Multi-mode biological imaging device and system and light source switching and adjusting device

Abstract

The utility model relates to the technical field of biological imaging, in particular to a multi-mode biological imaging device and system and a light source switching and adjusting device. According to the multi-mode biological imaging device, the doublet lens is arranged, the doublet lens can realize light source multiplexing through total reflection and vertical transmission, coating is not needed, and the utilization rate of light power by total reflection and vertical transmission is high, so that the cost is reduced, and the utilization rate of the light power is improved at the same time. Meanwhile, the focusing lens, the beam expanding lens, the light beam folding module and the collimating lens are arranged between the light source and the doublet lens, shaping of the light beams input into the doublet lens can be achieved, the size of the light beams can be adjusted by changing the positions of the beam expanding lens and the light beam folding module, and the device is suitable for different application scenes. In addition, one light source and two imaging modules are adopted in the device, and multiplexing of the light source is achieved by changing the position of the doublet lens.

Description

Technical Field

[0001] The utility model relates to the technical field of biological imaging, and in particular to a multimodal biological imaging device and system, and a light source switching and adjusting device. Background Art

[0002] In the field of multimodal in vivo biological imaging, different types of imaging modules (such as near-infrared camera with lens module, visible light camera with lens module, photoacoustic probe imaging module, etc.) are usually required to collect the emission light groups of the calibration objects (the calibration objects are generally ICG (indocyanine green) fluorescent dyes, rare earth fluorescent dyes, biological fluorescent substances, etc.) in the organism after excitation by the light source.

[0003] In existing biological imaging systems, each imaging module is usually equipped with a separate light source module, which results in a large number of light source modules in the device, low utilization rate, and high overall equipment cost. Some devices also use a light source multiplexing mode. In order for the light spot to act on the organism, the multiplexing mode requires the use of a multi-faceted mirror to assist in the deflection of the light beam. The reflectivity of the reflective film coated on the mirror cannot reach 100% utilization of total internal reflection, so the multi-faceted mirror method will cause light power loss. Utility Model Content

[0004] In view of this, the embodiments of the present invention provide a multimodal biological imaging device and system, and a light source switching and adjusting device to solve the technical problems of high cost or high loss of biological imaging systems in the prior art.

[0005] The technical solution provided by the embodiment of the utility model is as follows:

[0006] The first aspect of the embodiment of the utility model provides a multimodal biological imaging device, which includes: a light source, a focusing lens, a beam expanding lens, a beam folding module, a collimating lens, a doublet lens, a first imaging module, a second imaging module and a stage, wherein the stage includes a first biological imaging position and a second biological imaging position; the light source is used to output a light beam; the focusing lens is used to converge the light beam output by the light source; the beam expanding lens is used to adjust the light beam converged by the focusing lens when approaching or moving away from the focusing lens; the beam folding module is used to spatially fold and adjust the light beam expanded by the beam expanding lens when approaching or moving away from the beam expanding lens; the collimating lens Used to collimate the light beam after the light beam folding module performs spatial folding and light beam adjustment; when imaging the first biological imaging position, the double-glued lens is located at the first preset position, the collimated light beam output by the collimating lens is totally reflected by the double-glued lens and then irradiated to the first biological imaging position, and the first imaging module collects image information of the first biological imaging position; when imaging the second biological imaging position, the double-glued lens is located at the second preset position, the collimated light beam output by the collimating lens is vertically irradiated to the double-glued lens, the double-glued lens transmits the vertically incident light beam to the second biological imaging position, and the second imaging module collects image information of the second biological imaging position.

[0007] The multimodal biological imaging device provided in this embodiment is provided with a double-glued lens in the device. The double-glued lens can realize light source reuse through total reflection and vertical transmission, and does not need to be coated. The total reflection and vertical transmission have a high utilization rate of light power, so that the device reduces the cost while also improving the utilization rate of light power. At the same time, a focusing lens, a beam expander lens, a beam folding module and a collimating lens are provided between the light source and the double-glued lens, which can not only realize the shaping of the light beam input to the double-glued lens, but also adjust the size of the light beam by changing the position of the beam expander lens and the beam folding module, which is suitable for different application scenarios. In addition, the device adopts one light source and two imaging modules, and realizes the reuse of the light source by changing the position of the double-glued lens.

[0008] In an optional embodiment, the double-cemented lens includes a first lens and a second lens that are glued together, the first lens is used to receive a light beam output by a light source, and the second lens is used to output the light beam, the refractive index of the first lens is greater than the refractive index of the second lens, and the critical angle when the light beam is totally reflected on the first lens is determined according to the ratio of the refractive index of the first lens to the refractive index of the second lens.

[0009] In this embodiment, a double-cemented lens is formed by using the first lens and the second lens, thereby making it possible to fix the critical angle of total reflection of the double-cemented lens and not be affected by the environment, thereby improving the stability of the device.

[0010] The second aspect of the embodiment of the utility model provides a light source switching and adjustment device, which includes: a first bracket, a second bracket, a first linear motion module, a second linear motion module, a fixed base, and a double-cemented lens, a focusing lens, a beam expanding lens, a beam folding module and a collimating lens in the multimodal biological imaging device of any one of the first aspects of the embodiment of the utility model; the focusing lens, the collimating lens, the first bracket and the second bracket are fixed on the inner surface of the fixed base; the beam expanding lens is fixed in the first bracket, and the beam folding module is fixed in the second bracket; the first linear motion module is fixed on the outer surface of the fixed base, the first linear motion module is connected to the first bracket, and the first linear motion module is used to drive the first bracket to drive the beam expanding lens to move between the focusing lens and the beam folding module to change the size of the light spot irradiated at the first biological imaging position or the second biological imaging position; the second linear motion module is fixed on the outer surface of the fixed base, the second linear motion module is connected to the second bracket, and the second linear motion module is used to drive the second bracket to drive the beam folding module to move to change the size of the light spot irradiated at the first biological imaging position or the second biological imaging position.

[0011] In this embodiment, the focusing lens, the beam expanding lens, the beam folding module and the collimating lens are integrated into the light source switching and adjusting device, and two brackets and two linear motion modules are arranged in the light source switching and adjusting device. The movement of the beam expanding lens and the beam folding module is controlled by the two linear motion modules, thereby realizing two-stage adjustment of the spot size.

[0012] In an optional embodiment, the beam folding module includes a first reflector and a second reflector, and the beam folding module is arranged at the edge of the light path formed by the light source, the focusing lens, the beam expanding lens, the beam folding module and the collimating lens.

[0013] In this embodiment, a first reflector and a second reflector are arranged in the light folding module, and the folding of the spatial light beam is achieved through the relative reflection of the two reflectors. Under the same magnification, compared with a straight light path, it has the obvious advantage of a smaller volume. At the same time, the light beam folding module is arranged at the edge position, so when a larger light spot is required, its moving space is not restricted by other lenses, thereby increasing the scalability of the light source switching and adjustment device.

[0014] In an optional embodiment, the device also includes: a first light hole, a second light hole, a third bracket and a rotational motion module; the double-glued lens is fixed in the third bracket, the rotational motion module is fixed to the outer surface of the fixed base, the rotational motion module is connected to the third bracket, and the rotational motion module is used to drive the third bracket to drive the double-glued lens to move, so that the double-glued lens is in a first preset position or a second preset position; when the double-glued lens is in the first preset position, the light beam totally reflected by the double-glued lens is irradiated to the first biological imaging position through the first light hole; when the double-glued lens is in the second preset position, the light beam vertically transmitted by the double-glued lens is irradiated to the second biological imaging position through the second light hole.

[0015] In this embodiment, by providing a third bracket and a rotational motion module, the double-cemented lens can be controlled to rotate between the first preset position and the second preset position, thereby achieving precise control of the double-cemented lens. At the same time, the first light hole and the second light hole are provided in the device to ensure that the light beam can be irradiated at the corresponding biological position through the light holes.

[0016] A third aspect of an embodiment of the utility model provides a multimodal biological imaging system, the system comprising: a warehouse body having a storage space, a multimodal biological imaging device according to any one of the first aspects of the embodiment of the utility model, and a light source switching adjustment device according to any one of the second aspects of the embodiment of the utility model; a partition is arranged inside the warehouse body, and the partition divides the storage space of the warehouse body into a first warehouse body and a second warehouse body; the light source switching adjustment device, a first imaging module and a second imaging module are arranged in the first warehouse body and fixed on the partition, and the partition includes a light hole corresponding to the light inlet holes of the two imaging modules and the light outlet hole of the light source switching adjustment device; the sample stage is arranged in the second warehouse body and fixed on the lower surface of the inside of the second warehouse body, and the second warehouse body has an opening, and a door body that can be opened and closed is arranged at the opening to replace the organism to be tested on the sample stage.

[0017] In this embodiment, the multimodal biological imaging device and the light source switching adjustment device are integrated into the warehouse body, and a partition is provided in the warehouse body, which provides support for the multimodal biological imaging device and the light source switching adjustment device; and the warehouse body also includes an opening and a door body, which is convenient for replacing the organism to be tested, and the door body is closed during imaging to ensure that the imaging process is not disturbed by the external environment.

[0018] In an optional embodiment, the system further includes: a three-dimensional displacement platform, and the loading platform is fixed to the lower surface of the second chamber body through the three-dimensional displacement platform.

[0019] In this embodiment, by arranging a three-dimensional displacement platform in the chamber body, the stage can be moved in all directions to ensure that the desired imaging result is finally obtained.

[0020] A fourth aspect of an embodiment of the utility model provides a method for adjusting the spot size, characterized in that it is applied to the multimodal biological imaging device of any one of the first aspect of the embodiment of the utility model or the light source switching adjustment device of any one of the second aspect of the embodiment of the utility model, and the method includes: when increasing the spot size, moving the beam expander lens along the optical axis close to the focusing lens to coarsely adjust the spot size, and moving the beam folding module along the optical axis away from the beam expander lens to finely adjust the spot size; when reducing the spot size, moving the beam expander lens along the optical axis away from the focusing lens to coarsely adjust the spot size, and moving the beam folding module along the optical axis close to the beam expander lens to finely adjust the spot size.

[0021] In this embodiment, a beam expander lens is used for coarse adjustment, and a beam folding module is used for fine adjustment. That is, through the two-stage adjustment of the beam expander lens and the beam folding module, the adjustment range of the spot size can be effectively expanded, and large-span spot size adjustment can be achieved. At the same time, through the different adjustment accuracies of coarse adjustment and fine adjustment, the speed and accuracy of spot adjustment can be improved.

[0022] A fifth aspect of an embodiment of the utility model provides a multimodal biological imaging method, characterized in that it is applied to a multimodal biological imaging system of any one of the third aspects of the embodiments of the utility model, and the method includes: placing the organism to be tested on the loading platform through the opening of the second chamber body and closing the door body; turning on the light source, and collecting image information of the organism to be tested based on the first imaging module or the second imaging module; adjusting the three-dimensional displacement platform to move in the horizontal direction according to the position of the organism to be tested in the image information so that the test area of ​​the organism to be tested is placed in the imaging center of the first imaging module or the second imaging module; adjusting the three-dimensional displacement platform to move in the vertical direction or adjusting the first imaging module or the second imaging module according to the clarity of the image information; adjusting the spot size using the spot size adjustment method of the fourth aspect of the embodiment of the utility model according to the positional relationship between the light spot and the test area in the image information; and performing emission light imaging on the calibration object in the test area.

[0023] In this embodiment, during the multimodal imaging process, the position of the biological being to be measured, the image clarity and the spot size are adjusted based on the collected image information, thereby ensuring that the obtained emission light imaging image can meet the required requirements, laying a solid foundation for the subsequent observation process of the emission light group. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the specific implementation methods of the utility model or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the utility model. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0025] Figure 1 Schematic diagram of a light path for adjusting a light spot in a multimodal biological imaging device according to an embodiment of the present utility model;

[0026] Figure 2 It is a structural block diagram of a multimodal biological imaging device in an embodiment of the utility model;

[0027] Figure 3 A perspective view of a light source switching and adjusting device in an embodiment of the utility model;

[0028] Figure 4 It is a cut-away side view of the light source switching and adjusting device in the embodiment of the utility model;

[0029] Figure 5 This is a view of the light source switching and adjusting device in the embodiment of the utility model without the outer shell;

[0030] Figure 6 Schematic diagram of a multimodal biological imaging system in an embodiment of the present utility model;

[0031] Figure 7 This is a flow chart of the method for adjusting the light spot size in an embodiment of the utility model;

[0032] Figure 8 This is a flow chart of a multimodal biological imaging method in an embodiment of the present utility model;

[0033] Fig. 9 This is a flow chart of a multimodal biological imaging method in another embodiment of the present invention. DETAILED DESCRIPTION

[0034] As mentioned in the background technology, when a multi-faceted reflector is used for light source multiplexing, at least two reflectors are required to illuminate the output beam of the light source to the biological placement. If the reflectivity of the coated light beam reaches a high 95% (the cost of such a high reflectivity film in a specific band is relatively high), the optical power utilization rate is only 90%. In other words, while this solution has a high cost, the optical power loss is at least about 10%; if a general reflector is used, the reflectivity is about 90%, and the light utilization rate of the two mirrors is only 81%, and the optical power loss is close to 1 / 5. The excitation light power directly affects whether the calibration object in the organism produces emission light that can be clearly observed by the imaging module, thereby indirectly observing the characteristics of a specific tissue or organ of the organism. The more light the same light source loses in the optical path, the greater the impact on the final detection result.

[0035] In order to reduce the number of lenses and improve the effective utilization rate of light sources, the related art uses a complex mechanical structure to achieve the switching of lenses to achieve the light path switching effect. This method can reduce the power loss of the light beam caused by multiple reflections, but this method requires the design and processing of a complex switching mechanism in a small space, and the production cost is high.

[0036] In view of this, the present embodiment provides a multimodal biological imaging device, in which a double-cemented lens is arranged. The double-cemented lens can realize light source multiplexing through total reflection and vertical transmission, thereby reducing the cost and improving the utilization rate of optical power.

[0037] The technical solution of the utility model will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0038] In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance.

[0039] In the description of the present utility model, it should be noted that, unless otherwise clearly specified and limited, the terms "installation", "connection" and "connection" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, it can also be the internal connection of two components, it can be a wireless connection, or it can be a wired connection. For ordinary technicians in this field, the specific meanings of the above terms in the present utility model can be understood according to specific circumstances.

[0040] In addition, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0041] The present invention provides a multi-modal biological imaging device, such as Figure 1 and Figure 2As shown, the device includes: a light source 1, a focusing lens 11, a beam expanding lens 12, a beam folding module 13, a collimating lens 14, a double glued lens 2, a first imaging module 3, a second imaging module 4 and a stage 5, the stage 5 includes a first biological imaging position 51 and a second biological imaging position 52; the light source 1 is used to output a light beam; the focusing lens 11 is used to converge the light beam output by the light source; the beam expanding lens 12 is used to adjust the light beam converged by the focusing lens 11 when approaching or moving away from the focusing lens; the beam folding module 13 is used to approach or move away from the beam expanding lens 12, and spatially fold and adjust the light beam expanded by the beam expanding lens 12; the collimating lens 14 is used to spatially fold the light beam folding module and collimate the light beam after light beam adjustment; when imaging the first biological imaging position 51, the double-cemented lens 2 is located at the first preset position (the dotted line position in the figure), the collimated light beam output by the collimating lens 14 is totally reflected by the double-cemented lens 2 and then irradiated to the first biological imaging position 51, and the first imaging module 3 collects image information of the first biological imaging position 51; when imaging the second biological imaging position 52, the double-cemented lens 2 is located at the second preset position (the solid line position in the figure), the collimated light beam output by the collimating lens 14 is vertically irradiated to the double-cemented lens 2, the double-cemented lens 2 transmits the vertically incident light beam to the second biological imaging position 52, and the second imaging module 4 collects image information of the second biological imaging position 52.

[0042] Specifically, the first imaging module 3 and the second imaging module 4 may be modules capable of realizing image acquisition. In this embodiment, the first imaging module 3 and the second imaging module 4 may be near-infrared camera equipped with a lens filter module, a visible light camera equipped with a lens filter module, or PMT (Photomultiplier Tube), APD (Avalanche Photodiode), PD (Photo-Diode) and other imaging or light signal detection modules, etc. The first imaging module 3 and the second imaging module 4 may be the same or different, and this embodiment does not limit this. The light beam emitted by the light source 1 may be a laser beam. The first biological imaging position 51 and the second biological imaging position 52 may be two positions on the stage 5 for placing the organism to be tested, and the first biological imaging position 51 and the second biological imaging position 52 are also the detection centers of the first imaging module 3 and the second imaging module 4. When the light source 1 outputs a light beam to irradiate the first biological imaging position 51 or the second biological imaging position 52 through the double cemented lens 2, the first imaging module 3 or the second imaging module 4 can realize the imaging of the organism to be tested at the corresponding position.

[0043] The first preset position and the second preset position can be two positions with overlapping centers. That is, the center of the double-cemented lens 2 can be fixed, and then the double-cemented lens 2 can be rotated with its center as the origin. When it is rotated to the first preset position, the light beam of the light source 1 can be fully reflected and irradiated to the first biological imaging position 51, and when it is rotated to the second preset position, the light source 1 can be vertically transmitted to the second biological imaging position 52. The total reflection and vertical transmission have a low loss of optical power, and the use of the double-cemented lens 2 does not require coating on the lens surface, thereby avoiding the high cost of coating.

[0044] In an optional embodiment, if Figure 1 As shown, the double-cemented lens 2 includes a first lens 21 and a second lens 22 that are bonded together. The first lens 21 is used to receive the light beam output by the light source 1, and the second lens 22 is used to output the light beam. The refractive index n1 of the first lens 21 is greater than the refractive index n2 of the second lens 22. The critical angle when the light beam is totally reflected on the first lens 21 is determined according to the ratio of the refractive index of the first lens 21 to the refractive index of the second lens 22. The double-cemented lens 2 can be formed by vacuumizing and bonding the first lens 21 and the second lens 22 together. When the light beam is totally reflected, the incident angle (critical angle C) of the light beam when it is incident on the light-entering surface of the first lens 21 can be expressed as sinC=n1 / n2. In addition, if a single-piece lens is used to replace the double-cemented lens 2, since the refractive index of light in different environments such as conventional air, vacuum, salt fog environment, and liquid is different, when a single-piece lens is used, the critical angle will change when the total reflection is emitted on the single-piece lens. In this embodiment, a double-cemented lens 2 is used. Since the refractive indexes of the first lens 21 and the second lens 22 are fixed, the critical angle of the double-cemented lens 2 when total reflection occurs is fixed and is not affected by the external environment, thereby improving stability.

[0045] It should be noted that in the related art, the light source system in the living organism imaging system is fixed, and the size of the excitation light spot at the imaging working plane is fixed and cannot be adjusted. In order to collect images of different parts of the living organism, a laser with higher power and single wavelength is used in weak light detection. The spot formed by this laser is larger in size on the working plane, and all areas of the living animal's body are covered and irradiated.

[0046] However, in the field of weak light imaging, if the excitation light source is a high-power laser, when it is necessary to observe the reaction of local organs after the injection of the calibration drug for a long time, the whole body of the living organism will be irradiated, which will cause the organism to absorb too much heat, easily causing dehydration of the living organism, affecting the body function of the living organism, and even causing death. At the same time, the irradiation of the excitation light to the non-detection area of ​​the organism has a certain effect on the metabolism of the organism, thereby affecting the objective judgment of the performance of the substance injected into the organism. At the same time, if the size of the living organism to be tested is larger than the diameter of the working surface spot and the whole body needs to be stimulated to test the characteristics of the injected substance (such as observing the flow direction of the calibration substance in all blood vessels in the organism, the possible accumulation site and other characteristics), the irradiation spot is too small and cannot solve the problem of exciting the whole body of the light source.

[0047] Therefore, a device for adjusting the light spot has emerged in the related art. The device is equipped with three lenses arranged in sequence, and the size of the light spot is adjusted by the movement of the middle lens. However, the middle lens can only move in the limited space between the two side lenses, that is, the enlarged light spot size is limited, which is suitable for 3D printing, a device where the light spot size does not require much change.

[0048] However, in actual scientific research activities of the living biological imaging system, the imaging module needs to be equipped with a microscope lens to gather a small spot for imaging, or when the mouse is partially imaged, the spot size requirement is also small; when imaging slightly larger animals such as bread monkeys, the spot size is relatively large. When using the spot adjustment device in the related technology, a small spot is easy to achieve, but when a larger spot is required at the same time, the change in the spot size over such a large span is limited by the space size for adjustment, making it difficult to meet the requirements. If the requirements are to be met, a larger adjustment space is required, that is, the straight-line distance between the lenses on both sides must be set very large, the overall size of the module will be very large, the cost will increase, and a large space will be occupied.

[0049] At the same time, this method of adjusting the light spot is a single-stage adjustment. If the spot size control accuracy requirement is high, the motion adjustment module resolution is required to be high and the adjustment speed is slow; if the adjustment speed increases, the motion adjustment module resolution is low and the spot size control accuracy is low; the living biological imaging system usually requires both overall and local imaging, and then the images are fused to determine the fluorescent location. In both imaging processes, the spot size needs to be adjusted. Since the quenching time of some fluorescent substances is very short, if both the accuracy of the spot irradiation position and the fast spot switching time are to be guaranteed, the single-stage adjustment method in the relevant technology has obvious shortcomings.

[0050] Based on the shortcomings of the light spot adjustment in the related art, this embodiment also provides a light source switching adjustment device, such as Figure 3 , Figure 4 and Figure 5As shown, the device includes: a first bracket 121, a second bracket 133, a first linear motion module 122, a second linear motion module 134, a fixed base 61, and the double glued lens 2, the focusing lens 11, the beam expanding lens 12, the beam folding module 13 and the collimating lens 14 in the above-mentioned multimodal biological imaging device; the focusing lens 11, the collimating lens 14, the first bracket 121 and the second bracket 133 are fixed on the inner surface of the fixed base 61; the beam expanding lens 12 is fixed in the first bracket 121, and the beam folding module 13 is fixed in the second bracket 133; the first linear motion module 122 is fixed on the outer surface of the fixed base 61, and the first linear motion module 122 is fixed on the outer surface of the fixed base 61. The motion module 122 is connected to the first bracket 121, and the first linear motion module 122 is used to drive the first bracket 121 to drive the beam expander lens 12 to move between the focusing lens 11 and the beam folding module 13, thereby changing the size of the light spot irradiated at the first biological imaging position 51 or the second biological imaging position 52; the second linear motion module 134 is fixed on the outer surface of the fixed base 61, and the second linear motion module 134 is connected to the second bracket 133, and the second linear motion module 134 is used to drive the second bracket 133 to drive the beam folding module 13 to move, thereby changing the size of the light spot irradiated at the first biological imaging position 51 or the second biological imaging position 52.

[0051] Specifically, the outer shell of the light source 1 switching and adjusting device can be composed of a fixed base 61 and a cover plate 62, and the remaining structures are arranged on the fixed base 61. Figure 2 As shown, the light source 1 includes a laser light source 15 and a collimating lens 16. The collimating lens 16 is fixed to the fixed base 61 through a light hole. The tail optical fiber interface of the collimating lens 16 is located outside the fixed base 61 and is connected to the laser light source 15 through an optical fiber. The focusing lens 11 and the collimating lens 14 are fixed to the fixed base 61 through UV glue, and the beam expander lens 12 is fixed to the first bracket 121 through UV glue. The first bracket 121 is movably arranged on the fixed base 61. The beam folding module 13 is fixed to the second bracket 133 through UV glue, and the second bracket 133 is movably arranged on the fixed base 61.

[0052] The first linear motion module 122 and the second linear motion module 134 can use structures such as linear guide motors to achieve linear motion of the first bracket 121 and the second bracket 133, thereby ensuring that the optical axis of the beam expander lens 12 and the beam folding module 13 does not change during the motion process. The first linear motion module 122 and the second linear motion module 134 can be implemented by any current structure that can drive the first bracket 121 and the second bracket 133 to move, and this embodiment does not specifically limit its structure.

[0053] In an optional embodiment, the beam folding module 13 includes a first reflector 131 and a second reflector 132, and the beam folding module 13 is arranged at the edge of the optical path formed by the light source 1, the focusing lens 11, the beam expanding lens 12, the beam folding module 13 and the collimating lens 14. Specifically, the second bracket 133 may include two sub-brackets, and the two sub-brackets respectively fix the first reflector 131 and the second reflector 132. By arranging the first reflector 131 and the second reflector 132 in the beam folding module 13, the folding of the spatial light beam can be achieved through the relative reflection of the two reflectors. Under the same magnification, compared with the straight optical path, the beam folding module 13 has the obvious advantage of being smaller in size. At the same time, for the optical path formed by the light source 1, the focusing lens 11, the beam expanding lens 12, the beam folding module 13 and the collimating lens 14, the beam folding module 13 is arranged at the edge of the optical path, that is, the light source 1, the focusing lens 11, the beam expanding lens 12 and the collimating lens 14 are arranged on one side of the beam folding module 13, such as on the left side of the beam folding module 13. Therefore, when a larger light spot is required, the moving space of the beam folding module 13 is not limited by other lenses, thereby increasing the scalability of the switching adjustment device of the light source 1.

[0054] In an optional embodiment, the device also includes: a first light hole 71, a second light hole 72, a third bracket 23 and a rotational motion module 24; the double-cemented lens 2 is fixed in the third bracket 23, the rotational motion module 24 is fixed on the outer surface of the fixed base 61, the rotational motion module 24 and the third bracket 23 are connected, and the rotational motion module 24 is used to drive the third bracket 23 to drive the double-cemented lens 2 to move, so that the double-cemented lens 2 is in the first preset position or the second preset position; when the double-cemented lens 2 is in the first preset position, the light beam totally reflected by the double-cemented lens 2 is irradiated to the first biological imaging position 51 through the first light hole 71; when the double-cemented lens 2 is in the second preset position, the light beam vertically transmitted by the double-cemented lens 2 is irradiated to the second biological imaging position 52 through the second light hole 72.

[0055] Specifically, the double-glued lens 2 is fixed in the third bracket 23 by UV glue, and the bottom of the third bracket 23 is rotatably fixed in the fixed base 61. The rotational motion module 24 can drive the third bracket 23 and the double-glued lens 2 inside it to rotate around the center, so that the double-glued lens 2 can achieve total reflection and vertical transmission of the light beam. In addition, the light source 1 switching and adjusting device only integrates a plurality of lenses and other structures, that is, the stage is arranged outside the light source 1 switching and adjusting device, so the light source 1 switching and adjusting device also includes a first light hole 71 (deflection light hole) and a second light hole 72 (vertical light hole), the first light hole 71 can allow the light beam fully reflected by the double-glued lens 2 to pass through and illuminate the first biological imaging position, and the second light hole 72 can allow the light beam vertically transmitted by the double-glued lens 2 to pass through and illuminate the second biological imaging position.

[0056] In addition, it should be noted that in the light source 1 switching and adjusting device, the central axes of the light source 1, the focusing lens 11, the beam expanding lens 12, the beam folding module 13, the collimating lens 14 and the doublet lens 2 coincide. At the same time, the first light hole 71 and the optical axis of the deflected light path formed by these structures are collinear, and the second light hole 72 and the optical axis of the vertical light path formed by these structures are collinear.

[0057] Since the light source switching adjustment device only integrates the device for adjusting the light beam, in order to integrate the above-mentioned multi-modal biological imaging device, this embodiment also provides a multi-modal biological imaging system, such as Figure 6 As shown, the system includes: a warehouse body 8 with a storage space, the above-mentioned multimodal biological imaging device and the above-mentioned light source switching adjustment device 9; a partition 81 is arranged inside the warehouse body 8, and the partition 81 divides the storage space of the warehouse body 8 into a first warehouse body and a second warehouse body; the light source switching adjustment device 9, the first imaging module 3 and the second imaging module 4 are arranged in the first warehouse body and fixed on the partition 81, and the partition 81 includes a light hole corresponding to the light inlet holes of the two imaging modules and the light outlet hole of the light source switching adjustment device 9; the sample stage 5 is arranged in the second warehouse body and fixed on the lower surface of the second warehouse body, and the second warehouse body has an opening, and a door body 82 that can be opened and closed is arranged at the opening to replace the organism on the sample stage.

[0058] Specifically, the warehouse body 8 can be composed of a rectangular parallelepiped, and the partition 81 is arranged in the height direction of the warehouse body 8, that is, the height direction of the warehouse body 8 is perpendicular to the horizontal plane when the warehouse body 8 is in use. The first warehouse body and the second warehouse body divided by the partition 81 can also be called the upper warehouse body and the lower warehouse body. The two imaging modules and the light source switching adjustment device 9 are arranged in the upper warehouse body, and the stage 5 is arranged in the lower warehouse body. At the same time, in order for the light beam in the light source switching adjustment device 9 to irradiate the stage, and the two imaging modules to collect the imaging images on the stage, the partition 81 includes light holes corresponding to the light inlet holes of the two imaging modules and the light outlet holes of the light source switching adjustment device 9, wherein the light outlet holes of the light source switching adjustment device 9 are the first light holes 71 and the second light holes 72 in the light source switching adjustment device 9.

[0059] In addition, in order to facilitate the replacement of the organism to be tested on the stage, an openable and closable door 82 is provided at the opening of the second chamber. When imaging is required, the door 82 is opened, and the organism to be tested is placed in the first organism imaging position 51 or the second organism imaging position 52 of the stage 5 of the second chamber, and then the door 82 is closed for imaging. In this way, the imaging process can be realized in a closed space, and interference from external light can be prevented.

[0060] In an optional embodiment, if Figure 6 As shown, the system further includes: a three-dimensional displacement platform 50, and the stage 5 is fixed to the lower surface of the second chamber body through the three-dimensional displacement platform 50. Specifically, the three-dimensional displacement platform 50 can realize the movement of the stage 5 in three directions, so as to realize high-definition imaging of a preset area of ​​the biological subject to be tested.

[0061] This embodiment also provides a method for adjusting the spot size, which is applied to a multi-modal biological imaging device or a light source switching adjustment device, such as Figure 7 As shown, the method comprises the following steps:

[0062] Step S101, when increasing the spot size, the beam expander lens is moved closer to the focusing lens along the optical axis to roughly adjust the spot size, and the beam folding module is moved away from the beam expander lens along the optical axis to finely adjust the spot size;

[0063] Step S102, when reducing the spot size, move the beam expander lens away from the focusing lens along the optical axis to roughly adjust the spot size, and move the beam folding module closer to the beam expander lens along the optical axis to finely adjust the spot size.

[0064] Specifically, in the multimodal imaging process, in order to achieve imaging of different parts of the biological subject to be measured, it may be necessary to adjust the required spot size. In this embodiment, the spot size is adjusted by moving the positions of the beam expander lens and the beam folding module, wherein when the beam expander lens approaches the focusing lens along the optical axis, the exit spot size becomes larger; when the beam expander lens moves in the direction away from the focusing lens along the optical axis, the exit spot size becomes smaller; when the beam folding module approaches the beam expander lens along the optical axis direction of the beam expander lens, the amplification effect of the beam folding module on the spot is reduced, and the exit spot size becomes smaller; when the beam folding module moves away from the beam expander lens along the optical axis direction of the beam expander lens, the amplification effect of the beam folding module on the spot is increased, and the exit spot size becomes larger.

[0065] Therefore, when it is necessary to increase the spot size, the first linear motion module can drive the first bracket and drive the beam expander lens to move along the optical axis in a direction close to the focusing lens, or the second linear motion module can drive the second bracket to drive the beam folding module to move along the optical axis in a direction away from the beam expander lens. In this embodiment, since the beam expander lens and other structures are arranged on one side of the beam folding module, there is no adjustment device behind the beam folding module, and the beam expander lens is in front of the beam folding module, the output beam of the beam expander lens also needs to be adjusted by the beam folding module before it can be output, that is, the output beam of the beam expander lens will also be affected by the beam folding module, that is, the beam folding module can be understood as a compensation structure of the beam expander lens. Therefore, when it is necessary to increase the spot size, the beam expander lens can be adjusted first to achieve coarse adjustment, and then the beam folding module can be adjusted to achieve fine adjustment.

[0066] Similar to increasing the spot size, when the spot size needs to be reduced, the first linear motion module can also drive the first bracket and drive the beam expander lens to move along the optical axis away from the focusing lens to achieve coarse adjustment, and then the second linear motion module can drive the second bracket to drive the beam folding module to move along the optical axis towards the beam expander lens to achieve fine adjustment.

[0067] It should be noted that in this embodiment, the first linear motion module is used to achieve coarse adjustment, and the second linear motion module is used to achieve fine adjustment. Therefore, the resolution of the first linear motion module can be set higher than the resolution of the second linear motion module, thereby achieving fast and fine adjustment.

[0068] This embodiment also provides a multimodal biological imaging method, which is applied to a multimodal biological imaging system, such as Figure 8 and Fig. 9 As shown, the method comprises the following steps:

[0069] Step S201, place the organism to be tested on the stage through the opening of the second chamber, and close the door. Specifically, place the organism to be tested on the stage calibration area, which is the first organism imaging position or the second organism imaging position. The organism to be tested can be a mouse or other organisms.

[0070] Step S202, turn on the light source, and collect image information of the organism to be tested based on the first imaging module or the second imaging module. Specifically, before the first imaging module and the second imaging module collect image information, the filter wheel of the imaging module can be placed in a hollow position (i.e., without a filter hole), and then collect image information. The collected image information includes the image of the entire organism to be tested.

[0071] Step S203, according to the position of the organism to be tested in the image information, the three-dimensional displacement platform is adjusted to move in the horizontal direction so that the area to be tested of the organism to be tested is placed in the imaging center of the first imaging module or the second imaging module. Specifically, in the collected image information, the specific part that needs to be imaged or observed, that is, the area to be tested, can be determined first. The part can be a specific organ of the organism to be tested, or it can be the entire organism to be tested. After determining the area to be tested, it is determined by the collected image information whether the area to be tested is in the center of the imaging module. If it is not in the center, it can be adjusted by adjusting the three-dimensional displacement platform. During the adjustment, it can be adjusted according to the relative coordinates of the center of the area to be tested and the imaging center. During the adjustment process, real-time monitoring feedback can be provided through the image information collected by the imaging module.

[0072] Step S204, according to the clarity of the image information, the three-dimensional displacement platform is adjusted to move in the vertical direction or the first imaging module or the second imaging module is adjusted. Specifically, when the center of the area to be measured is adjusted to the center of the imaging module, that is, the centers of the two coincide, it can be determined whether the clarity of the area to be measured in the image information meets the requirements. When it does not meet the requirements, the three-dimensional displacement platform can be adjusted to move in the vertical direction; when the two imaging modules have an automatic zoom function, the two imaging modules can be adjusted to zoom, so that the area to be measured can be automatically and clearly imaged within the depth of field.

[0073] Step S205, the spot size is adjusted by using a spot size adjustment method according to the positional relationship between the spot in the image information and the area to be measured. Specifically, when the clarity of the collected image information meets the requirements, it can be checked whether the spot size just covers the area to be measured. If it does not just cover, the beam expansion lens and the beam folding module can be adjusted by the above-mentioned spot size adjustment method.

[0074] Step S206, the calibration object in the test area is imaged with emitted light. Specifically, when the image clarity, the position of the test area, and the spot size meet the requirements, the filter wheel of the imaging module can be switched to the filter position for filtering the laser beam, and then the imaging module is used to image the test area to observe the emission of light from the calibration object in the test organism. In addition, the light power and gradient exposure time can be adjusted according to the emission light imaging effect to obtain the required test image.

[0075] In addition, the multimodal bio-imaging method can be used to form images of local irradiation of the mouse organs by a small spot of excitation light and images of the whole mouse after the excitation light is expanded. Among them, the local aggregation and metabolism of the injected calibration substance in the organ can be evaluated through local observation, and the movement, aggregation and metabolism of the injected calibration substance in all blood vessels can be comprehensively evaluated through overall observation.

[0076] Although the exemplary embodiments and their advantages have been described in detail, those skilled in the art may make various changes, substitutions and modifications to these embodiments without departing from the spirit of the utility model and the scope of protection defined by the appended claims, and such modifications and variations all fall within the scope defined by the appended claims. For other examples, those of ordinary skill in the art should readily understand that the order of the process steps may be changed while maintaining the scope of protection of the utility model.

[0077] In addition, the scope of application of the present invention is not limited to the processes, mechanisms, manufactures, material compositions, means, methods and steps of the specific embodiments described in the specification. From the disclosure of the present invention, it will be easily understood by those skilled in the art that the processes, mechanisms, manufactures, material compositions, means, methods or steps that currently exist or will be developed in the future, which perform substantially the same functions as the corresponding embodiments described in the present invention or obtain substantially the same results, can be applied according to the present invention. Therefore, the claims attached to the present invention are intended to include these processes, mechanisms, manufactures, material compositions, means, methods or steps within their scope of protection.

Claims

1. A multimodal biological imaging device, characterized in that: The device comprises: a light source, a focusing lens, a beam expanding lens, a beam folding module, a collimating lens, a doublet lens, a first imaging module, a second imaging module and an object stage, wherein the object stage comprises a first biological imaging position and a second biological imaging position; The light source is used to output a light beam; The focusing lens is used to converge the light beam output by the light source; The beam expander lens is used to adjust the light beam converged by the focusing lens when it is close to or far away from the focusing lens; The beam folding module is used to move closer to or farther away from the beam expanding lens, and to perform spatial folding and beam adjustment on the beam expanded by the beam expanding lens; The collimating lens is used to collimate the light beam after the light beam folding module performs spatial folding and light beam adjustment; When imaging a first biological imaging position, the doublet lens is located at a first preset position, the collimated light beam output by the collimating lens is totally reflected by the doublet lens and then irradiated to the first biological imaging position, and the first imaging module collects image information of the first biological imaging position; When imaging a second biological imaging position, the doublet lens is located at a second preset position, the collimated light beam output by the collimating lens is vertically irradiated to the doublet lens, the doublet lens transmits the vertically incident light beam to the second biological imaging position, and the second imaging module collects image information of the second biological imaging position.

2. The multimodal biological imaging device according to claim 1, characterized in that: The double-cemented lens includes a first lens and a second lens that are glued together, the first lens is used to receive the light beam output by the light source, and the second lens is used to output the light beam, the refractive index of the first lens is greater than the refractive index of the second lens, and the critical angle of the light beam when total reflection occurs on the first lens is determined according to the ratio of the refractive index of the first lens to the refractive index of the second lens.

3. A light source switching and adjusting device, characterized in that: The device comprises: a first bracket, a second bracket, a first linear motion module, a second linear motion module, a fixed base, a double glued lens, a focusing lens, a beam expanding lens, a beam folding module and a collimating lens in the multimodal biological imaging device according to claim 1 or 2; The focusing lens, the collimating lens, the first bracket and the second bracket are fixed on the inner surface of the fixed base; The beam expansion lens is fixed in the first bracket, and the beam folding module is fixed in the second bracket; The first linear motion module is fixed to the outer surface of the fixed base, the first linear motion module is connected to the first bracket, and the first linear motion module is used to drive the first bracket to drive the beam expander lens to move between the focusing lens and the beam folding module to change the spot size irradiated at the first biological imaging position or the second biological imaging position; The second linear motion module is fixed on the outer surface of the fixed base, and the second linear motion module is connected to the second bracket. The second linear motion module is used to drive the second bracket to drive the beam folding module to move, thereby changing the spot size irradiated at the first biological imaging position or the second biological imaging position.

4. The light source switching and adjusting device according to claim 3, characterized in that: The beam folding module comprises a first reflector and a second reflector, and the beam folding module is arranged at the edge of the optical path formed by the light source, the focusing lens, the beam expanding lens, the beam folding module and the collimating lens.

5. The light source switching and adjusting device according to claim 3, characterized in that: The device further comprises: a first light-through hole, a second light-through hole, a third bracket and a rotational motion module; The double-glued lens is fixed in the third bracket, the rotational motion module is fixed on the outer surface of the fixed base, the rotational motion module is connected to the third bracket, and the rotational motion module is used to drive the third bracket to drive the double-glued lens to move, so that the double-glued lens is in the first preset position or the second preset position; When the doublet lens is at a first preset position, the light beam totally reflected by the doublet lens is irradiated to a first biological imaging position through the first light hole; When the doublet lens is at the second preset position, the light beam vertically transmitted by the doublet lens is irradiated to the second biological imaging position through the second light-transmitting hole.

6. A multimodal biological imaging system, characterized in that: The system comprises: a warehouse body having a containing space, the multimodal biological imaging device according to claim 1 or 2, and the light source switching and adjusting device according to any one of claims 3 to 5; A partition is provided inside the warehouse body, and the partition divides the storage space of the warehouse body into a first warehouse body and a second warehouse body; The light source switching adjustment device, the first imaging module and the second imaging module are arranged in the first chamber and fixed on the partition, and the partition includes a light through hole corresponding to the light inlet holes of the two imaging modules and the light outlet hole of the light source switching adjustment device; The loading platform is arranged in the second warehouse body and fixed on the lower surface of the second warehouse body. The second warehouse body has an opening, and a door body that can be opened and closed is arranged at the opening to replace the organism to be tested on the loading platform.

7. The multimodal biological imaging system according to claim 6, characterized in that: The system further comprises: a three-dimensional displacement platform, and the loading platform is fixed to the lower surface of the second warehouse body through the three-dimensional displacement platform.

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