JP5555910B2 - Photoacoustic measurement system - Google Patents

Description

  The present invention relates to a photoacoustic measurement system, and is particularly suitable for use in order to make it possible to observe the state of a sample to be measured using a photoacoustic effect.

In general, when intermittent excitation light (hereinafter referred to as intermittent light) is irradiated on the sample surface, a temperature change occurs on the sample surface, and a sound wave is generated. Such a phenomenon is called a photoacoustic effect, and a photoacoustic microscope has been proposed in which an image of a sample is obtained using the photoacoustic effect.
Patent Document 1 discloses a photoacoustic microscope that detects a photoacoustic wave with a microphone and displays an image (photoacoustic image) of a sample on a television monitor based on the detected photoacoustic wave.

  However, the conventional technique has a problem that it is difficult to obtain detailed information of the sample because only the acoustic attenuation coefficient is captured among the acoustic wave properties.

JP-A-4-213053

  The present invention has been made in view of such problems, and an object of the present invention is to make it possible to obtain more detailed information about a sample than in the past by using a photoacoustic effect.

The photoacoustic measurement system of the present invention is attached to a sample and detects a vibration detection element that detects the vibration of the sample, and light that irradiates the sample to which the vibration detection element is attached with excitation light having an arbitrary intermittent period. An acoustic microscope, a light emitting means for applying excitation light of the intermittent period to the photoacoustic microscope, and a surface on which the vibration detection element of the sample is attached, is excited inside the sample by the excitation light of the intermittent period. The vibration of the sample detected by the vibration detection element is obtained in order to obtain the frequency of the composite resonance frequency of the medium and the vibration detection element between the material at an arbitrary point of the photoacoustic wave source to be excited. A frequency deriving unit having a correlation detecting unit for performing correlation detection on the acoustic signal, wherein the cos component of the acoustic signal correlated and detected by the correlation detecting unit is set to zero. A frequency deriving unit for obtaining a frequency to be obtained, and the light emitting unit for irradiating the excitation light having the intermittent period to the sample attached to the vibration detecting element at a complex resonance frequency obtained by the frequency deriving unit. And a first sound wave property deriving unit that obtains at least one of the sound velocity of the sample and the Young's modulus of the sample as the sound wave property using the complex resonance frequency obtained by the frequency deriving unit. And second sound wave property deriving means for obtaining a depth from the surface of the sample to which the vibration detecting element is attached to the substance contained in the sample as sound wave properties, the frequency deriving means The excitation light of the intermittent period having the quantum mechanical absorption wavelength of the substance contained in the sample is irradiated onto the sample attached to the vibration detecting element. A first frequency deriving means for obtaining the composite resonance frequency when it is, the sample excitation light of the intermittent period is attached to the vibration detecting device having a wavelength not reaching the interior of the material contained in the sample And second frequency deriving means for obtaining the composite resonance frequency when irradiated, wherein the second acoustic wave property deriving means is the first frequency deriving means and the second frequency deriving means. And determining the depth from the surface of the sample to which the vibration detecting element is attached to the substance contained in the sample, based on the composite resonance frequency obtained by the above and the thickness of the sample. It is characterized by.

FIG. 1 is a diagram illustrating an example of a configuration of a photoacoustic measurement system according to an embodiment of the present invention. FIG. 2 is a diagram illustrating an embodiment of the present invention and an example of a state of a sample fixed to a PZT vibrator. FIG. 3 shows an embodiment of the present invention, and is a diagram showing an example of a topography of frequency shift in the sample shown in FIG. FIG. 4 shows an embodiment of the present invention and is a diagram showing an example of a topography of the vibration damping rate in the sample 3 shown in FIG.

Hereinafter, an embodiment of the present invention will be described.
FIG. 1 is a diagram illustrating an example of a configuration of a photoacoustic measurement system.
In FIG. 1, the photoacoustic measurement system includes a light emitting diode array (a plurality of light emitting diodes constituting a light emitting diode array) 1, a photoacoustic resonance microscope 20, a CCD camera 18, a monitor 17, and PZT (zirconate titanate). Lead) vibrator 4, XY operation sample stage 5, sample stage drive device 19, vibration detection circuit 6, tuning amplifier 7, vector voltmeter 9, VF converter 11, and computer-controlled pulse generator 13 A diode power controller 14, a specific diode switch 15, and a PC (personal computer) 12.

  On the XY operation sample stage 5, a PZT vibrator 4 which is an example of a vibration detection element is attached. The sample 3 is attached and fixed to the surface of the PZT vibrator 4. FIG. 2 is a diagram illustrating an example of a state of the sample 3 fixed to the PZT vibrator 4. As shown in FIG. 2, in this embodiment, a case where a substantially equilateral triangular aluminum plate (aluminum adhesive tape) is used as the sample 3 is illustrated. Note that the thickness of the sample 3 is 0.13 mm.

  The sample stage driving device 19 has an X direction sample stage driving device 19a and a Y direction sample stage driving device 19b. The X-direction sample stage drive device 19a is for moving the XY operation sample stage 5 in the X-axis direction (lateral direction toward FIG. 1). The Y-direction sample stage drive device 19b is for moving the XY operation sample stage 5 in the Y-axis direction (depth direction in FIG. 1). These X-direction sample stage drive device 19a and Y-direction sample stage drive device 19b have, for example, a pulse motor, receive a control signal transmitted from the PC 12, and operate the pulse motor based on the received control signal. Thus, the XY operation sample stage 5 is driven.

  The photoacoustic resonance microscope 20 has a half mirror 2. When intermittent light having a beam diameter of, for example, about 50 [μm] is emitted from the light emitting diode array 1, the intermittent light is transmitted to the half mirror 2. And irradiate the sample 3. Then, the light signal excited on the surface of the sample 3 passes through the inside of the sample 3 and strikes the surface of the PZT vibrator 4. Thereby, a periodic pressure change occurs in the PZT vibrator 4 and the surrounding gas, and a sound wave is generated.

  Moreover, when the sample 3 is irradiated with intermittent light, reflected light is generated from the sample 3. This reflected light is taken into the CCD camera 18 through the half mirror 2. The CCD camera 18 generates image data of the sample 3 based on the captured reflected light, and displays the generated image data on the monitor 17. The monitor 17 is, for example, an LCD (Liquid Crystal Display). In addition to the half mirror 2, a lens 21 for irradiating the sample 3 with intermittent light, a lens 22 for guiding the intermittent light to the half mirror 2, and the like are provided inside the photoacoustic resonance microscope 20. Yes.

The PZT vibrator 4 is a piezoelectric element. Therefore, when a signal of light excited on the surface of the sample 3 fixed to the PZT vibrator 4 passes through the inside of the sample 3 and hits the surface of the PZT vibrator 4, the PZT vibrator 4 vibrates. An electric signal (that is, an acoustic signal) corresponding to the vibration is generated (detected).
The vibration detection circuit 6 is a circuit for amplifying an acoustic signal generated by the PZT vibrator 4. Specifically, the vibration detection circuit 6 is a current amplification circuit including a positive feedback circuit. Since the vibration detection circuit 6 includes a positive feedback circuit, the resonance characteristic value Q of the PZT vibrator 4 can be increased.

The tuning amplifier 7 amplifies the acoustic signal output from the vibration detection circuit 6 based on the tuning signal output from the PC 12. Specifically, tuned amplifier 7 includes an amplifier circuit for amplifying a frequency band including a composite resonance frequency f _t.
Here, the composite resonance frequency _ft will be described.
It is assumed that a vibration detection element (for example, PZT vibrator 4) having a thickness of L [m] has a fundamental resonance frequency of f _R [Hz]. When a sample having a thickness of ΔL [m] (for example, sample 3) is attached to this vibration detection element (when attached), the overall resonance frequency of the vibration detection element and the sample is the basic resonance frequency of the vibration detection element. a frequency slightly lower frequency than f _R, a composite resonance frequency f _t of the thickness L + [Delta] L length of the [m] as one wavelength. Thus, the composite resonance frequency _ft is the overall resonance frequency of the vibration detecting element and the sample. As will be described later, in this embodiment, the PC 12 controls each unit so that intermittent light is emitted from the diode array 1 at the composite resonance frequency f _t .

The computer control pulse generator (synthesizer) 13 generates a reference signal 10 having the same frequency as the composite resonance frequency f _t based on the control signal transmitted from the PC 12. The control signal is a signal indicating a composite resonance frequency f _t, which is determined by the PC12 as described later.
The vector voltmeter 9 measures the voltage level and phase of the acoustic signal output from the tuned amplifier 7 using the reference signal 10 having the same frequency as the composite resonance frequency f _t . Specifically, the vector voltmeter 9 includes a phase detection circuit for the sin component and a phase detection circuit for the cos component, and the reference signal 10 having the same frequency as the composite resonance frequency f _t by these phase detection circuits. To perform autocorrelation detection. Thereby, the sin component and the cos component of the acoustic signal output from the tuning amplifier 7 can be separated. The vector voltmeter 9 transmits the sin component and the cos component of these acoustic signals to the VF converter 11. As described above, in this embodiment, as a reference signal a signal of a composite resonance frequency f _t, by correlation detection of the measured acoustic signals, sensitivity and signal-to-noise ratio of the measured acoustic signal and a (SN ratio) Can be raised.

  The VF converter 11 digitizes the sin component and the cos component of the acoustic signal transmitted from the vector voltmeter 9. The sin component and the cos component of the digitized acoustic signal are taken into the PC 12.

  The PC 12 includes a ROM and a hard disk that store programs and data, a CPU that executes the programs, a work area when the CPU executes the programs, and a RAM that functions as a temporary storage area for data. The PC 12 also includes a user interface such as a keyboard and a mouse, and a display for displaying an image based on a processing result executed by the CPU.

The PC 12 generates a light intensity instruction signal and a diode selection instruction signal in addition to the tuning signal 8 to the tuning amplifier 7 and the control signal to the computer control pulse generator 13 described above.
Specifically, the PC 12 stores light emission intensity in advance for each wavelength of light emitted from each diode array of the light emitting diode array 1. Then, the PC 12 is a light having an appropriate intensity corresponding to the wavelength of light emitted from the light emitting diode array 1 (composite resonance frequency f _t ), based on the sin component and the cos component of the digitized acoustic signal. An intensity indication signal is generated and transmitted to the diode power controller 14.

Moreover, PC12 is a sin component of the digitized acoustic signal, on the basis of the cos component, among the plurality of diodes included in the diode array 1 is used to emit intermittent light composite resonance frequency f _t A diode selection instruction signal for selecting a diode is generated and transmitted to the specific diode switch 15.

The diode power controller 14 is based on the light intensity indication signal output from the PC 12 and the reference signal 10 transmitted from the computer control pulse generator 13 and having the same frequency as the composite resonance frequency f _t. The light intensity emitted from the diode array 1 is determined, and a light intensity signal indicating the determined light intensity is transmitted to the specific diode switch 15.

Based on the light intensity signal transmitted from the diode power controller 14 and the diode selection instruction signal transmitted from the PC 12, the specific diode switch 15 generates a complex resonance frequency f _t from the diodes included in the diode array 1. A pulse signal (diode power pulse) for emitting intermittent light is output to the diode. Thereby, intermittent light is emitted from the light emitting diode array 1 at the composite resonance frequency f _t [Hz].
Here, an example of a method for determining the composite resonance frequency f _t [Hz] will be described.
First, since the PZT vibrator 4 to which the sample 3 is attached is equivalent to an RLC series resonance circuit, it can be expressed as the following equations (1) to (3) as solutions in a steady state.

Here, I _s (t) is a steady current [A], ω is an angular frequency [rad / s], and ω ₀ is a resonance angular frequency [rad / s]. R is the resistance [Ω] of the RLC series resonance circuit equivalent to the PZT vibrator 4 to which the sample 3 is attached, and L is the reactance of the RLC series resonance circuit equivalent to the PZT vibrator 4 to which the sample 3 is attached. [H].
The constant A _ab shown in the equation (2) is an absorptive amplitude, and the constant _Bel shown in the equation (3) is an elastic amplitude. Note that the value of the attenuation intensity in the PZT vibrator 4 to which the sample 3 is attached depends on A _ab sin ωt in the first term on the right side of the equation (1).
The constant _Be1 shown in the equation (3) becomes 0 (zero) at the composite resonance frequency f _t . Therefore, in the present embodiment, the PC 12 obtains the frequency at which the constant B _el (cos component) shown in Equation (3) becomes 0 (zero) as the composite resonance frequency frequency f _t [Hz]. Then, the PC 12 transmits a control signal to be transmitted to the computer control pulse generator 13, a light intensity instruction signal to be transmitted to the diode power controller 14, and a specific diode switch 15 based on the obtained composite resonance frequency f _t. A diode selection instruction signal to be generated. As described above, in the present embodiment, intermittent light is emitted at the complex resonance frequency frequency f _t [Hz] at which the constant _Bel shown in the equation (3) is 0 (zero).

Next, the sound wave physical properties required by the PC 12 will be described. In the PC 12 provided in the optical microscope apparatus of the present embodiment, the vibration attenuation coefficient α, the sound velocity ν, the Young's modulus E, the vibration attenuation ratio τ, and the concentration I ₀ of the specific substance in the sample 3 are used as sound wave properties. The depth D from the surface of the sample 3 to the specific substance is obtained.

(Vibration damping factor τ)
When a constant force F [N] is applied to the PZT vibrator 4 to which the sample 3 is attached, the voltage V [V] generated in the PZT vibrator 4 is given by the following equation (4). .
V = kF (4)

Here, k is a mechanical electroacoustic conversion constant. This mechanical electroacoustic conversion constant is obtained by synthesizing the entire electromechanical conversion constant of the sample 3 and the PZT vibrator 4 (the mechanical electroacoustic conversion constant of the sample 3 and the mechanical electroacoustic conversion constant of the PZT vibrator 4). Stuff).
Further, when the resistance of the RLC series resonance circuit equivalent to the PZT vibrator 4 to which the sample 3 is attached is R [Ω] and the resonance current in the RLC series resonance circuit is I [A], the PZT vibrator 4 is generated. The voltage V [V] is given by the following equation (5).
V = RI (5)
From the equations (4) and (5), the following equation (6) is established.
R = kF / I (6)
Thus, since the force F applied to the PZT vibrator 4 to which the sample 3 is attached is measured at a constant level, an equivalent RLC series resonance circuit to the PZT vibrator 4 to which the sample 3 is attached is provided. The resistance R is proportional to the reciprocal of the resonance current I in the RLC series resonance circuit.
From the equation (6), the vibration damping rate τ is expressed by the following equation (7).

  Here, L is the reactance [H] of the RLC series resonance circuit equivalent to the PZT vibrator 4 to which the sample 3 is attached.

  In this embodiment, the reactance L of the RLC series resonance circuit equivalent to the PZT vibrator 4 to which the sample 3 is attached, the force F applied to the PZT vibrator 4 to which the sample 3 is attached, and the PZT vibration The mechanical electroacoustic conversion constant k of the child 4 is made constant. The PC 12 acquires the reactance L, the force F, and the mechanical electroacoustic conversion constant k based on the user's operation of the user interface provided in the PC 12, and stores them in a hard disk or the like in advance.

Then, the PC 12 obtains the amplitude (resonance current I) of the sin component when the cos component becomes 0 (zero) based on the sin component and the cos component of the acoustic signal, and the obtained amplitude (resonance current I) and Then, the previously stored reactance L, force F, and mechanical electroacoustic conversion constant k are substituted into the equation (7), and the vibration attenuation rate τ (the overall vibration attenuation rate of the sample 3 and the PZT vibrator 4). Ask for.
The vibration attenuation rate τ is the overall vibration attenuation rate of the sample 3 and the PZT vibrator 4 (a combination of the vibration attenuation rate of the sample 3 and the vibration attenuation rate of the PZT vibrator 4). Among them, the vibration attenuation rate of the PZT vibrator 4 can be regarded as being constant, and is sufficiently smaller than the vibration attenuation rate of the sample 3.

In the present embodiment, the sample 3 is irradiated with light having a short wavelength λ _V having a shallow depth that penetrates into the sample 3 from the diode array 1 (hereinafter referred to as short wavelength light). Request vibration damping factor tau _V at 3. Here, the short wavelength λ _V refers to a wavelength that does not reach a specific substance contained in the sample 3, for example. For example, the vibration attenuation rate τ _s is measured by measuring the amplitude of the acoustic signal obtained from the PZT vibrator 4 when the sample 3 is irradiated with short-wavelength light, and the measured amplitude of the acoustic signal is expressed by I in equation (11). Can be obtained by substituting for.

(Vibration damping coefficient α)
The PC 12 obtains the vibration damping coefficient α in the sample 3 attached to the PZT vibrator 4 based on the vibration damping rate τ obtained using the equation (7) as described above. The vibration damping coefficient α is proportional to the inverse of the amplitude (resonance current I) of the acoustic signal.

(Sonic velocity ν, Young's modulus E)
In order to resonate the PZT vibrator 4 to which the sample 3 is attached when the sample 3 is irradiated with intermittent light at the composite resonance frequency f _t , the following equation (8) must be satisfied.
T _t = T _R + ΔT (8)
Here, T _t is the sample 3 and the PZT vibrator 4, the time that sound speed propagated [s], T _R is the time the PZT vibrator 4 sound speed propagated [s], [Delta] T is This is the time [s] during which the sound velocity propagates through the sample 3. Thus, T _t is the period of the vibration mode in which the added value (= L + ΔL) of the thickness ΔL of the sample 3 and the thickness L of the vibration detection element (for example, the PZT vibrator 4) is one wavelength. Become.
Here, when the sound speed in the sample 3 is ν, the following equation (9) is established. Therefore, the sound speed ν [m / s] is expressed by the following equation (10). Further, the relationship between the Young's modulus E [Pa] of the sample 3 and the sound velocity ν is expressed by the following equation (11).

Here, [Delta] L is the thickness of the sample 3 [m], f _R is resonant frequency of the PZT vibrator 4 [Hz], f _t is a composite resonance frequency [Hz], Δf (= f _R -f _t) is the frequency shift [Hz], [rho is the density of the sample ³ [kg / m 3].
The PC 12 acquires the thickness ΔL of the sample 3, the resonance frequency f _R of the PZT vibrator 4, and the density ρ of the sample 3 based on an operation by a user of a user interface provided in the PC 12, and stores it in a hard disk or the like in advance. Remember.
The PC 12 obtains the frequency shift Δf from the composite resonance frequency f _t determined as described above and the resonance frequency f _R of the PZT vibrator 4 stored in advance. Then, the PC 12 substitutes the obtained frequency deviation Δf, the thickness ΔL of the sample 3 and the resonance frequency f _R of the PZT vibrator 4 stored in advance in the equation (10), and the PZT vibrator The sound speed ν in the sample 3 attached to 4 is obtained. Thereafter, the PC 12 obtains the Young's modulus E of the sample 3 by substituting the obtained sound velocity ν and the density ρ of the sample 3 stored in advance into the equation (11).

In the present embodiment, in addition to the composite resonance frequency f _t sound velocity occurring sample 3 affixed to PZT vibrator 4 when irradiated with chopped light to the sample 3 at [nu, short wavelength light from the diode array 1 When the sample 3 is irradiated, the sample 3 is irradiated with the absorption light having the sound velocity ν _V generated in the sample 3 attached to the PZT vibrator 4 and the quantum mechanical absorption wavelength λ _s of the specific substance in the sample 3. In this case, the speed of sound ν _s generated in the sample 3 attached to the PZT vibrator 4 is also obtained.

  When the density ρ and the Young's modulus E of the sample 3 are not constant and are expressed as a function of location, it is possible to know the density ρ and the Young's modulus E of the sample 3 from the speed ν.

(Depth D from the surface of sample 3 to the specified substance)
The PC 12 calculates Δf _{V based on the} composite resonance frequency f _tV and f _R generated in the sample 3 attached to the PZT vibrator 4 when the sample 3 is irradiated with the short wavelength light from the diode array 1 obtained as described above. (= F _tV -f _R ) is defined. Further, when the sample 3 is irradiated with absorption light having a wavelength of the quantum mechanical absorption wavelength λ _s of the specific substance in the sample 3, the composite resonance frequencies f _ts and f generated in the sample 3 attached to the PZT vibrator 4. _{From R} , Δf _s (= f _ts −f _R ) is defined. By substituting the thickness ΔL of the sample 3 stored in advance into the following equation (12), the depth D [m] from the surface of the sample 3 to the specific substance is obtained.
D = ΔL {1− (Δf _s / Δf _V )} (12)

(Concentration I ₀ of specific substance in sample 3)
The concentration I _{0 of the} specific substance at the position of the depth D [m] from the surface of the sample 3 is expressed by the following equation (13).

Here, τ _s is vibration attenuation in the sample 3 attached to the PZT vibrator 4 when the sample 3 is irradiated with absorption light having a wavelength of the quantum mechanical absorption wavelength λ _s of the specific substance in the sample 3. a rate, I _s is the intensity of the resultant acoustic signal by applying the absorbed light to the sample 3.
PC12 determines the intensity I _s of the audio signal obtained by irradiating the absorbed light to the sample 3. Then, the PC 12 assigns the depth D [m] from the surface of the sample 3 by substituting the obtained intensity I _{s of the} acoustic signal and the vibration damping rate τ _s obtained as described above into the equation (13). Obtain the concentration I _{0 of the} specific substance at the position of

(Create topograph)
The PC 12 performs the above-described measurement at a plurality of locations on the XY plane when obtaining the above-described acoustic wave properties, for example, the sound velocity ν, Young's modulus E, vibration damping rate τ, and a specific substance in the sample 3 The topography (three-dimensional image data) of the concentration I ₀ , the depth D from the surface of the sample 3 to the specific substance, and the frequency transition Δf is generated and displayed on the display. Further, the PC 12 stores the data of these topographs on, for example, a hard disk.

Specifically, in order to generate a topograph, the PC 12 uses a sample stage driving device so that the position of the sample 3 facing the photoacoustic resonance microscope 20 is a position (a plurality of predetermined positions) set in advance on a hard disk or the like. 19 (X direction sample stage drive unit 19a and Y direction sample stage drive unit 19b) are sequentially driven. Then, the PC 12 performs the above-described measurement at a plurality of positions, and the sound velocity ν, Young's modulus E, vibration damping ratio τ, specific substance concentration I _{0 in} the sample 3 and the surface of the sample 3 are specified at the plurality of positions. A depth D to the substance and a frequency transition Δf are obtained, and a topograph (three-dimensional image data) is generated based on the obtained result. A display provided in the PC 12 displays the generated topograph.

  The PC 12 acquires a frequency shift Δf suitable for obtaining the sound velocity ν and the Young's modulus E from the topography of the frequency transition Δf based on the operation of the user interface of the PC 12 and the acquired frequency. The sound speed ν and Young's modulus E of the sample 3 can be obtained using the shift Δf.

  FIG. 3 is a diagram showing an example topograph of the frequency shift Δf in the sample 3 shown in FIG. FIG. 4 is a diagram showing an example of a topograph of the vibration damping rate τ in the sample 3 shown in FIG. 3 and 4, 40 points are obtained per 2 [mm], and a positional resolution of ± 50 [μm] is obtained.

  Sample 3 was formed by cutting an aluminum plate (aluminum adhesive tape) with scissors into a substantially equilateral triangle. From this, the topographs 300 and 400 shown in FIGS. 3 and 4 show that one side of the sample 3 (the side on the right side) is turned up. At the center of the sample 3, the frequency shift Δf is low, and it can be seen that the sample 3 is well bonded to the PZT vibrator 4. That is, in the central portion of the sample 3 where the sample 3 is well bonded to the PZT vibrator 4, the time for the acoustic signal to propagate through the sample 3 is shortened, and thus the frequency shift Δf is lowered.

  In the present embodiment, the PC 12 acquires the frequency shift Δf having a relatively gentle and low value in the center portion of the sample 3 in the topograph 300 of the frequency shift Δf based on the user interface operation by the user. Then, the sound velocity ν and Young's modulus E of the sample 3 are obtained.

As described above, in the present embodiment, the light is generated from the PZT vibrator 4 by irradiating the surface (upper face) of the sample 3 to be measured fixed (adhered) to the surface (upper face) of the PZT vibrator 4 with intermittent light. based on the amplitude of the acoustic signal, obtains a composite resonance frequency f _t, so that the intermittent light of the complex resonance frequency f _t of the determined intermittent light from the diode array 1 for controlling the diode light-emitting state of the array 1 so as to irradiate I made it. Then, using the obtained composite resonance frequency f _t , the sound wave physical properties such as the sound velocity ν and Young's modulus E of the sample 3 were obtained. Therefore, not only the vibration attenuation rate but also various sound wave physical properties can be obtained, and more detailed information of the sample 3 can be obtained than the prior art by utilizing the photoacoustic effect. Therefore, for example, it is possible to perform a biopsy or the like with high accuracy.

Further, since the vibration attenuation rate α, the vibration attenuation rate τ, and the depth D from the surface of the sample 3 to the specific substance are obtained, more detailed information of the sample 3 can be obtained.
Furthermore, the topography (three-dimensional image data) of the sound velocity ν, Young's modulus E, vibration damping rate τ, concentration I ₀ of the specific substance in the sample 3, depth D from the surface of the sample 3 to the specific substance, and frequency transition Δf Is generated and displayed on the display, the state of the sample 3 can be easily recognized visually by the user. Therefore, for example, cancer cells that proliferated abnormally in biopsy samples and normal cells around them can be easily distinguished visually using a topograph (for example, a Young's modulus E or a topography with a speed of sound ν (considering density)). It becomes possible to do.

  Furthermore, since the frequency shift Δf used to determine the sound speed ν and the Young's modulus E is determined based on the topograph 300, the sound speed ν and the Young's modulus E can be determined more accurately.

In this embodiment, the acoustic signal is processed into a form that can be processed by the PC 12 using the VF converter 11. However, the acoustic signal is processed into a form that can be processed by the PC 12 using an AD converter instead of the VF converter 11. May be processed.
In this embodiment, the sound velocity ν and the Young's modulus E of the sample 3 are obtained using the frequency shift Δf acquired based on the operation by the user referring to the topograph 300 of the frequency shift Δf. This is not always necessary. That is, from the topograph 300 of the frequency deviation Δf, the PC 12 itself determines the frequency deviation Δf for obtaining the sound velocity ν and the Young's modulus E of the sample 3, and the determined frequency deviation Δf is used to determine the frequency deviation Δf of the sample 3. The speed of sound ν and Young's modulus E may be obtained. In determining the frequency deviation Δf, for example, the lowest value of the frequency deviation Δf in the topograph 300 of the frequency deviation Δf may be used, or the average value of the frequency deviation Δf in the topograph 300 of the frequency deviation Δf is used. Alternatively, a minimum value or an average value in a region where the change of the frequency shift Δf in the topography 300 of the frequency shift Δf is not more than a threshold value may be used.

  In this embodiment, intermittent light is emitted using a light emitting diode, but it is not always necessary to use a light emitting diode. For example, a laser diode may be used. Further, the light source such as a light emitting diode or a laser diode may be plural or one. Moreover, although the case where the beam diameter is 50 [μm] is illustrated, the beam diameter is not limited to this, and can be set to 1 [μm] or less, for example. If the beam diameter is reduced, the position resolution can be improved.

  In this embodiment, the X-direction sample stage drive device 19a and the Y-direction sample stage drive device 19b are driven to drive the XY operation sample stage 5 in two directions, the X-axis direction and the Y-axis direction. The XY working sample stage 5 may be driven only in one direction in the X-axis direction and the Y-axis direction.

  In this embodiment, the case where the PZT vibrator 4 is used as the vibration detection element has been described as an example. However, the vibration detection element is not limited to the PZT vibrator (piezoelectric element), and the vibration of the sample 3 is measured. Any element may be used as long as it is an element to be detected. For example, a magnetostrictive resonance vibrator, a PDF synthetic resonance vibrator, an electrostatic induction synthetic resonance vibrator, an electromagnetic induction type synthetic resonance vibrator, a light detection synthetic resonance vibrator, or the like can be used as the vibration detection element.

  The embodiment of the present invention described above can be realized by a computer executing a program. Further, a means for supplying the program to the computer, for example, a computer-readable recording medium such as a CD-ROM recording such a program, or a transmission medium for transmitting such a program may be applied as an embodiment of the present invention. it can. A program product such as a computer-readable recording medium in which the program is recorded can also be applied as an embodiment of the present invention. The above programs, computer-readable recording media, transmission media, and program products are included in the scope of the present invention.

  In addition, the above-described embodiments are merely examples of implementation in carrying out the present invention, and the technical scope of the present invention should not be construed as being limited thereto. That is, the present invention can be implemented in various forms without departing from the technical idea or the main features thereof.

  According to the present invention, the vibration detection element attached to the sample and detecting the vibration of the sample, and any photoacoustic wave source group column excited from the surface of the sample attached to the vibration detection element toward the inside Since the composite resonance frequency with the medium between the distance from one point is obtained based on the acoustic signal indicating the vibration of the sample detected by the vibration detection element, using the composite resonance frequency, Many sound wave properties can be obtained.

Claims (5)

A vibration detecting element attached to the sample and detecting the vibration of the sample;
A photoacoustic microscope that irradiates excitation light of an arbitrary intermittent period to the sample to which the vibration detection element is attached,
A light emitting means for providing excitation light of the intermittent period to the photoacoustic microscope;
The medium and the vibration detection between the surface of the sample on which the vibration detection element is attached and the substance at any one point of the photoacoustic wave source excited inside the sample by the excitation light of the intermittent period A frequency deriving unit having a correlation detecting unit for correlating and detecting an acoustic signal indicating the vibration of the sample detected by the vibration detecting element in order to obtain a frequency of a complex resonant frequency with the element; Frequency derivation means for obtaining a frequency at which the cos component of the acoustic signal correlation-detected by the correlation detection means becomes zero;
Control means for controlling the light-emitting means so that the excitation light of the intermittent period is irradiated to the sample attached to the vibration detecting element at the composite resonance frequency obtained by the frequency deriving means;
A first acoustic wave property deriving unit that obtains at least one of a sound velocity in the sample and a Young's modulus of the sample as a sound wave property using the complex resonance frequency obtained by the frequency deriving unit;
Second sound wave property deriving means for obtaining a depth from the surface of the sample to which the vibration detecting element is attached to the substance contained in the sample as sound wave property,
The frequency deriving unit obtains the complex resonance frequency when the intermittent light having the quantum mechanical absorption wavelength of the substance contained in the sample is irradiated to the sample attached to the vibration detecting element. First frequency deriving means;
Second frequency deriving means for obtaining the composite resonance frequency when the intermittent light having a wavelength that does not reach the inside of the substance included in the sample is irradiated to the sample attached to the vibration detecting element; Further comprising
The second acoustic wave property deriving unit is configured to generate the vibration of the sample based on a composite resonance frequency obtained by the first frequency deriving unit and the second frequency deriving unit and a thickness of the sample. A photoacoustic measurement system comprising obtaining a depth from a surface on which a detection element is attached to the substance contained in the sample. From the light emitting means, the vibration detection by being irradiated to the sample which the excitation light of the intermittent period is attached to the vibration detecting element having a frequency based on the quantum mechanical absorption wavelength of the substance contained in the sample 2. The light according to claim 1, further comprising: a third sound wave property deriving unit that obtains a vibration attenuation rate of the sample as a sound wave property using an acoustic signal indicating the vibration of the sample detected by an element. Acoustic measurement system. From the light emitting means, the vibration detection by being irradiated to the sample which the excitation light of the intermittent period is attached to the vibration detecting element having a frequency based on the quantum mechanical absorption wavelength of the substance contained in the sample using an acoustic signal indicating a vibration of the sample detected by the element, and a vibration damping factor obtained by the third wave properties deriving means using the sound signal, the concentration of the substance contained in the sample The photoacoustic measurement system according to claim 2, further comprising: a fourth sound wave property deriving unit that obtains the sound wave property as a sound wave property. A position changing means for changing a relative position between the sample and the photoacoustic microscope;
The photoacoustic measurement system according to any one of claims 1 to 3, wherein the sound wave physical property is obtained at each position changed by the position changing means.   5. The photoacoustic measurement system according to claim 4, further comprising display means for displaying on a display device a three-dimensional image based on sound wave physical properties obtained at each position changed by the position changing means.

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