Multi-fluorescence imaging device capable of adjusting visual field area and optical tomography

Abstract

The invention discloses a multi-fluorescence imaging device capable of adjusting visual field area and optical tomography, which comprises a multi-wavelength light source, the multi-wavelength light source comprises a wavelength variable light source or a light source array, and the wavelength variable light source and the light source array are independent and can realize multi-wavelength output. The optical fibers are mounted on the multi-wavelength light source and transmit light according to different wavelengths, the optical fibers are circularly placed at certain intervals, and the diameter of the optical fibers is changed according to applied voltage and applied temperature to form an annular magnetic disk. The wavelength of the exciting light can be freely adjusted by utilizing a multi-wavelength light source or realizing the exciting light with variable wavelength, a plurality of contrast agents are excited to obtain a multi-wavelength fluorescence image, the characteristics of the plurality of contrast agents can be simultaneously observed, and the universal fluorescence imaging device is widely applied to multi-antigen analysis and treatment. The method can be used for measuring lesion light cross-sectional images and has the advantage of analyzing lesion cross-sectional structures in real time.

Description

Technical Field

[0001] The invention relates to the technical field of multi-fluorescence imaging, in particular to a multi-fluorescence imaging device capable of adjusting the field of view and optical tomography. Background Art

[0002] Fluorescence imaging devices can be used in clinical trials, animal experiments, two-phase induction surgery, etc. They focus excitation light with one wavelength, illuminate the observation area through an objective lens, and observe changes and structures. Conventional fluorescence imaging systems cannot use light sources with multiple wavelengths to excite multiple contrast agents at the same time. The wavelength of the excitation light is not variable, and multiple fluorescence images cannot be observed simultaneously. The working distance cannot be automatically measured to adjust the field of view of a single or overlapping light source, and the optical tomography of the lesion structure cannot be adjusted. When using a laser light source, the fluorescence characteristics may be reduced due to speckle patterns and multimode optical noise. "Speckle pattern" refers to the phenomenon of scattered points in the laser image being interfered with, that is, under laser interference, bright or dark spots are scattered in the image. "Multimode optical noise" refers to the phenomenon that image noise is generated by multimode different beam profiles that are not a single mode; these two phenomena can be combined as signals obtained as different openings to reduce the impact of interference. "Optical tomography" is an optical technology that uses light to examine the internal structure of tissues. It is a non-contact optical imaging technology that can visualize the internal structure of biological tissues. Therefore, it is necessary to develop a new fluorescence imaging system that can utilize a multi-wavelength light source or realize variable-wavelength excitation light to simultaneously obtain multi-wavelength fluorescence images of multiple contrast agents and simultaneously obtain optical tomography images of the lesions. In fluorescence imaging technology, the technology is also required to be able to automatically measure the action distance, freely adjust the field of view area of ​​single or overlapping light sources, and suppress speckle patterns and multimode light noise, so as to obtain high-quality fluorescence images.

[0003] To this end, we provide a multi-fluorescence imaging device with adjustable field of view and optical tomography. Summary of the invention

[0004] The object of the present invention is to provide a multi-fluorescence imaging device capable of adjusting the field of view and optical tomography, so as to solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above-mentioned purpose, the present invention provides the following technical solutions: a multi-fluorescence imaging device capable of adjusting the field of view and optical tomography, comprising a multi-wavelength light source, wherein the multi-wavelength light source comprises a wavelength-variable light source or a light source array, wherein the wavelength-variable light source and the light source array are two independent types capable of realizing multi-wavelength output, and a plurality of optical fibers installed in the multi-wavelength light source and transmitting light at different wavelengths, wherein the plurality of optical fibers are arranged in a circle at a certain interval, and a ring-shaped disk is formed by changing the diameter according to the applied voltage and the applied temperature, and further comprising a light source connector, a power separator, a wavelength separator, a wavelength-variable filter, a light irradiator, a diffuser, a lens, a 3CCD, a distance measuring sensor, a controller, a variable disk, a fixed disk and an illuminator, wherein the controller is respectively connected to the multi-wavelength light source and the wavelength-variable filter.

[0006] Preferably, it also includes a reflector, a beam splitter and a second light irradiator, and the illuminating lamp is installed at a position between the variable disk and the fixed disk.

[0007] Preferably, the variable disk is arranged on a fixed disk, the optical fiber is connected to the variable disk, and the distance measuring sensor is arranged on the variable disk.

[0008] Preferably, the wavelength-variable light source is an FDML laser, a frequency-variable laser or a wavelength-variable laser.

[0009] Preferably, the wavelength separator separates the light of the wavelength-variable light source into a plurality of wavelengths through the wavelength separator, and is characterized in that different wavelengths are respectively transmitted through different optical fibers.

[0010] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention utilizes a multi-wavelength light source or realizes variable-wavelength excitation light, and can freely adjust the wavelength of the excitation light. By exciting multiple contrast agents, a multi-wavelength fluorescence image is obtained, and the characteristics of multiple contrast agents can be observed simultaneously. The present invention is a universal fluorescence imaging device widely used in multi-antigen analysis and treatment, and can measure optical tomographic images of lesions, with the advantage of real-time analysis of lesion tomographic structures.

[0011] 2. The present invention can freely adjust the field of view area of ​​a single or overlapping light source with one system by automatically measuring the action distance, so the observation area and light power can be freely adjusted. It can be used as a fluorescence microscope and a fluorescence imaging system for clinical trials, animal experiments, two-phase induction surgery, etc. It can suppress the speckle pattern and multimode light noise generated by the laser light source and provide high-quality fluorescence images. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1This is a diagram showing the composition of a fluorescent imaging device system of the present invention, which is based on a multi-wavelength light source and can simultaneously observe multiple fluorescent images, can observe optical tomographic images of lesions, and can adjust the field of view area through automatic distance measurement; Figure 2 This is a diagram showing the composition of a fluorescent imaging device system based on a multi-wavelength light source, which can simultaneously observe multiple fluorescent images and adjust the field of view area by automatically measuring the distance; Figure 3 This is a system composition diagram of a light irradiation device for a fluorescence imaging device based on a multi-wavelength light source in the first state of the present invention, which can simultaneously observe multiple fluorescence images and adjust the field of view area by automatically measuring the distance; Figure 4 This is a system composition diagram of a light irradiation device for a fluorescence imaging device based on a multi-wavelength light source in the second state of the present invention, which can simultaneously observe multiple fluorescence images and adjust the field of view area by automatically measuring the distance; Figure 5 This is a system composition diagram of a light irradiation device for a fluorescence imaging device based on a multi-wavelength light source in the third state of the present invention, which can simultaneously observe multiple fluorescence images and adjust the field of view area by automatically measuring the distance; Figure 6 A disk plan view of a light irradiation device for a fluorescence imaging device based on a multi-wavelength light source, capable of simultaneously observing multiple fluorescence images and adjusting the field of view area through automatic distance measurement; Figure 7 This is a light irradiation plane diagram of the present invention; Figure 8 This is an oblique view of an optical fiber used in a light irradiation device for a fluorescence imaging device of the present invention, which is based on a multi-wavelength light source and can simultaneously observe multiple fluorescence images and adjust the field of view area through automatic distance measurement.

[0013] In the figure: 10 multi-wavelength light source, 11 wavelength variable light source, 12 light source array, 20 wavelength separator, 22 light source connector, 24 power separator, 30 optical fiber, 32 diffuser, 34 lens, 40 light irradiator, 42 variable disk, 44 lighting lamp, 45 distance measuring sensor, 46 fixed disk, 50 3CCD, 60 wavelength variable filter, 70 controller, 80 reflector, 90 beam splitter, 100 second light irradiator. DETAILED DESCRIPTION

[0014] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0015] See also Figure 1-8 , a multi-fluorescence imaging device capable of adjusting the field of view and optical tomography, comprising a multi-wavelength light source 10, wherein the multi-wavelength light source 10 comprises a wavelength-variable light source 11 or a light source array 12, wherein the wavelength-variable light source 11 and the light source array 12 are two independent types capable of realizing multi-wavelength output, and a plurality of optical fibers 30 installed on the multi-wavelength light source 10 and transmitting light at different wavelengths, wherein the plurality of optical fibers 30 are arranged in a circle at a certain interval and form an annular disk according to the change in diameter of applied voltage and applied temperature, and further comprising a light source connector 22, a power separator 24, a wavelength separator 20, a wavelength-variable filter 60, a light irradiator 40, a diffuser 32, a lens 34, a 3CCD 50, a distance measuring sensor 45, a controller 70, a variable disk 42, a fixed disk 46 and an illuminator 44, wherein the controller 70 is connected to the multi-wavelength light source 10 and the wavelength-variable filter 60, respectively.

[0016] The illumination lamp 44 further includes a reflector 80 , a beam splitter 90 and a second light irradiator 100 . The illumination lamp 44 is installed at a position between the variable disk 42 and the fixed disk 46 .

[0017] Furthermore, the lighting lamp 44 is a white light LED. The lighting lamp 44 as a whole provides bright light in the visible light wavelength region, which serves to distinguish biological samples or other objects. The exterior of the lighting lamp 44 forms a fixed disk 46 equivalent to the fuselage. The fixed disk 46 serves as a support for installing the variable disk 42 and the lighting lamp 44. The fixed disk 46 can be made of various hard metals or various plastics with strength.

[0018] Furthermore, multiple optical fibers 30 are arranged in a circle at certain intervals, and an annular disk whose diameter can be changed by applying voltage, current, temperature, etc. At least one of the optical fibers 30 on the disk can adjust the angle according to the voltage, current, and temperature. An optical system for measuring the optical tomographic image of the lesion is implemented through a reflector 80 and a beam splitter 90, and a distance measurement sensor 45 for automatically measuring the action distance; the optical fibers 30 are formed on the annular disk at a certain angle, and voltage, current and temperature can be applied to the disk to automatically adjust the field of view area from the disk to the overlapping area of ​​the output beams or the point where the optical axes overlap, while realizing multi-contrast agent multi-fluorescence imaging in the overlapping area of ​​the output beams.

[0019] The variable disk 42 is disposed on the fixed disk 46 , the optical fiber 30 is connected to the variable disk 42 , and the distance measuring sensor 45 is disposed on the variable disk 42 .

[0020] The variable-wavelength light source 11 is a light irradiation device characterized by FDML laser, frequency-variable laser, or wavelength-variable laser.

[0021] The light from the light source is separated into optical signals of multiple wavelengths by the wavelength separator 20 , and then the optical signals of different wavelengths are transmitted through the corresponding optical fibers 30 .

[0022] The light source includes LED, LD, solid state laser, quantum dot laser or semiconductor optical amplifier light source, and the light irradiation device is characterized by optical fiber 30 laser.

[0023] By utilizing a multi-wavelength light source or realizing variable-wavelength excitation light, the wavelength of the excitation light can be freely adjusted. By exciting multiple contrast agents to obtain a multi-wavelength fluorescence image, the characteristics of multiple contrast agents can be observed simultaneously. This is a universal fluorescence imaging device widely used in multi-antigen analysis and treatment. It can measure optical tomographic images of lesions and has the advantage of real-time analysis of the lesion tomographic structure.

[0024] Furthermore, if the light source is a laser, a diffuser 32 and an optical system will be installed at the end of the optical fiber 30 to prevent speckle patterns and multi-mode optical noise.

[0025] Furthermore, the light source of multiple wavelengths is a light irradiation device characterized by a wavelength-variable light source 11, a multi-wavelength light source 10 or a light source array 12. The multi-wavelength light source 10 refers to a light irradiation device characterized by including a multi-wavelength laser light source with multi-wavelength output in the wavelength region. The light sources are formed with different wavelengths. When there are multiple array light sources, the wavelength emitted by each light source is transmitted through different optical fibers 30.

[0026] Furthermore, the light source is a multi-array light source composed of light sources generating different wavelengths, and has a light source coupler for combining the wavelengths transmitted in the multi-array light sources and the light emitted by the light source coupler.

[0027] Furthermore, the multiple optical fibers 30 on the disk can apply voltage, current and temperature, and input the optical tomographic image information of the lesion into the fluorescent imaging device of the image sensor in the form of 3CCD 50 or 3CMOS through the reflector 80 and the beam splitter 90.

[0028] Furthermore, the multi-wavelength light source 10 and the wavelength variable filter 60 are adjusted by the controller 70. The multi-wavelength light source 10 is connected to the disk through multiple optical fibers 30. A diffuser 32 and a lens 34 are installed at the end of the optical fiber 30 located on the variable disk 42. The light source through the diffuser 32 and the lens 34 is irradiated onto most contrast agents. The diffuser 32 can be realized by rough processing the surface of the end of the optical fiber 30 or by building a liquid nanoparticle polymer inside. The laser of the diffuser 32 is expanded through the lens. Moreover, not all ends of the optical fibers 30 require the diffuser 32. Instead, whether the diffuser 32 and the lens 34 are needed depends on the light source being irradiated. That is to say, if the light source is an LED, the diffuser 32 is not needed. However, if the light source is a laser, the diffuser 32 and the lens 34 are needed. The formation of the diffuser 32 at the end of the optical fiber 30 of the output light beam can eliminate the speckle pattern and multimode noise, solve the problem of reduced fluorescence image quality, and thus obtain high-quality fluorescence images.

[0029] Further, such as Figure 2 As shown, a plurality of optical fibers 30 are fixed obliquely on the variable disk 42, that is, the optical fibers 30 emitting light of different wavelengths are fixed obliquely on the variable disk 42 at an angle of θ. If voltage, current or temperature is applied to the variable disk 42, the variable disk 42 will expand, and the spacing between the optical fibers 30 fixed on the disk will also increase, so that the overlapping area of ​​the light beams output from the optical fibers 30 will also move away from the disk, and the distance from the disk of the light irradiation module to the overlapping area of ​​the output light beams of the optical fibers 30 or the overlapping point of the optical axis, the working distance will become longer, and the working distance refers to the vertical distance from the light irradiation module to the sample; by using multiple wavelengths to appropriately adjust the voltage, current or temperature applied to the disk, the working distance between the disk and the overlapping area of ​​the output light beam can be adjusted and automatically measured, and the field of view area can be automatically adjusted, so that multiple fluorescent images generated by multiple contrast agents can be viewed at the same time, and multiple contrast agents can be placed therein using a multi-wavelength light source 10 or an excitation light with variable wavelength, and multi-wavelength fluorescent images can be obtained at the same time, and the field of view area of ​​a single or overlapping light source can be freely adjusted by automatically adjusting and measuring the working distance, and the light intensity irradiated on the sample can be freely adjusted, thereby adjusting the observation area and light output of the fluorescent image.

[0030] Further, such as Figure 2 As shown, in the case of using a light source array 12 multi-array light source, the light source array 12 is a collection of multiple light sources generating different wavelengths, that is, λ1, λ2...λn are a collection of light sources emitting different wavelengths. The light source array 12 multi-array light source is composed of light sources generating different wavelengths, each of which is connected to an optical fiber 30, and is directly transmitted to the light irradiator 40 and the second light irradiator 100 through N optical fibers 30. In the light irradiator 40 and the second light irradiator 100, the light beam output through the optical fiber 30 is as shown in FIG. Figure 1In the state shown, multiple nanoparticles are irradiated, and the irradiated light beam excites multiple contrast agents. The wavelength-variable light source 11 and the wavelength-variable filter 60 are adjusted by the controller 70, and a multi-wavelength fluorescence image can be obtained through the image sensor, especially the 3CCD 50.

[0031] Further, such as Figure 3 As shown, the wavelength-variable light source 11 refers to an FDML laser, a frequency-variable laser or a wavelength-variable laser. The light source generated by the wavelength-variable light source 11 is separated into N wavelengths by a wavelength separator 20, which are separated into λ1, λ2...λn; each separated wavelength moves to the light irradiator 40 and the second light irradiator 100 through N optical fibers 30, and the optical fiber 30 forms N optical fibers 30 so that each separated wavelength is transmitted separately, and each of the N separated wavelengths is transmitted to the light irradiator 40 and the second light irradiator 100 through the N optical fibers 30. In the light irradiator 40 and the second light irradiator 100, the light beam output through the optical fiber 30 will be irradiated by multiple contrast agents, and the irradiated light beam will be excited by multiple contrast agents. The wavelength-variable light source 11 and the wavelength-variable filter 60 are adjusted by the controller 70, and a multi-wavelength fluorescence image is obtained by the image sensor, especially the 3CCD 50.

[0032] Further, such as Figure 2 and Figure 5 A collective light source array 12 of multiple light sources is used, each light source generates a different wavelength, such as Figure 5 As shown, the light source generated by the light source array 12 will be transmitted to the light source connector 22. The light source connector 22 combines different input wavelengths. The wavelengths combined in the light source connector 22 are transmitted through the power separator 24. In the power separator 24, according to the different powers, they are divided into M power levels, and then transmitted to the light illuminator 40 and the second light illuminator 100 through the optical fiber 30. After being classified by power intensity, they are separated into P1, P2...PM and transmitted to the light illuminator 40 and the second light illuminator 100.

[0033] Further, such as Figure 3 and 4 As shown, in the light irradiator 40 and the second light irradiator 100, the light beam output through the optical fiber 30 is irradiated onto multiple nanoparticles, the irradiated light beam excites multiple contrast agents, and the wavelength-variable light source 11 and the wavelength-variable filter 60 are adjusted by the high controller 70. Through the image sensor, especially the 3CCD 50, a multi-wavelength fluorescence image can be obtained.

[0034] Further, such as Figure 6As shown, the variable disk 42 is a part where optical fibers 30 emitting wavelengths transmitted by a light source are placed at a certain interval. N optical fibers 30 are installed at a certain interval. If there are N optical fibers 30, the optical fibers 30 are installed at an interval of 360 degrees / N. As shown in the figure, the variable disk 42 has a ring shape with a hole formed in the center. N optical fibers 30 are installed at different wavelengths at intervals in the middle through the hole in the middle, so that fluorescent images generated by multiple contrast agents can be obtained on the image sensor; if a voltage, current, or temperature is applied to the variable disk (42), the diameter of the variable disk (42) can be changed. If the diameter of the disk changes, the position of the optical fibers 30 inserted at a certain interval in the disk will change, so the field of view area will change. When a voltage or temperature is applied to the disk, it is made of a polymer or PZT material that expands.

[0035] Further, such as Figure 7 As shown, the light is divided into four wavelengths, and the lights of different wavelengths are emitted through four optical fibers 30, which are separated at an angle of 90 degrees.

[0036] Further, such as Figure 8 As shown, a diffuser 32 and a lens 34 are mounted on the end of the optical fiber located on the light irradiator.

[0037] Specifically, the present invention can simultaneously excite the characteristics of multiple contrast agents, measure multiple fluorescence images, measure optical tomography images of lesions, automatically measure the motion distance, and simultaneously adjust the field of view area and light output. It is used in fluorescence imaging equipment, and utilizes a multi-wavelength light source 10 that generates multiple wavelengths. By adjusting the field of view area of ​​a single or overlapping light source, various fluorescence images generated by multiple contrast agents can be observed simultaneously, and optical tomography images of lesions can be measured, and the field of view area and light power can be adjusted. Through a system, the wavelength is variable, and by adjusting the field of view area of ​​a single or overlapping light source, multiple fluorescence images generated by multiple fluorescent bodies can be observed simultaneously, and optical tomography images of lesions can be measured. The observation area and light power of the fluorescence image can be freely adjusted. In particular, by utilizing the multi-wavelength light source 10, a light irradiation device for a fluorescence imaging device can be provided, and multiple fluorescence images of multiple fluorescent bodies can be measured simultaneously.

[0038] By automatically measuring the action distance, the field of view area of ​​a single or overlapping light source can be freely adjusted with one system, so the observation area and light power can be freely adjusted. It can be used as a fluorescence microscope and a fluorescence imaging system for clinical trials, animal experiments, two-phase induction surgery, etc. It can suppress the speckle pattern and multimode optical noise generated by the laser light source and provide high-quality fluorescence images.

[0039] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A multi-fluorescence imaging device with adjustable field of view and optical tomography, characterized in that: The invention comprises a multi-wavelength light source (10), wherein the multi-wavelength light source (10) comprises a wavelength-variable light source (11) or a light source array (12), wherein the wavelength-variable light source (11) and the light source array (12) are two types that can independently realize multi-wavelength output, and a plurality of optical fibers (30) installed in the multi-wavelength light source (10) and transmitting light at different wavelengths, wherein the plurality of optical fibers (30) are arranged in a circle at a certain interval and change in diameter according to applied voltage and applied temperature to form an annular disk, and further comprises a light source connector (22), a power separator (24), a wavelength separator (20), a wavelength-variable optical filter (60), a light irradiator (40), a diffuser (32), a lens (34), a 3CCD (50), a distance measuring sensor (45), a controller (70), a variable disk (42), a fixed disk (46) and an illuminating lamp (44), wherein the controller (70) is connected to the multi-wavelength light source (10) and the wavelength-variable optical filter (60) respectively.

2. The multi-fluorescence imaging device with adjustable field of view and optical tomography according to claim 1, characterized in that: It also includes a reflector (80), a beam splitter (90) and a second light illuminator (100), and the illumination lamp (44) is installed at a position between the variable disk (42) and the fixed disk (46).

3. The multi-fluorescence imaging device with adjustable field of view and optical tomography according to claim 2, characterized in that: The variable disk (42) is arranged on a fixed disk (46), the optical fiber (30) is connected to the variable disk (42), and the distance measuring sensor (45) is arranged on the variable disk (42).

4. The multi-fluorescence imaging device with adjustable field of view and optical tomography according to claim 3, characterized in that: The wavelength-variable light source (11) is an FDML laser, a frequency-variable laser or a wavelength-variable laser.

5. The multi-fluorescence imaging device with adjustable field of view and optical tomography according to claim 4, characterized in that: The wavelength separator (20) separates the light of the wavelength-variable light source (11) into a plurality of wavelengths through the wavelength separator (20), and is characterized in that different wavelengths are respectively transmitted through different optical fibers (30).

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