Photoacoustic measurement device having optimized geometry and non-invasive blood glucose measurement device using same

Abstract

Disclosed is a photoacoustic measurement method for quantitatively measuring components of a sample by using a laser pulse having a prescribed wavelength and an ultrasonic sensor having a prescribed frequency band. The photoacoustic measurement method may comprise the steps of, when the incident position of a laser pulse, the beam width of the laser pulse, and the relative position of an ultrasonic sensor are determined from the given frequency band of the ultrasonic sensor and the given position of a photoacoustic region in a sample: (a) oscillating the laser pulse with prescribed pulse energy and a prescribed pulse width to be incident onto the photoacoustic region in the sample; (b) detecting, by means of the ultrasonic sensor, photoacoustic waves generated in the photoacoustic region in the sample by the incident laser pulse, and acquiring sampling data by sampling the waveforms of the detected photoacoustic waves at a prescribed sampling rate; and (c) storing the sampling data. Furthermore, the distance from the photoacoustic region to the ultrasonic sensor may be determined on the basis of the wavelength of a frequency belonging to the frequency band of the ultrasonic sensor, and the beam width of the laser pulse may be determined on the basis of the half wavelength of the maximum frequency belonging to the frequency band of the ultrasonic sensor.

Description

Photoacoustic measuring device having optimized geometry and non-invasive blood glucose measuring device using the same

[0001] The present disclosure relates to a photoacoustic measuring device capable of obtaining information regarding components within a sample using photoacoustic phenomena. More specifically, the present disclosure relates to a photoacoustic measuring device having a miniaturized form factor.

[0002] Photoacoustic phenomena are events in which a material generates sound when illuminated by light, as it absorbs the light, heats up locally, and undergoes expansion and contraction. The sound waves or ultrasound generated by photoacoustic phenomena can be measured by acoustic sensors and utilized to visualize the internal structure of a material or analyze the components within a sample.

[0003] Meanwhile, blood glucose measurement is crucial in diabetes management. Although blood sampling is the most accurate method, undergoing repeated daily blood draws is quite painful for diabetic patients. Consequently, technologies for non-invasive blood glucose measurement without blood sampling have been developed, and photoacoustic-based non-invasive blood glucose measurement technology is one such example.

[0004] Photoacoustic signals measured with glucose solutions at the laboratory level exhibit characteristic changes depending on glucose concentration, and theoretically, the glucose concentration in the solution can be estimated from the pattern of such changes. However, in practice, when measuring photoacoustic signals on human tissues such as skin, it is not easy to identify changes in blood glucose concentration from the measured photoacoustic signals.

[0005] The technical problem of the present disclosure is to provide a photoacoustic measuring device capable of obtaining more accurate information regarding components within a sample using photoacoustics.

[0006] The technical problem of the present disclosure is to provide a photoacoustic measuring device with optimized geometry and a miniaturized form factor.

[0007] The technical problems of the present disclosure are not limited to those mentioned above, and other unmentioned technical problems will be clearly understood by a person skilled in the art from the description below.

[0008] The means for solving the problem are provided to introduce, in a simplified form, some concepts that are described in more detail in the detailed description of the present disclosure, and are not intended to identify the essential concepts of the present disclosure or to determine the scope of the present disclosure.

[0009] A photoacoustic measurement method according to one aspect of the present disclosure is a photoacoustic measurement method for measuring components of a sample using photoacoustics generated by a laser pulse having a predetermined wavelength, wherein when the incident position of the laser pulse, the beam width of the laser pulse, and the relative position of the ultrasonic sensor are each determined from a given frequency band of the ultrasonic sensor and a given position of a photoacoustic generating region within the sample, the method comprises: (a) oscillating a laser pulse with a predetermined pulse energy and pulse width and incidenting it toward a photoacoustic generating region within the sample; (b) detecting photoacoustics generated in the photoacoustic generating region within the sample by the incident laser pulse with an ultrasonic sensor, and obtaining sampling data by sampling the waveform of the detected photoacoustics at a predetermined sampling rate; and (c) storing the sampling data, wherein the distance from the photoacoustic generating region to the ultrasonic sensor is determined based on the wavelength of a frequency belonging to the frequency band of the ultrasonic sensor, and the beam width of the laser pulse may be determined based on half the wavelength of the maximum frequency belonging to the frequency band of the ultrasonic sensor.

[0010] According to an embodiment, the photoacoustic measurement method may further include the step of coherently averaging the sampling data of each frame obtained while repeating steps (a) to (c) for N frames (N is a natural number greater than or equal to 2).

[0011] According to the embodiment, N can be determined in the range of 100 or more and 1000 or less.

[0012] According to the embodiment, step (b) may be performed such that the sampling of the ultrasonic sensor is performed 100 times or more and 3000 times or less.

[0013] According to an embodiment, the start time of the oscillation of the laser pulse in step (a) and the start time of the sampling of the photoacoustic waveform detected in step (b) are synchronized with each other, and the sampling of the photoacoustic waveform in step (b) may not be performed between the start time of the storage of the sampling data in step (c) and the start time of the oscillation of the laser pulse of the next frame.

[0014] According to an embodiment, the pulse width of the laser pulse can be determined such that twice the time difference between the maximum and minimum pressures of the thermobaric wave generated within the sample by the pulse energy of the laser pulse is included within a period range corresponding to the frequency band of the ultrasonic sensor.

[0015] According to an example, the time difference between the maximum and minimum pressures of the thermopressure wave occurring within the sample is given by the following formula

[0016]

[0017] It is calculated based on, where δt is the time difference, τ is the pulse width of the laser pulse beam, R is the radius of the photoacoustic generation area, and υ is the speed of sound in the fluid.

[0018] According to an embodiment, the laser pulse has a high-speed axis and a low-speed axis in the beam cross-section, and can be incident on the sample in a state aligned such that the low-speed axis of the beam cross-section is directed toward the ultrasonic sensor.

[0019] According to an embodiment, the beam width of the low-velocity axis of the laser pulse can be determined based on half the wavelength of the maximum frequency of the frequency band of the ultrasonic sensor.

[0020] According to an embodiment, the distance from the center of the photoacoustic generating region to the center of the measurement surface of the ultrasonic sensor can be determined based on the wavelength of the center frequency of the frequency band of the ultrasonic sensor.

[0021] According to an embodiment, the distance between the photoacoustic generating area and the ultrasonic sensor may be determined based on a distance that reduces the proximity effect caused by a wavelength belonging to the frequency band of the ultrasonic sensor to below a predetermined reference value.

[0022] A recording medium having a program recorded according to another aspect of the present disclosure can execute a photoacoustic measurement method in an information processing device equipped with a light source and an ultrasonic sensor.

[0023] A photoacoustic measuring device according to another aspect of the present disclosure may include a light source that emits a laser pulse having a predetermined wavelength, a light source driving unit that drives the light source to emit a laser pulse having a predetermined pulse energy and pulse width, an optical element that incidents the laser pulse emitted from the light source onto a photoacoustic generating region within a sample, an ultrasonic sensor that detects photoacoustics generated in the photoacoustic generating region within the sample by the laser pulse within a predetermined frequency band, a sampling unit that samples the waveform of the detected photoacoustics at a predetermined sampling rate to acquire sampling data, a memory that stores the sampling data, and an analysis unit that calculates a quantitative or qualitative measurement result regarding the components of the sample from the sampling data, and the distance from the photoacoustic generating region to the ultrasonic sensor may be determined based on the wavelength of a frequency belonging to the frequency band of the ultrasonic sensor, and the beam width of the laser pulse may be determined based on half the wavelength of the maximum frequency belonging to the frequency band of the ultrasonic sensor.

[0024] According to the embodiments, the measurement data may include quantitative or qualitative information regarding the components of a specific substance within the sample under investigation.

[0025] According to the embodiment, the measurement data may include information regarding the concentration of glucose in the dermis layer of the skin or in the blood vessels.

[0026] To further clarify the advantages and features of the present disclosure, the description of the present disclosure will be provided with reference to the embodiments illustrated in the accompanying drawings. Since these drawings depict only typical embodiments of the present disclosure, they should not be construed as limiting the scope of the present disclosure.

[0027] According to the photoacoustic measuring device according to the technical concept of the present disclosure, information regarding components within a sample can be obtained more accurately by using photoacoustics.

[0028] According to the photoacoustic measuring device according to the technical concept of the present disclosure, it is possible to provide robust performance against noise with a miniaturized form factor and optimized geometry.

[0029] The effects obtainable from the exemplary embodiments of the present disclosure are not limited to those mentioned above, and other unmentioned effects can be clearly derived and understood by those skilled in the art from the description of the exemplary embodiments of the present disclosure below. That is, unintended effects resulting from the implementation of the exemplary embodiments of the present disclosure can also be derived by those skilled in the art from the exemplary embodiments of the present disclosure.

[0030] The embodiments, aspects, advantages, and other features of the present disclosure will be better understood by reading the following detailed description with reference to the accompanying drawings, in which the same letters in the drawings indicate the same parts throughout the drawings.

[0031] FIG. 1 is a schematic block diagram illustrating a photoacoustic measuring device according to embodiments.

[0032] FIGS. 2 and 3 are conceptual diagrams illustrating the geometry between the width of the laser pulse beam, the distribution of the beam within the sample, and the ultrasonic sensor measurement surface when a laser pulse beam is irradiated onto a sample to analyze components within the sample using a photoacoustic measuring device according to the embodiments.

[0033] FIG. 4 is a diagram illustrating, in sequence, the operation of measuring photoacoustics by oscillating a laser pulse once in a photoacoustic measurement method according to embodiments.

[0034] FIG. 5 is a diagram illustrating, over time, the operation of measuring photoacoustics by oscillating a laser pulse once in a photoacoustic measurement method according to the embodiments.

[0035] FIG. 6 is a diagram illustrating, in sequence, the operation of measuring photoacoustics by repeatedly oscillating laser pulses in a photoacoustic measurement method according to embodiments.

[0036] FIG. 7 is a diagram illustrating, over time, the operation of measuring photoacoustics by repeatedly oscillating laser pulses in a photoacoustic measurement method according to embodiments.

[0037] For example, some components of the device in the drawings may be represented by conventional symbols. The drawings may primarily depict specific details relevant to understanding the embodiments of the present disclosure, and details that are readily understood by a person skilled in the art may be omitted or simplified to maintain the visibility of the drawings. Some components of the drawings may not be drawn to their actual proportions for the sake of simplification or convenience of explanation.

[0038] The terms used in the embodiments have been selected to be as widely used as possible in consideration of the context of this disclosure; however, these may vary depending on the intent of those skilled in the art, case law, the emergence of new technologies, etc. Additionally, in specific cases where the applicant has arbitrarily selected a term, its meaning will be described in detail in the relevant description. Therefore, terms used in this disclosure should be defined not merely by their names, but based on their meanings and the overall context of this disclosure.

[0039] Singular expressions may include plural expressions unless the context clearly indicates otherwise. Terms used herein, including technical or scientific terms, may have the same meaning as generally understood by those skilled in the art as described in this disclosure.

[0040] When a part of a specification is described as "including" a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but may include additional components. Furthermore, terms such as "part" or "module" as used in the specification refer to a unit that processes at least one function or operation, and this may be implemented in hardware or software, or as a combination of hardware and software.

[0041] Hereinafter, embodiments will be described in detail with reference to the drawings.

[0042] FIG. 1 is a schematic block diagram illustrating a photoacoustic measuring device according to embodiments, and FIG. 2 and FIG. 3 are conceptual diagrams illustrating the geometry between the width of the laser pulse beam, the distribution of the beam within the sample, and the ultrasonic sensor measurement surface when a laser pulse beam is irradiated onto a sample to analyze components within the sample using a photoacoustic measuring device according to embodiments.

[0043] Referring to FIGS. 1, 2 and 3 together, the photoacoustic measuring device (1) may include a light source unit (10), a light source (11), an optical element (12), an optical aperture (13), an optical path (14), a light source driving unit (20), an ultrasonic sensor (30), a sampling unit (40), a memory (50), and an analysis unit (60).

[0044] According to an embodiment, the light source unit (10) may have a light source (11) embedded inside. For example, the light source (11) may be a light-emitting diode (LED) or a laser diode (LD) that directly generates light.

[0045] According to an embodiment, the light source unit (10) may further incorporate one or more optical elements (12) necessary to induce light generated by the light source (11) and to control optical properties. For example, the optical element (12) is any one or more combinations of optical elements such as a lens, a zoom lens, a reflective mirror, a dichroic mirror, a beam splitter, a prism, an optical fiber, a grating, a polarizer, etc., and is not limited to the elements listed herein.

[0046] Control signals and power for driving the light source (11) may be provided from the light source driving unit (20). The light source driving unit (20) can drive the light source (11) with a predetermined light output and light emission time by supplying control signals and power to the light source (11).

[0047] The light source unit (10) may include an optical opening (13) so that light emitted by the light source (11) can pass through optical elements (12) and finally be emitted from the light source unit (10) toward the irradiated sample (70).

[0048] A beam of light (15) passing through the optical aperture (13) of the light source unit (10) can pass through the optical path (14) and be incident on the irradiated sample (70). According to an embodiment, the optical path (14) is an optically transparent optical guide or a tube, and may further be provided with a dust cover or an acoustic coupler as needed. According to an embodiment, the optical path (14) may not be separately provided, and the optical aperture (13) may face the irradiated sample (70).

[0049] In the investigation sample (70), light generates photoacoustics in the intended photoacoustic generation area, and when the generated photoacoustics reaches the ultrasonic sensor (30), the ultrasonic sensor (30) can output an analog ultrasonic signal.

[0050] The analog ultrasonic signal output from the ultrasonic sensor (30) is digitized by a sampling unit (40) operating at a predetermined sampling rate, and the digitized ultrasonic signal is stored in memory (50) as measurement data, either as is or after undergoing a predetermined post-processing. An analysis unit (60) can analyze the measurement data in memory (50). According to an embodiment, the irradiated sample is skin, and the measurement data may include quantitative or qualitative information regarding the components of a specific substance within the dermis layer of the skin. The analysis unit (60) may be implemented, for example, as a processor or a Neural Processing Unit (NPU).

[0051] The ultrasonic sensor (30) can detect photoacoustics transmitted from the irradiated sample (70) by acoustically contacting the irradiated sample (70) with its measurement surface. The ultrasonic sensor (30) may have an acoustic axis, and typically the measurement surface of the ultrasonic sensor (30) may be orthogonal to the acoustic axis.

[0052] According to an embodiment, the photoacoustic measuring device (1) can measure quantitative information of specific substances within the dermis layer, such as glucose concentration, oxygen saturation, and glycated hemoglobin concentration, by irradiating a laser pulse beam of a predetermined wavelength onto the skin to induce a photoacoustic effect in the dermis layer and measuring the generated ultrasonic sound.

[0053] In FIG. 2, a laser pulse beam (15) passes through an optical path (14) and is incident on an irradiated sample (70). The laser pulse beam (15) is a parallel light beam or a non-parallel light beam focused at a predetermined focal point. As the laser pulse beam (15) travels through the irradiated sample (70), it loses energy and weakens as it is gradually absorbed by the material within the sample. The energy absorbed by the material within the irradiated sample (70) causes the material to thermally expand and contract according to predetermined physical properties, thereby generating photoacoustics. The region within the irradiated sample (70) that absorbs the energy of the laser pulse beam (15) to generate photoacoustics can be called a photoacoustic generation region (80).

[0054] If the laser pulse beam (15) is a parallel light beam, the photoacoustic generating region (80) will have a cylindrical shape with a generally constant cross-sectional area along the optical axis (Z1). If the laser pulse beam (15) is a non-parallel light beam, the photoacoustic generating region (80) can be abstracted into a truncated cone shape, i.e., a frustum of a cone, in which the cross-sectional area gradually decreases or increases along the optical axis (Z1), or a double cone shape, i.e., a shape that gradually decreases and then increases again. For convenience of explanation in the description below and in FIG. 2, it is assumed that the laser pulse beam (15) is a non-parallel light beam and the focal position is inside the irradiated sample (70), so the photoacoustic generating region (80) has a truncated cone shape that gradually narrows along the optical axis (Z1). Here, despite the term cone, the cross-section does not necessarily mean that it is a circle in the strict sense, and the cross-section encompasses various shapes of beam cross-sections that can realistically be formed by light sources and optical elements, including elliptical, rectangular, and rounded rectangular shapes. Meanwhile, the following description may be consistent even if the cross-sectional area of ​​the photoacoustic generating region (80) is constant, increases monotonically along the direction of the optical axis (Z1), or becomes smaller and then larger again.

[0055] For example, if the sample (70) is skin, it can be simplified into an epidermal layer (71) that is about 0.1 mm thick, a dermal layer (72) that is about 2 to 3 mm thick, and a subcutaneous fat layer (73) that is less than that. According to Figure 3 (b) of the unpublished literature [1], near-infrared rays in the near-infrared band of about 750 nm to 1000 nm can penetrate up to 2 to 5 mm inside the skin when the light source is directly incident on the skin. Therefore, a laser beam in the band of about 750 to 1000 nm, preferably in the band of 750 to 940 nm, loses about 50% to 90% of its energy while passing through the epidermal and dermal layers. Since the epidermal layer is very thin compared to the dermal layer, it can be estimated that almost all of the energy lost by the laser beam is absorbed in the dermal layer, and some of the absorbed energy causes photoacoustic phenomena in the dermal layer.

[0056] Accordingly, assuming that the material is uniformly distributed within the dermis layer (72), the photoacoustic generating region (80), which is the area through which the laser pulse beam (15) passes within the dermis layer (72), can be described as an area where photoacoustic waves of a size corresponding to the amount of energy absorbed at each location are generated.

[0057] The center (C1) of the photoacoustic generation region (80) can be defined as a geometric center that takes into account the distribution of energy absorption within the photoacoustic generation region (80). This center (C1) of the photoacoustic generation region (80) can be determined in a manner similar to how the center of mass of an object is determined by considering the distribution of mass instead of the distribution of energy absorption.

[0058] The acoustic waves generated in the photoacoustic generation area (80) are generally composed mainly of radial (R) components that spread out orthogonally to the optical axis (Z1) direction, because the components in the optical axis (Z1) direction cancel each other out. Therefore, the ultrasonic sensor (30) can detect some of the acoustic waves that propagate approximately in the radial direction in the photoacoustic generation area (80).

[0059] According to an embodiment, given a predetermined pulse energy and pulse width for a light source driving unit (20) to generate a laser pulse beam (15) from a light source (11) having a predetermined wavelength, a predetermined frequency band and sampling rate for an ultrasonic sensor (30) to detect a photoacoustic wave, and an intended location (B1, C1) of a photoacoustic generation area (80), a geometry including an incident position (A1) of the laser pulse beam (15), a beam width (W) of the laser pulse beam, an incident position (A1) of the photoacoustic generation area (80) within an irradiated sample (70) by the laser pulse beam (15), and locations (A2, B2, C2) of the ultrasonic sensor (30) can be determined as follows.

[0060] Considering the geometry as in FIG. 3 with respect to the incident position (A1) and beam width (W) of the laser pulse beam (15), the center (C1) of the photoacoustic generation area (80), and the center (C2) of the ultrasonic sensor (30), the ultrasonic sensor (30) must be able to detect acoustic waves generated at any position between the incident position (A1) and the apogee (B1) within the photoacoustic generation area (80) through a given frequency band.

[0061] To this end, the wavelength range of acoustic waves that can be detected by the ultrasonic sensor (30) may be set to include acoustic waves having a wavelength corresponding to the distance from any position between the incident position (A1) and the apogee (B1) within the photoacoustic generation area (80) to the measurement surface of the ultrasonic sensor (30). Specifically, the wavelength range of acoustic waves that can be detected by the ultrasonic sensor (30) may be set as follows.

[0062] The shortest wavelength in the wavelength range, that is, the first candidate for a wavelength that is not shorter, can be set to a first wavelength (L1) corresponding to twice the length of the beam width (W) at the incident position (A1) of the photoacoustic generation region (80). Since the laser pulse beam (15) has a wide beam width at the incident position (A1), acoustic waves generated at a point far from the beam and acoustic waves generated at a point near the beam that have a wavelength shorter than the first wavelength (L1) corresponding to twice the length of the beam width (W) may cancel each other out and act as noise when they reach the ultrasonic sensor (30). Therefore, it may be more advantageous for the ultrasonic sensor (30) not to detect acoustic waves shorter than the first wavelength (L1).

[0063] The second candidate for the shortest wavelength among the wavelength range can be set as the second wavelength (L2), which is the longest wavelength among acoustic waves that are generated near the incident position (A1) of the photoacoustic generation area (80) and can reach the near point (A2) of the ultrasonic sensor (30). Among the acoustic waves between the incident position (A1) and the near point (A2) of the ultrasonic sensor, acoustic waves with wavelengths shorter than the second wavelength (L2) may cancel each other out at the near point (A2) of the ultrasonic sensor (30) while the photoacoustic phenomenon is sustained, and act as noise. Therefore, it may be more advantageous for the ultrasonic sensor (30) not to detect acoustic waves with wavelengths shorter than the second wavelength (L2).

[0064] The first candidate for the longest wavelength among the wavelength range, that is, a wavelength that is not longer, can be set as the third wavelength (L3) of the longest wavelength among acoustic waves that originate from the far point (B1) of the photoacoustic generation area (80) and reach the far point (B2) of the ultrasonic sensor (30).

[0065] The second candidate for the longest wavelength among the wavelength ranges can be set by considering the proximity effect of the acoustic waves generated because the ultrasonic sensor (30) is placed in close proximity to the photoacoustic generation area (80). Since the larger the proximity effect, the larger the acoustic waves of that wavelength are detected than the actual ones, it may be desirable to exclude wavelengths with a large proximity effect from the wavelength range to be detected. The influence of the proximity effect of the acoustic waves is It can be expressed as a function of , where r is the distance from the measurement location to the sound source and is a sound wave. As the value decreases, in other words, as the wavelength at the same distance r decreases, the wavelength becomes smaller. As the larger the value, the greater the proximity effect, it can serve as a criterion for determining the upper limit of the wavelength range of the acoustic wave to be measured at a given r.

[0066] Theoretically, the proximity effect of acoustic waves If the value is greater than 1, the effect decreases to about 1 dB or less, and If the value is greater than 2, the effect decreases to 0.2dB or less. Therefore, wavelength this If set to a smaller value, the proximity effect can be suppressed. For example, if the threshold for the magnitude of the proximity effect is set to 1 to be relatively tolerant of the proximity effect, the wavelength The upper limit of is , if the threshold is set to 2 to be relatively strict regarding proximity effects, the wavelength The upper limit of is am.

[0067] For example, if r is defined as the distance (D3) between the far point (B2) of the ultrasonic sensor (30) and the far point (B1) of the photoacoustic generating area (80), or the distance (D4) between the center (C2) of the ultrasonic sensor (30) and the center (C1) of the photoacoustic generating area (80), the upper limit of the wavelength range is D3, 2 D3, D4, or 2 It can be set to D4.

[0068] Accordingly, the ultrasonic sensor (30) has a lower limit of, for example, a first wavelength (L1) or a second wavelength (L2) and an upper limit of, for example, a third wavelength (L3), or D3, 2 D3, D4, or 2 If the ultrasonic sensor (30) is configured to detect acoustic waves of a wavelength included in the wavelength range of D4, it can sufficiently detect acoustic waves occurring at any location between the incident position (A1) and the apogee (B1).

[0069] Furthermore, the wavelength range of acoustic waves that the ultrasonic sensor (30) can detect can be set to necessarily include one or more intentionally selected wavelengths.

[0070] According to the embodiment, the wavelength range may be set to necessarily include a fourth wavelength (L4) corresponding to the distance between the center (C1) of the photoacoustic generation area (80) and the center (C2) of the ultrasonic sensor (30).

[0071] As explained above, the wavelength range of the ultrasonic sensor (30) can be set, and the frequency band of the ultrasonic sensor (30) can also be set from this.

[0072] Meanwhile, the ultrasonic sensor (30) typically has the best performance near a specific center frequency within a frequency band and tends to have lower performance in the bands surrounding such center frequency. Therefore, if a selected main frequency among the acoustic waves generated within the photoacoustic generation area (80) is set as the center frequency of the ultrasonic sensor (30), the magnitude of the photoacoustic signal that the ultrasonic sensor (30) can detect from the photoacoustic generation area (80) can be maximized. For example, the distance between the center (C1) of the photoacoustic generation area (80) and the center (C2) of the ultrasonic sensor (30) can be set based on the wavelength of the center frequency of the ultrasonic sensor (30).

[0073] Meanwhile, the sampling rate of the sampling unit (40) does not need to be higher than twice the highest frequency of the frequency band of the ultrasonic sensor (30), so it can be set from the frequency band of the given ultrasonic sensor (30).

[0074] Meanwhile, in FIG. 3, (a) is a three-dimensional drawing of the optical path (14) and the ultrasonic sensor (30), and (b) is a drawing of the AA' cross-section.

[0075] The laser pulse beam (15) has a beam cross-section that is closer to an ellipse or a rounded rectangle than a circle, and may have a fast axis (F) and a slow axis (S). The fast axis of the beam is a direction in which the beam diverges relatively large and spreads widely, and the slow axis of the beam is a direction in which the beam diverges relatively small and spreads narrowly.

[0076] As depicted in FIG. 3, when the laser pulse beam (15) is aligned so that the low-speed axis (S) is directed toward the ultrasonic sensor (30), the laser pulse beam (15) and the ultrasonic sensor (30) may face each other by the width of the relatively longer high-speed axis (F). On the other hand, when the high-speed axis (F) is positioned so that it is directed toward the ultrasonic sensor (30), the laser pulse beam (15) and the ultrasonic sensor (30) may face each other by only the width of the relatively shorter low-speed axis (S).

[0077] Therefore, when the low-speed axis (S) is aligned to face the ultrasonic sensor (30), the ultrasonic sensor (30) can detect more photoacoustic signals in the radial direction (R) spreading out from the laser pulse beam (15) compared to when the high-speed axis (F) is aligned to face the ultrasonic sensor (30).

[0078] If the low-speed axis (S) of the laser pulse beam (15) is positioned to face the ultrasonic sensor (30), the beam width (W) of FIG. 2 may correspond to the beam width of the low-speed axis (S).

[0079] For example, if the geometry given for photoacoustic measurement with respect to a specific component in the dermis layer of the skin is as follows and the sound wave speed in the skin can be approximated to about 1500 m / s, i.e., 1.5 mm / µs, then the photoacoustic generation area (80) and the geometry of the ultrasonic sensor (30) can be set as follows according to the frequency band of the ultrasonic sensor (30).

[0080] The given frequency band of the exemplary ultrasonic sensor (30) is 0.33 to 1.25 MHz, and the radius of the measurement surface of the ultrasonic sensor (30) is given as 2 mm. In order for the photoacoustic generating region (80) to be formed within the dermis layer of the skin, the depth from the incident position (A1) of the laser pulse beam (15) to the center (C1) of the photoacoustic generating region (80) is given as approximately 1 mm, and the depth to the apogee (B1) of the photoacoustic generating region (80) is given as approximately 2 mm, which is the depth of the dermis layer. Also, by definition, frequency (f) = speed of sound (v) / wavelength (L).

[0081] Since the first wavelength (L1), which is twice the length of the beam width (W) at the incident position (A1) of the laser pulse beam (15), corresponds to a wavelength of 1.2 mm at 1.25 MHz, which is the highest frequency among the frequencies in the frequency band of the ultrasonic sensor (30), the beam width (W) can be set to be 0.6 mm, which is half of that, or narrower. In other words, the beam width (W) can be determined based on half the wavelength of the maximum frequency in the frequency band of the ultrasonic sensor (30). Specifically, the beam width (W) can be determined to be equal to or narrower than half the wavelength of the maximum frequency in the frequency band of the ultrasonic sensor (30).

[0082] The distance (D3) between the far point (B1) of the photoacoustic generation area (80) and the far point (B2) of the ultrasonic sensor (30) can be set to approximately 4.5 mm based on the wavelength of approximately 4.5 mm, which is the lowest frequency of 0.33 MHz among the frequencies belonging to the frequency band of the ultrasonic sensor (30).

[0083] The distance from the incident position (A1) of the photoacoustic generating area (80) to the apogee (B2) of the ultrasonic sensor (30) can be determined to be approximately 4 mm from the approximate right triangle formed by each position (A1, B1, B2), and accordingly, the distance (D1) from the incident position (A1) of the photoacoustic generating area (80) to the proximal point (A2) of the ultrasonic sensor (30) can be determined to be approximately 2 mm. Furthermore, the distance (D4) from the center (C1) of the photoacoustic generating area (80) to the center (C2) of the ultrasonic sensor (30) can be set to approximately 3.2 mm.

[0084] Meanwhile, the present disclosure may set the pulse width of the laser pulse beam (15) based on the time difference between the maximum pressure and the minimum pressure of the thermal pressure wave calculated by the wavelength length belonging to the frequency band of the ultrasonic sensor (30) and the magnitude of the pulse energy of the laser pulse beam (15).

[0085] According to the mechanism of the photoacoustic effect on a fluid, the pressure Pt generated in the fluid by a very short laser pulse beam can be approximated by the following mathematical equation 1.

[0086]

[0087] Here, E is the energy of the laser pulse, Rb is the beam radius of the laser pulse, is the fluid absorption coefficient, is the thermal expansion coefficient of the fluid, ε is the acoustic velocity in the fluid, and Cp is the specific heat of the fluid.

[0088] In the case of skin with an absorption coefficient of about 10^-5 cm-1, the photoacoustic source (PA source) can be considered as a cylinder shape because the laser beam penetrates deep into the fluid while maintaining its radius. Furthermore, if the duration of the laser pulse beam is similar to or shorter than the time it takes for the photoacoustic pulse generated by the laser pulse beam to move radially out of the photoacoustic source, the amplitude of the pressure wave Ps observed at any location away from the photoacoustic source can be approximated as shown in Equation 2 below.

[0089]

[0090] Here, E is the energy of the laser pulse, is the fluid absorption coefficient, is the coefficient of thermal expansion of the fluid, ε is the speed of sound in the fluid, Cp is the specific heat of the fluid, Rs is the radius of the photoacoustic source region (PA source radius), and r is the distance from the center of the photoacoustic source region to the observation location.

[0091] Furthermore, the distribution p(r, t) of the pressure wave according to distance and time can be expressed as Equation 3.

[0092]

[0093]

[0094]

[0095] E is the energy of the laser pulse, α is the fluid absorption coefficient, is the coefficient of thermal expansion of the fluid, ε is the speed of sound in the fluid, Cp is the specific heat of the fluid, R is the diameter of the photoacoustic generation region, and r is the distance from the center of the photoacoustic generation region to the observation position. is the duration of one pulse, is a wave shape function. The wave shape function of a pressure wave can be a wave shape in which a relatively strong and short compressive pulse is followed by a relatively weak and wide rarefaction pulse so as to simulate a thermopressure wave of a fluid.

[0096] From Equation 3, the time difference δt between the peak of the compression pulse, which is the maximum pressure point, and the peak of the rarefaction pulse, which is the minimum pressure point, can be approximated as shown in Equation 4 below.

[0097]

[0098] Here, ε is the single pulse width of the laser pulse, R is the diameter of the photoacoustic generation region, is the speed of sound in the fluid.

[0099] According to an embodiment, using a wave having a period equal to twice the time difference δt between the maximum and minimum pressures of a photoacoustic thermobaric wave by a laser pulse beam according to Equation 4, the pulse width of the laser pulse beam (15) is such that the frequency of such wave is included in the frequency band of the ultrasonic sensor (30). You can set it.

[0100] In the case of the above exemplary geometry, the pulse width of the laser pulse beam (15) corresponds to the 0.33–1.25 MHz band, which is one of the exemplary frequency bands of the ultrasonic sensor (30). If the range of is calculated exemplarily using Equation 4, the pulse width The range of can be set to about 0.6 μs or about 600 ns or less.

[0101] If the distance from the center (C1) of the photoacoustic generation area (80) to the center (C2) of the ultrasonic sensor (30), i.e., 2.6 μs, which is one period of the center frequency of 0.38 MHz estimated at the fourth wavelength (L4), corresponds to twice δt of Equation 4, the pulse width If calculated exemplarily using Equation 4, the pulse width It can be set to about 0.5 μs, or about 500 ns or less.

[0102] but, go As it becomes smaller compared to , the influence on δt decreases. If go If it is 1 / 5 or less shorter than Arithmetically, any value is acceptable, but the pulse width is too short During this time, the energy that the pulse beam can deliver may be insufficient, or it may become difficult to drive the light source.

[0103] Along with the frequency band of the exemplary ultrasonic sensor (30) above, which is 0.33–0.75 MHz band or 0.33–1.25 MHz band, pulse width In the case where this is 0.1 μs, the time difference δt between the maximum and minimum pressures of the thermobaric wave according to Equation 4 is R = 0.3 mm, If the value is 1.5 mm / µs, it is approximately 0.53 µs, and the frequency with a period of twice this time difference δt is approximately 0.95 MHz, which can be included in the 0.33 to 1.25 MHz band, which is an exemplary frequency band of the ultrasonic sensor (30).

[0104] FIG. 4 is a diagram illustrating, in sequence, the operation of measuring photoacoustics by oscillating a laser pulse once in a photoacoustic measurement method according to embodiments.

[0105] Referring to FIG. 4, a photoacoustic measurement method for measuring the components of a sample using photoacoustics generated by a laser pulse having a predetermined wavelength according to an embodiment may be based on the position of the incident position (A1) of the laser pulse beam (15), the beam width (W) of the laser pulse beam (15), and the relative positions (A2, B2, C2) of the ultrasonic sensor (30) being determined from a given frequency band of the ultrasonic sensor (30) and a given position of the photoacoustic generating region (80) within the irradiated sample (70), respectively, and the ultrasonic sensor (30) being positioned adjacent to the incident position (A1) of the laser pulse beam (15) according to such geometry.

[0106] The photoacoustic measurement method (S40) according to the embodiment may begin with the step (S41) in which a photoacoustic measurement device (1) emits a laser pulse beam (15) with a predetermined pulse energy and pulse width and directs it toward a photoacoustic generating region (80) within an irradiated sample (70).

[0107] In step (S42), the photoacoustic measuring device (1) detects photoacoustics generated in the photoacoustic generation area (80) within the irradiated sample (70) by the incident laser pulse beam (15) using an ultrasonic sensor (30) within a predetermined frequency band, and can obtain sampling data by sampling the waveform of the detected photoacoustics at a predetermined sampling rate.

[0108] In step (S43), the photoacoustic measuring device (1) can store the sampling data in memory (50).

[0109] According to an embodiment, the frequency band of the ultrasonic sensor (30) may include one or more frequencies in which the distance from the photoacoustic generation area (80) according to the given geometry to the ultrasonic sensor (30) is one wavelength.

[0110] According to an embodiment, the sampling rate for the ultrasonic sensor (30) may be determined such that the length is twice the beam width (W) of the laser pulse beam (15) according to the given geometry, or the length of either the incident position (A1) of the laser pulse beam (15) and the distance (L2) between the ultrasonic sensor (30) is at least twice the ultrasonic frequency with respect to one wavelength.

[0111] According to an embodiment, in step (S42), the photoacoustic measuring device (1) can perform detection while the sampling of the ultrasonic sensor is performed 100 times or more and 3000 times or less. The number of samplings may be determined by the length of time during which quantitative or qualitative information regarding the composition of a substance within the irradiated sample (70) is effectively maintained in the photoacoustic signal. If the number of samplings is too short compared to the time of effective information retention, the information cannot be sufficiently analyzed, whereas if the number of samplings is too high, the time required for acquisition will be long, and more time required for analysis and information processing performance will be required.

[0112] In step (S44), the photoacoustic measuring device (1) can extract quantitative or qualitative information regarding the components of a substance by analyzing the sampling data stored in the memory (50) in the analysis unit (60).

[0113] FIG. 5 is a diagram illustrating, over time, the operation of measuring photoacoustics by oscillating a laser pulse once in a photoacoustic measurement method according to the embodiments.

[0114] Referring to FIG. 5, according to the photoacoustic measurement method according to the embodiment, the photoacoustic measurement device (1) first activates the power of the light source driving unit (20), the ultrasonic sensor (30), and the sampling unit (40) at a first timing (T1) and can perform the necessary preparation operations during predetermined preparation times (D1, D2). When preparation is complete, the photoacoustic measurement device (1) activates the light source driving unit (20) at a second timing (T2) to drive the light source (11) for a predetermined pulse width (Tp), and synchronizes with this to start receiving and sampling acoustic waves from the ultrasonic sensor (30). After the pulse width (Tp) has passed from the second timing (T2), the light source (11) stops oscillating. The sampling unit (40) generates sampling data by performing 2048 samplings, for example, during a sampling interval (Tadc), with a sampling interval (Ts) for the analog acoustic wave signal received from the ultrasonic sensor (30).

[0115] At the third timing (T3), the photoacoustic measuring device (1) stores the sampling data of one generated sampling frame in the memory (50) during the recording interval (Tw), and at the fourth timing (T4), the power to the light source driving unit (20) and the ultrasonic sensor (30) can be cut off.

[0116] Next, the photoacoustic measuring device (1) can analyze the sampling data in the analysis unit (60) to extract quantitative or qualitative information regarding the material components in the investigation sample (70).

[0117] FIG. 6 is a diagram illustrating, in sequence, the operation of measuring photoacoustics by repeatedly oscillating laser pulses in a photoacoustic measurement method according to embodiments.

[0118] Referring to FIG. 6, the photoacoustic measurement method (S60) according to the embodiment, similar to the photoacoustic measurement method (S40) of FIG. 4, is a photoacoustic measurement method for measuring the components of a sample using photoacoustics generated by a laser pulse having a predetermined wavelength. When the incident position (A1) of the laser pulse beam (15), the beam width (W) of the laser pulse beam (15), and the relative positions (A2, B2, C2) of the ultrasonic sensor (30) are each determined from a given frequency band of the ultrasonic sensor (30) and a given position of the photoacoustic generation area (80) within the irradiated sample (70), the ultrasonic sensor (30) may be based on a state in which the ultrasonic sensor (30) is positioned adjacent to the incident position (A1) of the laser pulse beam (15) according to such geometry.

[0119] The photoacoustic measurement method (S60) according to the embodiment may begin with the step (S61) in which a photoacoustic measurement device (1) emits a laser pulse beam (15) with a predetermined pulse energy and pulse width and directs it toward a photoacoustic generating region (80) within an irradiated sample (70).

[0120] In step (S62), the photoacoustic measuring device (1) detects photoacoustics generated in the photoacoustic generation area (80) within the irradiated sample (70) by the incident laser pulse beam (15) using an ultrasonic sensor (30) within a predetermined frequency band, and can obtain sampling data by sampling the waveform of the detected photoacoustics at a predetermined sampling rate.

[0121] In step (S63), the photoacoustic measuring device (1) can store the sampling data in memory (50).

[0122] According to an embodiment, the frequency band of the ultrasonic sensor (30) may include one or more frequencies in which the distance from the photoacoustic generation area (80) according to the given geometry to the ultrasonic sensor (30) is one wavelength.

[0123] According to an embodiment, the sampling rate for the ultrasonic sensor (30) may be determined such that the length is twice the beam width (W) of the laser pulse beam (15) according to the given geometry, or the length of either the incident position (A1) of the laser pulse beam (15) and the distance (L2) between the ultrasonic sensor (30) is at least twice the ultrasonic frequency with respect to one wavelength.

[0124] According to an embodiment, in step (S62), the photoacoustic measuring device (1) can perform detection while the sampling of the ultrasonic sensor is performed 100 times or more and 3000 times or less.

[0125] The procedures from pulse beam oscillation in step (S61) to sampling data storage in step (S63) constitute one sampling frame.

[0126] In step (S64), the photoacoustic measuring device (1) determines whether the number of sampling frames N (N is a natural number greater than or equal to 2) has reached a predetermined target number, and if it has not yet reached, it returns to step (S61), and if it has reached, it proceeds to step (S65).

[0127] According to an embodiment, N can be determined in a range of, for example, 100 to 1000. If N is, for example, 1000 times or more, the time required for the total measurement increases, and the required memory capacity may also increase. On the other hand, if N is, for example, less than 100 times, it is difficult to sufficiently improve the signal-to-noise ratio.

[0128] In step (S65), the photoacoustic measuring device (1) can coherently average the sampling data of multiple sampling frames. Coherent averaging is a procedure of averaging the sampling data at the same sampling point for each sampling frame, and the noise that may occur during each pulse beam oscillation, photoacoustic pressure wave generation, ultrasonic detection, and sampling process can be reduced and the signal-to-noise ratio (SNR) can be greatly improved.

[0129] According to an embodiment, the photoacoustic measuring device (1) can perform coherent averaging after passing through all sampling frames. In another embodiment, the photoacoustic measuring device (1) can perform coherent averaging by averaging the sampling data acquired for each sampling frame with the sampling data of the previous sampling frame.

[0130] In step (S66), the photoacoustic measuring device (1) can extract quantitative or qualitative information regarding the components of a substance by analyzing the sampling data stored in the memory (50) in the analysis unit (60).

[0131] FIG. 7 is a diagram illustrating, over time, the operation of measuring photoacoustics by repeatedly oscillating laser pulses in a photoacoustic measurement method according to embodiments.

[0132] Referring to FIG. 7, according to the photoacoustic measurement method according to the embodiment, the photoacoustic measurement device (1) can first activate the power of the light source driving unit (20), the ultrasonic sensor (30), and the sampling unit (40) at a first timing (T1), similar to the case of FIG. 5, and perform the necessary preparation operations during the predetermined preparation times (D1, D2).

[0133] When preparation is complete, the photoacoustic measuring device (1) activates the light source driving unit (20) at the second timing (T2) to drive the light source (11) for a predetermined pulse width (Tp) to acquire the first sampling frame, and synchronizes with this, begins receiving and sampling acoustic waves from the ultrasonic sensor (30). After the pulse width (Tp) has passed from the second timing (T2), the light source (11) stops oscillating. The sampling unit (40) begins to generate sampling data by performing 2048 samplings, for example during a sampling interval (Tadc), with a sampling interval (Ts) for the analog acoustic wave signal received from the ultrasonic sensor (30).

[0134] At the third timing (T3), the photoacoustic measuring device (1) stores the sampling data of one generated sampling frame in memory (50) during the recording interval (Tw). The sampling interval (Tadc) and the recording interval (Tw) constitute one sampling frame interval (Tframe).

[0135] From the fourth timing (T4) to the fifth timing (T5), the photoacoustic measuring device (1) repeats the operation from the second timing (T2) to the fourth timing (T4) to acquire a second sampling frame. The photoacoustic measuring device (1) repeats this repetition N times (N is a natural number greater than or equal to 2) up to the sixth timing (T6), and cuts off the sensor power and the light source power. At the seventh timing (T7), the photoacoustic measuring device (1) coherently averages the N sampling data acquired during the N sampling frames.

[0136] Next, the photoacoustic measuring device (1) can analyze the sampling data in the analysis unit (60) to extract quantitative or qualitative information regarding the material components in the investigation sample (70).

[0137] As described above, exemplary embodiments have been disclosed in the drawings and specification. Although specific terms have been used to describe the embodiments in this specification, they are used only for the purpose of explaining the technical concept of the present disclosure and are not intended to limit the meaning or the scope of the present disclosure as defined in the claims. Therefore, those skilled in the art will understand that various modifications and equivalent alternative embodiments are possible therefrom.

[0138] [Explanation of the symbol]

[0139] 1 Photoacoustic measuring device

[0140] 10 Light source section

[0141] 11 light source

[0142] 12 optical elements

[0143] 13 optical aperture

[0144] 14 Gwanggwang-ro

[0145] 15 laser pulse beam

[0146] 20 Light source driving unit

[0147] 30 ultrasonic sensors

[0148] 40 Sampling section

[0149] 50 memory

[0150] 60 Analysis Department

[0151] 70 survey samples

Claims

1. A photoacoustic measurement method for measuring the components of a sample using a laser pulse having a predetermined wavelength and an ultrasonic sensor having a predetermined frequency band, wherein When the incident position of the laser pulse, the beam width of the laser pulse, and the relative position of the ultrasonic sensor are each determined from the given frequency band of the ultrasonic sensor and the given position of the photoacoustic generation region within the sample, (a) a step of generating the laser pulse with a predetermined pulse energy and pulse width and directing it toward a photoacoustic generating region within the sample; (b) detecting photoacoustics generated in the photoacoustic generation region within the sample by the incident laser pulse using the ultrasonic sensor, and obtaining sampling data by sampling the waveform of the detected photoacoustics at a predetermined sampling rate; and (c) includes the step of storing the above sampling data, The distance from the above photoacoustic generation region to the above ultrasonic sensor is determined based on the wavelength of a frequency belonging to the frequency band of the above ultrasonic sensor, and A photoacoustic measurement method characterized in that the beam width of the laser pulse is determined based on half the wavelength of the maximum frequency belonging to the frequency band of the ultrasonic sensor.

2. In Claim 1, A photoacoustic measurement method characterized by further including a step of coherently averaging the sampling data of each frame acquired while repeating steps (a) to (c) for N frames (N is a natural number greater than or equal to 2).

3. A photoacoustic measurement method according to claim 2, characterized in that N is determined in the range of 100 or more and 1000 or less.

4. A photoacoustic measurement method according to claim 2, wherein step (b) is characterized in that sampling of the ultrasonic sensor is performed 100 times or more and 3000 times or less.

5. A photoacoustic measurement method according to claim 2, wherein the start time of the oscillation of the laser pulse in step (a) and the start time of the sampling of the detected photoacoustic waveform in step (b) are synchronized with each other, and the sampling of the photoacoustic waveform in step (b) is not performed between the start time of the storage of the sampling data in step (c) and the start time of the oscillation of the laser pulse of the next frame.

6. A photoacoustic measurement method according to claim 1, characterized in that the pulse width of the laser pulse is determined such that twice the time difference between the maximum pressure and minimum pressure of the thermobaric wave generated within a sample by the pulse energy of the laser pulse is included within a period range corresponding to the frequency band of the ultrasonic sensor.

7. In Claim 6, The time difference between the maximum and minimum pressures of the thermobaric wave occurring within the above sample is given by the following formula It is calculated based on, where δt is the time difference, is the pulse width of the laser pulse beam, R is the diameter of the photoacoustic generation region, A photoacoustic measurement method characterized by the speed of sound in a fluid.

8. A photoacoustic measurement method according to claim 1, characterized in that the laser pulse has a high-speed axis and a low-speed axis in the beam cross-section, and is incident on the sample in a state aligned such that the low-speed axis of the beam cross-section is directed toward the ultrasonic sensor.

9. A photoacoustic measurement method according to claim 8, characterized in that the beam width of the low-velocity axis of the laser pulse is determined based on half the wavelength of the maximum frequency of the frequency band of the ultrasonic sensor.

10. A photoacoustic measurement method according to claim 1, characterized in that the distance from the center of the photoacoustic generating region to the center of the measurement surface of the ultrasonic sensor is determined based on the wavelength of the center frequency of the frequency band of the ultrasonic sensor.

11. A photoacoustic measurement method according to claim 1, characterized in that the distance between the photoacoustic generating region and the ultrasonic sensor is determined based on a distance that reduces the proximity effect caused by a wavelength belonging to the frequency band of the ultrasonic sensor to below a predetermined reference value.

12. A recording medium having a program recorded thereon for executing a photoacoustic measurement method according to any one of claims 1 to 11 in an information processing device equipped with a light source and an ultrasonic sensor.

13. A light source that emits laser pulses having a predetermined wavelength; A light source driving unit that drives the light source so that the light source emits the laser pulse having a predetermined pulse energy and pulse width; An optical element that incidents a laser pulse emitted from the above light source into a photoacoustic generating region within the sample; An ultrasonic sensor that detects photoacoustics generated in a photoacoustic generation region within the sample by the above laser pulse within a predetermined frequency band; A sampling unit that acquires sampling data by sampling the detected photoacoustic waveform at a predetermined sampling rate; A memory for storing the above sampling data; and A photoacoustic measuring device comprising an analysis unit that produces quantitative or qualitative measurement results regarding the components of a sample from the above-mentioned sampling data, The distance from the above photoacoustic generation region to the above ultrasonic sensor is determined based on the wavelength of a frequency belonging to the frequency band of the above ultrasonic sensor, and A photoacoustic measuring device characterized in that the beam width of the laser pulse is determined based on half the wavelength of the maximum frequency belonging to the frequency band of the ultrasonic sensor.

14. A photoacoustic measuring device according to claim 13, characterized in that the pulse width of the laser pulse is determined such that twice the time difference between the maximum pressure and the minimum pressure of the thermobaric wave generated within a sample by the pulse energy of the laser pulse is included within a period range corresponding to the frequency band of the ultrasonic sensor.

15. A photoacoustic measuring device according to claim 13, characterized in that the laser pulse has a high-speed axis and a low-speed axis in the beam cross-section, and is incident on the sample in a state aligned such that the low-speed axis of the beam cross-section is directed toward the ultrasonic sensor.

16. A photoacoustic measuring device according to claim 15, characterized in that the beam width of the low-velocity axis of the laser pulse is determined based on half the wavelength of the maximum frequency of the frequency band of the ultrasonic sensor.

17. A photoacoustic measuring device according to claim 13, characterized in that the distance between the photoacoustic generating region and the ultrasonic sensor is determined based on a distance that reduces the proximity effect caused by a wavelength belonging to the frequency band of the ultrasonic sensor to below a predetermined reference value.

18. A photoacoustic measuring device according to claim 13, characterized in that the distance from the center of the photoacoustic generating region to the center of the measuring surface of the ultrasonic sensor is determined based on the wavelength of the center frequency of the frequency band of the ultrasonic sensor.

19. In Claim 13, A photoacoustic measuring device characterized in that the above measurement data includes quantitative or qualitative information regarding the components of a specific substance within the above-mentioned sample.

20. A photoacoustic measuring device according to claim 13, characterized in that the measurement data includes information regarding the concentration of glucose in the dermal layer of the skin or in the blood vessels.

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