CN101303315B - Optical fiber common focusing micro spectrum and imaging apparatus of cell analysis - Google Patents

Optical fiber common focusing micro spectrum and imaging apparatus of cell analysis Download PDF

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Publication number
CN101303315B
CN101303315B CN2008100356985A CN200810035698A CN101303315B CN 101303315 B CN101303315 B CN 101303315B CN 2008100356985 A CN2008100356985 A CN 2008100356985A CN 200810035698 A CN200810035698 A CN 200810035698A CN 101303315 B CN101303315 B CN 101303315B
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optical fiber
cell
analysis system
micro
information
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CN101303315A (en
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王成
方宝英
蔡文杰
陈家璧
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University of Shanghai for Science and Technology
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University of Shanghai for Science and Technology
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Abstract

The invention relates to an optical fiber confocal microspectroscopy and image forming apparatus, specifically to a cell detecting device, which is a combination of an optical fiber confocal spectral analysis system, a microscopic imaging positioning system and a data analysis system, capable of simultaneously acquiring cell microscopic images and microspectroscopy medical information. A white light source is taken as the light source for lighting; the optical fiber confocal spectral analysis system transmits the lighting light to illuminate the cell, receives the backward scattered optical signals carrying cell information, and acquires the optical spectrum information; the microscopic image-forming system obtains the image information reflecting the cell shape and structure; the data analysis system simultaneously acquires the microscopic image of the cell to be tested and the optical spectrum information reflecting the cell shape and biochemistry characteristic. The early cancerated cells can be diagnosed by comparing the differences of normal cell and cancerated cell on the microscopic image and optical spectrum.

Description

The optical fiber common focusing micro spectrum of cell analysis and imaging device
Technical field
The present invention relates to a kind of optical system, particularly a kind of optical system of biomedical cell detection technical field.
Background technology
The raising year by year of cancer morbidity rate and mortality ratio is for the application apparatus field that is used for early diagnosis of cancer proposes new challenge.In biological tissue's canceration process, there is very big difference in the relative normal cell with structure of the form of cancerous tumor cell, this volume that is embodied in cancer cell increases, obvious increase of nucleus and profile are irregular, and DNA (deoxyribonucleic acid) (DNA) inclusions and chromosomal quality that nucleus comprises change.These variations that the form of cell and biochemical component take place will inevitably pair cell micro-image and optical spectra characteristic produce significant impact, this is the important evidence that detects of early-stage cancer just also.
Sum up the current research result and show that the goldstandard of diagnosing tumor is the microscopic examination of pathological section, but micro-image also is the morphological feature of reacting cells; And analyzing wastes time and energy, and doctor subjective factors influences diagnostic result morely.All there are some defectives in the detection means based on optical means in current exploitation, as the spy laser confocal microscope is the focus of current research, but also can only obtain the variation of histocyte three-dimensional configuration, provide diseases analysis qualitatively, compare with traditional pathological analysis, just can be implemented in body, do not have wound, cell imaging analysis in real time remains qualitatively; Unique advantages such as spectral analysis technique has fast, sensitive, accurate, but spectral investigation obtains the average optical characteristic of organizer all at organizing aspect at present, does not reach the cell aspect, the resolution of diseases analysis is not high, and specificity is relatively poor.So existing medical detection means can't or effectively detect and to make a definite diagnosis cancer early stage.
Summary of the invention
The present invention be directed to prior art and can not on cellular level, obtain the cellular morphology information of ad-hoc location and the technical matters of spectral information, a kind of optical fiber common focusing micro spectrum and imaging device have been proposed, it is the cell detection device that burnt spectral analysis technique of optical fiber copolymerization and microoptic imaging technique are merged mutually, this device can obtain the spectral information of morphosis information and the reflection cellular morphology and the composition characteristic of tested cell simultaneously, obtains the analysis-by-synthesis information that tested cell is qualitative, quantitative, locate.
Technical scheme of the present invention is: optical fiber common focusing micro spectrum and imaging device, comprise light-source illuminating system, the burnt spectroscopic analysis system of optical fiber copolymerization, micro-imaging and positioning system, data analysis system, luminous source system provides light source for the burnt spectroscopic analysis system of optical fiber copolymerization; The burnt spectroscopic analysis system of optical fiber copolymerization transmits the illumination light irradiating cell, and receives the light signal of the backscattering that carries cell information, obtains spectral information and enters the data analysis system analysis; Micro-imaging and positioning system are thrown light on by illuminator, and the image information that obtains reflection cellular morphology and structure enters data analysis system; Data analysis system obtains the micro-image of tested cell and the spectral information of reflection cellular morphology and composition characteristic simultaneously.
Described white lumination system comprises white light source, fiber coupler and coupled lens group, and illumination light enters the coupled lens group through the luminous energy of fiber coupler transmission light source, and coupled lens group focused light source energy is to sample.
The burnt spectroscopic analysis system of described optical fiber copolymerization comprises fiber coupler, coupled lens group, 3-D scanning platform and optical fiber CCD spectrometer, the back scattering light signal of sample scattering and absorption characteristic is collected by the coupled lens group and is coupled in the optical fiber of fiber coupler on the 3-D scanning platform, optical fiber is connected with optical fiber CCD spectrometer thus again, realize the conversion of photosignal, the 3-D scanning platform is used to adjust the position of tested cell.
Described micro-imaging and positioning system comprise inversion type biology microscope mirror system and CCD camera, and inversion type biology microscope mirror system obtains the micro-image of tested cell, observation cellular morphology structure; Receive micro-image by the CCD camera simultaneously, be transferred to data analysis system.
Described data analysis system is a multi-purpose computer, and computing machine is connecting optical fiber CCD spectrometer and CCD camera, obtains and analyze the signal spectrum of the tested cell of optical fiber CCD spectrometer transmission; Receive the cell microscopic image information of CCD camera transmission simultaneously, analyze the integrated information of form, composition and the optical characteristics of tested cell.
Beneficial effect of the present invention is: the present invention is in conjunction with the burnt technology of optical fiber copolymerization, back scattering spectral analysis technique and micro-imaging technique, the micro-image that obtains specific cells simultaneously and the cell detection device of spectral information have been proposed to be applicable to, the integrated information of obtaining cell that can be real-time.This has just solved present technology can not obtain the tissue morphology information of ad-hoc location and the technical matters of spectral information on cellular level.For cancer except that the microscopic morphology information that detects cancerous tumor cell, obtain the spectrum of corresponding cell biochemical component simultaneously, both comprised in the spectral information that metamorphosis was to the scattering of light characteristic variations, the change information that has also comprised the optical absorption characteristics that the composition variation causes in the cell, cell analysis apparatus in conjunction with these two kinds of detection techniques, can in time find the early stage canceration of cell, so that cancer is implemented diagnosis comprehensively and timely.And current micro-imaging technique and CCD spectral technique all are the detection techniques of comparative maturity, and the CCD spectral technique can carry out real-time analysis, so, device utilization provided by the invention has advanced technology now, improves the accuracy of detection of cancerous tumor cell greatly, can reduce the detection cost greatly simultaneously.
Description of drawings
Fig. 1 is the system architecture diagram of optical fiber common focusing micro spectrum of the present invention and imaging device;
Fig. 2 is the system light path figure of optical fiber common focusing micro spectrum of the present invention and imaging device.
Embodiment
The system architecture diagram of optical fiber common focusing micro spectrum and imaging device the present invention includes as shown in Figure 1, light-source illuminating system 11; The burnt spectroscopic analysis system 12 of optical fiber copolymerization; Micro-imaging and positioning system 13; Data analysis system 14.Luminous source system 11 provides light source for the burnt spectroscopic analysis system 12 of optical fiber copolymerization; The burnt spectroscopic analysis system 12 of optical fiber copolymerization transmits the illumination light irradiating cells, and receives the light signal of the backscattering that carries cell information, obtains spectral information and enters data analysis system 14 analyses; Micro-imaging and positioning system 13 enter data analysis system 14 from the image information that burnt spectroscopic analysis system 12 acquired informations of optical fiber copolymerization convert reflection cellular morphology and structure to; Data analysis system obtains the micro-image of tested cell and the spectral information of reflection cellular morphology and composition characteristic simultaneously.
The system light path figure of optical fiber common focusing micro spectrum and imaging device as shown in Figure 2, described white lumination system 11 comprises white light source 1, fiber coupler 2 and coupled lens group 3 (collimation lens and convergent lens).Wherein white light source can adopt traditional white light source----iodine-tungsten lamp light source, is used to provide illumination light, and wavelength can reduce system cost so greatly at 390-2900nm, also can adopt white light laser, and the resolution characteristic of system can be provided like this.The effect of the fiber coupler in the described illuminator is that illumination light is entered the coupled lens group through the luminous energy of fiber coupler transmission light source, and described coupled lens group focused light source energy is to sample.Lighting source iodine-tungsten lamp 1, fiber coupler 2 and coupled lens group (collimation lens and convergent lens) 3.Illumination light is one tunnel Optical Fiber Transmission and 3 couplings of coupled lens group in fiber coupler 2, and spotlighting is to sample.
The burnt spectroscopic analysis system 12 of described optical fiber copolymerization comprises fiber coupler 2, coupled lens group 3 and 3-D scanning platform 4 and optical fiber CCD spectrometer 7.Fiber coupler 2, one tunnel transmission white light source, 1 energy is after coupled lens group 3, focus on the white light energy to sample by coupled lens group 3, the back scattering light signal that comprises sample scattering and absorption characteristic simultaneously on the sample is coupled in another road optical fiber 6 of fiber coupler 2 by 3 collections of coupled lens group, optical fiber is connected with optical fiber CCD spectrometer 7 thus again, realizes the conversion of photosignal.3-D scanning platform 4 is used to adjust the position of tested cell.After optical fiber CCD spectrometer 7 is realized the photosignal conversion, obtain and analyze the signal spectrum of tested cell by computing machine 8.
Described micro-imaging and positioning system 13 can be used inversion type biology microscope mirror system 9, illuminated detection cell is located on three-dimensional sample platform 4, and obtain the micro-image of tested cell, observation cellular morphology structure; And can receive micro-image to computing machine 8 by CCD camera 5, be convenient to the storage and the analysis of image.
Described data analysis system 14 is a multi-purpose computer 8, and computing machine is connecting optical fiber CCD spectrometer 7 and CCD camera 5, obtains and analyze the signal spectrum of the tested cell of optical fiber CCD spectrometer 7 transmission; Simultaneously, also receive the cell microscopic image information of CCD camera 5 transmission, so just can analyze the integrated information of form, composition and the optical characteristics of tested cell simultaneously.
In the total system, the illumination light that white light source 1 provides is through fiber coupler 2 transmission, by coupled lens group 3, focus on and navigate on the tested cell sample, the optical fiber of popping one's head in simultaneously receives the backscatter signal light of sample, through fibre bundle 6 outputs, be transferred to optical fiber CCD spectrometer 7, input computing machine 8 obtains the spectral information of cell.The optical axis coincidence of the image-forming objective lens of the optical axis of coupled lens group 3 and inverted microscope 9, can use same lighting source like this is that two detection systems (the burnt spectroscopic analysis system 12 of optical fiber copolymerization and micro-imaging and positioning system 13) provide illumination simultaneously, also be convenient to receive the micro-image of tested cell, so just make computing machine 8 obtain the spectral information and the shape information of tested cell simultaneously by inverted microscope and CCD camera 5.Wherein the numerical aperture of the numerical aperture of single-mode fiber and coupled lens group 3 is complementary, and such beneficial effect is to make the transfer efficiency that improves luminous energy.Utilize luminous energy better, improve the structural form of measurement cell interior and the contrast of composition information.
Described data analysis system 14 comprises to the demonstration of the photosignal of common focusing micro spectrum system 12 output and analysis and to the demonstration and the analysis of the picture signal of 5 outputs of CCD camera in micro-imaging and the positioning system 13.Data analysis system 14 indispensabilities be a multi-purpose computer 8, computing machine 8 is connecting optical fiber CCD spectrometer 7 in the burnt spectroscopic analysis system 12 of optical fiber copolymerization and the CCD camera 5 in micro-location and the imaging system 13, obtains the signal spectrum of the tested cell of analyzing the spectrometer transmission; Simultaneously, also receive the cell microscopic image information of CCD camera 5 transmission, so just can analyze the integrated information of form, composition and the optical characteristics of tested cell simultaneously.

Claims (1)

1. optical fiber common focusing micro spectrum and imaging device, comprise light-source illuminating system, the burnt spectroscopic analysis system of optical fiber copolymerization, micro-imaging and positioning system, data analysis system, described light-source illuminating system comprises white light source, fiber coupler and coupled lens group, illumination light enters the coupled lens group through the luminous energy of fiber coupler transmission light source, coupled lens group focused light source energy is to sample, and light-source illuminating system provides light source for the burnt spectroscopic analysis system of optical fiber copolymerization; The burnt spectroscopic analysis system of described optical fiber copolymerization comprises fiber coupler, the coupled lens group, 3-D scanning platform and optical fiber CCD spectrometer, the back scattering light signal of sample scattering and absorption characteristic is collected by the coupled lens group and is coupled in the optical fiber of fiber coupler on the 3-D scanning platform, optical fiber is connected with optical fiber CCD spectrometer thus again, realize the conversion of photosignal, the 3-D scanning platform is used to adjust the position of tested cell, the burnt spectroscopic analysis system transmission of described optical fiber copolymerization illumination light irradiating cell, and receive the light signal of the backscattering carry cellular morphology and composition information, obtain spectral information and enter the data analysis system analysis; Described micro-imaging and positioning system comprise inversion type biology microscope mirror system and CCD camera, and inversion type biology microscope mirror system obtains the micro-image of tested cell, observation cellular morphology structure; Receive micro-image by the CCD camera simultaneously, be transferred to data analysis system; Described data analysis system is a multi-purpose computer, and computing machine is connecting optical fiber CCD spectrometer and CCD camera, obtains and analyze the signal spectrum of the tested cell of optical fiber CCD spectrometer transmission; Receive the cell microscopic image information of CCD camera transmission simultaneously, analyze the integrated information of form, composition and the optical characteristics of tested cell.
CN2008100356985A 2008-04-08 2008-04-08 Optical fiber common focusing micro spectrum and imaging apparatus of cell analysis Expired - Fee Related CN101303315B (en)

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CN104568857B (en) * 2015-01-29 2017-10-17 山东大学 A kind of two-dimentional light scattering quiescence cells instrument method and device
CN105067617A (en) * 2015-07-21 2015-11-18 上海理工大学 Cell recognition apparatus and method based on phase contrast image and confocal scattering microspectrum
CN106814365B (en) * 2017-01-17 2019-08-16 深圳立仪科技有限公司 Fiber spectrum is copolymerized burnt measuring device
CN106872376A (en) * 2017-02-15 2017-06-20 深圳立仪科技有限公司 Copolymerization Jiao's measurement apparatus and method of spectral balance
CN109297949B (en) * 2018-09-19 2024-04-05 上海镭立激光科技有限公司 Tumor cell detection method and device by combining microscopic image with transmission Raman spectrum
TWI664582B (en) * 2018-11-28 2019-07-01 靜宜大學 Method, apparatus and system for cell detection

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