CN110464309A - A kind of fluorescent endoscopic imgaing system across scale - Google Patents
A kind of fluorescent endoscopic imgaing system across scale Download PDFInfo
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- CN110464309A CN110464309A CN201910794851.0A CN201910794851A CN110464309A CN 110464309 A CN110464309 A CN 110464309A CN 201910794851 A CN201910794851 A CN 201910794851A CN 110464309 A CN110464309 A CN 110464309A
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- exciting light
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
- A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
- A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
Abstract
The invention discloses a kind of fluorescent endoscopic imgaing systems across scale, comprising: lighting unit and micro-imaging unit；Lighting unit is transmitted to macroscopical spectroscopy unit, Jie's sight imaging unit and microcosmic high-resolution imaging unit for emitting the first exciting light and/or the second exciting light, and by the fluorescence that the first exciting light and/or the second exciting light generate；Macroscopical spectroscopy unit generates fluorescence spectra for obtaining the first fluorescence signal, and according to the first fluorescence signal；It is situated between and sees imaging unit for obtaining the second fluorescence signal, and generates to be situated between according to the second fluorescence signal and see distributed image；Microcosmic high-resolution imaging unit generates Nano medication fluorogram, nanoshell fluorogram and cell membrane distribution map for obtaining third fluorescence signal, and according to third fluorescence signal；The system is monitored intracellular drug transport by the realization of Nano medication fluorogram, nanoshell fluorogram and cell membrane distribution map, and realizes the cellular pharmacokinetics characteristic research in living animal deep tissues.
Description
Technical field
The present invention relates in medicine optical microscopy imaging technical field more particularly to a kind of fluorescence endoscopic across scale at
As system.
Background technique
With the development of medical technology, optical microscopy imaging obtains extensive in the projects such as medicine observation, inspection, detection
Using；Existing medical imaging technology includes: in a variety of endoscope systems, such as optical fibre endoscope, fujinon electronic video endoscope, ultrasound
Sight glass etc. and a variety of optical microscopies, such as laser work focus micro-imaging, two-photon micro-imaging etc..
However, the basic research for Nano medication clinical precursor internal dynamics characteristic, will not only investigate it in target cell
Interior drug transport characteristic also needs the animal overall distribution, the intravascular DYNAMIC DISTRIBUTION characteristic, main metabolic organ that disclose Nano medication
The aggregation and damage of (liver, kidney etc.) and the DYNAMIC DISTRIBUTION characteristic of target organ target tissue.Although various living imaging systems (CT
US MRI PET SPECT etc.) can all show that Nano medication is more gathered at pathological tissues/organ, but still can not observe
Whether it, which enters in target cell, is had an effect or is pumped out by target cell, and the degree of impairment of main metabolic organ can not be also evaluated.
It is current in the prior art, although various endoscope systems can identify the tissue damage characteristic of housing surface, point
The requirement of Intracellular drug monitoring is not achieved in resolution；And the drug transport that various optical microscopies have high-resolution intracellular
Detection function, but can not achieve the cellular pharmacokinetics characteristic research in living animal deep tissues.It summarizes existing
The application range and spatial resolution of various imaging techniques, it is evident that entirety, organ, group can in vivo be realized by lacking one kind
It knits and the system of cells Synchronous imaging, this is in medicine needed for the development of optical imaging technique.
Therefore, it is necessary to propose a kind of endoscopic imaging system across scale.
Summary of the invention
This application provides a kind of fluorescent endoscopic imgaing system across scale, may be implemented to intracellular drug transport into
Row monitoring, and solve optical image technology in the prior art and cannot achieve the cellular pharmacokinetics in living animal deep tissues
The technical issues of characteristic research.
The present invention provides a kind of fluorescent endoscopic imgaing system across scale, the system comprises: lighting unit and it is micro- at
As unit；
Wherein, the micro-imaging unit include: macroscopical spectroscopy unit, be situated between see imaging unit and microcosmic high-resolution at
As unit；
The lighting unit for emitting the first exciting light and/or the second exciting light, and by first exciting light and/or
Second exciting light is transmitted separately to macroscopical spectroscopy unit, gives an account of and see imaging unit and the microcosmic high-resolution
Imaging unit；
The macroscopic view spectroscopy unit is used to obtain incident first exciting light or second excitation
The first fluorescence signal that fluorescent samples generate, and generate according to first fluorescence signal fluorescence spectrum of the fluorescent samples
Figure；
It gives an account of and sees first exciting light or described that imaging unit is used to obtain incidence based on the fluorescence spectra
The second fluorescence signal that fluorescent samples described in second excitation generate, and it is described glimmering according to second fluorescence signal acquisition
Jie of light sample sees distributed image；
The microcosmic high-resolution imaging unit is used for based on first excitation for giving an account of sight distributed image acquisition incidence
The third fluorescence signal of fluorescent samples described in light and second excitation, and height is carried out according to the third fluorescence signal
Resolution imaging, to obtain the Nano medication fluorogram, nanoshell fluorogram and cell for observing the fluorescent samples in real time
Film distribution map.
Optionally, the lighting unit includes: light source assembly and main optical path system；
The light source assembly includes: the first continuous conductor laser and the second continuous conductor laser；
The main optical path system includes: the first reflective mirror, the first dichroic mirror, first adjusts slide, the first Amici prism, the
Two adjust slide, the second Amici prism and the second reflective mirror；
First exciting light that first continuous conductor laser issues successively passes through first dichroic mirror, institute
State the first adjusting slide, first Amici prism, the second adjusting slide, second Amici prism and described second instead
Light microscopic；
Second exciting light that second continuous conductor laser issues successively passes through first reflective mirror, institute
State the first dichroic mirror, the first adjusting slide, first Amici prism, the second adjusting slide, second light splitting
Prism and second reflective mirror；
Wherein, first Amici prism is used to first exciting light or second exciting light light splitting being transmitted to institute
Macroscopical spectroscopy unit is stated, and first exciting light or second exciting light are successively transmitted to described second and adjust glass
Piece；
Wherein, second Amici prism is used to first exciting light or second exciting light light splitting being transmitted to institute
Sight imaging unit is given an account of, and first exciting light or second exciting light are transmitted to second reflective mirror；
Wherein, second reflective mirror is described microcosmic for first exciting light and second exciting light to be transmitted to
High-resolution imaging unit.
Optionally, the light source assembly further include: the first electric driven sun visor and the second electric driven sun visor；
First electric driven sun visor is between first continuous conductor laser and first dichroic mirror；
Second electric driven sun visor is between second continuous conductor laser and first reflective mirror.
Optionally, macroscopical spectroscopy unit includes: the second dichroic mirror, the first lens, the first fiber optic bundle, the first filter
Wave plate, the second lens and Fluorescence Spectrometer；
First Amici prism is used to first exciting light or second exciting light being transmitted to described second pair
Look mirror；
Second dichroic mirror is used to first exciting light or second exciting light being transmitted to first lens；
First lens are used to for first exciting light of preset wavelength or second exciting light being coupled into described
First fiber optic bundle；
First fiber optic bundle is used to for first exciting light or second exciting light being transmitted at fluorescent samples, and
It is collected after first exciting light or second exciting light excite the fluorescent samples and is obtained by the port of the first fiber optic bundle
The first fluorescence signal arrived, and first fluorescence signal after collection is successively transmitted to first fiber optic bundle, described
One lens and second dichroic mirror；
Second dichroic mirror is used to carry out the fluorescence signal and first exciting light or second exciting light
Separation, and first fluorescence signal total reflection is transmitted to first filter plate；
First filter plate is for first fluorescence signal to be filtered, and by filtered described first
Fluorescence signal is transmitted to second lens；
Second lens are used to filtered first fluorescence signal being transmitted to the Fluorescence Spectrometer, to obtain
Fluorescence spectra.
Optionally, giving an account of and seeing imaging unit includes: third dichroic mirror, the third lens, the second fiber optic bundle, lenticule group
Part, the first object lens, the second filter plate, the 4th lens and multiplication imaging device；
Second Amici prism is used to successively for first exciting light or second exciting light to be transmitted to described the
Three dichroic mirrors and the third lens；
The third lens are used to for first exciting light of preset wavelength or second exciting light being coupled into described
Second fiber optic bundle；
Second fiber optic bundle is used to first exciting light or second exciting light being transmitted to the lenticule group
Part；
The lenticule component is used to be adjusted the beam size of first exciting light or second exciting light,
And first exciting light of proper beam or second exciting light are transmitted to first object lens；
First object lens are used for transmission at first exciting light or second exciting light to fluorescent samples, and are collected
The second fluorescence signal that first exciting light or second exciting light obtain after exciting to the fluorescent samples, and will
Second fluorescence signal after collection is successively transmitted to the lenticule component, second fiber optic bundle, second lens
And the third dichroic mirror；
The third dichroic mirror is used for second fluorescence signal and first exciting light or second exciting light
It is separated, and second fluorescence signal total reflection is transmitted to second filter plate；
Second filter plate is for being filtered second fluorescence signal, and by filtered described second
Fluorescence signal is transmitted to the 4th lens；
Filtered institute second is stated fluorescence signal and is transmitted to the multiplication imaging device by the 4th lens, to be situated between
See distributed image.
Optionally, the lenticule component includes: the 5th lens, the 6th lens and the 7th lens；
First exciting light or second exciting light successively pass through the 5th lens, the 6th lens and described
7th lens, to adjust the beam size of first exciting light or second exciting light.
Optionally, the microcosmic high-resolution imaging unit includes: the 4th dichroic mirror, the 5th dichroic mirror, the 6th dichroic mirror, vibration
Mirror, 4F system, the second object lens, third fiber optic bundle, the 8th lens, self-focusing lens, third filter plate, the 9th lens, more than first
Mode fiber, the first photomultiplier tube, the 4th filter plate, the tenth lens, the second multimode fibre, the second photomultiplier tube, the 5th filter
Wave plate, the 11st lens, third multimode fibre and third photomultiplier tube；
The third Amici prism is used to first exciting light and second exciting light being successively transmitted to institute simultaneously
State the 4th dichroic mirror, the 5th dichroic mirror, the 6th dichroic mirror and the galvanometer；
The galvanometer is used to first exciting light and second exciting light carrying out light beam scanning, to obtain scanning light
Beam, and the scanning light beam is transmitted to the 4F system；
The 4F system is used to adjust the beam size of the scanning light beam, and scanning light beam adjusted is transmitted to institute
State the second object lens；
Second object lens are used to the scanning light beam being coupled into the third fiber optic bundle；
The third fiber optic bundle is used to the scanning light beam being transmitted to the 8th lens；
8th lens are used to the scanning light beam being coupled into the self-focusing lens；
The self-focusing lens is used to for the scanning light beam being transmitted at fluorescent samples, and collects the scanning light beam pair
The third fluorescence signal that fluorescent samples obtain after being excited, and the third fluorescence signal is reversely successively transmitted to described
Eight lens, the third fiber optic bundle, second object lens, the 4F system, the galvanometer, the 6th dichroic mirror, described
Five dichroic mirrors and the 4th dichroic mirror；
Wherein, the 4th dichroic mirror is used for by isolated 4th fluorescence signal of the third fluorescence signal, and to institute
It states the 4th fluorescence signal and is totally reflected and be successively transmitted to the third filter plate, the 9th lens, the first multimode light
Fine and described first photomultiplier tube, to obtain cell membrane distribution map；
Wherein, the 5th dichroic mirror is used for by isolated 5th fluorescence signal of the third fluorescence signal, and to institute
It states the 5th fluorescence signal and is totally reflected and be successively transmitted to the 4th filter plate, the tenth lens, the second multimode light
Fine and described second photomultiplier tube, to obtain Nano medication distribution map；
Wherein, the 6th dichroic mirror is used for by isolated 6th fluorescence signal of the third fluorescence signal, and to institute
It states the 6th fluorescence signal and is totally reflected and be successively transmitted to the 5th filter plate, the 11st lens, the third multimode
Optical fiber and the third photomultiplier tube, to obtain Nano medication distribution map.
Optionally, the 4F system includes: the 12nd lens and the 13rd lens；
First exciting light and second exciting light from the 12nd lens to the 13rd lens transmission, with
Adjust the beam size of first exciting light and second exciting light.
A kind of fluorescent endoscopic imgaing system across scale provided by the invention, the system comprises: lighting units and micro-
Imaging unit；Wherein, the micro-imaging unit includes: macroscopical spectroscopy unit, is situated between and sees imaging unit and microcosmic high-resolution
Imaging unit；The lighting unit for emitting the first exciting light and/or the second exciting light, and will first exciting light with/
Or second exciting light be transmitted to macroscopical spectroscopy unit, give an account of sight imaging unit and the microcosmic high-resolution at
As unit；The macroscopic view spectroscopy unit is used to obtain incident first exciting light or second excitation is received
The first fluorescence signal that rice shell and Nano medication generate, and the nanoshell is generated according to first fluorescence signal and described is received
The fluorescence spectra of rice drug；It gives an account of to see imaging unit and be used to obtain incident described first based on the fluorescence spectra and swash
The second fluorescence signal that nanoshell described in luminous or described second excitation and the Nano medication generate, and according to described
Second fluorescence signal obtains the nanoshell and Jie of the Nano medication sees distributed image；The microcosmic high-resolution imaging unit
For based on nanometer described in first exciting light and second excitation for giving an account of sight distributed image acquisition incidence
The third fluorescence signal of shell and the Nano medication, and high-resolution imaging is carried out according to the third fluorescence signal, to obtain
For observing the Nano medication cross-film, the Nano medication fluorogram of leakage and control release, nanoshell fluorogram and thin in real time
After birth distribution map；The system is realized by Nano medication fluorogram, nanoshell fluorogram and cell membrane distribution map to intracellular
Drug transport is monitored, and realizes the cellular pharmacokinetics characteristic research in living animal deep tissues.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those skilled in the art without creative efforts, can also basis
These attached drawings obtain other attached drawings.
Fig. 1 is a kind of fluorescent endoscopic imgaing system architecture diagram across scale provided by the invention；
Fig. 2 is lighting unit structure schematic diagram provided in an embodiment of the present invention；
Fig. 3 is the structural schematic diagram of macroscopical spectroscopy unit provided in an embodiment of the present invention；
Fig. 4 is the structural schematic diagram of the sight imaging unit provided in an embodiment of the present invention that is situated between；
Fig. 5 is the structural schematic diagram of microcosmic high-resolution imaging unit provided by the embodiments of the present application；
Fig. 6 is a kind of overall structure figure of the fluorescent endoscopic imgaing system across scale provided by the invention.
Specific embodiment
In order to make the invention's purpose, features and advantages of the invention more obvious and easy to understand, below in conjunction with the present invention
Attached drawing in embodiment, technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described reality
Applying example is only a part of the embodiment of the present invention, and not all embodiments.Based on the embodiments of the present invention, those skilled in the art
Member's every other embodiment obtained without making creative work, shall fall within the protection scope of the present invention.
In the prior art, although various endoscope systems can identify the tissue damage characteristic of surface of wall, resolution ratio
The requirement of Intracellular drug monitoring is not achieved；And inspection of the various optical microscopies with the intracellular drug transport of high-resolution
Brake, but can not achieve the cellular pharmacokinetics characteristic research in living animal deep tissues；
In order to solve the defect of the above-mentioned prior art, the present invention proposes a kind of fluorescent endoscopic imgaing system across scale, can
Intracellular drug transport is monitored with realizing, and solves optical image technology in the prior art and cannot achieve living animal
The technical issues of cellular pharmacokinetics characteristic research in deep tissues.
The present invention provides a kind of fluorescent endoscopic imgaing system across scale, please refers to Fig. 1 and Fig. 6, and Fig. 1 is provided by the invention
A kind of fluorescent endoscopic imgaing system architecture diagram across scale, Fig. 6 are a kind of fluorescence endoscopic imaging across scale provided by the invention
The overall structure figure of system；
The system includes: lighting unit 100 and micro-imaging unit 200；
Wherein, micro-imaging unit 200 includes: macroscopical spectroscopy unit 201, is situated between and sees imaging unit 202 and microcosmic height
Resolution imaging unit 203；
Lighting unit 100 is for emitting the first exciting light and/or the second exciting light, and by the first exciting light and/or second
Exciting light is transmitted separately to macroscopical spectroscopy unit 201, is situated between and sees imaging unit 202 and microcosmic high-resolution imaging unit 203；
Macroscopical spectroscopy unit 201 is used to obtain incident the first exciting light or the second excitation fluorescent samples and produces
The first raw fluorescence signal, and according to the fluorescence spectra of the first fluorescence signal generation fluorescent samples；
It is situated between and sees the first exciting light or the second excitation that imaging unit 202 is used to obtain incidence based on fluorescence spectra
The second fluorescence signal that fluorescent samples generate, and distributed image is seen according to Jie that the second fluorescence signal obtains fluorescent samples；
Microcosmic high-resolution imaging unit 203 is used to swash based on the first exciting light and second for seeing distributed image acquisition incidence that is situated between
It shines and excites the third fluorescence signal of fluorescent samples, and high-resolution imaging is carried out according to third fluorescence signal, to be used for
Nano medication fluorogram, nanoshell fluorogram and the cell membrane distribution map of observation fluorescent samples in real time.
In an embodiment of the present invention, which includes: lighting unit 100, is situated between macroscopical spectroscopy unit 201
See imaging unit 202 and microcosmic high-resolution imaging unit 203；Wherein, the effect of lighting unit 100 is realized to light splitting, light intensity
It adjusts and functions, the light sources of lighting unit 100 such as wavelength selection can directly adopt continuous conductor laser, which issues
The wavelength of laser (exciting light) be 488nm/ nanometer and 650nm/ nanometers, by the adjusting slide in preset path to laser
(exciting light) carries out light intensity and arbitrarily adjusts, and is carried out at light splitting by the Amici prism in preset path to laser (exciting light)
Reason, so that laser/exciting light respectively enters macroscopical spectroscopy unit 201 according to preset path, Jie sees imaging unit 202 and micro-
See high-resolution imaging unit 203；
Further, fluorescent samples include: the first fluorescence dye of nanoshell, Nano medication, cell membrane, targeted nano shell
The third fluorescent dye of material, the second fluorescent dye of targeted nano drug and target cell membrane；
In the present embodiment, the first exciting light of 488nm wavelength is mainly used for exciting the first fluorescence dye of targeted nano shell
Expect FITC, the wavelength of fluorescence which emits after being excited is about 520nm, for existing in imaging to nanoshell
Distribution situation in tissue；First exciting light of 488nm wavelength be also used to excite target cell membrane third fluorescent dye DIO or
The homemade third fluorescent dye in person laboratory, the wavelength of fluorescence which emits after being excited is about 500nm, with reality
Now to the significant notation of cell membrane；Second exciting light of 650nm wavelength is mainly used for exciting the Cy5 series of targeted nano drug
Second fluorescent dye, the wavelength of fluorescence which emits after being excited is about 670nm, when reaching to Nano medication
Wait the purpose of tracking；It should be noted that exciting light need to enter macroscopical spectroscopy unit 201, Jie sees imaging unit 202 and micro-
High-resolution imaging unit 203 is seen, to realize the excitation to above-mentioned fluorescent dye, specifically, the exciting light of 488nm/650nm wavelength
Into macroscopical spectroscopy unit 201, by the excitation to corresponding fluorescent dye, to be collected into fluorescence spectra；According to glimmering
The target position that the selection of light spectrogram needs to monitor enters Jie in the exciting light of 488nm/650nm wavelength and sees imaging unit 202
Afterwards, by exciting to corresponding fluorescent dye, distributed image is seen to obtain being situated between；And the exciting light of 488nm and 650nm wavelength
After entering microcosmic high-resolution imaging unit 203 simultaneously, according to being situated between, sight distributed image excites fluorescent dye, realizes high-resolution
Imaging, to obtain for observing Nano medication cross-film in real time, the Nano medication fluorogram that Nano medication release and control discharge, receiving
Rice shell fluorogram and cell membrane distribution map；
In the present embodiment, nanometer can be met according to Nano medication fluorogram, nanoshell fluorogram and cell membrane distribution map
The basic research of In vivo kinetics characteristic before clinical drug by investigating its drug transport characteristic in target cell, and is disclosed and is received
Animal overall distribution, intravascular DYNAMIC DISTRIBUTION characteristic, the aggregation of main metabolic organ and the damage of rice drug and target organ target
The DYNAMIC DISTRIBUTION characteristic of tissue, to realize that observing whether Nano medication enters in target cell has an effect or pumped by target cell
Out, and evaluation main metabolic organ degree of impairment.
Referring to Fig. 2, Fig. 2 is lighting unit structure schematic diagram provided in an embodiment of the present invention；The lighting unit 100 packet
It includes: light source assembly and main optical path system；
Light source assembly includes: the first continuous conductor laser 1 and the second continuous conductor laser 2；
Main optical path system includes: that the first reflective mirror 5, the first dichroic mirror 6, first adjust slide 7, the first Amici prism 8, the
Two adjust slide 9, the second Amici prism 10 and the second reflective mirror 11；
The first exciting light that first continuous conductor laser 1 issues successively passes through the first dichroic mirror 6, first and adjusts slide
7, the first Amici prism 8, second adjusts slide 9, the second Amici prism 10 and the second reflective mirror 11；
Second continuous conductor laser 2 issue the second exciting light successively pass through the first reflective mirror 5, the first dichroic mirror 6,
First adjusts slide 7, the first Amici prism 8, second adjusts slide 9, the second Amici prism 10 and the second reflective mirror 11；
Wherein, the first Amici prism 8 is used to the first exciting light or the light splitting of the second exciting light being transmitted to macroscopical spectrum analysis
Unit 201, and the first exciting light or the second exciting light are successively transmitted to the second adjusting slide 9；
Wherein, the second Amici prism 10, which is used to the first exciting light or the light splitting of the second exciting light being transmitted to Jie, sees imaging unit
202, and the first exciting light or the second exciting light are transmitted to the second reflective mirror 11；
Wherein, the second reflective mirror 11 is used to the first exciting light and the second exciting light being transmitted to microcosmic high-resolution imaging unit
203。
In embodiments of the present invention, the effect of the lighting unit 100 is realized to light splitting, light intensity regulating and wavelength selection etc.
The light source of function, lighting unit 100 can directly adopt continuous conductor laser, wherein the first continuous conductor laser 1 hair
The wavelength of first laser (the first exciting light) out is 488nm/ nanometers, and the second of the second continuous conductor laser 2 sending swashs
The wavelength of light (the second exciting light) is 650nm/ nanometers；First continuous conductor laser 1, the second continuous conductor laser 2
The first exciting light, the second exciting light issued, enters main optical path system according to preset light transmission path, to realize to sending
First exciting light, the second exciting light carry out light splitting and light intensity regulating processing, and the present embodiment is by using the first reflective mirror 5, the
It is reflective that one dichroic mirror 6, first adjusts the adjusting of slide 7, second slide 9, the first Amici prism 8, the second Amici prism 10 and second
The combination of the components such as mirror 11 can be achieved to carry out the laser (exciting light) after sending light splitting and light intensity regulating, wherein reflective mirror
It can be installed and be set according to scheduled installation settings scheme with dichroic mirror combination, the installation and setting are primarily directed to first
The installation of position and direction angle and setting of reflective mirror 5, the first dichroic mirror 6, form preset path, the first reflective mirror 5 is used for the
The second exciting light for the 650nm that two continuous conductor lasers 2 issue is reflected, so that the second exciting light is transmitted to first pair
Look mirror 6, the first dichroic mirror 6 is for reflecting the second exciting light of 650nm wavelength, so that the second exciting light after reflection
Into main optical path system, meanwhile, the first exciting light that it is 488nm by wavelength that the first dichroic mirror 6, which is also used to, is swashed with control first
Light (the first exciting light) enters main optical path system according to preset path；And it is installed and is set according to scheduled installation settings scheme
It sets the tone and saves slide and Amici prism, form the preset path in main optical path system, so that leading to after exciting light enters main optical path system
The adjusting slide crossed in preset path carries out light intensity to laser (exciting light) and arbitrarily adjusts, and passes through the light splitting rib in preset path
Mirror carries out light-splitting processing to laser (exciting light), so that laser/exciting light respectively enters macroscopical spectrum analysis according to preset path
Unit 201 is situated between and sees imaging unit 202 and microcosmic high-resolution imaging unit 203；
In the present embodiment, three kinds of fluorescence that the two-way exciting light which includes generates cooperate real-time working simultaneously, just
The characteristics such as the cross-film characteristic of drug, the leakage of drug and control release, and preferred, the present invention can be observed in real time by image
Used two-way laser is common laser, can excite various other fluorescent dyes, keeps the selection of fluorescent marker special
Property is greatly improved.
Further, light source assembly further include: the first electric driven sun visor 3 and the second electric driven sun visor 4；
First electric driven sun visor 3 is between the first continuous conductor laser 1 and the first dichroic mirror 6；
Second electric driven sun visor 4 is between the second continuous conductor laser 2 and the first reflective mirror 5.
In the present embodiment, first electric driven sun visor 3 and the second electric driven sun visor 4 are by Electric control, packet
Containing state is opened/closed, it is mainly used for being switched on or off the path that excitation enters main optical path system；It should be noted that same
One moment had and only exciting light enters macroscopical spectroscopy unit 201 and the sight imaging unit 202 that is situated between all the way, at this time, it may be necessary to logical
It is continuous to the first continuous conductor laser 1 and the second semiconductor respectively to cross the first electric driven sun visor 3 and the second electric driven sun visor 4
The transmission optical path of the exciting light of laser 2 is switched on or off；Specifically, when the first electric driven sun visor 3 is opened, then second
Electric driven sun visor 4 is in close state, have and only the first continuous conductor laser 1 issue 488nm wavelength exciting light
Into macroscopical spectroscopy unit 201 and it is situated between and sees imaging unit 202, when the second electric driven sun visor 4 is in the open state, then first
Electric driven sun visor 3 is in close state, have and only the second continuous conductor laser 2 issue 650nm wavelength exciting light
Into macroscopical spectroscopy unit 201 and the sight imaging unit 202 that is situated between；Further, for microcosmic high-resolution imaging unit 203,
The exciting light of 488nm and 650nm wavelength is needed according to preset path while being entered, at this time, it may be necessary to open simultaneously the first electric gear
Tabula rasa 3 and the second electric driven sun visor 4, so that two kinds of exciting lights enter main optical path system simultaneously.
Referring to Fig. 3, Fig. 3 is the structural schematic diagram of macroscopical spectroscopy unit provided in an embodiment of the present invention；The macroscopic view
Spectroscopy unit 201 include: the second dichroic mirror 12, the first lens 13, the first fiber optic bundle 14, the first filter plate 15, second thoroughly
Mirror 16 and Fluorescence Spectrometer 17；
First Amici prism 8 is used to the first exciting light or the second exciting light being transmitted to the second dichroic mirror 12；
Second dichroic mirror 12 is used to the first exciting light or the second exciting light being transmitted to the first lens 13；
First lens 13 are used to the first exciting light of preset wavelength or the second exciting light being coupled into the first fiber optic bundle 14；
First fiber optic bundle 14 is used to for the first exciting light or the second exciting light being transmitted at fluorescent samples, and passes through the first light
The first fluorescence signal obtained after the first exciting light or the second exciting light excite fluorescent samples is collected in the port of fine beam 14, and will
The first fluorescence signal after collection is successively transmitted to the first fiber optic bundle 14, the first lens 13 and the second dichroic mirror 12；
Second dichroic mirror 12 is used to separate fluorescence signal with the first exciting light or the second exciting light, and glimmering by first
Optical signal total reflection is transmitted to the first filter plate 15；
First filter plate 15 is passed for the first fluorescence signal to be filtered, and by filtered first fluorescence signal
Transport to the second lens 16；
Second lens 16 are used to filtered first fluorescence signal being transmitted to Fluorescence Spectrometer 17, to obtain fluorescence spectrum
Figure.
In embodiments of the present invention, which is mainly used for the glimmering of macroscopical snoop tag nanoshell
The photoluminescence spectrum intensity of light spectral intensity and marking nano drug judges blood vessel by detecting obtained photoluminescence spectrum intensity macroscopic view
The concentration distribution situation of middle nanoshell and Nano medication.The basic functional principle of the channel light is as follows: before two-way laser
It is equipped with electric driven sun visor (the first electric driven sun visor 3SH1 and the second electric driven sun visor 4SH2), when SH1 is opened, SH2 should locate
(or SH1 is in close state when SH2 opening) in off position only swashs in macroscopical spectroscopy unit 201 all the way at this time
Luminous 488nm (or 650nm) exists, and exciting light reaches the second dichroic mirror 12 after the first Amici prism 8 (SP1) first
(DM2), then it is coupled in the first fiber optic bundle 14 (FB1 contains 3000 optical fiber) by the first lens 13 (L1), exciting light passes through
After realizing that the excitation to fluorescent samples, the port that the first fluorescence signal of generation passes through fiber optic bundle again are collected after first fiber optic bundle 14
It is returned at the second dichroic mirror 12 (DM2) along original optical path, the second dichroic mirror 12 (DM2) herein is primarily used to realize to excitation
The separation of optical signal and fluorescence signal, the fluorescence signal after separation are reflected to detection optical path, using the first filter plate 15
(F1) to the filtering of non-signal light, and the second lens 16 (L2) are transmitted to, finally enter Fluorescence Spectrometer 17 (SD), it is final to realize
Effective detection of photoluminescence spectrum intensity.The place that macroscopical spectroscopy unit 201 needs to pay attention to is that have two-way exciting light in channel
With two-way fluorescence, therefore in optical path the second dichroic mirror 12 (DM2) require it is very high, the second dichroic mirror 12 (DM2) must meet
To the total reflection of two kinds of wavelength of 520nm and 670nm in addition light will be detected simultaneously thoroughly to the full impregnated of two kinds of wavelength of 488nm and 650nm
The first filter plate 15 (F1) in road is rotating filtering piece group, and the band that wavelength is 520nm should be selected when wavelength of fluorescence is 520nm
Pass filter piece, if wavelength of fluorescence should select the band pass filter that wavelength is 670nm when being 670nm.
Referring to Fig. 4, Fig. 4 is the structural schematic diagram of the sight imaging unit provided in an embodiment of the present invention that is situated between；Jie sees imaging
Unit 202 includes: third dichroic mirror 18, the third lens 19, the second fiber optic bundle 20, lenticule component, the filter of the first object lens 24, second
Wave plate 25, the 4th lens 26 and multiplication imaging device 27；
Second Amici prism 10 is used to successively for the first exciting light or the second exciting light to be transmitted to third dichroic mirror 18 and the
Three lens 19；
The third lens 19 are used to the first exciting light of preset wavelength or the second exciting light being coupled into the second fiber optic bundle 20；
Second fiber optic bundle 20 is used to the first exciting light or the second exciting light being transmitted to lenticule component；
Lenticule component is for being adjusted the beam size of the first exciting light or the second exciting light, and by proper beam
The first exciting light or the second exciting light be transmitted to the first object lens 24；
First object lens 24 are used for transmission at the first exciting light or the second exciting light to fluorescent samples, and collect the first exciting light
Or second exciting light fluorescent samples are excited after obtained the second fluorescence signal, and by the second fluorescence signal after collection according to
It is secondary to be transmitted to lenticule component, the second fiber optic bundle 20, the second lens 16 and third dichroic mirror 18；
Third dichroic mirror 18 is for separating the second fluorescence signal with the first exciting light or the second exciting light, and by the
The total reflection of two fluorescence signals is transmitted to the second filter plate 25；
Second filter plate 25 is passed for being filtered to the second fluorescence signal, and by filtered second fluorescence signal
Transport to the 4th lens 26；
Filtered institute second is stated fluorescence signal and is transmitted to multiplication imaging device 27 by the 4th lens 26, is divided with obtaining being situated between seeing
Cloth image.
In the present embodiment, which sees imaging unit 202 and is mainly used for seeing micro-imaging to active somatic cell Jie, by aforementioned
Macroscopical spectroscopy unit 201 find the stronger target position of fluorescence signal (i.e. Nano medication or nanoshell aggregation compare
More places) after, then carry out real-time wide field Jie with the sight imaging unit 202 that is situated between and see imaging, observe drug in real time in the form of images
Distribution situation in the blood vessel, same excitation light source are also derived from two the first continuous conductor lasers of laser 1
(Laser1) and the second continuous conductor laser 2 (Laser2), when the first electric driven sun visor 3 (SH1) is opened, second is electronic
Light barrier 4SH2 should be in closed state (or when the second electric driven sun visor 4 (SH2) opening, at the first electric driven sun visor 3SH1
In closed state), only exciting light 488nm (or 650nm) exists all the way in macroscopical spectroscopy unit 201 at this time, laser
Enter the third lens 19 (L3) afterwards by third dichroic mirror 18 (DM3), the effect of the third lens 19L3 herein is exactly by exciting light
It is coupled in the second fiber optic bundle 20 (FB2 contains 10000 optical fiber), then by lenticule component (L5, L6 and L7) to passing through the
The light beam of two fiber optic bundle 20FB2 is adjusted, and the size of light beam is equal to the diameter of the pupil of the first object lens 24 (OBJ1), pupil
Diameter is 1cm, so that light beam is just full of the pupil of the first object lens 24 (OBJ1, diameter 1cm), it is made to give full play to the first object lens
24 performance finally reaches and excites fluorescence at fluorescent samples, obtains after the second fluorescence signal is collected by the first object lens 24 along original
After optical path returns to third dichroic mirror 18 (DM3), it is reflected to detection optical path, after the filtering of the second filter plate 25 (F2), is passed
The 4th lens 26 (L4) are transported to, and enters multiplication imaging device 27 (EMCCD) and carries out the sight micro-imaging that is situated between, to obtain macroscopical distribution
Figure.It should be noted that be situated between the third dichroic mirror 18 (DM3) selected in the optical path for seeing imaging unit 202 and macroscopical spectrum analysis
The second dichroic mirror 12 (DM2) in unit 201 is identical and rotating filtering piece group (F2) and macroscopical spectroscopy unit 201
In the first filter plate 15 (F1) be identical.
Further, lenticule component includes: the 5th lens 21, the 6th lens 22 and the 7th lens 23；
First exciting light or the second exciting light successively pass through the 5th lens 21, the 6th lens 22 and the 7th lens 23, to adjust
The beam size of whole first exciting light or the second exciting light.
In the present embodiment, the lenticule component seen in imaging unit 202 that is situated between is made of three lens, the lenticule component
Include: the 5th lens 21, the 6th lens 22 and the 7th lens 23, wherein the 6th lenticule is located at the 5th lenticule and the 7th micro-
Between lens, in the same size, the 5th lenticule, the 6th lenticule, of the 5th lenticule, the 6th lenticule, the 7th lenticule
The center of seven lenticules is located at same straight line, so that the 5th lenticule, the 6th lenticule, the 7th lenticule successively bracketing settings,
To realize the adjustment to the beam size of the first exciting light or the second exciting light so that the light beam of exciting light just with the first object lens
24 pupil size is consistent, so that the performance of the first object lens 24 is not fully exerted and utilizes.
Referring to Fig. 5, Fig. 5 is the structural schematic diagram of microcosmic high-resolution imaging unit provided by the embodiments of the present application；This is micro-
See high-resolution imaging unit 203 include: the 4th dichroic mirror 28, the 5th dichroic mirror 29, the 6th dichroic mirror 30, galvanometer 31,4F system,
Second object lens 34, third fiber optic bundle 35, the 8th lens 36, self-focusing lens 37, third filter plate 38, the 9th lens 39, first
Multimode fibre 40, the first photomultiplier tube 41, the 4th filter plate 42, the tenth lens 43, the second multimode fibre 44, the second photoelectricity times
Increase pipe 45, the 5th filter plate 46, the 11st lens 47, third multimode fibre 48 and third photomultiplier tube 49；
Third Amici prism is used to for the first exciting light and the second exciting light being successively transmitted to the 4th dichroic mirror 28, the simultaneously
Five dichroic mirrors 29, the 6th dichroic mirror 30 and galvanometer 31；
Galvanometer 31 is used to the first exciting light and the second exciting light carrying out light beam scanning, to obtain scanning light beam, and will sweep
Beam Propagation is retouched to 4F system；
4F system is used to adjust the beam size of scanning light beam, and scanning light beam adjusted is transmitted to the second object lens
34；
Second object lens 34 are used to scanning light beam being coupled into third fiber optic bundle 35；
Third fiber optic bundle 35 is used to scanning light beam being transmitted to the 8th lens 36；
8th lens 36 are used to scanning light beam being coupled into self-focusing lens 37；
Self-focusing lens 37 for scanning light beam to be transmitted at fluorescent samples, and collect scanning light beam to fluorescent samples into
The third fluorescence signal obtained after row excitation, and third fluorescence signal is reversely successively transmitted to the 8th lens 36, third optical fiber
Beam 35, the second object lens 34,4F system, galvanometer 31, the 6th dichroic mirror 30, the 5th dichroic mirror 29 and the 4th dichroic mirror 28；
Wherein, the 4th dichroic mirror 28 is used for by isolated 4th fluorescence signal of third fluorescence signal, and to the 4th fluorescence
Signal, which is totally reflected, is successively transmitted to third filter plate 38, the 9th lens 39, the first multimode fibre 40 and the first photomultiplier transit
Pipe 41, to obtain cell membrane distribution map；
Wherein, the 5th dichroic mirror 29 is used for by isolated 5th fluorescence signal of third fluorescence signal, and to the 5th fluorescence
Signal, which is totally reflected, is successively transmitted to the 4th filter plate 42, the tenth lens 43, the second multimode fibre 44 and the second photomultiplier transit
Pipe 45, to obtain Nano medication distribution map；
Wherein, the 6th dichroic mirror 30 is used for by isolated 6th fluorescence signal of third fluorescence signal, and to the 6th fluorescence
Signal, which is totally reflected, is successively transmitted to the 5th filter plate 46, the 11st lens 47, third multimode fibre 48 and third photoelectricity times
Increase pipe 49, to obtain Nano medication distribution map.
In embodiments of the present invention, which is high-resolution based endoscopic imaging channel, is seen by being situated between
After Jie of imaging unit 202 sees micro-imaging, macroscopical distribution map of available Nano medication or nanoshell, since macroscopic view is distributed
The resolution ratio of figure is lower, can not see more structural informations, therefore, need to further choose the second target position, then utilize
Microcosmic high-resolution imaging unit 203 carries out high-resolution imaging to the second target position；Have in the microcosmic high-resolution imaging unit 203
Two excitation light paths and three detection optical paths, wherein the first exciting light of a length of 488nm of two-way exciting light medium wave excites two simultaneously
Kind fluorescent dye: the fluorescent dye FITC of the targeted nano shell and fluorescent dye DIO of target cell membrane dyestuff, and wavelength is
The second exciting light of 650nm is then the Cy5 line fluorescent dyestuff for exciting targeted nano drug, and two-way light is reflective by second
After mirror 11 (M2) reflection, pass sequentially through jointly the 4th dichroic mirror 28, the 5th dichroic mirror 29 and the 6th dichroic mirror 30 (DM4, DM5 and
DM6), then arrive at galvanometer 31 (GM) and carry out light beam scanning, into the 12nd lens 32 (L12) and the 13rd lens 33 (L13)
The 4f system of composition enters the second object lens 34 (OBJ2) after being adjusted to scanning light beam, and the second object lens 34 herein mainly will
Scanning light beam was coupled in third fiber optic bundle 35 (FB3 contains >=30000), was existed by the scanning light beam after third fiber optic bundle 35
It is coupled in the self-focusing lens 37 (GRIN Lens) of refractive index gradient variation by the 8th lens 36 (L8), passes through self-focusing
Lens 37 realize that the scanning to fluorescent samples excites, and the third fluorescence signal of generation passes through self-focusing lens 37 again and collects along former light
Road returns；
In this embodiment, it is by wavelength that microcosmic tri- tunnel 203 Zhong of high-resolution imaging unit detection optical path, which is respectively as follows: the first,
The 6th fluorescence signal for the fluorescent dye FITC of the first excitation targeted nano shell of 488nm, generation returns to the 6th
It is reflected to detection optical path after dichroic mirror 30 (DM6), the 11st is entered after the 5th filter plate 46 (F5) filters non-signal light
Lens 47 (L11), are coupled in third multimode fibre 48 (DMF3) after being focused by the 11st lens 47, third multimode here
Optical fiber 48 can also play the role of aperture not only with communicating optical signals, filter the stray light around focal spot to reach raising figure
Then six fluorescence signals with high resoluting information are imported into third by third multimode fibre 48 by the target of the resolution ratio of picture
The conversion that photosignal is realized in photomultiplier tube 49 (PMT3), the acquisition of image is realized finally by imaging software；Specifically,
6th dichroic mirror 30 by third fluorescence signal the first exciting light and the second exciting light separate, with obtain comprising first swash
The 6th luminous fluorescence signal, and the refraction of the 6th fluorescence signal is transmitted to the 5th filter plate 46, the 5th filter plate 46 is by the 6th
Fluorescence signal is filtered, and filtered 6th fluorescence signal is transmitted to the 11st lens 47, the 11st lens 47
Filtered institute the 6th is stated into fluorescence signal and is coupled into third multimode fibre 48, third multimode fibre 48 is used to believe the 6th fluorescence
It number is filtered, to obtain the 6th fluorescence signal of high-resolution, and the 6th fluorescence signal of high-resolution is transmitted to third photomultiplier transit
Pipe 49, third photomultiplier tube 49 are used to the 6th fluorescence signal of high-resolution carrying out photoelectric signal transformation, to obtain nanoshell point
Butut；
Meanwhile second is produced by the fluorescent dye DIO for the first excitation target cell membrane that wavelength is 488nm
The 4th raw fluorescence signal returns to the 4th dichroic mirror 28 (DM4) by collecting, and is reflected into detection by the 4th dichroic mirror 28 (DM4)
Optical path by the filtering of the 4th filter plate 42 (F4), and is transmitted to the tenth lens 43 (L10), and the tenth lens 43 are by the 4th fluorescence
Signal is coupled in the first multimode fibre 40 (DMF1), then after the first photomultiplier tube 41 (PMT1) carries out photoelectric conversion
Import the acquisition that imaging software realizes high-resolution fluorescence signal image；Specifically, the 4th dichroic mirror 28 will be in third fluorescence signal
The first exciting light and the second exciting light separated, to obtain the 4th fluorescence signal comprising the first exciting light, and by the 4th
Fluorescence signal refraction is transmitted to third filter plate 38, and the 4th fluorescence signal is filtered by third filter plate 38, and incited somebody to action
The 4th fluorescence signal after filter is transmitted to the 9th lens 39, and filtered institute the 4th is stated fluorescence signal and is coupled by the 9th lens 39
First multimode fibre 40, the first multimode fibre 40 is for being filtered the 4th fluorescence signal, to obtain the 4th fluorescence of high-resolution
Signal, and the 4th fluorescence signal of high-resolution is transmitted to the first photomultiplier tube 41, the first photomultiplier tube 41 is used for high score
Distinguish that the 4th fluorescence signal carries out photoelectric signal transformation, to obtain cell membrane distribution map；
The third is produced by the Cy5 line fluorescent dyestuff for the second excitation targeted nano drug that wavelength is 650nm
The 5th raw fluorescence signal returns to the 5th dichroic mirror 29 (DM5) after collecting, and is reflected into detection optical path by the 5th dichroic mirror 29,
Enter the tenth lens 43 (L10) after the 4th filter plate 42 (F4) is to the filtering processing of non-signal light, the tenth lens 43 are by the
Five fluorescence signals are coupled in the second multimode fibre 44 (DMF2), then carry out photoelectricity by the second photomultiplier tube 45 (PMT2)
The acquisition that imaging software realizes high-resolution fluorescence signal image is imported after conversion；Specifically, the 5th dichroic mirror 29 is by third fluorescence
The first exciting light and the second exciting light in signal are separated, to obtain the 5th fluorescence signal comprising the second exciting light, and
The refraction of 5th fluorescence signal is transmitted to the 4th filter plate 42, the 5th fluorescence signal is filtered by the 4th filter plate 42,
And filtered 5th fluorescence signal is transmitted to the tenth lens 43, filtered institute the 5th is stated fluorescence signal by the tenth lens 43
It is coupled into the second multimode fibre 44, the second multimode fibre 44 is for being filtered the 5th fluorescence signal, to obtain high-resolution the
Five fluorescence signals, and the 5th fluorescence signal of high-resolution is transmitted to the second photomultiplier tube 45, the second photomultiplier tube 45 is used for
The 5th fluorescence signal of high-resolution is subjected to photoelectric signal transformation, to obtain Nano medication distribution map；
In embodiments of the present invention, available by three detection optical paths of above-mentioned microcosmic high-resolution imaging unit 203
Fluorescence distribution image, the fluorescence distribution figure of nanoshell and the distribution map of cell membrane of Nano medication, and by real-time monitoring this
The variation of three kinds of images can effectively study the cross-film process of nanoshell, the leakage of Nano medication and control release characteristics.
Further, 4F system includes: the 12nd lens 32 and the 13rd lens 33；
First exciting light and the second exciting light are transmitted from the 12nd lens 32 to the 13rd lens 33, with the first excitation of adjustment
The beam size of light and the second exciting light.
In the present embodiment, which includes 4F system, and the 4F system is by the 12nd lens 32
It is formed with the 13rd lens 33, wherein galvanometer 31 (GM) of the 12nd lens 32 in microcosmic high-resolution imaging unit 203,
Second object lens 34 of 13rd lens 33 in microcosmic high-resolution imaging unit 203, the first exciting light and the second exciting light are same
When enter in microcosmic high-resolution imaging unit 203, after coming out from the transmission of galvanometer 31, first reach the 12nd lens 32, then by the
12 lens 32 are transmitted to the 13rd lens 33, and are continued to be transmitted to the second object lens 34, further, 4F by the 13rd lens 33
System can be adjusted the beam size of the first exciting light and the second exciting light, so that light beam adjusted is just with
The pupil size of two object lens 34 is consistent, gives full play to the performance of the second object lens 34；Further, 4F system can be also used for pair
The image planes of imaging are translated, to obtain suitable image planes position, to obtain high-resolution imaging image planes.
A kind of fluorescent endoscopic imgaing system across scale provided by the invention, system include: lighting unit and micro-imaging
Unit；Wherein, micro-imaging unit includes: macroscopical spectroscopy unit, is situated between and sees imaging unit and microcosmic high-resolution imaging unit；
Lighting unit is for the first exciting light of transmitting and/or the second exciting light, and the first exciting light and/or the second exciting light are transmitted to
Macroscopical spectroscopy unit is situated between and sees imaging unit and microcosmic high-resolution imaging unit；Macroscopical spectroscopy unit for obtain into
The first fluorescence signal that the first exciting light or the second excitation nanoshell and Nano medication penetrated generate, and it is glimmering according to first
Optical signal generates the fluorescence spectra of nanoshell and Nano medication；Being situated between, it is incident for being obtained based on fluorescence spectra to see imaging unit
The first exciting light or the second fluorescence signal for generating of the second excitation nanoshell and Nano medication, and according to the second fluorescence
Jie of signal acquisition nanoshell and Nano medication sees distributed image；Microcosmic high-resolution imaging unit is used to see distributed image based on being situated between
The third fluorescence signal of incident the first exciting light and the second excitation nanoshell and Nano medication is obtained, and according to third
Fluorescence signal carries out high-resolution imaging, to obtain the nanometer for observing Nano medication cross-film, leakage and control release in real time
Drug fluorogram, nanoshell fluorogram and cell membrane distribution map；The system by Nano medication fluorogram, nanoshell fluorogram and
The realization of cell membrane distribution map is monitored intracellular drug transport, and realizes the cell medicine generation in living animal deep tissues
Dynamical Characteristics.
In several embodiments provided herein, it should be understood that disclosed system, it can be by others side
Formula is realized.For example, constructive embodiment described above is only schematical, for example, the connection of " optical fibre device ", only
Only a kind of logic function connection type is practical to have other connection type, such as multiple identical devices when realizing
Or component can be combined or can be integrated into another system, or some features can be ignored or not executed.Another point, institute
Display or the mutual coupling, direct-coupling or communication connection discussed can be through some interfaces, can also be other
Form.
In addition, each function " optical fibre device " in each embodiment of the present invention can integrate in a system, it can also
To be that the function integrated device for separately constituting a part exists, or two or more integrating devices.Above-mentioned collection
It both can take the form of hardware realization at device, it can also be real using the form of software, the function integrated device of combination of hardware
It is existing.
It should be noted that for the various method embodiments described above, describing for simplicity, therefore, it is stated as a series of
Combination of actions, but those skilled in the art should understand that, the present invention is not limited by the sequence of acts described because
According to the present invention, certain steps can use other sequences or carry out simultaneously.Secondly, those skilled in the art should also know
It knows, the embodiments described in the specification are all preferred embodiments, and related actions and modules might not all be this hair
Necessary to bright.
In the above-described embodiments, it all emphasizes particularly on different fields to the description of each embodiment, there is no the portion being described in detail in some embodiment
Point, it may refer to the associated description of other embodiments.
The above are to a kind of description of the generation system of high energy dissipation orphan resonance rectangle pulse provided by the present invention,
For those skilled in the art, thought according to an embodiment of the present invention, has in specific embodiments and applications
Change place, to sum up, the contents of this specification are not to be construed as limiting the invention.
Claims (8)
1. a kind of fluorescent endoscopic imgaing system across scale, which is characterized in that the system comprises: lighting unit and micro-imaging
Unit；
Wherein, it includes: macroscopical spectroscopy unit that the micro-imaging unit is macro, is situated between and sees imaging unit and microcosmic high-resolution imaging
Unit；
The lighting unit is for emitting the first exciting light and/or the second exciting light, and by first exciting light and/or described
Second exciting light is transmitted separately to macroscopical spectroscopy unit, gives an account of and see imaging unit and the microcosmic high-resolution imaging
Unit；
The macroscopic view spectroscopy unit is used to obtain incident first exciting light or second excitation fluorescence sample
The first fluorescence signal that product generate, and according to the fluorescence spectra of first fluorescence signal generation fluorescent samples；
It gives an account of and sees imaging unit for swashing based on incident first exciting light of fluorescence spectrum acquisition or described second
The second fluorescence signal that the excitation fluorescent samples that shine generate, and the fluorescent samples are obtained according to second fluorescence signal
Jie see distributed image；
The microcosmic high-resolution imaging unit be used for based on give an account of see distributed image obtain incident first exciting light and
Fluorescent samples third fluorescence signal described in second excitation, and high-resolution is carried out according to the third fluorescence signal
Imaging, to obtain Nano medication fluorogram, nanoshell fluorogram and the cell membrane distribution for observing the fluorescent samples in real time
Figure.
2. a kind of fluorescent endoscopic imgaing system across scale as described in claim 1, which is characterized in that the lighting unit packet
It includes: light source assembly and main optical path system；
The light source assembly includes: the first continuous conductor laser and the second continuous conductor laser；
The main optical path system includes: the first reflective mirror, the first dichroic mirror, the first adjusting slide, the first Amici prism, the second tune
Save slide, the second Amici prism and the second reflective mirror；
First exciting light that first continuous conductor laser issues successively passes through first dichroic mirror, described the
One adjusts slide, first Amici prism, described second adjusts slide, second Amici prism and described second reflective
Mirror；
Second exciting light that second continuous conductor laser issues successively passes through first reflective mirror, described the
One dichroic mirror, described first adjust slide, first Amici prism, the second adjusting slide, second Amici prism
And second reflective mirror；
Wherein, first Amici prism is used to for first exciting light or second exciting light light splitting being transmitted to described macro
Spectroscopy unit is seen, and first exciting light or second exciting light are successively transmitted to described second and adjust slide；
Wherein, second Amici prism is used to that first exciting light or second exciting light light splitting to be transmitted to and be given an account of
Imaging unit is seen, and first exciting light or second exciting light are transmitted to second reflective mirror；
Wherein, second reflective mirror is used to first exciting light and second exciting light being transmitted to the microcosmic high score
Distinguish imaging unit.
3. a kind of fluorescent endoscopic imgaing system across scale as claimed in claim 2, which is characterized in that the light source assembly also wraps
It includes: the first electric driven sun visor and the second electric driven sun visor；
First electric driven sun visor is between first continuous conductor laser and first dichroic mirror；
Second electric driven sun visor is between second continuous conductor laser and first reflective mirror.
4. a kind of fluorescent endoscopic imgaing system across scale as claimed in claim 2, which is characterized in that the macroscopic view spectrum analysis
Unit includes: the second dichroic mirror, the first lens, the first fiber optic bundle, the first filter plate, the second lens and Fluorescence Spectrometer；
First Amici prism is used to first exciting light or second exciting light being transmitted to second dichroic mirror；
Second dichroic mirror is used to first exciting light or second exciting light being transmitted to first lens；
First lens are used to first exciting light of preset wavelength or second exciting light being coupled into described first
Fiber optic bundle；
First fiber optic bundle is used to for first exciting light or second exciting light being transmitted at fluorescent samples, and passes through
First exciting light or second exciting light are collected to obtaining after fluorescent samples excitation in the port of first fiber optic bundle
First fluorescence signal, and first fluorescence signal after collection is successively transmitted to first fiber optic bundle, described first thoroughly
Mirror and second dichroic mirror；
Second dichroic mirror is used to separate the fluorescence signal with first exciting light or second exciting light,
And first fluorescence signal total reflection is transmitted to first filter plate；
First filter plate is for first fluorescence signal to be filtered, and by filtered first fluorescence
Signal is transmitted to second lens；
Second lens are used to filtered first fluorescence signal being transmitted to the Fluorescence Spectrometer, to obtain fluorescence
Spectrogram.
5. a kind of fluorescent endoscopic imgaing system across scale as claimed in claim 3, which is characterized in that given an account of sight imaging unit
Include: third dichroic mirror, the third lens, the second fiber optic bundle, lenticule component, the first object lens, the second filter plate, the 4th lens and
Double imaging device；
Second Amici prism is used to successively for first exciting light or second exciting light to be transmitted to the third double
Look mirror and the third lens；
The third lens are used to first exciting light of preset wavelength or second exciting light being coupled into described second
Fiber optic bundle；
Second fiber optic bundle is used to first exciting light or second exciting light being transmitted to the lenticule component；
The lenticule component is used to be adjusted the beam size of first exciting light or second exciting light, and will
First exciting light or second exciting light of proper beam are transmitted to first object lens；
First object lens are used for transmission at first exciting light or second exciting light to fluorescent samples, and described in collection
The second fluorescence signal that first exciting light or second exciting light obtain after exciting to the fluorescent samples, and will collect
Second fluorescence signal afterwards is successively transmitted to the lenticule component, second fiber optic bundle, second lens and institute
State third dichroic mirror；
The third dichroic mirror is used to carry out second fluorescence signal and first exciting light or second exciting light
Separation, and second fluorescence signal total reflection is transmitted to second filter plate；
Second filter plate is for being filtered second fluorescence signal, and by filtered second fluorescence
Signal is transmitted to the 4th lens；
Filtered institute second is stated fluorescence signal and is transmitted to the multiplication imaging device by the 4th lens, is divided with obtaining being situated between seeing
Cloth image.
6. a kind of fluorescent endoscopic imgaing system across scale as claimed in claim 5, which is characterized in that the lenticule component packet
Contain: the 5th lens, the 6th lens and the 7th lens；
First exciting light or second exciting light successively pass through the 5th lens, the 6th lens and the described 7th
Lens, to adjust the beam size of first exciting light or second exciting light.
7. a kind of fluorescent endoscopic imgaing system across scale as claimed in claim 3, which is characterized in that the microcosmic high-resolution at
As unit include: the 4th dichroic mirror, the 5th dichroic mirror, the 6th dichroic mirror, galvanometer, 4F system, the second object lens, third fiber optic bundle,
8th lens, self-focusing lens, third filter plate, the 9th lens, the first multimode fibre, the first photomultiplier tube, the 4th filtering
Piece, the tenth lens, the second multimode fibre, the second photomultiplier tube, the 5th filter plate, the 11st lens, third multimode fibre and
Third photomultiplier tube；
The third Amici prism is used to for first exciting light and second exciting light being successively transmitted to described the simultaneously
Four dichroic mirrors, the 5th dichroic mirror, the 6th dichroic mirror and the galvanometer；
The galvanometer is used to first exciting light and second exciting light carrying out light beam scanning, to obtain scanning light beam,
And the scanning light beam is transmitted to the 4F system；
The 4F system is used to adjust the beam size of the scanning light beam, and scanning light beam adjusted is transmitted to described the
Two object lens；
Second object lens are used to the scanning light beam being coupled into the third fiber optic bundle；
The third fiber optic bundle is used to the scanning light beam being transmitted to the 8th lens；
8th lens are used to the scanning light beam being coupled into the self-focusing lens；
The self-focusing lens is used to for the scanning light beam being transmitted at fluorescent samples, and collects the scanning light beam to fluorescence
The third fluorescence signal that sample obtains after being excited, and the third fluorescence signal is reversely successively transmitted to the described 8th thoroughly
It is mirror, the third fiber optic bundle, second object lens, the 4F system, the galvanometer, the 6th dichroic mirror, 5th pair described
Look mirror and the 4th dichroic mirror；
Wherein, the 4th dichroic mirror is used for isolated 4th fluorescence signal of the third fluorescence signal, and to described the
Four fluorescence signals be totally reflected successively be transmitted to the third filter plate, the 9th lens, first multimode fibre and
First photomultiplier tube, to obtain cell membrane distribution map；
Wherein, the 5th dichroic mirror is used for isolated 5th fluorescence signal of the third fluorescence signal, and to described the
Five fluorescence signals be totally reflected successively be transmitted to the 4th filter plate, the tenth lens, second multimode fibre and
Second photomultiplier tube, to obtain Nano medication distribution map；
Wherein, the 6th dichroic mirror is used for isolated 6th fluorescence signal of the third fluorescence signal, and to described the
Six fluorescence signals, which are totally reflected, is successively transmitted to the 5th filter plate, the 11st lens, the third multimode fibre
And the third photomultiplier tube, to obtain Nano medication distribution map.
8. a kind of fluorescent endoscopic imgaing system across scale as described in claim 1, which is characterized in that the 4F system includes:
12nd lens and the 13rd lens；
First exciting light and second exciting light are from the 12nd lens to the 13rd lens transmission, with adjustment
The beam size of first exciting light and second exciting light.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910794851.0A CN110464309B (en) | 2019-08-27 | 2019-08-27 | Cross-scale fluorescence endoscopic imaging system |
Applications Claiming Priority (1)
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