CN110221051A - A kind of double scale nanometer drug detection in vivo systems of dual wavelength and sequential control method - Google Patents
A kind of double scale nanometer drug detection in vivo systems of dual wavelength and sequential control method Download PDFInfo
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Abstract
The invention discloses a kind of double scale nanometer drugs of dual wavelength in physical examination examining system and sequential control method, system includes: the laser that wavelength is 488nm, wavelength is the laser of 650nm, 488nm laser shutter, 650nm laser shutter, first reflective mirror, first dichroic mirror, half slide, Amici prism, first liquid crystal tunable filter, first liquid crystal tunable filter controller, Fluorescence Spectrometer, Optic transmission fiber beam, second liquid crystal tunable filter, second liquid crystal tunable filter controller, electron multiplication CCD, image-carrying fiber bundle, small-sized microcobjective and PC host computer；Method orderly carries out the detection of different fluorescent samples while guaranteeing the durability of system, provides guarantee for the correct processing of later period fluorescence data.
Description
Technical field
The present invention relates to Nano medication technical field of medical detection, the double scale nanometer drugs of especially a kind of dual wavelength are in body
Monitoring system and sequential control method.
Background technique
Nano medication is the nanoparticle in pharmacy, has very big surface area, compared with ordinary preparation, chemical activity
Height, effect is strong, and infiltration rate is fast.Since the size of nanometer reagent is minimum, the penetration capacity in organism is strong, with material appropriate
The nanometer formulation of material and technique production, is adjusted the distribution of drug in vivo.Therefore the stability of drug can be improved in Nano medication
And circulation time, enhancing targeting absorbability improve drug distribution and metabolic process.
Nano medication becomes the hot spot of drug research with its distinctive advantage, but its clinical transformation efficiency is extremely low, basic former
Because being a lack of the druggability appraisement system of preclinical system.Nano medication fluorochromine is reflected by detecting fluorescence
Stability, targeting and the metabolic process etc. of Nano medication in vivo are the evaluation most common methods of Nano medication drug effect.Usually
Using marking nanos shells such as dyestuff FITC (ex/em:480nm/520nm), the Tissue distribution of nanoshell is observed, discloses Nano medication
Targeting Effect；Drug labelling is carried out with cy5 serial (ex/em:650/670nm), leakage and the control release for observing drug are special
Property.Fluorescence is mainly detected by histotomy at present, the method is primarily present following problems: on the one hand can not be in same animal
The overall data of All Time point is obtained in vivo, and different experiments interindividual variation is larger, can not carry out dynamic to animal pattern
Observation in real time, it is desirable to which the data for obtaining difference can only remake histotomy, and histotomy could be into after needing to handle animal
Row, obtained experimental result are not necessarily the true situation of living animal；On the other hand fluorescent dye is detected by histotomy
Method scale it is more single, the distribution situation of Nano medication within the organization can only be obtained, Nano medication can not be obtained in blood
In dynamic change.
Traditional Nano medication is surveyed in physical examination and is generally realized using the method for radio nuclide imaging, this method spatial resolution
It is low, can only observe Nano medication in animal body certain organ radioactivity aggregation.Furthermore a radio nuclide imaging experiment can only be examined
A kind of radioactive element is surveyed, cannot achieve the detection of nanoshell and medical separation situation, therefore the leakage and control of drug can not be analyzed
The characteristics such as system release.
Summary of the invention
Technical problem to be solved by the present invention lies in provide a kind of double scale nanometer drug detection in vivo systems of dual wavelength
And sequential control method keeps two submodules orderly to the detection of different fluorescent samples while guaranteeing the durability of system
It carries out, provides guarantee for the correct processing of later period fluorescence data.
In order to solve the above technical problems, the present invention provides a kind of double scale nanometer drug detection in vivo systems of dual wavelength, packet
It includes: laser 2 that laser 1 that wavelength is 488nm, wavelength are 650nm, 488nm laser shutter 3,650nm laser shutter
5, the first reflective mirror 7, the first dichroic mirror 8, half slide 9, Amici prism 10, the first liquid crystal tunable filter 12,
One liquid crystal tunable filter controller 13, Fluorescence Spectrometer 15, Optic transmission fiber beam 17, the second liquid crystal tunable filter 20,
On second liquid crystal tunable filter controller 21, electron multiplication CCD23, image-carrying fiber bundle 25, small-sized microcobjective 29 and PC
Position machine 30；Wherein: the laser 2 that the laser 1 and wavelength that wavelength is 488nm are 650nm excites corresponding nanoshell and drug
Two kinds of fluorescent dyes enter main optical path using the laser that the first reflective mirror 7 and the first dichroic mirror 8 issue two lasers
In, the exciting light that 488nm laser shutter 3 and 650nm laser shutter 5 jointly control only one wavelength in main optical path is deposited
, and be applied in combination by half slide 9 and Amici prism 10 and assign to laser in two submodules of system；First
Submodule changes from the angle monitor plasma drug level of macroscopic view, using Optic transmission fiber beam 17, the first liquid crystal tunable filter
12 and Fluorescence Spectrometer 15, the first liquid crystal tunable filter controller 13 and Fluorescence Spectrometer 15 pass through USB and PC host computer
30 are connected, and host computer can supervise in place respectively according to timing control laser shutter, liquid crystal tunable filter and Fluorescence Spectrometer
The fluorescence signal of drug and the fluorescence signal of marking nano carrier in toy Major Vessels are surveyed, reflects drug in blood in real time
Macroscopical metabolic condition and stability；Second submodule from microcosmic angle in institutional framework fluorescence carry out it is micro- at
Picture, using image-carrying fiber bundle 25, small-sized microcobjective 29, the second liquid crystal tunable filter 20 and electron multiplication CCD23, second
Liquid crystal tunable filter controller 21 is connected with electron multiplication CCD23 by USB with PC host computer 30, and host computer is according to timing
Laser shutter, liquid crystal tunable filter and electron multiplication CCD, PC host computer 30 are controlled by electron multiplication CCD23 acquisition time
Two images add pseudo- color and be fused together, nano-carrier fluorescence signal and packet in toy certain organs can be detected in place
The drug fluorescence signal wrapped up in, from enrichment, distribution, leakage and tissue damage of the micro-scale analysis Nano medication in metabolic organ
Situation can realize the orderly progress of two submodules acquisition by the timing control of PC host computer.
Preferably, 488nm laser shutter 3 and 650nm laser shutter 5 are the list with highly sensitive and response time
Chip optical shutter, switch activator time are only 4.08ms.
Preferably, Fluorescence Spectrometer 15 is marine optics QEPro, and electron multiplication CCD23 is ANDOR iXon Life.
Preferably, image-carrying fiber bundle 25 has 30000 optical fiber.
Preferably, Optic transmission fiber beam 17 include quartzy protection zone 31, stainless steel probe 32, handle 33, fiber optic splitter 34,
Incident optical 35 and receive optical fiber 36；Quartzy protection zone 31 includes one in stainless steel probe 32 and enters before stainless steel probe 32
It penetrates optical fiber and the six roots of sensation receives optical fiber, incident light fibril and receive optical fiber and be divided into incident optical 35 in fiber optic splitter 34
With receive optical fiber 36.
Correspondingly, a kind of sequential control method of the double scale nanometer drug detection in vivo systems of dual wavelength, including walk as follows
It is rapid:
(1) start to inject in Nano medication to animal body in experiment, then start to monitor fluorescence signal；
(2) in a sampling period, plasma drug level monitoring submodule first works, and 488nm laser shutter 3 is beaten
It opens, 650nm laser shutter 5 is closed, and the setting of the first liquid crystal tunable filter 12 is 520nm, Fluorescence Spectrometer by wavelength
The fluorescence intensity of nanoshell in 15 operation detection blood plasma；After the completion of the fluorescence intensity detection of nanoshell in blood plasma, 488nm swashs
Light device shutter 3 is closed, and 650nm laser shutter 5 is opened, and it is 670nm, fluorescence that wavelength, which is arranged, in the first liquid crystal tunable filter 12
The fluorescence intensity of Nano medication in 15 operation detection blood plasma of spectrometer；
(3) after the completion of the detection of plasma drug level monitoring submodule, institutional framework drug distribution monitors submodule BOB(beginning of block) work
Make；488nm laser shutter 3 is closed first, and 650nm laser shutter 5 is opened, and the setting of the second liquid crystal tunable filter 20 is logical
Crossing wavelength is 670nm, and electron multiplication CCD23 work carries out micro-imaging to the fluorescence of Nano medication in tissue and observes its distribution feelings
Condition, then 488nm laser shutter 3 is opened, and 650nm laser shutter 5 is closed, and the setting of the second liquid crystal tunable filter 20 is logical
Crossing wavelength is 520nm, and electron multiplication CCD23 work carries out micro-imaging to the fluorescence of nanoshell in tissue and observes its distribution feelings
Condition；After the completion of one sampling period detection, according to the sample frequency of setting, next sampling period is waited for.
Preferably, the liquid crystal tunable filter response time is less than 40ms, and when the response of common optical filter conversioning wheel
Between generally be greater than 1s, liquid crystal tunable filter and be not present mechanical wear.
It is received in All Time point blood vessel in same animal body the invention has the benefit that the present invention can be acquired in body
The concentration distribution situation of rice shell and drug, and to nanoshell in tissue and drug micro-imaging, to observe its distribution situation in real time,
By the pharmacodynamic characteristics of both dimensional analysis Nano medications, foundation is provided for the clinical use of Nano medication；It can arbitrarily more
Sampled point is changed, traditional histotomy is overcome and observes cumbersome problem；Liquid crystal tunable filter is different from common optical filtering
Piece conversioning wheel, the response time that the response time is less than 40ms and common optical filter conversioning wheel are generally greater than 1s, liquid crystal tunable
Mechanical wear is not present in humorous optical filter, more stable in the use of long-time high load capacity；Host computer uses timing control laser
Device shutter, liquid crystal tunable filter, Fluorescence Spectrometer and electron multiplication CCD, since laser shutter and liquid crystal tunable are filtered
The response time of light device is all extremely short, therefore fluorescence can be overcome in body acquisition, is acquired due to caused by the factors such as subject breathing
The problem of point drift, to more accurately be fused together the fluorescence data of two different wave lengths.
Detailed description of the invention
Fig. 1 is system structure diagram of the invention.
Fig. 2 is Optic transmission fiber beam structural schematic diagram of the invention.
Fig. 3 is Optic transmission fiber beam probe section enlarged diagram of the invention.
Fig. 4 is incident optical section enlarged diagram of the invention.
Fig. 5 receives fiber cross-sections enlarged diagram for of the invention.
Fig. 6 is that different fluorescent sample different scales of the invention monitor time diagram.
Fig. 7 is device action time diagram of the invention.
Wherein, 1, the laser that wavelength is 488nm；2, wavelength is the laser of 650nm；3,388nm laser shutter；4,
488nm laser shutter controller；5,650nm laser shutter；6,650nm laser shutter controller；7, the first reflective mirror；
8, the first dichroic mirror；9, half slide；10, Amici prism；11, the second dichroic mirror；12, the first liquid crystal tunable filters
Device；13, the first liquid crystal tunable filter controller；14, the first lens；15, Fluorescence Spectrometer；16, the second lens；17, it passes
Light fiber optic bundle；18, the second reflective mirror；19, third dichroic mirror；20, the second liquid crystal tunable filter；21, the second liquid crystal tunable
Humorous control device of the light filter；22, the third lens；23, electron multiplication CCD；24, the 4th lens；25, image-carrying fiber bundle；26, the 5th thoroughly
Mirror；27, the 6th lens；28, the 7th lens；29, small-sized microcobjective；30, PC host computer；31, quartzy protection zone；32, stainless
Steel probe；33, handle；34, fiber optic splitter；35, incident optical；36, receive optical fiber.
Specific embodiment
As shown in Figure 1, a kind of double scale nanometer drug detection in vivo systems of dual wavelength, comprising: wavelength is the laser of 488nm
Device 1, laser 2,488nm laser shutter 3, the 488nm laser shutter controller 4,650nm laser that wavelength is 650nm
Shutter 5,650nm laser shutter controller 6, the first reflective mirror 7, the first dichroic mirror 8, half slide 9, Amici prism
10, the second dichroic mirror 11, the first liquid crystal tunable filter 12, the first liquid crystal tunable filter controller 13, the first lens
14, Fluorescence Spectrometer 15, the second lens 16, Optic transmission fiber beam 17, the second reflective mirror 18, third dichroic mirror 19, the second liquid crystal can
Tunable filter 20, the second liquid crystal tunable filter controller 21, the third lens 22, electron multiplication CCD23, the 4th lens
24, image-carrying fiber bundle 25, the 5th lens 26, the 6th lens 27, the 7th lens 28, small-sized microcobjective 29 and PC host computer 30；
Wherein: the laser 2 that the laser 1 and wavelength that wavelength is 488nm are 650nm excites two kinds of fluorescence of corresponding nanoshell and drug
Coloring agent is entered in main optical path using the laser that the first reflective mirror 7 and the first dichroic mirror 8 issue two lasers, and 488nm swashs
The exciting light that light device shutter 3 and 650nm laser shutter 5 jointly control only one wavelength in main optical path exists, and passes through two
/ mono- slide 9 and Amici prism 10, which are applied in combination, assigns to laser in two submodules of system；First submodule is from macro
The angle monitor plasma drug level of sight changes, using Optic transmission fiber beam 17, the first liquid crystal tunable filter 12 and fluorescence light
Spectrometer 15, the first liquid crystal tunable filter controller 13 and Fluorescence Spectrometer 15 are connected by USB with PC host computer 30, upper
Machine can distinguish in-situ monitor petty action owner according to timing control laser shutter, liquid crystal tunable filter and Fluorescence Spectrometer
The fluorescence signal of intravascular drug and the fluorescence signal of marking nano carrier are wanted, reflects the macroscopic view metabolism of drug in blood in real time
Situation and stability；Second submodule carries out micro-imaging to the fluorescence in institutional framework from microcosmic angle, using biography picture
Fiber optic bundle 25, small-sized microcobjective 29, the second liquid crystal tunable filter 20 and electron multiplication CCD23, the second liquid crystal tunable
Control device of the light filter 21 is connected with electron multiplication CCD23 by USB with PC host computer 30, and host computer is fast according to timing control laser
Door, liquid crystal tunable filter and electron multiplication CCD, PC host computer 30 are by two images of electron multiplication CCD23 acquisition time
Add pseudo- color and be fused together, it is glimmering that the drug of nano-carrier fluorescence signal and package in toy certain organs can be detected in place
Optical signal passes through from enrichment, distribution, leakage and tissue damage situation of the micro-scale analysis Nano medication in metabolic organ
The timing control of PC host computer can realize the orderly progress of two submodules acquisition.
It is furnished with 3 He of 488nm laser shutter before the laser 2 that the laser 1 and wavelength that wavelength is 488nm are 650nm
650nm laser shutter 5, they are fast with respective controller 488nm laser shutter controller 4 and 650nm laser respectively
Door controller 6 is connected, and two laser shutter controllers are connected by USB with PC host computer 30, by PC host computer 30 according to timing
Control laser shutter being opened and closing, when 488nm laser shutter 3 is opened, 650nm laser shutter 5 be in closed state (or
When person's 650nm laser shutter 5 is opened, 488nm laser shutter 3 is in close state), it is only excited all the way in optical path at this time
Light 488nm (or 650nm) exists.Half slide 9 and Amici prism 10 are used cooperatively distributes laser in any proportion
It is monitored in submodule and institutional framework drug distribution monitoring submodule to plasma drug level.
In plasma drug level monitoring submodule, exciting light arrives first at the second dichroic mirror 11 after light splitting, then
It is coupled in Optic transmission fiber beam 17 by the second lens 16, exciting light is realized after passing through Optic transmission fiber beam 17 to fluorescence sample in blood plasma
The excitation of product, the fluorescence signal of generation pass through after the collection port of Optic transmission fiber beam 17 along original optical path again back to the second dichroic mirror
At 11, the second dichroic mirror 11 herein is primarily used to realize the separation to exciting light and fluorescence signal, the fluorescence letter after separation
Number be reflected to detection optical path, the filtering using the first liquid crystal tunable filter 12 to non-signal light, most afterwards through first thoroughly
Mirror 14, which focuses, enters Fluorescence Spectrometer 15, and collected signal is passed to PC host computer 30 by USB by fluorescence spectrum 15, finally
Realize effective detection of photoluminescence spectrum intensity.Wherein the first liquid crystal tunable filter 12 and the first liquid crystal tunable filter control
Device 13 processed is connected, and the first liquid crystal tunable filter controller 13 is connected by USB with PC host computer 30, PC host computer 30 according to
Timing is according to the type of the opening and closing situation and fluorescent sample of 488nm laser shutter 3 and 650nm laser shutter 5 control the
The band-pass wavelength and bandwidth of one liquid crystal tunable filter 12.
In institutional framework drug distribution monitoring submodule, laser 1 or wavelength that exciting light is 488nm from wavelength
Plasma drug level is not entered into through half slide 9 and the light splitting of Amici prism 10 for the laser that the laser of 650nm issues
Monitor the part of submodule.Laser enters the 4th lens 24 after passing through double color plate third dichroic mirror 19, herein the 4th saturating 24 work
With being exactly that will excite optically coupling in image-carrying fiber bundle 25 (containing 30000 optical fiber), then pass through the 5th lens 26, the 6th lens
27, the 7th lens 28 are adjusted the light beam by image-carrying fiber bundle 25, and the size of light beam is made just to be full of small-sized micro- object
The pupil of mirror 29 gives full play to the performance of object lens, finally reaches after tissue excites fluorescence, fluorescence signal to collect by object lens along original
After optical path returns to third dichroic mirror 19, it is reflected to detection optical path, by the filtering of the second liquid crystal tunable filter 20 and the
Enter electron multiplication CCD23 after the adjustment of three lens 22, electron multiplication CCD23 is connected using USB3.0 with PC host computer 30, in PC
Image is carried out in host computer 30 adds the processing such as pseudo- color and fusion, carries out microcosmic micro-imaging.Same second liquid crystal tunable
Optical filter 20 is connected with the second liquid crystal tunable filter controller 21, and the second liquid crystal tunable filter controller 21 passes through
USB is connected with PC host computer 30, and PC host computer 30 is according to timing according to 488nm laser shutter 3 and 650nm laser shutter 5
Opening and closing situation and fluorescent sample type control the second liquid crystal tunable filter 20 band-pass wavelength and bandwidth.
The present invention is quickly turned using the optical shutter of one chip, liquid crystal tunable filter and specific sequential control method
The detection to different scale and different fluorescent samples is changed, and then ensures collection point and the acquisition time almost phase of different fluorescent samples
Together, guarantee is provided for the correct processing of fluorescence data.
The present invention spectrometer high using small in size, high sensitivity and signal-to-noise ratio, outfit refrigeration mode detector can be realized low
Optical detection, and reduce spectral error.It is well suited for the application of the low luminosity scene of such as fluorescence detection.
The image processing and analyzing module that the present invention realizes can realize Data Management Analysis while data acquire, point
Experimental result is analysed to improve experimental implementation process in time according to demand.
As shown in Fig. 2, for the plasma drug level that designs of the present invention monitor Optic transmission fiber beam 17 used in submodule by
Including quartzy protection zone 31, stainless steel probe 32, handle 33, fiber optic splitter 34, incident optical 35 and receive the composition of optical fiber 36.
Quartzy protection zone 31 with a thickness of 3 ㎜, incident and outgoing area overlapping can be made to increase, the excitation of fluorescence is improved and collect effect
Rate.
As shown in figure 3, for the section that the present invention pops one's head in, since the scene that plasma drug level monitoring submodule uses is special
Very, need to detect the fluorescence intensity in blood vessel, probe will be enough to carefully.The diameter of optical fiber is in the probe that the present invention designs
0.2 ㎜, using arrangement mode shown in Fig. 3, an intermediate optical fiber is incident optical, and the surrounding six roots of sensation is to receive optical fiber.
The probe that the present invention designs improves the excitation of fluorescence and collects effect while blood vessel can be directed at by meeting probe
Rate.
As shown in figure 4, being the section of incident optical 35 of the present invention, exciting light is focused on into optical fiber by the second lens 16 and is cut
On face, it will excite optically coupling in incident optical 35.
As shown in figure 5, receive the section of optical fiber 36 for the present invention, since spectrometer is detected by slit,
It devising six and receives the special arrangement mode of optical fiber, appropriate adjustment can allow more fluorescence to penetrate slit when installation,
Improve the sensitivity that Fluorescence Spectrometer 15 detects.
As shown in fig. 6, monitoring timing for the different fluorescent sample different scales that the present invention designs, start to inject in experiment
In Nano medication to animal body, then start to monitor fluorescence signal.Use plasma drug level first in a sampling period
The fluorescent sample in submodule detection blood plasma is monitored, the fluorescence intensity of nanoshell is first detected, then detects the fluorescence of Nano medication
Intensity.After the completion of plasma drug level monitors submodule detection, institutional framework drug distribution monitors submodule and starts to work.Because
488nm laser shutter 3 and 650nm laser shutter 5 are mechanical structure, in order to reduce its abrasion, first to nanometer in tissue
The fluorescence of drug carries out micro-imaging and observes its distribution situation, then carries out micro-imaging observation to the fluorescence of nanoshell in tissue
Its distribution situation.After the completion of one sampling period detection, according to the sample frequency of setting, next sampling period is waited for.
As shown in fig. 7, monitoring timing, the device action of design for above-mentioned different fluorescent sample different scales for the present invention
Control sequential.The laser 2 that the laser 1 and wavelength that wavelength is 488nm are 650nm is connected on 220V power supply, is maintained a normally open.
488nm laser shutter 3 and 650nm laser shutter 5 are connected by respective controller with PC host computer 30, by PC host computer
Its opening and closing of 30 controls.Corresponding rectangle indicates its opening in figure, otherwise closes.First liquid crystal tunable filter 12 and second
Liquid crystal tunable filter 20 is connected by respective controller with PC host computer 30, controls its band-pass wavelength by PC host computer 30
And bandwidth, corresponding rectangle indicates that its fluorescence issued by nanoshell, corresponding triangle indicate that it passes through nanometer in figure
The fluorescence that drug issues.Fluorescence Spectrometer 15 is connected by USB with PC host computer 30, be can control it on PC host computer 30 and is opened
Begin acquisition and acquisition time (time of integration), corresponding rectangle indicates that it starts to acquire in figure, its acquisition time of width means.
In one acquisition, by Fluorescence Spectrometer 15 acquisition time control laser shutter opening time length and control liquid crystal can
Tunable filter passes through the length of corresponding fluorescence times.Electron multiplication CCD23 is connected by USB with PC host computer 30, on PC
It can control it on the machine 30 of position and start acquisition and acquisition time (time of integration), corresponding rectangle indicates that it starts to adopt in figure
Collection, its acquisition time of width means.In one acquisition, beaten by the acquisition time control laser shutter of electron multiplication CCD23
The length of ETAD expected time of arrival and departure simultaneously controls the length that liquid crystal tunable filter passes through corresponding fluorescence times.One sampling period detection is completed
Afterwards, according to the sample frequency of setting, next sampling period is waited for.
The sequential control method that the present invention designs makes two submodules to difference while guaranteeing the durability of system
The detection of fluorescent sample orderly carries out, and provides guarantee for the correct processing of later period fluorescence data, is the control core of system, is
The basis of Nano medication Toxicity Analysis.
Claims (7)
1. a kind of double scale nanometer drug detection in vivo systems of dual wavelength characterized by comprising wavelength is the laser of 488nm
Device (1), laser (2), 488nm laser shutter (3), the 650nm laser shutter (5), the first reflective mirror that wavelength is 650nm
(7), the first dichroic mirror (8), half slide (9), Amici prism (10), the first liquid crystal tunable filter (12), first
Liquid crystal tunable filter controller (13), Fluorescence Spectrometer (15), Optic transmission fiber beam (17), the second liquid crystal tunable filter
(20), the second liquid crystal tunable filter controller (21), electron multiplication CCD (23), image-carrying fiber bundle (25), small-sized micro- object
Mirror (29) and PC host computer (30)；Wherein: laser (2) excitation that the laser (1) and wavelength that wavelength is 488nm are 650nm
Two kinds of fluorescent dyes of corresponding nanoshell and drug, make two lasers using the first reflective mirror (7) and the first dichroic mirror (8)
The laser of sending enters in main optical path, and 488nm laser shutter (3) and 650nm laser shutter (5) jointly control in main optical path
The exciting light of only one wavelength exists, and is applied in combination by half slide (9) and Amici prism (10) by laser point
Into two submodules of system；First submodule changes from the angle monitor plasma drug level of macroscopic view, using biography light light
Fine beam (17), the first liquid crystal tunable filter (12) and Fluorescence Spectrometer (15), the first liquid crystal tunable filter controller
(13) it is connected with Fluorescence Spectrometer (15) by USB with PC host computer (30), host computer is according to timing control laser shutter, liquid crystal
Tunable filter and Fluorescence Spectrometer can distinguish the fluorescence signal and label of drug in in-situ monitor toy Major Vessels
The fluorescence signal of nano-carrier reflects drug macroscopical metabolic condition in blood and stability in real time；Second submodule from
Microcosmic angle in institutional framework fluorescence carry out micro-imaging, using image-carrying fiber bundle (25), small-sized microcobjective (29),
Second liquid crystal tunable filter (20) and electron multiplication CCD (23), the second liquid crystal tunable filter controller (21) and electricity
Son multiplication CCD (23) is connected by USB with PC host computer (30), and host computer is according to timing control laser shutter, liquid crystal tunable
Two images of electron multiplication CCD (23) acquisition time are added pseudo- color and melted by optical filter and electron multiplication CCD, PC host computer (30)
It is combined, the drug fluorescence signal of nano-carrier fluorescence signal and package in toy certain organs can be detected in place, from
Micro-scale analyzes enrichment, distribution, leakage and tissue damage situation of the Nano medication in metabolic organ, passes through PC host computer
Timing control can realize the orderly progress of two submodules acquisition.
2. the double scale nanometer drug detection in vivo systems of dual wavelength as described in claim 1, which is characterized in that 488nm laser
Device shutter (3) and 650nm laser shutter (5) are the one chip optical shutter with highly sensitive and response time, switch activator
Time is only 4.08ms.
3. the double scale nanometer drug detection in vivo systems of dual wavelength as described in claim 1, which is characterized in that Fluorescence Spectrometer
It (15) is marine optics QEPro, electron multiplication CCD (23) is ANDOR iXon Life.
4. the double scale nanometer drug detection in vivo systems of dual wavelength as described in claim 1, which is characterized in that image-carrying fiber bundle
(25) there are 30000 optical fiber.
5. the double scale nanometer drug detection in vivo systems of dual wavelength as described in claim 1, which is characterized in that Optic transmission fiber beam
(17) include quartzy protection zone (31), stainless steel probe (32), handle (33), fiber optic splitter (34), incident optical (35) and
Receive optical fiber (36)；Quartzy protection zone (31) is popped one's head in stainless steel before (32), includes an incident light in stainless steel probe (32)
Fibril and the six roots of sensation receive optical fiber, incident light fibril and receive optical fiber and are divided into incident optical (35) in fiber optic splitter (34)
With receive optical fiber (36).
6. a kind of sequential control method of the double scale nanometer drug detection in vivo systems of dual wavelength, which is characterized in that including as follows
Step:
(1) start to inject in Nano medication to animal body in experiment, then start to monitor fluorescence signal；
(2) in a sampling period, plasma drug level monitoring submodule first works, and 488nm laser shutter (3) is opened,
650nm laser shutter (5) is closed, and the first liquid crystal tunable filter (12) setting is 520nm, Fluorescence Spectrometer by wavelength
(15) fluorescence intensity of the nanoshell in operation detection blood plasma；After the completion of the fluorescence intensity detection of nanoshell in blood plasma, 488nm
Laser shutter (3) is closed, and 650nm laser shutter (5) is opened, and the first liquid crystal tunable filter (12) setting wavelength is
670nm, the fluorescence intensity of Nano medication in Fluorescence Spectrometer (15) operation detection blood plasma；
(3) after the completion of the detection of plasma drug level monitoring submodule, institutional framework drug distribution monitors submodule and starts to work；It is first
First 488nm laser shutter (3) is closed, and 650nm laser shutter (5) is opened, the second liquid crystal tunable filter (20) setting
It is 670nm by wavelength, electron multiplication CCD (23) work carries out micro-imaging to the fluorescence of Nano medication in tissue and observes its point
Cloth situation, then 488nm laser shutter (3) is opened, and 650nm laser shutter (5) is closed, the second liquid crystal tunable filter
(20) setting is 520nm by wavelength, and electron multiplication CCD (23) work carries out micro-imaging sight to the fluorescence of nanoshell in tissue
Examine its distribution situation；After the completion of one sampling period detection, according to the sample frequency of setting, next sampling week is waited for
Phase.
7. the sequential control method of the double scale nanometer drug detection in vivo systems of dual wavelength as claimed in claim 6, feature
It is, the liquid crystal tunable filter response time is less than 40ms.
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