CN109730626B - Cavity endoscope detection device and three-dimensional nonlinear laser scanning cavity endoscope - Google Patents

Cavity endoscope detection device and three-dimensional nonlinear laser scanning cavity endoscope Download PDF

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CN109730626B
CN109730626B CN201910099524.3A CN201910099524A CN109730626B CN 109730626 B CN109730626 B CN 109730626B CN 201910099524 A CN201910099524 A CN 201910099524A CN 109730626 B CN109730626 B CN 109730626B
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lens
signals
detection device
optical fiber
illumination
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CN109730626A (en
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吴润龙
王爱民
江文茂
吴丹磊
胡炎辉
徐阳阳
程和平
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Beijing Chaoweijing Biological Technology Co ltd
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Beijing Chaoweijing Biological Technology Co ltd
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Abstract

The embodiment of the invention provides a cavity endoscope detection device and a three-dimensional nonlinear laser scanning cavity endoscope. The cavity endoscope detection device comprises a handle shell and a detection tube, wherein a relay lens and an objective lens are arranged in a detection channel of the detection tube, and a first optical path and a second optical path are formed, and the first optical path comprises a collimating lens, a micro-electromechanical scanning galvanometer, a lens, a dichroic mirror, the relay lens and the objective lens; the second optical path includes an objective lens, a relay lens, and a dichroic mirror. The cavity endoscope detection device and the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention adopt the first optical path and the second optical path arranged in the inner space of the handle shell and the detection tube, so as to realize the excitation of autofluorescent substances and the acquisition of two-photon and second harmonic signals, wherein the detection tube can be prolonged according to the needs by adopting the relay lens, so that the detection requirements on gastrointestinal tissues, oral tissues and the like are met, and the operation is simple and the use is convenient.

Description

Cavity endoscope detection device and three-dimensional nonlinear laser scanning cavity endoscope
Technical Field
The embodiment of the invention relates to the technical field of laser scanning endoscopes, in particular to a cavity endoscope detection device and a three-dimensional nonlinear laser scanning cavity endoscope.
Background
Gastrointestinal malignancy is the second leading cause of cancer death in the developed world population, and this trend has become more apparent in recent years. Surgical radical excision is mainly adopted for treating malignant tumor of gastrointestinal tract, but the specific range of the surgical excision needs to be determined when the surgical radical excision is carried out, so that the benign and malignant tumor, the infiltration depth, the metastasis condition, the existence of cancer residues at the incisional edge and the like need to be known before the operation is carried out. Therefore, preoperative gastrointestinal biopsy is an important diagnostic evidence for histological diagnosis of gastrointestinal tumors. And according to tumor size, growth position, infiltration depth, etc., gastric cancer is classified into gastric total incision, gastric sub-total incision, partial gastrectomy, endoscopic submucosal or submucosal resection, etc.
At present, the biopsy under the gastrointestinal endoscope is usually based on the gastrointestinal endoscope, and is carried out imaging by CT, MRI and the like as assistance, or is evaluated and stored by a traditional white-light laparoscope or endoscope.
However, imaging with the aid of CT, MRI, etc. on the basis of a gastrointestinal endoscope has some unavoidable drawbacks, such as easy bleeding from the intestinal canal or tumor during operation, need for manual pulling or squeezing, delay of time due to repeated endoscopic biopsy when the gastrointestinal endoscope cannot pass through the intestinal canal, and need for additional emergency hemostasis if severe bleeding is caused, etc. However, the auxiliary examination means such as CT and MRI cannot accurately judge the infiltration depth of early gastrointestinal tumor and the lymph node metastasis in clinical practice. The ultrasonic endoscope is used for judging the T stage of the gastrointestinal tumor, and the literature reports that the accuracy is only 44.7% -78%, which is insufficient to become a reliable diagnosis standard. The ultrasonic endoscope has poor preoperative evaluation effect on the partial excision operation, cannot accurately subdivide gastrointestinal mucosa layers, and has poor N-stage effect. Therefore, in view of the current auxiliary diagnosis technology of gastrointestinal tract, a new diagnosis device for gastrointestinal tract tumor is needed to detect gastrointestinal tract tissue information in situ in real time.
Disclosure of Invention
Aiming at the technical problems in the prior art, the embodiment of the invention provides a cavity endoscope detection device and a three-dimensional nonlinear laser scanning cavity endoscope.
In a first aspect, an embodiment of the present invention provides a cavity endoscopic detection apparatus, including:
handle casing and probe tube, the handle casing with probe tube fixed connection, be provided with the detection passageway in the probe tube, be provided with relay lens and objective in the detection passageway, the objective is located the entrance of detection passageway, the objective the relay lens with the light path structure that sets up in the handle casing forms first light path and second light path, the axle center of detection passageway with the coincidence of probe tube axle center, wherein:
the first optical path sequentially comprises a collimating lens, a micro-electromechanical scanning galvanometer, a lens, a dichroic mirror, the relay lens and the objective lens, wherein the collimating lens, the micro-electromechanical scanning galvanometer, the lens, the dichroic mirror, the relay lens and the objective lens are positioned between an optical fiber universal interface and the channel opening in the handle shell, and the first optical path is used for conducting laser signals received by the collimating lens from the optical fiber universal interface to the channel opening;
the second optical path sequentially comprises the objective lens, the relay lens and the dichroic mirror, wherein the objective lens, the relay lens and the dichroic mirror are positioned between the passage opening and the optical fiber universal interface, and the second optical path is used for conducting optical signals collected by the objective lens from the passage opening to the optical fiber universal interface.
In a second aspect, embodiments of the present invention provide a three-dimensional nonlinear laser scanning cavity endoscope, comprising:
the device comprises a fluorescence collection device, a scanning acquisition controller, a femtosecond pulse laser, an optical fiber coupling module and the cavity endoscope detection device provided by the first aspect of the embodiment of the invention, wherein the fluorescence collection device and the optical fiber coupling module are both in optical fiber communication connection with the cavity endoscope detection device, and the fluorescence collection device and the cavity endoscope detection device are both electrically connected with the scanning acquisition controller, wherein:
the femtosecond pulse laser is used for outputting pulse laser signals to the optical fiber coupling module;
the optical fiber coupling module is used for coupling the pulse laser signals output by the femtosecond pulse laser and transmitting the pulse laser signals to the collimating lens in the cavity endoscope detection device;
the cavity endoscope detection device is used for receiving the pulse laser signals, outputting the pulse laser signals to autofluorescent substances in living cells, acquiring fluorescent signals and second harmonic signals generated after the autofluorescent substances are excited through the objective lens, and outputting the fluorescent signals and the second harmonic signals to the fluorescent collection device;
The fluorescence collection device is used for respectively converting the fluorescence signal and the second harmonic signal into corresponding electric signals after receiving the fluorescence signal and the second harmonic signal;
the scanning acquisition controller is used for controlling the micro-electromechanical scanning galvanometer to scan the pulse laser signals and synchronously acquiring the electric signals.
The cavity endoscope detection device provided by the embodiment of the invention adopts a structure mode that a handle shell and a detection tube are fixedly connected, a first optical path and a second optical path are arranged in the inner space of the two components to form a handheld cavity endoscope detection device, and the first optical path comprises a collimating lens, a micro-electromechanical scanning galvanometer, a lens, a dichroic mirror, the relay mirror and the objective lens and is used for conducting laser signals for exciting autofluorescent substances; the second light path comprises an objective lens and the dichroic mirror and is used for collecting two-photon signals and second harmonic signals, wherein the adoption of the relay lens enables the detection tube to be prolonged as required, so that the detection needs of gastrointestinal tissues, oral tissues and intrauterine tissues in the abdominal cavity are met, and the method is simple to operate and convenient to use.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions of the prior art, the following description will briefly explain the drawings used in the embodiments or the description of the prior art, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a first embodiment of a device for endoscopic detection in a cavity;
FIG. 2 is a schematic diagram of a second embodiment of a device for endoscopic detection in a cavity;
FIG. 3 is a schematic diagram III of a structure of a endoscopic detection device provided by an embodiment of the present invention;
FIG. 4 is a schematic structural diagram of a endoscopic detection device provided in an embodiment of the present invention;
FIG. 5 is a schematic view of a three-dimensional nonlinear laser scanning cavity endoscope according to an embodiment of the present invention;
FIG. 6 is a schematic diagram II of a three-dimensional nonlinear laser scanning cavity endoscope according to an embodiment of the present invention;
FIG. 7 is a schematic diagram of a fluorescence collection device according to an embodiment of the present invention;
FIG. 8 is a schematic diagram of a box-type combined structure of a three-dimensional nonlinear laser scanning cavity endoscope according to an embodiment of the present invention;
FIG. 9 is a second schematic diagram of a box-type combined structure of a three-dimensional nonlinear laser scanning cavity endoscope according to an embodiment of the present invention;
FIG. 10 is a schematic view of a desktop structure of an endoscope with a three-dimensional nonlinear laser scanning cavity according to an embodiment of the present invention;
FIG. 11 is a schematic diagram of a desktop structure of a three-dimensional nonlinear laser scanning cavity endoscope.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
At present, imaging is carried out based on a gastroenteroscope by taking CT, MRI and the like as assistance to obtain relevant information such as benign and malignant tumor, infiltration depth, metastasis condition, existence of cancer residues at a cutting edge and the like, and the imaging method has the defects in specific operation, such as easy bleeding of an intestinal canal or a tumor body, need of manual traction or extrusion, delay caused by repeated endoscopic biopsy when the gastroenteroscope cannot pass through the intestinal canal, and need of additional first aid hemostasis if severe bleeding is caused. However, the auxiliary examination means such as CT and MRI cannot accurately judge the infiltration depth of early gastrointestinal tumor and the lymph node metastasis in clinical practice. The ultrasonic endoscope is used for judging the T stage of the gastrointestinal tumor, the literature reports that the accuracy is only 44.7% -78%, the ultrasonic endoscope is insufficient to become a reliable diagnosis standard, the ultrasonic endoscope has poor preoperative judgment effect on the partial excision operation, the gastrointestinal mucosa layer cannot be accurately subdivided, and the N stage effect is poor.
Whereas conventional white light laparoscopes and endoscopes are capable of assessing many gastrointestinal disorders, the technique is limited to detecting gross morphological changes. Although suspicious regions are easily found, these techniques are related to false positive rate, specificity, and the like, as compared to in vivo detection techniques. White light endoscopy is associated with extensive errors in microscopic change diagnosis, including the diagnosis of ulcerative colitis or Barrett's oesophagus and flat adenomatous dysplasia. Confocal endoscopes have received extensive attention in combination with laser technology, fluorescence detection technology, rapid scanning technology, and the like, because of their ability to detect mucosal changes at the microscopic level, and the potential for replacement of tissue biopsies, the imaging technology has high sensitivity and specificity. However, the confocal endoscopic imaging technology is still limited by imaging depth and fluorescent dye, and because the gastrointestinal sample has strong absorption and scattering to visible light, the imaging depth is only in a shallow surface layer, and a specific fluorescent dye developer is also required to be injected, the operation is too complicated, and the relevant information such as the infiltration depth of tumor, the metastasis condition, the existence of cancer residues at the surgical incision edge and the like can not be accurately obtained.
The two-photon microscopic imaging technology adopts a femtosecond pulse laser with longer wavelength as an excitation light source, has the characteristics of deep imaging depth, small photodamage, small photobleaching area, high fluorescence collection efficiency and the like, and has epoch-making significance in deep imaging of biological tissues. W.Denk et al, university of Conneler, 1990 developed the first two-photon fluorescence microscope in the world, using multiphoton microscopy imaging techniques based on nonlinear optics and femtosecond pulsed lasers. The technology can rapidly obtain the tissue structure and the cell morphology of the specimen in real time by utilizing the self-fluorescence generated by cells in living tissues and the second harmonic generated by collagen tissues. As early as 1986, the second harmonic was used in skin studies and in coronary microscopy imaging studies, confirming its feasibility to be used for the observation of biological tissues. MPM may also be an important tool in cancer research. The autofluorescence generated by the cells is derived from Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD) in the cells, the wavelength of NADH is 460nm, and the secondary oscillation harmonic wave of collagen is 370-390 nm, so a multiphoton microscope in the range of 780-940 nm is usually selected when observing tumor specimen tissues. MPM imaging is not only comparable to standard tumor histopathology, but also provides additional information on tumor neogenesis processes, as reflected in the metabolic levels of tumor tissue cells by measuring the ratio NADH/FAD.
Using multiphoton imaging techniques, multiphoton microscopes can provide real-time gastrointestinal tissue structure and cell morphology information. The multiphoton imaging technology has the characteristics of no need of externally marking tissues, extremely sensitivity to collagen, small photodamage to tissues, deep penetration depth and the like, and can be applied to optical biopsy of gastrointestinal tumors. There are no clinically available two-photon laparoscope, endoscope and cavity endoscope detection device based on two-photon imaging to detect gastrointestinal tissue information in situ in real time.
In order to detect gastrointestinal tissue information in situ and in real time, an embodiment of the present invention provides a cavity endoscopic detection device, fig. 1 is a schematic structural diagram of the cavity endoscopic detection device provided in the embodiment of the present invention, as shown in fig. 1, the cavity endoscopic detection device includes:
handle casing 11 and probe tube 12, handle casing 11 and probe tube 12 fixed connection are provided with the detection passageway in the probe tube 12, are provided with relay lens 122 and objective 121 in the detection passageway, and objective 121 is located the access port department of detection passageway, and objective 121, relay lens 122 and the light path structure that sets up in the handle casing 11 form first light path and second light path, and the axle center of detection passageway and probe tube 12 axle center coincidence, wherein:
The first optical path sequentially comprises a collimating lens 112, a micro-electromechanical scanning galvanometer 114, a lens 115, a dichroic mirror 116, a relay lens 122 and an objective lens 121, which are positioned between the optical fiber universal interface 111 and the passage opening in the handle shell 11, wherein the first optical path is used for conducting the laser signals received by the collimating lens 112 from the optical fiber universal interface 111 to the passage opening;
the second optical path sequentially includes an objective lens 121, a relay lens 122 and a dichroic mirror 116 between the access port and the optical fiber universal interface 111, where the second optical path is used for conducting the optical signal collected by the objective lens 121 from the access port to the optical fiber universal interface 111.
Specifically, the cavity endoscope detection device provided by the embodiment of the invention integrates two light paths, one is a first light path for conducting a laser signal, and the laser signal is mainly used for exciting an autofluorescent substance; the other is to collect and conduct two-photon signals generated after the autofluorescent substance is excited and second harmonic signals; the partial light path structures in the two light paths comprise a collimating lens 112, a micro-electromechanical scanning galvanometer 114, a lens 115 and a dichroic mirror 116, which are integrated in a handle shell 11, a relay lens 122 and an objective lens 121 are integrated in a detection tube 12, the objective lens 121 is arranged at a channel port of the detection channel, the relay lens 122 is arranged in the detection channel and is used for conducting two-photon signals and second harmonic signals acquired by the objective lens 121 to the dichroic mirror 116 in a long distance, the image surface of the objective lens 121 coincides with the focal surface of the relay lens 122, and the effect of the relay lens is that the laser signal scanning area passing through the micro-electromechanical scanning mirror is conducted to the image surface of the objective lens 121 in a ratio of 1:1 at first. The relay lens further transmits the optical signal collected by the objective lens 121 to the optical path structure part in the handle housing, and collects the optical signal through the optical fiber bundle of the optical path structure, wherein the dichroic mirror 116 may be a long-pass short-reflecting dichroic mirror 116 or a short-pass long-reflecting dichroic mirror 116, that is, when the long-pass short-reflecting dichroic mirror 116 is provided, the pulse laser signal for exciting the autofluorescent substance is transmitted, and the collected two-photon signal and the second harmonic signal are reflected, as shown in fig. 1, and at this time, the intracavity endoscope detection device may be a laparoscope detection device; fig. 2 is a schematic diagram of a second embodiment of the present invention, where, as shown in fig. 2, when the dichroic mirror is a short-pass long-pass dichroic mirror, a pulse laser signal for exciting an autofluorescent substance is reflected, a collected two-photon signal and a second harmonic signal are transmitted, the dichroic mirror reflects a laser signal emitted from the optical fiber universal interface 111 and incident on the dichroic mirror 116 after passing through the collimating lens 112, the mems scanning galvanometer 114 and the lens 115, to the objective lens 121, and transmits the two-photon signal and the second harmonic signal collected by the objective lens 121, and at this time, the cavity endoscope detection device may be a detection device of an oral mirror, where the detection device of an oral mirror also includes two parts of the handle housing 11 and the detection tube 12.
The cavity endoscope detection device provided by the embodiment of the invention adopts a structure mode that a handle shell and a detection tube are fixedly connected, a first optical path and a second optical path are arranged in the inner space of the two components to form a handheld cavity endoscope detection device, and the first optical path comprises a collimating lens, a liquid lens, a micro-electromechanical scanning galvanometer, a lens, a dichroic mirror, a relay mirror and an objective lens and is used for conducting laser signals for exciting autofluorescent substances; the second light path comprises an objective lens and a dichroic mirror for collecting two-photon signals and second harmonic signals, wherein the adoption of the relay lens enables the detection tube to be prolonged as required, so that the detection needs of gastrointestinal tissues and oral tissues are met, and the relay lens is simple to operate and convenient to use.
On the basis of the above embodiments, the optical path structure in the endoscopic detection device provided by the embodiment of the present invention further includes a liquid lens, and fig. 3 is a schematic diagram of a third structural diagram of the endoscopic detection device provided by the embodiment of the present invention, as shown in fig. 3, the liquid lens 113 is located between the collimating lens 112 and the mems scanning galvanometer 114, so as to form a new first optical path, where the new first optical path sequentially includes the collimating lens 112, the liquid lens 113, the mems scanning galvanometer 114, the lens 115, the dichroic mirror 116, and the objective lens 121, which are located between the optical fiber universal interface 111 and the channel port. That is, the liquid lens 113 is arranged such that the liquid lens 113 is applied with a voltage or a current to generate a corresponding curve on the surface of the liquid lens 113, so that the parallel light emitted from the alignment lens 112 generates different optical powers. The specific light path is: the laser signal is emitted from the optical fiber, is parallel to enter the liquid lens 113 after passing through the collimating lens 112, generates corresponding focal power according to the loaded voltage or current signal from the liquid lens 113, and the emitted converging or diverging light is transmitted to the objective lens 121 through the relay lens 122 and then converged on the sample after passing through the micro-electromechanical scanning galvanometer 114, the lens 115 and the dichroic mirror 116. The focal power change introduced by the liquid lens 113 can enable the focal point of the laser signal emitted from the opening of the objective lens 121 to move back and forth in the depth direction, the response speed of the liquid lens 113 is very high, and the scanning frequency is in the order of KHz, so that rapid scanning imaging in the depth direction can be realized. Wherein the liquid lens 113 is equivalent to a parallel plate glass when no voltage or current signal is applied, has no optical power to the laser signal and does not cause any shift of the focus after the objective lens 121, thereby realizing three-dimensional stereoscopic imaging.
On the basis of the above embodiments, a plurality of illumination channels are further disposed in the probe tube in the endoscope probe device provided by the embodiment of the present invention, fig. 4 is a schematic structural diagram of the endoscope probe device provided by the embodiment of the present invention, and as shown in fig. 4, illumination optical fiber bundles for transmitting illumination light signals are disposed in the illumination channels 123, where the illumination channels 123 are uniformly distributed with the axis of the probe channel as the center. That is, a plurality of illumination channels 123 are further arranged in the detection tube of the endoscope detection device in the cavity, more than one illumination channel 123 is arranged in each channel, the illumination optical fiber bundles are arranged in each channel, the illumination optical fibers have a certain aperture angle, the illumination optical fibers can be directly used for divergent illumination without lenses, the illumination channels 123 are uniformly distributed by taking the axle center of the detection channel as the center, and uniform illumination is provided for the endoscope detection device in the cavity, so that the state of a tissue region to be detected in front of an objective lens can be conveniently observed in a working mode.
On the basis of the above embodiments, an observation channel is further disposed in the detection tube in the endoscope detection device provided by the embodiment of the present invention, as shown in fig. 4, the observation channel is located between the detection channel and the illumination channel, where:
An observation lens 124 is arranged at the channel opening of the observation channel, and the observation lens 124 is connected with a bright field optical fiber bundle in the observation channel and is used for acquiring image information of a tissue region to be detected in front of the objective lens. Namely, an observation channel is further arranged in a detection tube of the cavity endoscope detection device provided by the embodiment of the invention, the observation channel is positioned between the detection channel and the illumination channel, and an observation lens 124 and a bright field optical fiber bundle are arranged, wherein the bright field optical fiber bundle is an imaging optical fiber bundle and is used for transmitting image information of a tissue region to be detected before an objective lens captured by the observation lens 124, wherein one observation channel can be used for forming binocular observation for two observation channels, and a three-dimensional bright field cavity endoscope function is realized.
On the basis of the above embodiments, an adsorption channel is further disposed in the probe tube in the endoscope probe device provided by the embodiment of the present invention, as shown in fig. 4, the adsorption channel 125 is located between the illumination channel and the edge of the probe tube. That is, the detection tube in the endoscopic detection device provided in the embodiment of the present invention is further provided with an adsorption channel 125 for adsorbing the endoscopic detection device in the cavity on the tissue to be detected, and negative pressure is formed in the adsorption channel 125 by extracting air in the adsorption channel 125, so that the endoscopic detection device in the cavity is adsorbed on the tissue to be detected, where the adsorption channel 125 is located between the illumination channel and the edge of the detection tube, that is, located at a position outside the illumination channel and near the side of the detection tube.
On the basis of the above embodiments, a button hole is formed in a handle housing of the endoscope detection device in the cavity provided by the embodiment of the invention, and a switching button is arranged in the button hole and is used for switching different optical filters so as to obtain illumination light signals with different wavelengths. Namely, a switching button is arranged in a button hole of a handle shell in the cavity endoscope detection device provided by the embodiment of the invention, and an optical filter for filtering illumination light signals with different wavelengths can be switched through the switching button, so that a worker can select the transmitted illumination light signals with different wavelengths, wherein the function of the switching button can be customized through software, and the corresponding function of the switching button can be modified.
On the basis of the above embodiments, the button hole in the endoscope detection device provided by the embodiment of the invention is further provided with an imaging button, and the imaging button is used for controlling an imaging module connected with the bright field optical fiber bundle to image the tissue region to be detected in front of the objective lens. Namely, an imaging button is arranged in a button hole of a handle shell in the cavity endoscope detection device provided by the embodiment of the invention, an imaging module connected with a bright field optical fiber bundle can be controlled to shoot and image a tissue region to be detected in front of an objective lens through the imaging button, and the functions of the imaging button can be customized through software to modify the corresponding functions.
On the basis of the above embodiments, the adsorption channel in the endoscopic detection device provided by the embodiment of the invention is an annular channel or a plurality of circular channels. The adsorption channel for adsorbing the endoscope detection device on the tissue to be detected can be an annular channel along the inner side of the detection tube or a plurality of circular channels so as to form a negative pressure large enough to enable the endoscope detection device to be adsorbed on the tissue to be detected.
The embodiment of the invention also provides a three-dimensional nonlinear laser scanning cavity endoscope, fig. 5 is a schematic structural diagram of the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention, as shown in fig. 5, the three-dimensional nonlinear laser scanning cavity endoscope includes:
fluorescence collection device 56, scan collection controller 531, femtosecond pulse laser, fiber coupling module, and cavity endoscope detection device 1 that each of the above-mentioned embodiments provided, fluorescence collection device 56 and fiber coupling module all are connected with cavity endoscope detection device 1 fiber communication, and fluorescence collection device 56 and cavity endoscope detection device 1 all are connected with scan collection controller 531 electricity, wherein:
the femtosecond pulse laser is used for outputting pulse laser signals to the optical fiber coupling module;
The optical fiber coupling module is used for coupling the pulse laser signals output by the femtosecond pulse laser and transmitting the pulse laser signals to a collimating lens in the cavity endoscope detection device 1;
the cavity endoscope detecting device 1 is used for receiving the pulse laser signal, outputting the pulse laser signal to an autofluorescent substance in a living body cell, acquiring a fluorescence signal and a second harmonic signal generated after the autofluorescent substance is excited through an objective lens, and outputting the fluorescence signal and the second harmonic signal to the fluorescence collecting device 56;
the fluorescence collection device 56 is configured to convert the fluorescence signal and the second harmonic signal into corresponding electrical signals after receiving the fluorescence signal and the second harmonic signal, respectively;
and the scanning acquisition controller 531 is used for controlling the micro-electromechanical scanning galvanometer to scan the pulse laser signal and synchronously acquire the electric signal.
Specifically, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention comprises a fluorescence collection device 56, a scanning acquisition controller 531, a femtosecond pulse laser, an optical fiber coupling module and a cavity endoscope detection device 1, so that the three-dimensional nonlinear laser scanning cavity endoscope which detects human gastrointestinal tissues and oral tissues by utilizing a two-photon imaging technology is formed, wherein the femtosecond pulse laser can emit pulse laser signals for exciting autofluorescent substances in human gastrointestinal tissues and oral tissue cells to generate multiphoton fluorescence signals and second harmonic signals, the fluorescence signals and the second harmonic signals in the cells are excited by using the femtosecond pulse laser of 920nm, the fluorescence signals of 500-600nm and the second harmonic signals of 460nm are excited, and the autofluorescent substances such as FAD or NADH in the cells are excited by the femtosecond pulse laser of 780nm to generate corresponding fluorescence signals and second harmonic signals, and the femtosecond pulse laser and the optical fiber coupling module are combined together to form a laser emission module 540;
The fluorescence collection device 56 integrates two signal collection light paths, namely a fluorescence signal collection light path and a second harmonic signal collection light path, so as to realize the collection of fluorescence signals and second harmonic signals respectively; the scan collection controller 531 controls the micro-electro-mechanical scanning galvanometer to scan the pulse laser signal and excite the autofluorescent substance to generate a fluorescent signal and a second harmonic signal, and collects a first electric signal and a second electric signal obtained by converting the fluorescent signal and the second harmonic signal by the fluorescent collection device 56; the three-dimensional nonlinear laser scanning cavity endoscope can be divided into a laparoscope and a stomatoscope according to the different structures of the cavity endoscope detection device 1. The resolution of the three-dimensional nonlinear laser scanning cavity endoscope can be set to 800nm, the imaging field of view can be 400 micrometers by 400 micrometers, and the imaging speed can be 26 frames (256×256 pixels) or 13 frames (512×512 pixels).
The three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention adopts the fluorescence collection device, the scanning acquisition controller, the femtosecond pulse laser, the optical fiber coupling module and the cavity endoscope detection device, so that the three-dimensional nonlinear laser scanning cavity endoscope which utilizes the two-photon imaging technology to detect gastrointestinal tissues and oral tissues of a human body is formed, the focal length of an objective lens is adjusted through a liquid lens, the three-dimensional scanning of the laser scanning microscope is realized, the intracellular autofluorescence substances are excited through the femtosecond pulse laser to obtain a multiphoton fluorescence signal and a second harmonic signal, the nonlinearity of the laser scanning microscope is realized, the fluorescence signal and the second harmonic signal are collected through the fluorescence collection device and are converted into corresponding electric signals, and further, a fluorescence image reflecting the cell tissue structure and the like are obtained through the electric signals.
Based on the above embodiments, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiments of the present invention further includes an illumination module and an imaging module, as shown in fig. 5, where the illumination module 534 and the imaging module 533 are all connected with the optical fiber of the cavity endoscope detection device, and the method includes:
the illumination module 534 sequentially includes an illumination lens 5342, a variable filter 5341, and an illumination light source 5343, the illumination lens 5342 being connected to the illumination fiber bundle, the illumination light source for providing an illumination light signal;
the imaging module 533 sequentially includes an imaging lens 5331 and a camera 5332, wherein the imaging lens 5331 is connected to the bright field optical fiber bundle, and the camera 5332 is used for acquiring image information of a tissue region to be detected. Namely, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention is further provided with an illumination module 534 and an imaging module 533, wherein the illumination module 534 sequentially comprises an illumination lens 5342, a variable optical filter 5341 and an illumination light source 5343, wherein the illumination light source can switch different optical filters through an electric variable optical filter rotating wheel to obtain illumination light signals with different wavelengths, and the basic principle is that when two-photon fluorescence imaging is not interfered, for example, autofluorescence and second harmonic waves are obtained, the three-dimensional nonlinear laser scanning cavity endoscope can be switched to a red or infrared optical filter to obtain illumination light signals with 370nm, 635nm or infrared 850nm and 940nm, and the illumination light signals are coupled into an illumination optical fiber bundle through the lens;
The imaging module 533 in turn includes an imaging lens and a camera, the lens focusing on the camera for imaging for direct viewing of the bright field. The two cameras correspond to the binocular field-improving optical fiber bundles, the multi-mode laparoscope is formed by field-improving imaging and two-photon imaging, the large-field sample observation is carried out by the field-improving binocular three-dimensional laparoscope mode, and the basic morphology of the sample is mainly observed. For suspicious or interested areas, the method can be switched to a two-photon mode to perform autofluorescence and second harmonic imaging, and the cell-level morphology of the sample is observed, so that a basis is provided for further judgment. Wherein the camera may be an imaging device based on an imaging device such as a CCD or CMOS.
On the basis of the above embodiments, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention further comprises an air extracting device, as shown in fig. 5, the air extracting device 52 mainly comprises an air extracting pump, the air extracting device is connected with the adsorption channel through an air extracting pipeline, an air extracting valve is arranged in the air extracting pipeline and is electrically connected with the air extracting device 52, the air extracting device 52 controls the air extracting flow of the air extracting pipeline by adjusting the opening and closing of the air extracting valve, so that the air extracting control of the adsorption channel is realized, the negative pressure in the adsorption channel is further adjusted, the cavity endoscope detecting device is adsorbed on tissues such as human intestines and stomach or oral cavity through the action of atmospheric pressure, and the motion artifact caused by the movement of organism tissues is reduced, so that the imaging is more stable and clear.
Based on the above embodiments, the three-dimensional nonlinear laser scanning cavity endoscope provided in the embodiments of the present invention further includes an industrial personal computer, as shown in fig. 5, wherein the industrial personal computer 532 is electrically connected with the scanning acquisition controller 531, where:
the industrial personal computer 532 is configured to acquire the first electrical signal and the second electrical signal acquired by the scan acquisition controller 531, generate a first fluorescent image based on the first electrical signal, and generate a second fluorescent image based on the second electrical signal. That is, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention further comprises an industrial personal computer 532 electrically connected with the scanning acquisition controller 531, the industrial personal computer 532 generates a first fluorescent image based on a first electric signal and generates a second fluorescent image based on a second electric signal, and the first fluorescent image and the second fluorescent image can be respectively used for displaying cell structure and fiber structure information, wherein control software is installed on the industrial personal computer, and a control instruction is sent to the scanner through the control software so as to control the scanning acquisition controller to acquire the first electric signal and the second electric signal.
Based on the above embodiments, the three-dimensional nonlinear laser scanning cavity endoscope provided in the embodiments of the present invention further includes a display, as shown in fig. 5, where the display 55 is electrically connected to the industrial personal computer 532, and is configured to display a first fluorescent image and a second fluorescent image. That is, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention further comprises a display 55 for displaying the first fluorescent image and the second fluorescent image, and a worker can directly acquire related information of the first fluorescent image and the second fluorescent image through the display 55.
Fig. 6 is a schematic diagram of a three-dimensional nonlinear laser scanning cavity endoscope according to a second embodiment of the present invention, where, as shown in fig. 6, the three-dimensional nonlinear laser scanning cavity endoscope also includes:
the fluorescence collection device 56, the scan collection controller 531, the femtosecond pulse laser, the optical fiber coupling module, and the cavity endoscope detection device 1, the air extraction device 52, the industrial personal computer 532, the illumination module 534, and the imaging module 533 provided in the above embodiments, wherein the fluorescence collection device 56 and the optical fiber coupling module are all in optical fiber communication connection with the cavity endoscope detection device 1, the fluorescence collection device 56 and the cavity endoscope detection device 1 are all electrically connected with the scan collection controller 531, wherein the functions of the above modules or devices are the same as those of the above embodiments, the femtosecond pulse laser and the optical fiber coupling module are combined together to form the laser emission module 540, the illumination module 534 sequentially comprises the illumination lens 5342, the variable optical filter 5341, and the illumination light source 5343, the imaging module 533 sequentially comprises the imaging lens and the camera, the cavity endoscope detection device 1 in the three-dimensional nonlinear laser scanning cavity endoscope detection device comprises a liquid lens in the optical path structure, the function is the same as the liquid lens contained in the above embodiments, and the optical path is the same as that of the liquid lens contained in the above embodiments.
On the basis of the above embodiments, fig. 7 is a schematic structural diagram of a fluorescence collection device according to an embodiment of the present invention, as shown in fig. 7, where the fluorescence collection device according to an embodiment of the present invention includes a collection fiber universal interface 881, a first photomultiplier 882, a second photomultiplier 883, a first collection optical path located between the collection fiber universal interface 881 and the first photomultiplier 882, and a second collection optical path located between the collection fiber universal interface 881 and the second photomultiplier 883, wherein:
the first collecting light path sequentially comprises a coupling collecting lens 81, an infrared filter 82, a first dichroic mirror 83, a first filter 84 and a first collecting lens 85, wherein the first collecting light path is used for collecting fluorescent signals received by the fluorescent collecting device, and the first photomultiplier 882 is used for converting the fluorescent signals into first electric signals;
the second collecting light path sequentially comprises a coupling collecting lens 81, an infrared filter 82, a first dichroic mirror 83, a second dichroic mirror 86, a second filter 87 and a second collecting lens 88, wherein the second collecting light path is used for collecting second harmonic signals received by the fluorescence collecting device, and the second photomultiplier 883 is used for converting the second harmonic signals into second electric signals. Namely, the fluorescence collection device provided by the embodiment of the invention has a double-path signal collection function, and integrates two paths of light paths, wherein the first dichroic mirror 83 in the first collection light path is a dichroic mirror for transmitting fluorescence signals, reflecting second harmonic waves, the second dichroic mirror 86 and the first dichroic mirror 83 are the same dichroic mirror for reflecting the second harmonic waves, the first filter 84 is used for transmitting fluorescence signals and filtering out other interference signals, the second filter 87 is used for transmitting corresponding second harmonic signals and filtering out other interference signals, for example, when 780nm femtosecond fiber lasers are used for exciting autofluorescence substances in abdominal cavities or oral cells of a human body, 390nm second harmonic signals and 450-600nm two-photon autofluorescence signals can be obtained, two paths of fluorescence can be separated through the dichroic mirror which is reflecting the second harmonic waves with more than 420nm, namely the first dichroic mirror 83, and the first filter 84 with 390+/-20 nm and the second filter 87 with 450-600nm can be used for obtaining clean second harmonic signals and fluorescence signals respectively.
Fig. 8 is a schematic diagram of a box-type combined structure of a three-dimensional nonlinear laser scanning cavity endoscope, as shown in fig. 8, a display 55 integrated on a box cover is integrated with a box body provided with each module, so that the whole equipment can be conveniently moved and a workplace can be conveniently replaced, and the display 55 can be externally placed on the box body when in use, so that a worker can conveniently obtain information on the display, wherein a cavity endoscope detection device 1 in the three-dimensional nonlinear laser scanning cavity endoscope is an stomatoscope detection device. After the three-dimensional nonlinear laser scanning cavity endoscope is used, a worker can carry the equipment box, and the equipment can be conveniently replaced in a workplace, especially in a hospital, a laboratory or an outdoor place.
Fig. 9 is a schematic diagram of a box-type combined structure of a three-dimensional nonlinear laser scanning cavity endoscope, as shown in fig. 9, a display 55 integrated on a box cover is integrated with a box body provided with each module, so that the whole equipment can be conveniently moved and a workplace can be conveniently replaced, and the display 55 can be externally placed on the box body when in use, so that a worker can conveniently obtain information on the display, wherein a cavity endoscope detection device 1 in the three-dimensional nonlinear laser scanning cavity endoscope is a laparoscope detection device, and a plurality of laparoscope detection devices can be simultaneously arranged. After the three-dimensional nonlinear laser scanning cavity endoscope is used, a worker can carry the equipment box, and the equipment can be conveniently replaced in a workplace, especially in a hospital, a laboratory or an outdoor place.
Based on the above embodiments, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiment of the invention has a plurality of cavity endoscope detection devices. The fluorescence collection device and the optical fiber coupling module provided by the embodiment of the invention can be simultaneously connected with the optical fibers of the plurality of cavity endoscope detection devices in a communication way, namely, the plurality of detection devices are integrated in the three-dimensional nonlinear laser scanning cavity endoscope system, so that the simultaneous detection of different parts of gastrointestinal tissues is realized, and the contrast analysis is performed.
Based on the above embodiments, the three-dimensional nonlinear laser scanning cavity endoscope provided by the embodiments of the present invention further includes an adjusting optical fiber, which is used for optical fiber transmission connection between the fluorescence collection device and the optical fiber coupling module and the cavity endoscope detection device, wherein:
the length of the adjusting optical fiber is adjustable. The fluorescent collection device and the optical fiber coupling module in the three-dimensional nonlinear laser scanning cavity endoscope are respectively connected with the cavity endoscope detection device in an optical fiber transmission mode through the adjustable-length adjusting optical fibers so as to realize flexible movement of the detection device according to different experimental scene requirements and avoid limitation of limited optical fiber length, wherein the adjustable-length adjusting optical fibers can be used for realizing application in various occasions by changing the optical fibers with different lengths, and the optical fibers with different lengths can be changed at any time according to requirements.
For the three-dimensional nonlinear laser scanning cavity endoscope provided by the above embodiments, another specific implementation manner is provided in the embodiment of the present invention, fig. 10 is a schematic diagram of a table structure of the three-dimensional nonlinear laser scanning cavity endoscope provided in the embodiment of the present invention, as shown in fig. 10, the three-dimensional nonlinear laser scanning cavity endoscope includes an air extraction device 52, a first device 53, a second device 54, a display 55, and a cavity endoscope detection device 1, where the first device 53 integrates a scanning acquisition controller and an industrial personal computer, the industrial personal computer is electrically connected with the display 55, the second device 54 integrates a femtosecond pulse laser, an optical fiber coupling module, a fluorescence collection device, an illumination module, and an imaging module, and the optical fiber coupling module and the fluorescence collection device are all in optical fiber transmission connection with the adsorption microscope detection device 51, and the cavity endoscope detection device 1 is an oral cavity mirror detection device for detecting the oral cavity tissue of a human body so as to understand the information of the benign malignancy, the infiltration depth, the transfer condition, whether the cancer remains or not, and the principle of the adsorption three-dimensional nonlinear laser scanning microscope is different from the above embodiments.
The embodiment of fig. 11 provides a schematic diagram of a desk-top structure of a three-dimensional nonlinear laser scanning cavity endoscope, as shown in fig. 11, the three-dimensional nonlinear laser scanning cavity endoscope also includes an air extractor 52, a first device 53, a second device 54, a display 55 and a cavity endoscope detection device 1, wherein the first device 53 is integrated with a scanning acquisition controller and an industrial personal computer, the industrial personal computer is electrically connected with the display 55, the second device 54 is integrated with a femtosecond pulse laser, an optical fiber coupling module, a fluorescence collection device, an illumination module and an imaging module, the optical fiber coupling module and the fluorescence collection device are all in optical fiber transmission connection with an adsorption microscope detection device 51, the cavity endoscope detection device 1 is a laparoscope detection device, and the laparoscope detection device is embedded into the abdomen of a human body to detect gastrointestinal tissues so as to know information such as benign and malignant tumors, infiltration depth, metastasis conditions, existence of cancer residues at a cutting edge and the like.
While the present invention has been described in connection with the embodiments illustrated in the drawings, it will be apparent to those skilled in the art that the present invention is not limited to the preferred embodiments of the present invention, and various modifications and variations can be made thereto by those skilled in the art on the basis of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application should be included in the protection scope of the present application.
The apparatus embodiments described above are merely illustrative, wherein elements illustrated as separate elements may or may not be physically separate, and elements shown as elements may or may not be physical elements, may be located in one place, or may be distributed over a plurality of network elements. Some or all of the modules may be selected according to actual needs to achieve the purpose of the solution of this embodiment. Those of ordinary skill in the art will understand and implement the present invention without undue burden.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (9)

1. A lumen endoscopic probe apparatus, comprising:
Handle casing and probe tube, the handle casing with probe tube fixed connection, be provided with the detection passageway in the probe tube, be provided with relay lens and objective in the detection passageway, the objective is located the entrance of detection passageway, the objective the relay lens with the light path structure that sets up in the handle casing forms first light path and second light path, the axle center of detection passageway with the coincidence of probe tube axle center, wherein:
the first optical path sequentially comprises a collimating lens, a micro-electromechanical scanning galvanometer, a lens, a dichroic mirror, the relay lens and the objective lens, wherein the collimating lens, the micro-electromechanical scanning galvanometer, the lens, the dichroic mirror, the relay lens and the objective lens are positioned between an optical fiber universal interface and the channel opening in the handle shell, and the first optical path is used for conducting laser signals received by the collimating lens from the optical fiber universal interface to the channel opening; the laser signal is used for exciting an autofluorescent substance;
the second optical path sequentially comprises the objective lens, the relay lens and the dichroic mirror which are positioned between the passage port and the optical fiber universal interface, wherein the second optical path is used for conducting optical signals collected by the objective lens from the passage port to the optical fiber universal interface; the second light path is used for collecting and transmitting two-photon signals generated after the autofluorescent substance is excited and second harmonic signals; the optical path structure further comprises a liquid lens, wherein the liquid lens is positioned between the collimating lens and the micro-electromechanical scanning galvanometer to form a new first optical path, the new first optical path sequentially comprises the collimating lens, the liquid lens, the micro-electromechanical scanning galvanometer, the lens, the dichroic mirror and the objective lens, which are positioned between the optical fiber universal interface and the channel port, and the image plane of the objective lens coincides with the focal plane of the relay lens.
2. The endoscopic detection device according to claim 1, wherein a plurality of illumination channels are further arranged in the detection tube, and illumination fiber bundles for transmitting illumination light signals are arranged in the illumination channels, wherein the illumination channels are uniformly distributed with the axis of the detection channels as the center.
3. The endoscopic detection device of claim 2, wherein an observation channel is further disposed within the detection tube, the observation channel being located between the detection channel and the illumination channel, wherein:
an observation lens is arranged at the channel opening of the observation channel and connected with the bright field optical fiber bundle in the observation channel, so as to acquire image information of the tissue region to be detected in front of the objective lens.
4. The endoscopic detection device of claim 2, wherein an adsorption channel is further disposed within the detection tube, the adsorption channel being located between the illumination channel and the detection tube edge.
5. The endoscopic detection device of claim 3, wherein a button hole is formed in the handle housing, and a switching button is disposed in the button hole, and the switching button is used for switching different optical filters to obtain the illumination light signals with different wavelengths.
6. The endoscopic detection device of claim 5, wherein an imaging button is further disposed within the button aperture, the imaging button for controlling an imaging module coupled to the bright field fiber optic bundle to image a region of tissue to be measured in front of the objective lens.
7. A three-dimensional nonlinear laser scanning cavity endoscope, comprising:
a fluorescence collection device, a scanning acquisition controller, a femtosecond pulse laser, an optical fiber coupling module, and the cavity endoscopic detection device of any one of claims 1-6, wherein the fluorescence collection device and the optical fiber coupling module are both in optical fiber communication connection with the cavity endoscopic detection device, and the fluorescence collection device and the cavity endoscopic detection device are both electrically connected with the scanning acquisition controller, wherein:
the femtosecond pulse laser is used for outputting pulse laser signals to the optical fiber coupling module;
the optical fiber coupling module is used for coupling the pulse laser signals output by the femtosecond pulse laser and transmitting the pulse laser signals to the collimating lens in the cavity endoscope detection device;
the cavity endoscope detection device is used for receiving the pulse laser signals, outputting the pulse laser signals to autofluorescent substances in living cells, acquiring fluorescent signals and second harmonic signals generated after the autofluorescent substances are excited through the objective lens, and outputting the fluorescent signals and the second harmonic signals to the fluorescent collection device;
The fluorescence collection device is used for respectively converting the fluorescence signal and the second harmonic signal into corresponding electric signals after receiving the fluorescence signal and the second harmonic signal;
the scanning acquisition controller is used for controlling the micro-electromechanical scanning galvanometer to scan the pulse laser signals and synchronously acquiring the electric signals.
8. The three-dimensional nonlinear laser scanning cavity endoscope of claim 7, further comprising an illumination module and an imaging module, both in optical fiber communication with the cavity endoscopic probe apparatus, wherein:
the illumination module sequentially comprises an illumination lens, a variable optical filter and an illumination light source, wherein the illumination lens is connected with the illumination optical fiber bundle, and the illumination light source is used for providing illumination light signals;
the imaging module sequentially comprises an imaging lens and a camera, wherein the imaging lens is connected with the bright field optical fiber bundle, and the camera is used for acquiring image information of a tissue region to be detected.
9. The three-dimensional nonlinear laser scanning cavity endoscope of claim 7, wherein the fluorescence collection device comprises a collection fiber optic universal interface, a first photomultiplier tube, a second photomultiplier tube, and a first collection optical path between the collection fiber optic universal interface and the first photomultiplier tube, a second collection optical path between the collection fiber optic universal interface and the second photomultiplier tube, wherein:
The first collecting light path sequentially comprises a coupling collecting lens, an infrared filter, a first dichroic mirror, a first filter and a first collecting lens, wherein the first collecting light path is used for collecting the fluorescent signals received by the fluorescent collecting device, and the first photomultiplier is used for converting the fluorescent signals into first electric signals;
the second collecting light path sequentially comprises the coupling collecting lens, the infrared filter, the first dichroic mirror, the second filter and the second collecting lens, wherein the second collecting light path is used for collecting the second harmonic signals received by the fluorescent collecting device, and the second photomultiplier is used for converting the second harmonic signals into second electric signals.
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