Photoacoustic detection imaging system and method based on optical waveguide resonance sensing

Abstract

The invention discloses a photoacoustic detection imaging system and method based on optical waveguide resonance sensing. The imaging system comprises a detection light source, a polarization assembly, a first focusing lens, a prism, an objective lens, a sensor, a spectroscope, a first polarization detection assembly, a second polarization detection assembly, a photoelectric detector, an exciting light source, a lens assembly, a first reflector, a second focusing lens, a second reflector, a two-dimensional mobile platform and an imaging processing terminal. The sensor is an optical waveguide resonance sensor. According to the imaging system, the combination of the sensor of the tightly limited detection electric field with extremely strong optical resonance and the coupling medium is arranged, so that the imaging system has ultra-high sensitivity and large-bandwidth photoacoustic detection capability; the exciting light irradiates the sample to generate the photoacoustic signal and acts with the coupling medium to obtain the detection light beam based on the light beam change, so that the photoacoustic microscopic imaging in a reflection mode can be realized, the three-dimensional microscopic imaging in a micrometer scale can be realized regardless of the thickness of the sample, and the depth resolution and the quality of the imaged image are greatly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of microscopic imaging, and in particular to a photoacoustic detection imaging system and method based on optical waveguide resonance sensing. Background Art

[0002] Photoacoustic imaging technology detects the instantaneous thermoelastic expansion caused by the specific strong absorption of pulsed laser energy by biological molecules through acoustic means, thereby being able to directly reflect the light absorption characteristic maps of different molecules. This technology reveals the molecular specificity of endogenous non-fluorescent chromophores (such as hemoglobin and melanin) in a label-free manner and shows great potential in biomedical research fields such as cancer histology, vascular anatomy, and brain activity monitoring. An important branch of this technology is optical resolution photoacoustic microscopy (OR-PAM), which can achieve micron and sub-micron level lateral resolution by using a microscopic objective lens to focus the excitation light, thereby revealing the morphological, functional, and molecular level information of biological samples at the cellular and subcellular levels. In the vast majority of OR-PAM systems, a transducer based on piezoelectric material is usually used to detect the time-domain photoacoustic signal generated by the instantaneous thermoelastic expansion of biological molecules. Due to the inherent physical properties of piezoelectric materials, the frequency bandwidth of piezoelectric transducers is relatively narrow (usually dozens of megahertz), while the pressure transients generated by microscopic structures usually have an extremely wide acoustic bandwidth from near direct current to hundreds of megahertz. Therefore, this affects the depth resolution of these OR-PAM systems, resulting in the inability to accurately obtain the depth position information of biological molecules and reducing the quality of the three-dimensional photoacoustic image drawing. Therefore, the optical resolution photoacoustic microscopy in the prior art methods has the problem of low depth resolution. Summary of the Invention

[0003] The embodiments of the present invention provide a photoacoustic detection imaging system and method based on optical waveguide resonance sensing, aiming to solve the problem of low depth resolution existing in the optical resolution photoacoustic microscopy in the prior art methods.

[0004] In a first aspect, the embodiments of the present invention provide a photoacoustic detection imaging system based on optical waveguide resonance sensing, wherein the photoacoustic detection imaging system includes a detection light source, a polarization component, a first focusing lens, a prism, an objective lens, a sensor, a beam splitter, a first polarization analyzer component, a second polarization analyzer component, a photodetector, an excitation light source, a lens component, a first reflector, a second focusing lens, a second reflector, a two-dimensional moving platform, and an imaging processing terminal; the sensor is an optical waveguide resonance sensor; The polarization component is disposed between the first focusing lens and the detection light source. The first focusing lens and the beam splitter are respectively disposed on two sides of the prism. The objective lens and the second reflector are respectively disposed at opposite ends of the prism. The sensor is disposed on a side of the objective lens facing away from the prism. The sensor and the two-dimensional moving platform are respectively disposed on two sides of the sample, and the two-dimensional moving platform drives the sample to move horizontally. A coupling medium is provided between the sensor and the sample. The detection light source emits a light beam that passes through the polarization component and the first focusing lens and then enters the prism. After being refracted by the prism, the light beam enters the objective lens and irradiates the sensor. The sensor is excited to generate a detection light beam that passes through the objective lens and enters the prism. The incident detection light beam is refracted again and then enters the beam splitter. The first polarization analyzer component is disposed between the photodetector and the beam splitter. The first reflector is disposed on the side of the beam splitter. The second polarization analyzer component is disposed between the photodetector and the first reflector. The beam splitter splits the incident light beam into a first light beam and a second light beam. The first light beam passes through the first polarization analyzer component and then enters the first probe of the photodetector. The second light beam is reflected by the first reflector and passes through the second polarization analyzer component and then enters the second probe of the photodetector. The two-dimensional moving platform, the photodetector, the detection light source, and the excitation light source are respectively communicatively connected to the imaging processing terminal. The lens assembly is disposed in front of the light beam output port of the excitation light source. The second focusing lens is disposed between the second reflector and the lens assembly.

[0005] In a second aspect, an embodiment of the present invention further provides a photoacoustic detection imaging method based on optical waveguide resonance sensing. The photoacoustic detection imaging method based on optical waveguide resonance sensing is applied to the photoacoustic detection imaging system as described in the first aspect. The photoacoustic detection imaging method includes: The detection light source emits detection laser light that passes through the polarization component and the first focusing lens and then enters the prism. After being refracted by the prism, the light beam enters the objective lens and irradiates the sensor. The excitation light source emits excitation light that passes through the lens assembly and the second focusing lens. Then, the light beam is reflected by the second reflector and sequentially passes through the prism and the objective lens and then irradiates the sensor. The excitation light passes through the sensor and is focused on the surface of the sample to generate a photoacoustic signal. The photoacoustic signal passes through the coupling medium to cause a change in the light beam to obtain a detection light beam. The detection light beam passes through the objective lens and enters the prism. The incident detection light beam is refracted again and then enters the beam splitter. The beam splitter splits the incident beam into a first beam and a second beam. The first beam passes through the first polarization analyzer assembly and then enters the first probe of the photodetector. The second beam is reflected by the first mirror, passes through the second polarization analyzer assembly, and then enters the second probe of the photodetector; The photodetector performs differential optical detection on the beams detected by the first probe and the second probe to obtain an electrical signal of the detected light change and outputs it to the imaging processing terminal; The imaging processing terminal controls the two-dimensional moving platform to drive the sample to move horizontally, so as to scan and acquire the electrical signals detected at various positions in the sample and store them; The imaging processing terminal performs three-dimensional reconstruction on the stored electrical signals to obtain photoacoustic three-dimensional microscopic image information with high spatial resolution.

[0006] An embodiment of the present invention provides a photoacoustic detection imaging system and method based on optical waveguide resonance sensing. The imaging system includes a detection light source, a polarization component, a first focusing lens, a prism, an objective lens, a sensor, a beam splitter, a first polarization analyzer assembly, a second polarization analyzer assembly, a photodetector, an excitation light source, a lens assembly, a first mirror, a second focusing lens, a second mirror, a two-dimensional moving platform, and an imaging processing terminal; the sensor is an optical waveguide resonance sensor. In the above imaging system, a combination of a sensor with a tightly confined detection electric field having extremely strong optical resonance and a coupling medium is set, which has the photoacoustic detection ability with ultra-high sensitivity and large bandwidth; by irradiating the sample with the excitation light to generate photoacoustic signals and acting on the coupling medium to cause changes in the incident beam to obtain the detection beam, it is possible to realize photoacoustic microscopic imaging in the reflection mode, and three-dimensional microscopic imaging at the micron scale can be realized regardless of the thickness of the sample, greatly improving the depth resolution and the quality of the imaging image; and it is possible to achieve a balance between the detection sensitivity and bandwidth of the photoacoustic signal, and while detecting with high sensitivity, taking into account the bandwidth response at the level of hundreds of megahertz. Description of the Drawings

[0007] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for description in the embodiments will be briefly introduced below. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0008] Figure 1 It is a structural diagram of the photoacoustic detection imaging system based on optical waveguide resonance sensing provided by the embodiment of the present invention; Figure 2 It is a partial structural diagram of the photoacoustic detection imaging system based on optical waveguide resonance sensing provided by the embodiment of the present invention; Figure 3The application effect diagram of the photoacoustic detection imaging system based on optical waveguide resonance sensing provided by the embodiment of the present invention; Figure 4 Another application effect diagram of the photoacoustic detection imaging system based on optical waveguide resonance sensing provided by the embodiment of the present invention; Figure 5 Yet another application effect diagram of the photoacoustic detection imaging system based on optical waveguide resonance sensing provided by the embodiment of the present invention; Figure 6 The method flow chart of the photoacoustic detection imaging method based on optical waveguide resonance sensing provided by the embodiment of the present invention; Reference numerals: 1, detection light source; S, polarization component; 2, polarizer; 3, half-wave plate; 4, quarter-wave plate; 5, first focusing lens; 6, prism; 7, objective lens; 8, sensor; 9, beam splitter; J1, first polarization analyzing component; 10, first polarizer; 11, first lens; J2, second polarization analyzing component; 13, second polarizer; 14, second lens; 15, photodetector; 16, excitation light source; T, lens assembly; 12, first reflector; 17, third lens; 18, fourth lens; 19, second focusing lens; 20, second reflector; 23, two-dimensional moving platform; 22, imaging processing terminal; 21, signal amplifier; 81, polydimethylsiloxane film; 82, glass slide. Detailed implementation manners

[0009] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0010] It should be understood that when used in this specification and the appended claims, the terms "comprises" and "comprising" indicate the presence of the described features, wholes, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, wholes, steps, operations, elements, components, and / or their combinations.

[0011] It should also be understood that the terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. As used in the specification of the present invention and the appended claims, unless the context clearly indicates otherwise, the singular forms "a", "an", and "the" are intended to include the plural forms.

[0012] It should also be further understood that the term "and / or" used in the specification and appended claims of the present invention refers to any combination and all possible combinations of one or more of the associated listed items, and includes these combinations.

[0013] A photoacoustic detection imaging system based on optical waveguide resonance sensing is disclosed in a specific embodiment of the present application. Among them, the photoacoustic detection imaging system includes a detection light source, a polarization component, a first focusing lens, a prism, an objective lens, a sensor, a beam splitter, a first polarization analyzer component, a second polarization analyzer component, a photodetector, an excitation light source, a lens assembly, a first reflector, a second focusing lens, a second reflector, a two-dimensional moving platform, and an imaging processing terminal; the sensor is an optical waveguide resonance sensor; the polarization component is arranged between the first focusing lens and the detection light source, the first focusing lens and the beam splitter are respectively arranged on both sides of the prism, the objective lens and the second reflector are respectively arranged at opposite ends of the prism, and the sensor is arranged on the side of the objective lens away from the prism; the sensor and the two-dimensional moving platform are respectively arranged on both sides of the sample, and the two-dimensional moving platform drives the sample to move horizontally; a coupling medium is arranged between the sensor and the sample; the detection light source emits a light beam that passes through the polarization component and the first focusing lens and then enters the prism, the light beam is refracted by the prism and then enters the objective lens and irradiates the sensor, the sensor is excited to generate a detection light beam that passes through the objective lens and enters the prism, and the incident detection light beam is refracted again and then enters the beam splitter; the first polarization analyzer component is arranged between the photodetector and the beam splitter, the first reflector is arranged on the side of the beam splitter, and the second polarization analyzer component is arranged between the photodetector and the first reflector; the beam splitter splits the incident light beam into a first light beam and a second light beam, the first light beam passes through the first polarization analyzer component and then enters the first probe of the photodetector, and the second light beam is reflected by the first reflector and passes through the second polarization analyzer component and then enters the second probe of the photodetector; the two-dimensional moving platform, the photodetector, the detection light source, and the excitation light source are respectively communicatively connected to the imaging processing terminal, the lens assembly is arranged in front of the light beam exit port of the excitation light source, and the second focusing lens is arranged between the second reflector and the lens assembly.

[0014] Among them, the detection light source emits a pulsed laser beam. After passing through the polarization component, the pulsed laser beam generates an adjustable polarized laser output. After passing through the first focusing lens, the laser is refracted by the prism and focused on the rear focal plane of the objective lens. When the parallel light passing through the objective lens is incident on the sensor, total internal reflection occurs and a localized and laterally reduced electromagnetic field is excited. At the same time, the excitation light source emits excitation light. After passing through the lens assembly and the second focusing lens, the light beam is reflected by the second mirror and sequentially passes through the prism and the objective lens and then irradiates the sensor. Due to the optically transparent property of the sensor, the objective lens can focus the excitation light through the sensor onto the sample surface to excite a photoacoustic signal. The photoacoustic signal passes through the coupling medium to cause a change in the light beam incident on the sensor through the objective lens. Then, the photoacoustic signal is superimposed on the reflected light beam corresponding to the light beam incident on the sensor through the objective lens. The reflected light beam with the superimposed photoacoustic signal is the detection beam. The detection beam passes through the objective lens and enters the prism. After being refracted by the prism, the detection beam enters the beam splitter. The beam splitter splits the incident light beam into a first light beam and a second light beam. The first light beam passes through the first polarization analyzing component and then enters the first probe of the photodetector. The second light beam is reflected by the first mirror and passes through the second polarization analyzing component and then enters the second probe of the photodetector. The photodetector performs differential optical detection on the light beams detected by the first probe and the second probe to obtain corresponding electrical signals. By scanning a position of the sample in the above steps, a corresponding set of electrical signals can be obtained. The sample is driven to move horizontally by the two-dimensional moving platform, so as to realize scanning of multiple positions of the sample to obtain the electrical signals corresponding to each position. Then, three-dimensional reconstruction is performed based on the stored electrical signals to obtain the photoacoustic three-dimensional microscopic image information of the sample.

[0015] In a more specific embodiment, the detection light source is a continuous pulsed helium-neon laser, and the laser wavelength generated by the detection light source is 615 - 650 nm. Preferably, the laser wavelength generated by the detection light source is 632.8 nm. Specifically, the polarization component includes a polarizer, a half-wave plate, and a quarter-wave plate; the polarizer is disposed on the side close to the detection light source. Among them, the excitation light source is a neodymium-doped yttrium aluminum garnet laser (Nd:YAG laser), and the wavelength of the excitation light generated by the excitation light source is 510 - 555 nm, and the pulse time is 0.8 - 5 ns; in a preferred embodiment, the wavelength of the excitation light generated by the excitation light source is 532 nm, and the pulse time is about 1.2 ns.

[0016] In a more specific embodiment, the first polarization analyzer assembly includes a first polarizer and a first lens; the second polarization analyzer assembly includes a second polarizer and a second lens; both the first lens and the second lens are disposed on a side close to the photodetector. Wherein, the cross-section of the prism is an isosceles trapezoid, and the first focusing lens and the beam splitter are respectively disposed relative to the inclined side surfaces of the trapezoid; the objective lens is disposed at an end corresponding to the upper base of the isosceles trapezoid of the prism; the second reflector is placed at an end corresponding to the lower base of the isosceles trapezoid of the prism.

[0017] By providing a first polarization analyzer assembly composed of a first polarizer and a first lens, and a second polarization analyzer assembly composed of a second polarizer and a second lens, after the detection beam generated by reflection passes through the beam splitter, the p-polarized light passes through the first polarizer with mutually orthogonal projection directions and is focused by the first lens, and the s-polarized light is reflected by the first reflector and then passes through the second polarizer with mutually orthogonal projection directions and is focused by the second lens; it can be set that both the first probe and the second probe of the photodetector are photodiodes, and the two beams of light passing through the first polarization analyzer assembly and the second polarization analyzer assembly are respectively focused on the two photodiodes of the balanced photodetector for differential optical detection.

[0018] Specifically, the prism can be set as an isosceles trapezoid, and the first focusing lens and the beam splitter are respectively disposed relative to the inclined side surfaces of the trapezoid, and the objective lens and the second reflector are respectively located at the two ends of the upper base and the lower base of the isosceles trapezoid; then the incident laser is refracted on one inclined surface of the prism, and the reflected detection beam is refracted on the other inclined surface of the prism, and the optical refractions of the two beams are exactly the same, ensuring that the beam can stably detect the photoacoustic signal. At the same time, the objective lens, the prism and the second reflector are on a straight line, so that the excitation light reflected by the second reflector can directly enter the objective lens and be focused on the imaging position of the sensor, improving the imaging quality.

[0019] In a more specific embodiment, the lens assembly includes a third lens and a fourth lens disposed opposite to each other, and the third lens and the fourth lens are combined into a 4F lens assembly. The 4F lens assembly can collimate the incident laser to optimize it into a collimated light with pure mode, thereby improving the quality of the excitation beam incident on the sensor.

[0020] In a more specific embodiment, such as Figure 2As shown, the sensor consists of a polydimethylsiloxane (PDMS) thin film and a glass slide, and the polydimethylsiloxane thin film is deposited on the side of the glass slide facing the sample. Among them, the sensor is an optical waveguide resonance (OWR) sensor prepared by a deposition method. This sensor is obtained by depositing polydimethylsiloxane on a glass slide. The thickness of the polydimethylsiloxane (PDMS) layer deposited on the glass slide is 350 nm; the objective lens can be a total internal reflection fluorescent (TIRF) objective lens.

[0021] The incident laser is a laser with a wavelength of 632.8 nm. This laser is coupled to the sensor through the objective lens at a specific incident angle (such as 62.45°), and a strongly resonant electric field with limited size is excited inside the PDMS thin film, enabling the sensor to theoretically respond to ultrasonic excitation in a bandwidth of hundreds of megahertz; the excitation light is a short pulse laser with a wavelength of 532 nm (pulse width in the nanosecond level), which is focused on the sample surface through the objective lens to generate broadband photoacoustic signals; due to the photoelastic effect, the photoacoustic pressure disturbs the PDMS thin film, causing a drastic impact on the waveguide resonance mode, resulting in a phase shift of the orthogonal polarization components of the reflected light. Light interference occurs in the transmission direction of the polarizer used to recombine the two polarization components. Therefore, by monitoring the light interference intensity that changes with time relative to the initial static condition, broadband detection of photoacoustic signals can be achieved, that is, the detection bandwidth of photoacoustic signals can be increased.

[0022] In a more specific embodiment, the photoacoustic detection imaging system further includes a signal amplifier. One end of the signal amplifier is connected to the imaging processing terminal, and the other end is connected to the photodetector.

[0023] To improve the detection effect, a signal amplifier can be set. The signal amplifier amplifies the electrical signal output by the photodetector, obtains an amplified signal and outputs it to the imaging processing terminal. The imaging processing terminal processes the amplified signal and obtains photoacoustic three-dimensional microscopic image information, which can further improve the quality of the microscopic image.

[0024] The embodiment of the present application also discloses a photoacoustic detection imaging method based on optical waveguide resonance sensing. Among them, the photoacoustic detection imaging method is applied to the photoacoustic detection imaging system based on optical waveguide resonance sensing as described in the above embodiment; as Figure 6 shown, the photoacoustic detection imaging method includes steps S1 to S8: S1. The detection light source emits detection laser light, which passes through the polarization component and the first focusing lens and then enters the prism. After the light beam is refracted by the prism, it enters the objective lens and irradiates the sensor; S2. After the excitation light source emits excitation light, which passes through the lens assembly and the second focusing lens, the light beam is reflected by the second mirror and sequentially passes through the prism and the objective lens and then irradiates the sensor. S3. The excitation light passes through the sensor and is focused on the sample surface to generate photoacoustic signals. The photoacoustic signals pass through the coupling medium to cause changes in the light beam to obtain a detection light beam. S4. The detection light beam passes through the objective lens and enters the prism. The incident detection light beam is refracted again and then enters the beam splitter. S5. The beam splitter splits the incident light beam into a first light beam and a second light beam. The first light beam passes through the first polarization analyzing component and then enters the first probe of the photodetector. The second light beam is reflected by the first mirror and passes through the second polarization analyzing component and then enters the second probe of the photodetector. S6. The photodetector performs differential optical detection on the light beams detected by the first probe and the second probe to obtain an electrical signal of the change in the detection light and outputs it to the imaging processing terminal. S7. The imaging processing terminal controls the two-dimensional moving platform to drive the sample to move horizontally to scan and acquire the electrical signals detected at various positions of the sample and store them. S8. The imaging processing terminal performs three-dimensional reconstruction on the stored electrical signals to obtain photoacoustic three-dimensional microscopic image information with high spatial resolution.

[0025] By carefully calibrating the optical illumination and acoustic detection, the coaxial configuration can ensure obtaining the best photoacoustic measurement results. A few drops of deionized water are dropped between the sensor and the sample as the coupling medium for the photoacoustic signals. When performing microscopic imaging of the sample, the sample is fixed on a two-dimensional displacement platform controlled by the imaging processing terminal through a LabVIEW program. When the two-dimensional displacement platform drives the sample to perform XY-direction translation, single-axis point scanning of the sample can be realized. At this time, the excitation light continuously excites photoacoustic signals at different positions of the sample, and the photoacoustic signals are converted into changes in the detection light by the sensor. The balanced photodetector converts the detected light intensity change into an electrical signal and then sends it to the imaging processing terminal through a signal amplifier. A high-performance data acquisition card is built into the imaging processing terminal, which can continuously store the photoacoustic signals. After one scan, the obtained data is subjected to three-dimensional reconstruction by the imaging processing terminal, and then high-spatial-resolution photoacoustic three-dimensional microscopic imaging of the sample can be realized.

[0026] The photoacoustic detection imaging system and method based on optical waveguide resonance sensing disclosed in this application have the following advantages during application: (1) The preparation process of the optical waveguide resonance photoacoustic sensor is simple. It does not require advanced technologies such as lithography and nanoimprinting. Only a spin coater and a thermal curing table are needed to fabricate the device, and the preparation of a nanoscale elastic polymer material film can be achieved with a simple process and low cost. (2) The optical waveguide resonance photoacoustic sensing method can achieve a balance between the detection sensitivity and bandwidth of photoacoustic signals. While detecting with high sensitivity, it also takes into account the bandwidth response at the level of hundreds of megahertz, and can achieve high-sensitivity detection and broadband response of broadband photoacoustic signals. (3) The optical transparency of the optical waveguide resonance photoacoustic sensor enables a photoacoustic microscopy imaging system in reflection mode. Therefore, regardless of the thickness of the sample, a three-dimensional microscopic imaging effect at the micron scale can be achieved, and three-dimensional imaging with a spatial resolution at the micron level can be performed on the sample.

[0027] In this invention, the feasibility of the optical waveguide resonance (OWR) photoacoustic detection method in principle is verified through simulation. It is calculated that the detection bandwidth of this method is in the range of hundreds of megahertz, and compared with the optical surface wave technology, it has higher detection sensitivity. The principle simulation results are as Figure 3 and Figure 4 shown. As can be seen from Figure 3 shown, the principle simulation diagram shows that the sensor has an excellent local effect on the electric field excited by the detection light. Most of the energy is confined in the PDMS film, and the layered detection intensities in the x-axis direction (corresponding to p polarization) and the y-axis direction (corresponding to s polarization, and the s polarization direction is perpendicular to the p polarization direction) are basically equal. Therefore, the detection sensitivities in the x-axis direction and the y-axis direction have good uniformity, and imaging with a micron-level spatial resolution can be achieved. The z-axis is the detection depth (the z-axis is perpendicular to the detection plane), the blue dashed box is the polydimethylsiloxane (PDMS) layer, and the upper part of the blue dashed box is the coupling medium; since the bandwidth response and the optical penetration depth are inversely proportional, this shows that the OWR sensor has an acoustic bandwidth response ability at the level of hundreds of megahertz. Compared with the surface wave technology, the detection sensitivity of the OWR sensor has been greatly improved, almost doubled, as specifically shown in Figure 4 shown.

[0028] Set the laser wavelength generated by the detection light source to 632.8 nm, and the wavelength of the excitation light generated by the excitation light source to 532 nm, with a pulse time of about 1.2 ns. Imaging is performed on small samples and large samples respectively, and the results are as Figure 5 shown. As can be verified by the experiment shown in Figure 5 , the above-mentioned reflection-mode photoacoustic microscopy imaging system based on optical waveguide resonance can achieve high-spatial-resolution photoacoustic three-dimensional imaging for both small samples (depigmented zebrafish larvae) and large samples (wild adult zebrafish), and the two-dimensional images also have high resolution.

[0029] In an embodiment of the present invention, there is provided a photoacoustic detection imaging system and method based on optical waveguide resonance sensing. The imaging system includes a detection light source, a polarization component, a first focusing lens, a prism, an objective lens, a sensor, a beam splitter, a first polarization analyzer component, a second polarization analyzer component, a photodetector, an excitation light source, a lens component, a first mirror, a second focusing lens, a second mirror, a two-dimensional moving platform, and an imaging processing terminal; the sensor is an optical waveguide resonance sensor. The above imaging system is provided with a combination of a sensor with a tightly confined detection electric field having extremely strong optical resonance and a coupling medium, and has the photoacoustic detection ability with ultra-high sensitivity and large bandwidth; by irradiating a sample with excitation light to generate a photoacoustic signal and acting on the coupling medium to cause a change in the incident light beam to obtain a detection light beam, it is possible to achieve photoacoustic microscopy imaging in the reflection mode, and three-dimensional microscopy imaging at the micron scale can be achieved regardless of the thickness of the sample, greatly improving the depth resolution and the quality of the imaging image; and it is possible to achieve a balance between the photoacoustic signal detection sensitivity and the bandwidth, and while detecting with high sensitivity, taking into account the bandwidth response of the order of hundreds of megahertz.

[0030] The above is only a specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of various equivalent modifications or substitutions, and these modifications or substitutions should all be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims

1. An optoacoustic detection and imaging system based on optical waveguide resonance sensing, characterized in that, The photoacoustic detection imaging system includes a detection light source, a polarization component, a first focusing lens, a prism, an objective lens, a sensor, a beam splitter, a first polarization analyzer component, a second polarization analyzer component, a photodetector, an excitation light source, a lens assembly, a first mirror, a second focusing lens, a second mirror, a two-dimensional moving platform, and an imaging processing terminal; the sensor is an optical waveguide resonance sensor; The polarization component is disposed between the first focusing lens and the detection light source. The first focusing lens and the beam splitter are respectively disposed on two sides of the prism. The objective lens and the second mirror are respectively disposed at opposite ends of the prism. The sensor is disposed on a side of the objective lens away from the prism. The sensor and the two-dimensional moving platform are respectively disposed on two sides of a sample, and the two-dimensional moving platform drives the sample to move horizontally. A coupling medium is provided between the sensor and the sample; The detection light source emits a light beam that passes through the polarization component and the first focusing lens and then enters the prism. After being refracted by the prism, the light beam enters the objective lens and irradiates the sensor. The sensor is excited to generate a detection light beam that passes through the objective lens and enters the prism. The incident detection light beam is refracted again and then enters the beam splitter; The first polarization analyzer component is disposed between the photodetector and the beam splitter. The first mirror is disposed on the side of the beam splitter. The second polarization analyzer component is disposed between the photodetector and the first mirror. The beam splitter splits the incident light beam into a first light beam and a second light beam. The first light beam passes through the first polarization analyzer component and then enters the first probe of the photodetector. The second light beam is reflected by the first mirror and passes through the second polarization analyzer component and then enters the second probe of the photodetector; The two-dimensional moving platform, the photodetector, the detection light source, and the excitation light source are respectively communicatively connected to the imaging processing terminal. The lens assembly is disposed in front of the light beam output port of the excitation light source. The second focusing lens is disposed between the second mirror and the lens assembly.

2. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 1, wherein The detection light source is a continuous pulse helium-neon laser, and the laser wavelength generated by the detection light source is 615 - 650 nm.

3. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 1 or 2, characterized in that, The polarization component includes a polarizer, a half-wave plate, and a quarter-wave plate; the polarizer is disposed on a side close to the detection light source.

4. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 3, wherein The excitation light source is a neodymium-doped yttrium aluminum garnet laser, and the wavelength of the excitation light generated by the excitation light source is 510 - 555 nm, and the pulse time is 0.8 - 5 ns.

5. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 4, characterized in that The first polarization analyzer component includes a first polarizer and a first lens; the second polarization analyzer component includes a second polarizer and a second lens; the first lens and the second lens are both disposed on a side close to the photodetector.

6. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 5, wherein The cross-section of the prism is an isosceles trapezoid. The first focusing lens and the beam splitter are respectively disposed relative to the inclined side surfaces of the trapezoid. The objective lens is disposed at an end of the prism corresponding to the upper base of the isosceles trapezoid. The second mirror is disposed at an end of the prism corresponding to the lower base of the isosceles trapezoid.

7. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 6, wherein The lens assembly includes a third lens and a fourth lens which are oppositely arranged, and the third lens and the fourth lens are combined into a 4F lens assembly.

8. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 7, characterized in that, The sensor is composed of a polydimethylsiloxane thin film and a glass slide, and the polydimethylsiloxane thin film is deposited on one side of the glass slide facing the sample.

9. The photoacoustic detection imaging system based on optical waveguide resonance sensing according to claim 8, wherein The photoacoustic detection imaging system further includes a signal amplifier, one end of the signal amplifier is connected to the imaging processing terminal, and the other end is connected to the photodetector.

10. An optoacoustic detection and imaging method based on optical waveguide resonance sensing, characterized in that, The photoacoustic detection imaging method based on optical waveguide resonance sensing is applied to the photoacoustic detection imaging system according to any one of claims 1-9; the photoacoustic detection imaging method includes: The detection light source emits detection laser light, which passes through the polarization component and the first focusing lens and then enters the prism. After being refracted by the prism, the light beam enters the objective lens and irradiates the sensor. The excitation light source emits excitation light, which passes through the lens assembly and the second focusing lens. Then, the light beam is reflected by the second mirror and sequentially passes through the prism and the objective lens and then irradiates the sensor. The excitation light passes through the sensor and is focused on the sample surface to excite photoacoustic signals. The photoacoustic signals pass through the coupling medium to cause changes in the light beam to obtain a detection light beam. The detection light beam passes through the objective lens and enters the prism, and the incident detection light beam is refracted again and then enters the beam splitter. The beam splitter splits the incident light beam into a first light beam and a second light beam. The first light beam passes through the first polarization analyzing component and then enters the first probe of the photodetector. The second light beam is reflected by the first mirror and passes through the second polarization analyzing component and then enters the second probe of the photodetector. The photodetector performs differential optical detection on the light beams detected by the first probe and the second probe to obtain an electrical signal of the change in the detection light and outputs it to the imaging processing terminal. The imaging processing terminal controls the two-dimensional moving platform to drive the sample to move horizontally, so as to scan and acquire the electrical signals for detecting each position in the sample and store them. The imaging processing terminal performs three-dimensional reconstruction on the stored electrical signals to obtain photoacoustic three-dimensional microscopic image information with high spatial resolution.

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