. In the fourth region, the direction of the transmission axis is orthogonal to the vibration direction of the linearly polarized light and is therefore almost blocked. Therefore, almost no light is detected in the light receiving unit corresponding to the fourth region.

[0243] If Figure 16 As shown in the lower left figure of , different light amounts are detected in the light receiving parts corresponding to the first to fourth areas. Figure 16 As shown, the pattern of the detected light intensity is the same as that of the linearly polarized light vibrating in the left and right directions ( Figure 16 Different patterns are detected (bottom left image in the figure).

[0244] In this manner, the measuring unit 120b detects different light intensity patterns with the two-dimensional sensor 122b depending on the direction of incident linearly polarized light. Therefore, the polarization state of the received polarized light can be detected based on the light intensity pattern detected by the two-dimensional sensor 122b.

[0245] In addition, Figure 15 In the example shown, the patterned polarizer 124b has four regions with different transmission axis directions, but the present invention is not limited thereto and may have multiple regions with different transmission axis directions. For example, the patterned polarizer 124b may have nine regions with different transmission axis directions.

[0246] Figure 17 This is a diagram conceptually showing another example of the measuring unit.

[0247] Figure 17 The measuring section 120 c shown includes a light receiving element 122 b , a polarizing plate 124 , a first phase difference plate 126 a , and a second phase difference plate 126 b .

[0248] The first phase difference plate 126a and the second phase difference plate 126b each have a patterned optical anisotropic layer. The patterned optical anisotropic layer has a plurality of units consisting of a plurality of band-shaped regions. The plurality of band-shaped regions have a constant phase difference and are divided into a plurality of band-shaped regions within the same plane. The slow axis of a band-shaped region has the same direction, while the slow axis of each band-shaped region has a different direction.

[0249] Furthermore, in the plane direction, the band-shaped regions of the patterned optically anisotropic layer of the first retardation plate 126 a and the band-shaped regions of the patterned optically anisotropic layer of the second retardation plate 126 b are arranged to intersect with each other.

[0250] Furthermore, the first phase difference plate 126 a and the second phase difference plate 126 b are different phase difference plates. For example, one is a λ / 4 plate and the other is a λ / 2 plate.

[0251] The patterned optically anisotropic layers of the first retardation plate 126 a and the second retardation plate 126 b are formed by using a liquid crystal composition containing a liquid crystal compound and aligning the liquid crystal compound in a predetermined alignment pattern.

[0252] The measurement unit 120c including the first phase plate 126a and the second phase plate 126b can distinguish the polarization states of incident light and perform measurement. A measurement unit having such a structure is described in detail in Japanese Patent No. 6616494.

[0253] Therefore, in Figure 15 In the measuring section 120b shown in FIG. 1 , when circularly polarized light is incident, as shown in FIG. Figure 16 As shown in the figure on the right side of , in the light receiving parts corresponding to the first to fourth areas, approximately the same amount of light is detected, so it is impossible to distinguish right-handed circularly polarized light from left-handed circularly polarized light. In addition, it is also impossible to distinguish non-polarized light. In contrast, in Figure 17 The measuring unit 120 c shown can distinguish not only linearly polarized light but also circularly polarized light.

[0254] And, in Figure 15 In the case of the measuring unit 120b shown in FIG. 1 , there is a problem that the positions of the regions of the pattern polarizing plate 124b and the light receiving units of the two-dimensional sensor 122b are easily offset. Figure 17 In the illustrated measurement unit 120 c , since only the first phase difference plate 126 a and the second phase difference plate 126 b are provided, positional deviation does not occur, and the polarization state of the received light can be detected with higher accuracy.

[0255] and, Figure 15 The measuring unit 120b and Figure 17 The two-dimensional sensor 122b of the measuring unit 120c shown in the figure preferably has a plurality of light receiving units 123 as a group and detects the polarization state of light in each group. Figure 18The example shown has n×m 3×3 groups of light receiving elements 123. Using such a two-dimensional sensor 122b enables detection of multiple polarization states. By detecting polarization states in multiple groups, calculating the optical rotation of aqueous humor for each group, and averaging the optical rotations, the accuracy of the obtained optical rotation can be further improved.

[0256] Furthermore, the measurement unit may perform multiple polarization state measurements. By performing multiple measurements, detecting the polarization state multiple times, calculating the optical rotation of aqueous humor based on each detection result, and averaging the optical rotations, the accuracy of the obtained optical rotation can be further improved.

[0257] Furthermore, by performing measurement in a group of a plurality of light receiving units or performing measurement a plurality of times, the optical rotation of the aqueous humor may be calculated from each detection result, and the optical rotations may be averaged.

[0258] <Calculation Department>

[0259] The calculation unit 140 calculates the optical rotation of the aqueous humor using information on the polarization state of the incident light emitted by the light source 110 and information on the polarization state of the reflected light measured by the measurement unit 120. Specifically, the calculation unit 140 performs the third step of the aforementioned method for measuring the concentration of an optically active substance to calculate the optical rotation of the aqueous humor. Furthermore, the calculation unit 140 can perform the fourth step to calculate the concentration of the optically active substance based on the optical rotation of the aqueous humor.

[0260] The calculation unit 140 is configured as a computer having a processing unit such as a CPU (Central Processing Unit) and a GPU (Graphics Processing Unit), memory such as RAM (Random Access Memory) and ROM (Read Only Memory), and storage media such as an HDD (Hard Disk Drive) and an SSD (Solid State Drive). A program for calculating the optical rotation of aqueous humor and / or a program for calculating the concentration of an optically active substance is stored in the ROM or the storage medium.

[0261] In the optically active substance concentration measuring device 100 , the information on the optical rotation of aqueous humor and / or the concentration of optically active substances calculated by the calculation unit 140 may be displayed on a display (not shown) or transmitted to other devices such as a smartphone.

[0262] And, in Figure 12In the illustrated example, the light source 110 includes the light emitting element 112 , the polarizing plate 114 , and the phase difference plate 116 , and the measuring unit 120 includes the phase difference plate 126 , the polarizing plate 124 , and the light receiving element 122 , but the present invention is not limited thereto.

[0263] For example, the light source 110 may include the light emitting element 112, the polarizing plate 114, and the phase difference plate 116, while the measuring unit 120 may not include the phase difference plate but include the polarizing plate 124 and the light receiving element 122. Alternatively, the light source 110 may not include the phase difference plate but include the light emitting element 112 and the polarizing plate 114, while the measuring unit 120 may include the phase difference plate 126, the polarizing plate 124, and the light receiving element 122. In other words, the light source 110 may include the light emitting element 112 and the polarizing plate 114, while the measuring unit 120 may include the polarizing plate 124 and the light receiving element 122, with either the light source 110 or the measuring unit 120 including the phase difference plate.

[0264] In addition, from the perspective of measuring the polarization state based on the principle of the rotating compensator ellipsometry method, the phase difference plate can be arranged on either the light source 110 or the measuring unit 120, but from the perspective of being able to measure the Mueller matrix, the phase difference plate is preferably arranged on both the light source 110 and the measuring unit 120.

[0265] The optically active substance concentration measuring method and the optically active substance concentration measuring apparatus of the present invention have been described in detail above. However, the present invention is not limited to the above examples, and various improvements and modifications can be made without departing from the scope of the present invention.

[0266] Explanation of symbols

[0267] 10-eye, 12, 12a, 12b-cornea, 14, 14a, 14b-aqueous humor, 16-lens, 100-optically active substance concentration measuring device, 110-light source, 112-light emitting element, 114, 124-polarizing plate, 116, 126-phase difference plate, 120, 120a to 120c-measuring unit, 122-light receiving element, 122b-two-dimensional sensor, 124b-patterned polarizing plate, 126a-first phase difference plate, 126b-second phase difference plate, 130-control unit, 140-calculating unit, Sin1-first incident light, Sin2-second incident light, Sout1-first reflected light, Sout2-second reflected light, θ1, θ2-angle, θ i - angle of incidence, N-perpendicular, H-section, DA-horizontal direction of the section.

Claims

1. A method for determining the concentration of an optically active substance, comprising: The first step is a step of irradiating first incident light as polarized light to the aqueous humor of the eye and measuring the polarization state of first reflected light obtained by reflecting the first incident light at the interface between the aqueous humor and the lens, wherein: irradiating the first incident light in such a manner that an angle θ1 formed between a normal to a tangent plane and the first incident light at a point where the first incident light intersects the surface of the crystal is smaller than a Brewster angle, thereby measuring a polarization state of the first reflected light; a second step of irradiating the aqueous humor of the eye with second incident light as polarized light and measuring the polarization state of second reflected light obtained by reflecting the second incident light at the interface between the aqueous humor and the crystalline lens, wherein the second incident light is irradiated so that an angle θ2 formed by the second incident light and a normal to a tangential surface at a point where the second incident light intersects the surface of the crystalline lens is equal to or greater than Brewster's angle, thereby measuring the polarization state of the second reflected light; a third step of calculating the optical rotation of the aqueous humor using the information on the polarization state of the first reflected light obtained in the first step and the information on the polarization state of the second reflected light obtained in the second step; and The fourth step is to calculate the concentration of the optically active substance in the aqueous humor according to the optical rotation of the aqueous humor.

2. The method for measuring the concentration of an optically active substance according to claim 1, wherein: Under the condition that the angle θ1 formed between the normal and the first incident light is different, the first step is performed multiple times to obtain information on the polarization state of the first reflected light in multiple first steps, and the third step is performed using the multiple pieces of information obtained.

3. The method for measuring the concentration of an optically active substance according to claim 1 or 2, wherein: Under the condition that the angle θ2 formed between the normal line and the second incident light is different, the second step is performed multiple times to obtain information on the polarization state of the second reflected light in multiple second steps, and the third step is performed using the multiple pieces of information obtained.

4. The method for measuring the concentration of an optically active substance according to claim 1 or 2, wherein: The first step is performed a plurality of times while changing the wavelength of the first incident light, thereby acquiring information on the polarization state of the first reflected light in the plurality of first steps, and the third step is performed using the acquired plurality of information.

5. The method for measuring the concentration of an optically active substance according to claim 1 or 2, wherein: The second step is performed a plurality of times while changing the wavelength of the second incident light, thereby acquiring information on the polarization state of the second reflected light in the plurality of second steps, and the third step is performed using the acquired plurality of information.

6. The method for measuring the concentration of an optically active substance according to claim 1 or 2, wherein: An angle θ2 formed between the normal line and the second incident light in the second step is larger than Brewster's angle.

7. The method for measuring the concentration of an optically active substance according to claim 1 or 2, wherein: The optically active substance is glucose.

8. The method for measuring the concentration of an optically active substance according to claim 1 or 2, wherein: In at least one of the first step and the second step, a two-dimensional sensor is used in which light receiving units that receive reflected light are two-dimensionally arranged.

9. The method for measuring the concentration of an optically active substance according to claim 1 or 2, wherein: The third step uses the information on the polarization state of the first reflected light obtained in the first step to obtain information on the optical characteristics of the cornea of ​​the eye. The optical rotation of the aqueous humor is calculated using information on the optical characteristics of the cornea and information on the polarization state of the second reflected light obtained in the second step.

10. An optically active substance concentration measuring device for carrying out the optically active substance concentration measuring method according to any one of claims 1 to 9, the optically active substance concentration measuring device comprising: a light source that irradiates incident light as polarized light into the aqueous humor of the eye; a measuring unit for measuring a polarization state of reflected light obtained by reflecting incident light at an interface between the aqueous humor and the lens; a control unit, configured to control an incident angle of the incident light; and The calculation unit calculates the optical rotation of the aqueous humor using information on the polarization state of the reflected light measured by the measurement unit.

11. The optically active substance concentration measuring device according to claim 10, wherein: The light source comprises a light emitting element and a polarizing plate, The measuring unit includes a polarizing plate and a light receiving element. At least one of the light source and the measurement unit includes a phase difference plate.

12. The optically active substance concentration measuring device according to claim 11, wherein: The light receiving element is a two-dimensional sensor having light receiving portions for receiving reflected light arranged two-dimensionally.

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