CN206057175U - A kind of cancer diagnosis system based on the autofluorescence life-span - Google Patents
A kind of cancer diagnosis system based on the autofluorescence life-span Download PDFInfo
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- CN206057175U CN206057175U CN201620831130.4U CN201620831130U CN206057175U CN 206057175 U CN206057175 U CN 206057175U CN 201620831130 U CN201620831130 U CN 201620831130U CN 206057175 U CN206057175 U CN 206057175U
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Abstract
This utility model belongs to technical field of medical equipment, specially a kind of cancer diagnosis system based on the autofluorescence life-span.Autofluorescence of this utility model using biological tissue, by the change in analysis of fluorescence life-span, detects whether cell carcinogenesis occur, so as to the foundation as cancer diagnosis.System is imported by optical fiber, diseased region can be imported by endoscope, optical fiber align tissue slice can also be carried out fluorescence lifetime detection, early detection be carried out to kinds cancer and surgical resection margins judge, be with a wide range of applications in fields such as biomedical and clinical diagnosises.The advantage of this utility model cancer diagnosis system is:Principle is simple, easy to operate, and detection speed is fast, and sensitivity is high, and specificity is high, is advantageously implemented in clinical diagnosises rapidly and accurately diagnosing cervical, intestinal cancer or pulmonary carcinoma.It is effective that this utility model changes obvious kinds cancer species to fluorescence lifetime after tissue canceration.
Description
Technical field
This utility model belongs to technical field of medical equipment, and in particular to a kind of cancer diagnosis system.
Background technology
At present, the mortality rate of cancer remains high, and becomes the first killer for threatening human health.According to statistics, 2012 it is complete
The cases of cancer more than 1,410 ten thousand increased newly in the range of ball, 8,200,000 people die from cancer.Wherein cervical cancer accounts for female cancer mortality rate the 4th
Position;Intestinal cancer accounts for deaths in men rate the 4th, women die rate the 3rd;Pulmonary carcinoma accounts for deaths in men rate first, women die rate
Second.Why its mortality rate remains high, and is largely because when clarifying a diagnosis and has had been enter into middle and advanced stage, loses
The chance of early treatment.Early diagnosiss are to affect the high low prognostic indicator of cancer life span length, quality of life most important
Factor, and the premise of early treatment.Using autofluorescence life tests technology can for the early diagnosiss of cancer provide according to
According to fluorescence lifetime is very sensitive to the microenvironment residing for fluorogen, and the physiological parameters such as ion concentration, pH value can be carried out quantitatively
Measurement, and the not impact of the factor such as stimulated luminescence Strength Changes, photobleaching.Therefore by detecting the autologous glimmering of tested biological specimen
The light life-span can obtain the information with regard to micro-environmental variations such as biological tissue's metabolism, realize examine highly sensitive to cancer
It is disconnected.
The content of the invention
The purpose of this utility model is to provide a kind of detection sensitivity high cancer diagnosis system, to realize to cervix uteri
The early diagnosiss of the kinds cancers such as cancer, intestinal cancer, pulmonary carcinoma, improve accuracy.
The cancer diagnosis system that this utility model is provided, is based on the tested biological specimen autofluorescence life-span.Which passes through
LASER Light Source, fluorescence lifetime signal pickup assembly and computer disposal, obtain autologous fluorescence lifetime information.Concrete structure such as Fig. 1
It is shown.The device scans integration of compact module by LASER Light Source 1, speculum group 2,3, dichroic mirror 4, the first collecting lenses group 5
Or optical fiber probe 6, the second reflecting mirror 8, the second collecting lenses group 9, light filter 10, detector 11, computer 12, display screen 13,
Synchronizing signal 14 is constituted.Wherein:
LASER Light Source 1, for producing the exciting light to Auto- fluorescence substance in tested biological specimen;
Speculum group 2,3, is connected with the LASER Light Source 1, for described exciting light is adjusted to dichroic mirror 4;
Dichroic mirror 4, is connected with the speculum group;Dichroic mirror 4 is for by the autologous glimmering of exciting light and tested biological specimen
Light is separated;
First collecting lenses group 5, is connected with the dichroic mirror 4, for assembling the exciting light and autofluorescence;
Scanning integration of compact module or optical fiber probe 6, are connected with the first collecting lenses group 5, for realizing to quilt
The scanning of inspection biological specimen or the endoscope detecting to biological tissue;
Second reflecting mirror 8, is connected with the dichroic mirror 4, for reflecting the autofluorescence of tested sample to light filter 10;
Second collecting lenses group 9, for assembling the autofluorescence reflected by the second reflecting mirror 8 to light filter 10;
Light filter 10, is connected with the second collecting lenses group 9, for filtering exciting light;
Photodetector 11, is connected with the light filter 10, for detecting the autofluorescence information of tested biological specimen;
Computer 12, is connected with the scanning integration of compact module 6, photodetector 11 and synchronizing signal 14.Meter
Calculation machine 12 is provided with:Time correlation single photon data collecting card, laser and photodetector Power Control card, scan module control
The hardware modules such as card;Wherein time correlation single photon data collecting card is used to obtaining and processing the letter for coming from photodetector 11
Number;Laser and photodetector control card are connected with LASER Light Source 1 and photodetector 11, for controlling LASER Light Source and light
The output of electric explorer;Scan module control card is connected with scanning integration of compact module 6, for controlling scan module.
Display screen 13, for showing the operation interface of above related software, and is presented the life-span or image information for collecting.
The signal of synchronizing signal is exported by LASER Light Source, and sends into scanning integration of compact module 6 and computer 12, is used for
Synchronous driver sweep signal and Single Photon Counting device.
In this utility model, the LASER Light Source can be using picosecond pulse laser for tested biological specimen shallow-layer
The one-photon excitation of Auto- fluorescence substance in tissue, it would however also be possible to employ femtosecond pulse laser is for tested biological specimen deep layer
The multiphoton excitation of Auto- fluorescence substance in tissue.
In this utility model, the laser wavelength allows excursion near ultraviolet to near-infrared(Such as 320 nanometers-
1400 nanometers), select different wave length and pulse width to be examined according to tested biological specimen fluorescent material, investigation depth requirement etc.
Survey.
In this utility model, using highly sensitive photomultiplier tube, photomultiplier tube array, CMOS (Complementary Metal Oxide Semiconductor) half
Conductor(CMOS)Or charge coupled cell(CCD)It is as photodetector 11, for detecting the single photon signal of autofluorescence, real
Highly sensitive detection is carried out to weak signal now.
In this utility model, Single Photon Counting device, the letter to photodetector detection in computer 12, are adopted
Number carry out the time domain measurement of fluorescence lifetime.
In this utility model, light filter 10 is passed through by the autofluorescence signal that the second collecting lenses group 9 is assembled(Cut-off colour filter
Piece)Input photodetector 11.
In this utility model, according to the difference of ingredient in tested biological specimen, the fluorescence lifetime information to obtaining is entered
The fitting of row list e index, double e indexes or many e index models.Specifically fitting algorithm formula is:
,
I(t) for after the tested biological specimen of excitation in the timetThe fluorescence intensity for detecting,nIt is tested biological sample
This fluorescent component number,t i It isiThe life-span size of individual fluorescence lifetime composition,a i It isiThe relative of individual fluorescence lifetime composition accounts for
Than,CIt is constant。The average life that fitting is obtainedt m For:。
In this utility model, using high performance light filter to can transmissible laser filter, and filter out other
Veiling glare, only remaining autofluorescence signal enter harvester, reduce background influence, improve signal to noise ratio.
In this utility model, tested biological specimen 7 can be biological tissue section, or in vivo tissue.
In this utility model, if it is biological tissue section to be detected biological specimen, structure 6 and its connecting line can be from
Remove in system, so as to the diagnostic system being simplified;If retaining the scanning integration of compact comprising GRIN Lens structure
Module and its connecting line, then can realize the fluorescence lifetime imaging to being detected biological tissue, can reach auxiliary and find target
The purpose of position;If the splanchnoscopy to biological tissue, then structure 6 and its connecting line can be substituted for optical fiber spy
Pin, so as to peep diagnosis in realizing.
In this utility model, scanning integration of compact module is mainly made up of GRIN Lens, reflecting mirror and micromachine.
Wherein, GRIN Lens are used for focused activating light in reflecting mirror;Reflecting mirror is connected with micromachine, by controlling micromachine
The parameters such as voltage are adjusting the variables such as the anglec of rotation of reflecting mirror, rotary speed, and then realize exciting light to tested biological specimen
The scanning imagery of zones of different size.
In this utility model, optical fiber probe is mainly by single-mode fiber, multimode fibre and miniaturization union joint composition.Single-mode optics
Fine to be used to guide exciting light, multimode fibre to be used to collect autofluorescence, miniaturization union joint is used to connect single-mode fiber and multimode
Optical fiber, so as to facilitate optical fiber probe that exciting and gathering for fluorescence is carried out into inside live body.
In this utility model, the fluorescence lifetime value of tested biological specimen is obtained by computer disposal.When tested biological sample
When this is human body cervical tissue, with 1.3-1.7 nanoseconds as diagnostic criteria, this diagnostic value may be different because of system for fluorescence lifetime value
It is slightly different, if the fluorescence lifetime value of sample is normal cervical tissues less than this standard, is cancer cervical tissue higher than this standard.
When tested biological specimen is that human body intestines is organized, then, with 1.5-1.9 nanoseconds as diagnostic criteria, this diagnostic value can for fluorescence lifetime value
Can be slightly different because of system difference, if the fluorescence lifetime value of sample is organized for intestinal cancer less than this standard value, higher than this standard value be
Normal structure.When tested biological specimen is human lung tissue, with 1.7-2.1 nanoseconds as diagnostic criteria, this examines fluorescence lifetime value
Disconnected value may be slightly different because of the corresponding time difference of system, if the fluorescence lifetime value of sample is pulmonary carcinoma group less than this standard diagnostics
Knit, be normal lung tissue higher than this standard value.
Using this utility model device, energy direct detection goes out the fluorescence lifetime information of tested biological specimen, respectively according to palace
The fluorescence lifetime diagnostic criteria value of neck cancer, intestinal cancer or pulmonary carcinoma, realizes the diagnosis to cervical cancer, intestinal cancer or pulmonary carcinoma.This cancer is examined
The advantage of disconnected method and apparatus is:Principle is simple, easy to operate, and detection speed is fast, and sensitivity is high, and specificity is high, is conducive to
Realize in clinical diagnosises rapidly and accurately diagnosing cervical, intestinal cancer or pulmonary carcinoma.The device changes to fluorescence lifetime after tissue canceration
Significantly kinds cancer species is effective, it is not limited to the species listed by example.
Description of the drawings
Fig. 1 is a kind of schematic device of method and system for cancer diagnosis of the present utility model.
Fig. 2 is the life information of the cervical tissue sample for using this utility model device, measuring and histiocyte aspect graph.
Fig. 3 is the intestinal tissue for measuring and the life information of lung tissue sample using this utility model device.
Label in Fig. 1:1 is LASER Light Source, and 2,3 is speculum group, and 4 is dichroic mirror, and 5 is the first collecting lenses group, and 6 is to sweep
Integration of compact module or optical fiber probe are retouched, 7 is tested sample, and 8 is the second reflecting mirror, and 9 is the second collecting lenses group, and 10 are filter
Color chips, 11 is photodetector, and 12 is computer, and 13 is display screen, and 14 is synchronizing signal.
Specific embodiment
Below in conjunction with the accompanying drawings and embodiment further describes this utility model.
Embodiment 1, makes a combination multi-pass of the present utility model according to Fig. 1 and detects the biological specimen autofluorescence life-span
For the device of cancer diagnosis.LASER Light Source 1 sends picosecond pulse laser or femtosecond pulse;The laser Jing that exciting light sends
The reflection of speculum group 2 and 3 adjusts exciting light to dichroic mirror 4;The dichroic mirror 4 is fully reflective to exciting light;What is reflected swashs
Light enters scanning integration of compact module or optical fiber probe 6 by the convergence of the first collecting lenses group 5;Scanning integration of compact mould
Block or optical fiber probe 6 focus on the exciting light after convergence on tested biological specimen;The autofluorescence that tested biological specimen sends
By scanning integration of compact module or optical fiber probe 6, then converge at dichroic mirror 4 through the first collecting lenses group 5;Dichroic mirror
4 is wholly transmissive by autofluorescence;Reflection of the autofluorescence after transmission by the second reflecting mirror 8;Autofluorescence after reflection is passed through
The second collecting lenses group 9 converges at light filter 10;Light filter 10 filters the exciting light transmitted by dichroic mirror 4 that may be present;
Autofluorescence is detected by photodetector 11;At the same time the synchronizing signal 14 of exciting light is transferred to the data of master computer 12 and adopts
In collection plate, the signal Jing Jing after photodetector 11 amplifies is provided with the master computer 12 of Single Photon Counting device and processes,
Software is processed finally by fluorescence lifetime and fits fluorescence lifetime information(Or fluorescence lifetime image information).
Embodiment 2, implements according to embodiment 1:Carry out the measurement of fluorescence lifetime imaging, system first to human body cervical tissue
In structure 6 be the scanning small-size module comprising GRIN Lens structure and its connecting line.Using 50MHz, 405 nm wavelength
Picosecond pulse laser the fluorescent material of tested cervical tissue is excited, laser focusing size be about 1-30 microns, glimmering
Light filter in light collection light path is the cut-off filter plate of 430 nm high passes.Signal Jing after photomultiplier tube 11 amplifies is by being provided with
After the main frame 12 of Single Photon Counting device is processed, software is processed by fluorescence lifetime and is fitted fluorescence lifetime value and is obtained glimmering
The result of light life diagram picture, as shown in Figure 2.
Result such as Fig. 2 institutes of fluorescence lifetime imaging measurement are carried out by using this utility model device to human body cervical tissue
Show, the left and right two width figure of Fig. 2 is respectively the fluorescence lifetime imaging figure and fluorescence lifetime attenuation curve of cervical tissue.Using this reality
Carried out with new device fluorescence lifetime imaging measurement result can clearly indicate normal and canceration cervical tissue form with
Difference in structure.The fluorescence lifetime value obtained after fluorescence lifetime software processes is respectively 1.28 nanoseconds and 2.03 nanoseconds.
Using the fluorescence lifetime diagnostic criteria in the inventive method for diagnosing cervical, for the system, diagnostic criteria is
1.60 nanoseconds, the fluorescence lifetime value of sample is normal cervical tissues less than this standard, is cancer cervical tissue higher than this standard.Cause
This it is diagnosable go out 1.28 nanoseconds be canceration cervical tissue for normal and 2.03 nanoseconds, it is consistent with pathological examination results.The method takes
The result consistent with pathology detection was obtained, but it is rapider than traditional pathology detection method, sensitive.
Embodiment 3, implements according to embodiment 1:The measurement of fluorescence lifetime is carried out to human body intestinal tissue.Using 50MHz, 405
The picosecond pulse laser of nm wavelength is excited to the fluorescent material of tested intestinal tissue, and the light filter in fluorescent collecting light path is
The cut-off filter plate of 430 nm high passes.Signal Jing after photomultiplier tube 11 amplifies is by being provided with Single Photon Counting device
Fluorescence lifetime attenuation curve such as Fig. 3 after the process of main frame 12, after fluorescence lifetime processes software fitting(It is left)It is shown, obtain
Fluorescence lifetime value is respectively 1.49 nanoseconds and 1.95 nanoseconds.Using the fluorescence lifetime diagnosis mark that intestinal cancer is diagnosed in this utility model
Standard, for the system, diagnostic criteria was 1.67 nanoseconds, and the fluorescence lifetime value of sample is intestinal cancer tissue less than this standard value,
It is normal structure higher than this standard value.Therefore it is diagnosable go out 1.95 nanoseconds be canceration intestinal tissue for normal and 1.49 nanoseconds, with disease
Reason inspection result is consistent.
Embodiment 4, implements according to embodiment 1:The measurement of fluorescence lifetime is carried out to human lung tissue.Using 50MHz, 405
The picosecond pulse laser of nm wavelength is excited to the fluorescent material of tested lung tissue, the light filter in fluorescent collecting light path
For the cut-off filter plate of 430 nm high passes.Signal Jing after photomultiplier tube 11 amplifies is by being provided with Single Photon Counting device
Main frame 12 process after, by fluorescence lifetime process software fitting after fluorescence lifetime attenuation curve such as Fig. 3(It is right)It is shown, obtain
Fluorescence lifetime value be respectively 1.61 nanoseconds and 2.15 nanoseconds.Using the fluorescence lifetime diagnosis mark of diagnosing in this utility model
Standard, for the system, diagnostic criteria was 1.92 nanoseconds, and the fluorescence lifetime value of sample is pulmonary carcinoma group less than this standard diagnostics
Knit, be normal lung tissue higher than this standard value.Therefore it is diagnosable go out 2.15 nanoseconds be canceration lung tissue for normal and 1.61 nanoseconds,
It is consistent with pathological examination results.
Claims (10)
1. a kind of cancer diagnosis system based on the autofluorescence life-span, it is characterised in that by LASER Light Source, speculum group is double-colored
Mirror, the first collecting lenses group, scanning integration of compact module or optical fiber probe, the second reflecting mirror, the second collecting lenses group, colour filter
Piece, photodetector, computer, display screen, synchronizing signal composition;Wherein:
The LASER Light Source, for producing the exciting light to Auto- fluorescence substance in tested biological specimen;
The speculum group, is connected with the LASER Light Source, for described exciting light is adjusted to dichroic mirror;
The dichroic mirror, is connected with the speculum group;Dichroic mirror is for by the autofluorescence of exciting light and tested biological specimen
Separate;
The first collecting lenses group, is connected with the dichroic mirror, for assembling the exciting light and autofluorescence;
The scanning integration of compact module or optical fiber probe, are connected with the first collecting lenses group, for realizing to tested
The scanning of biological specimen or the endoscope detecting to biological tissue;
Second reflecting mirror, is connected with the dichroic mirror, for reflecting the autofluorescence of tested sample to light filter;
The second collecting lenses group, for assembling by the autofluorescence of the second reflecting mirror reflection to light filter;
The light filter, is connected with the second collecting lenses group, for filtering exciting light;
The photodetector, is connected with the light filter, for detecting the autofluorescence information of tested biological specimen;
The computer, is connected with the scanning integration of compact module, photodetector and synchronizing signal;Computer is installed
There is hardware module:Time correlation single photon data collecting card, laser and photodetector Power Control card, scan module control
Card, wherein, time correlation single photon data collecting card is used to obtaining and processing the signal for coming from photodetector;Laser and light
Electric explorer control card is connected with LASER Light Source and photodetector, for controlling the output of LASER Light Source and photodetector
Power;Scan module control card is connected with scanning integration of compact module, for controlling scan module;
The display screen, for showing the operation interface of above related software, and shows relevant data and image information;
The signal of the synchronizing signal is exported by LASER Light Source, and sends into scanning integration of compact module and computer, for same
Step driver sweep signal and Single Photon Counting device.
2. the cancer diagnosis system based on the autofluorescence life-span according to claim 1, it is characterised in that described laser
Psec or femtosecond pulse laser of the light source using high repetition frequency, wherein, picosecond pulse laser is for tested biological sample
The one-photon excitation of Auto- fluorescence substance in this shallow layer tissue, femtosecond pulse laser is for tested biological specimen deep tissues
The multiphoton excitation of middle Auto- fluorescence substance.
3. the cancer diagnosis system based on the autofluorescence life-span according to claim 2, it is characterised in that the laser instrument
Wavelength allow excursion near ultraviolet to near-infrared, according to tested biological specimen fluorescent material, investigation depth require select
Different wave length and pulse width are detected.
4. the cancer diagnosis system based on the autofluorescence life-span according to claim 1,2 or 3, it is characterised in that tested
Biological specimen autofluorescence life information is different using single e index, double e indexes or many e index models according to sample ingredient
It is fitted.
5. the cancer diagnosis system based on the autofluorescence life-span according to claim 4, it is characterised in that equal according to sample
Even property is different, select the scope that laser instrument is focused on from less than 1 micron to hundreds of micron.
6. the cancer diagnosis system based on the autofluorescence life-span according to claim 1,2,3 or 5, it is characterised in that institute
It is biological tissue section or intravital tissue to state tested biological specimen.
7. the cancer diagnosis system based on the autofluorescence life-span according to claim 6, it is characterised in that if be detected
Sample is biological tissue section, then scan integration of compact module or optical fiber probe and its connecting line is removed from system, so as to
Cultivation system;If at this moment needing to increase imaging function, so as to aid in finding target location, then with scanning integration of compact
Module;If it is biological tissue to be detected sample, with optical fiber probe, so as to realize live body endoscope check.
8. the cancer diagnosis system based on the autofluorescence life-span according to claim 1,2,3,5 or 7, it is characterised in that
The scanning integration of compact module is mainly made up of GRIN Lens, reflecting mirror and micromachine;Wherein, GRIN Lens are used
In focused activating light in reflecting mirror;Reflecting mirror is connected with micromachine, anti-to adjust by the voltage parameter for controlling micromachine
The anglec of rotation, the rotary speed of mirror are penetrated, and then realizes scanning imagery of the exciting light to tested biological specimen zones of different size.
9. the cancer diagnosis system based on the autofluorescence life-span according to claim 8, it is characterised in that described optical fiber
Probe is by a root multimode fiber, a single-mode fiber and a miniaturization union joint composition.
10. the cancer diagnosis system based on the autofluorescence life-span according to claim 1,2,3,5,7 or 9, its feature exist
In described photodetector is that sensitivity is high, respond fast photomultiplier tube, photomultiplier tube array, complementary metal to be aoxidized
Thing quasiconductor or charge coupled cell.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN106092996A (en) * | 2016-08-03 | 2016-11-09 | 复旦大学 | A kind of cancer diagnosis system based on the autofluorescence life-span |
CN107421639A (en) * | 2017-05-05 | 2017-12-01 | 安徽谱泉光谱科技有限公司 | Plasma three-dimensional information diagnostic system during material surface handling process |
CN108120702A (en) * | 2017-11-30 | 2018-06-05 | 浙江大学 | A kind of super resolution fluorescence lifetime imaging method and device based on parallel detecting |
CN113203487A (en) * | 2021-03-18 | 2021-08-03 | 深圳大学 | Quantitative correction method and device for fluorescence lifetime deviation |
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2016
- 2016-08-03 CN CN201620831130.4U patent/CN206057175U/en active Active
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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CN106092996A (en) * | 2016-08-03 | 2016-11-09 | 复旦大学 | A kind of cancer diagnosis system based on the autofluorescence life-span |
CN106092996B (en) * | 2016-08-03 | 2024-03-15 | 复旦大学 | Cancer diagnosis system based on autofluorescence life |
CN107421639A (en) * | 2017-05-05 | 2017-12-01 | 安徽谱泉光谱科技有限公司 | Plasma three-dimensional information diagnostic system during material surface handling process |
CN107421639B (en) * | 2017-05-05 | 2023-09-29 | 安徽谱泉光谱科技有限公司 | Plasma three-dimensional information diagnosis system in material surface treatment process |
CN108120702A (en) * | 2017-11-30 | 2018-06-05 | 浙江大学 | A kind of super resolution fluorescence lifetime imaging method and device based on parallel detecting |
CN113203487A (en) * | 2021-03-18 | 2021-08-03 | 深圳大学 | Quantitative correction method and device for fluorescence lifetime deviation |
CN113203487B (en) * | 2021-03-18 | 2022-07-19 | 深圳大学 | Quantitative correction method and device for fluorescence lifetime deviation |
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