CN115607110A - Auto-fluorescence-based breast tumor detection system - Google Patents

Auto-fluorescence-based breast tumor detection system Download PDF

Info

Publication number
CN115607110A
CN115607110A CN202211271879.4A CN202211271879A CN115607110A CN 115607110 A CN115607110 A CN 115607110A CN 202211271879 A CN202211271879 A CN 202211271879A CN 115607110 A CN115607110 A CN 115607110A
Authority
CN
China
Prior art keywords
fluorescence
unit
signal
excitation light
data acquisition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202211271879.4A
Other languages
Chinese (zh)
Other versions
CN115607110B (en
Inventor
陈志峰
严剑锋
李嘉源
谢志坤
周洁林
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangzhou University
Original Assignee
Guangzhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangzhou University filed Critical Guangzhou University
Priority to CN202211271879.4A priority Critical patent/CN115607110B/en
Publication of CN115607110A publication Critical patent/CN115607110A/en
Application granted granted Critical
Publication of CN115607110B publication Critical patent/CN115607110B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0091Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for mammography

Abstract

The invention relates to a breast tumor detection system based on autofluorescence. The system comprises an excitation light source, a light conduction unit of a light conduction module, a transient detection unit and a data acquisition and processing unit; wherein the excitation light source is used for generating excitation light; the light conduction unit transmits the excitation light to irradiate the tissue to be detected, and an autofluorescence signal generated by the excited tissue to be detected is transmitted to the transient detection unit through the light conduction unit; the transient detection module comprises a high-speed response detector which converts the fluorescence signal into an electric signal; the data acquisition and processing unit comprises a data acquisition unit and a fluorescence life fitting module, wherein the data acquisition unit converts the electric signal output by the high-speed response detector into a digital signal; and the fluorescence fitting module performs convolution fitting processing on the digital signal to obtain the fluorescence lifetime of the autofluorescence signal. The breast tumor detection system has the advantages of low cost and small volume.

Description

Auto-fluorescence-based breast tumor detection system
Technical Field
The invention relates to the field of medical detection, in particular to the field of biological tissue spectrum detection.
Background
The fluorescence detection method is one of the tumor tissue screening detection methods which have been continuously developed in recent years, and can be classified into an autofluorescence detection method and a fluorescence probe detection method. In the autofluorescence method, excitation light with a specific wavelength acts on biological tissues to excite endogenous fluorophore molecules to enter an excited state, and photons are released to finally return to a ground state through a radiation relaxation process. Because the tissues have various endogenous fluorophores, the ratio of the endogenous fluorophores to normal tissues and tumor tissues and the fluorescence characteristics of the endogenous fluorophores are different, the normal tissues and the tumor tissues can be screened and judged by detecting the fluorescence spectrum or the fluorescence lifetime of autofluorescence generated by the tissues.
However, since the endogenous fluorophores of the tissue are complex and diverse, and the autofluorescence obtained by the same tissue under the excitation light with different wavelengths has great difference in spectral characteristic peak distribution or fluorescence lifetime, the determination of the appropriate excitation light wavelength for the specific tissue is crucial to the autofluorescence method. Currently, there are many reports on screening tumor tissues by using an autofluorescence method, but the research on fluorescence detection of breast tumors is relatively few.
In addition, because the fluorescence lifetime of the tissue itself is short, high-resolution transient measurement is often required in the existing high-performance fluorescence spectroscopy system to obtain a more accurate fluorescence lifetime. However, in the method, picosecond or femtosecond laser is used as a light source, and measurement is performed by using technologies such as a time-dependent single photon counter or pumping-detection, so that the whole system needs to consume huge cost, has relatively large volume, is difficult to popularize and apply, and is difficult to adapt to mobile measurement.
Disclosure of Invention
Based on the above, the present invention aims to provide a breast tumor detection system based on autofluorescence, which is low in cost, small in size, and specifically suitable for breast tumor tissue screening detection.
A breast tumor detection system based on autofluorescence comprises an excitation light source, a light conduction unit, a transient detection unit and a data acquisition and processing unit; wherein the excitation light source generates ultraviolet excitation light with a pulse width of hundred picoseconds and a repetition frequency of kilohertz; the light conduction unit transmits the excitation light to irradiate the tissue to be detected, and an autofluorescence signal generated by the excited tissue to be detected is transmitted to the transient detection unit through the light conduction unit; the transient detection unit comprises a high-speed response detector with response time in a subnanosecond level, and the high-speed response detector converts the fluorescent signal returned by the light conduction unit into an electric signal; the data acquisition and processing unit comprises a data acquisition unit and a fluorescence life fitting module, wherein the bandwidth of the data acquisition unit is at least 1GHz, the sampling rate is at least 4GS/s, the storage depth is at least 1Mpts, and the data acquisition and processing unit converts the electric signal output by the high-speed response detector into a digital signal; and the fluorescence fitting module performs convolution fitting processing on the digital signal to obtain the fluorescence lifetime of the autofluorescence signal.
The breast tumor detection system realizes accurate acquisition and calculation of fluorescence lifetime by using lower-cost and miniaturized facilities through the combination of an excitation light source, a high-speed response detector, a data acquisition unit and convolution fitting treatment, and has the advantages of low cost, good effect and easy popularization.
Further, the formula of the convolution fitting process in the detection system is as follows:
Figure BDA0003895305970000021
wherein
Figure BDA0003895305970000022
Figure BDA0003895305970000023
Where t and t' are both time, B is the normalization factor of the Gaussian response function, w is the response characteristic time of the system, and τ r Characteristic time of the rising edge of fluorescence, A 0 And t 0 Coordinate translation amounts of fluorescence intensity and time, respectively, and k is fluorescence attenuationNumber of processes, A i And τ i The amplitude and the lifetime of the corresponding fluorescence decay process, respectively;
the average fluorescence lifetime τ is calculated from the following formula:
Figure BDA0003895305970000024
further, an excitation light source in the detection system includes a laser and a collimator lens, wherein the laser is used for generating laser light, and the collimator lens is disposed on a light path of the laser light.
Furthermore, the light conducting unit in the detection system comprises a dichroic mirror, a first optical fiber coupling mirror, an optical fiber and a second optical fiber coupling mirror, wherein the dichroic mirror has high reflectivity for exciting light and high transmissivity for autofluorescence, is arranged on a light path of the exciting light and reflects the exciting light to the first optical fiber coupling mirror, and two ends of the optical fiber are respectively connected with the first optical fiber coupling mirror and the second optical fiber coupling mirror.
Further, a collimating lens, a first optical fiber coupling lens and a second optical fiber coupling lens in the detection system are quartz lenses, and the optical fibers are ultraviolet optical fibers.
Further, the detection system further comprises a spectroscope and a steady-state detection unit, wherein the spectroscope is arranged on an optical path of the autofluorescence signal output by the light conduction unit, and divides the fluorescence signal into a transient path and a steady-state path, and allows the fluorescence signal of the transient path to enter the transient detection unit and the fluorescence signal of the steady-state path to enter the steady-state detection unit; the steady-state detection unit comprises a fluorescence signal multi-channel band-pass filter device and a high-sensitivity detector which are sequentially arranged on a steady-state circuit, wherein the multi-channel band-pass filter device comprises at least two filter channels, and each filter channel can enable a fluorescence signal in a specific wavelength range to pass through; the high-sensitivity detector converts the light intensity of the fluorescent signals passing through different filtering channels into electric signals respectively; and the data acquisition unit is also used for carrying out integral acquisition on the electric signals output by the high-sensitivity detector to obtain fluorescence signal intensity values in different wavelength ranges.
Furthermore, the multichannel band-pass filter device in the detection system comprises four filter channels, the bandwidth of the filter channels is 10nm, and the central wavelengths of the filter channels are 400nm, 420nm, 430nm and 465nm respectively.
Furthermore, the multi-channel band-pass filter device in the detection system is a roller type band-pass filter plate group, and comprises a roller frame and 10nm band-pass filters with central wavelengths of 400nm, 420nm, 430nm and 465nm respectively.
Further, the excitation light wavelength in the detection system is 355nm.
Furthermore, the data acquisition processing unit in the detection system further comprises a light intensity numerical value processing module which processes the fluorescence signal intensity values of different wavelength ranges obtained by the data acquisition unit according to the formula (I) 2 +I 3 )/(I 1 +I 4 ) Performing an operation of formula I 1 、I 2 、I 3 、I 4 And sequentially obtaining the fluorescence signal intensity values of the filtering channels with the central wavelengths of 400nm, 420nm, 430nm and 465nm.
For a better understanding and practice, the invention is described in detail below with reference to the accompanying drawings.
Drawings
FIG. 1 is a schematic diagram of a breast tumor detection system according to the present invention;
FIG. 2 is a schematic structural diagram of a breast tumor detection system according to the present invention;
FIG. 3 is a schematic diagram of the fluorescence lifetime measurements of breast tumor tissue and breast tissue according to an example;
FIG. 4 is a diagram illustrating the detection results of fluorescence intensities of four characteristic wavelengths of breast tumor tissue and breast tissue according to the embodiment;
fig. 5 is a schematic diagram illustrating the results of the embodiment of collecting the fluorescence intensities of four characteristic wavelengths respectively from the breast tumor tissue and the breast tissue and calculating the R value.
Detailed Description
The invention provides a system for detecting the fluorescence life by utilizing a hectosecond excitation light source and a subnanosecond detector, aiming at the problems that in the prior art, the fluorescence life can be accurately measured only by combining a picosecond or femtosecond excitation light source with a time-related single photon counter or pumping-detecting and other measurement means, so that the whole detection system is high in cost and huge in volume. The data is post-processed by utilizing a convolution fitting method to remove the influence of system response broadening on the result, so that the system can be ensured to obtain accurate fluorescence service life, and the manufacturing cost and the whole volume of the system are greatly reduced. The following is a specific embodiment of the breast tumor detection system of the present invention.
Please refer to fig. 1 and fig. 2, which are a schematic frame diagram and a schematic structural diagram of the breast tumor detection system according to the present embodiment, and the system includes an excitation light source 1, a light conduction unit 2, a spectroscope 3, a transient detection unit 4, a steady detection unit 5, and a data acquisition and processing unit 7.
The excitation light source 1 includes a laser 11, an attenuator 12, and a collimator 13. Wherein the laser 11 generates uv laser light with a wavelength of 355nm, a pulse width of the order of hundred picoseconds and a repetition rate of the order of kilohertz. Preferably, the laser is a microchip solid pulse laser. The attenuator 12 and the collimator lens 13 are sequentially disposed on the optical path of the laser. Wherein the attenuator 12 is specifically an adjustable optical attenuator, which is used to attenuate the power of the laser light so as to obtain suitable excitation light, and in the present embodiment, the power of the excitation light is preferably 2mW. The collimating lens 13 is used for collimating the excitation light, and in the testing process, the focal length parameter of the collimating lens can be adjusted according to actual needs to obtain different diameters of the excitation light beams, preferably, the collimating lens is a quartz lens, and the quartz lens can prevent the glass from being excited by ultraviolet laser to emit fluorescence and causing influence on the detection result.
The light conduction unit 2 comprises a dichroic mirror 21 and a light conduction module, wherein the dichroic mirror 21 has high reflectivity for excitation light and high transmissivity for a fluorescence signal generated by a tissue to be detected, and is arranged on a light path of the excitation light, so that the excitation light generated by an excitation light source can be reflected into the light conduction module, and the light conduction module can enable the light signal to be transmitted in two directions. Specifically, in this embodiment, the light guide module includes a first fiber coupling mirror 22, an optical fiber 23, and a second fiber coupling mirror 24, and two ends of the optical fiber 23 are respectively connected to the first fiber coupling mirror 22 and the second fiber coupling mirror 24. The excitation light is reflected by the dichroic mirror, enters the first fiber coupling mirror 22, is coupled into the optical fiber 23, and is irradiated to the tissue 6 to be detected through the second fiber coupling mirror 24 to be excited. The autofluorescence signal generated after the tissue 7 to be detected is excited enters the optical fiber 23 through the second optical fiber coupling mirror 24 and exits to the dichroic mirror 21 through the first optical fiber coupling mirror 22. Preferably, the first fiber coupling mirror 22 and the second fiber coupling mirror 24 are quartz lenses, and the optical fiber 23 is an ultraviolet fiber. Since the dichroic mirror 21 has a high reflectivity for the excitation light and a high transmittance for the fluorescence signal generated by the tissue 6 to be detected, the autofluorescence signal outputted from the first fiber-coupled mirror 22 can pass through the dichroic mirror 21, while the scattered excitation light entrained therein can be reflected. And the quartz lens is used as the optical fiber coupling mirror and the ultraviolet optical fiber is used, so that the glass can be prevented from being excited by ultraviolet laser to emit fluorescence to influence a detection result. In other embodiments, the light guide module may also be composed of an open lens, so long as the excitation light and the autofluorescence signal can be transmitted along it.
The beam splitter 3 can split the incident light into two light beams, is arranged on the light path of the autofluorescence signal passing through the dichroic mirror 21, and is used for splitting the autofluorescence signal into a transient path and a steady path, and enabling the transient path to enter the transient detection unit and the steady path to enter the steady detection unit, so that the system can perform transient detection and steady detection at the same time.
The transient detection unit 4 includes a first focusing lens 41, a first optical filter 42, and a high-speed response detector 43, which are sequentially disposed on the transient path. Wherein the first focusing lens 41 is used for focusing the fluorescence signal of the transient path; the first optical filter 42 is a long-wave pass optical filter, which can pass the fluorescent signal and further filter out stray light; the high-speed response detector 43 is a photodetector with a response time in the order of sub-nanosecond, which converts a fluorescence signal varying with time into an analog electrical signal. Preferably, in this embodiment, the high-speed response detector 43 is a broadband avalanche diode, and the response time thereof can reach 1ns or even lower, so that the lifetime of the fluorescence signal can be better measured. In other embodiments, the lifetime of the fluorescence signal may be measured using a broadband photodiode with a sufficiently short response time.
The steady-state detection unit 5 comprises a multi-channel band-pass filter module 51, a second focusing lens 52, a second optical filter 53 and a high-sensitivity detector 54 which are sequentially arranged on the steady-state path. The multi-channel band-pass filter module 51 is used for passing a plurality of fluorescence signals with specific wavelengths, wherein the fluorescence signals with specific wavelengths at least comprise fluorescence signals with wavelengths of 400nm, 420nm, 430nm and 465nm. Specifically, the multi-channel band-pass filter module 51 in this embodiment is a roller-type band-pass filter set, which includes a roller frame and 10nm band-pass filters with central wavelengths of 400nm, 420nm, 430nm, and 465nm, where each of the filters forms a wavelength detection channel, and the filter channels can be switched by rotating the roller frame. The second focusing lens 52 is used for focusing the fluorescence signal passing through the multi-channel band-pass filter module 51. The second filter 53 is a long-wave pass filter, which can pass the fluorescent signal and further filter out stray light. The highly sensitive detector 54 is a photodetector that can sense the low intensity fluorescent signal and convert it into an electrical signal, and its sensitivity should be at least greater than 1200A/Lm. In particular, the highly sensitive detector 54 in this embodiment is preferably a photomultiplier tube with an anode sensitivity of typically 1500A/Lm and a peak response wavelength of 400nm, which effectively measures and converts the intensity of the fluorescence signal passing through each of the filtered channels into an electrical signal. In other embodiments, the intensity of the fluorescence signal may also be measured using an optoelectronic device, such as a highly sensitive avalanche diode.
The data acquisition and processing unit 7 comprises a data acquisition device, a fluorescence life fitting module and a light intensity numerical value processing module. The bandwidth of the data acquisition unit should be at least 1GHz, the sampling rate is at least 4GS/s, the storage depth is at least 1Mpts, and the data acquisition unit includes a transient acquisition module and a steady-state acquisition module, which respectively acquire the analog electrical signals output by the high-speed response detector 43 and the high-sensitivity detector 54 and convert the analog electrical signals into digital signals. Wherein the transient acquisition module is triggered by the rising edge of the analog signal output by the high-speed response detector 43 and converts it into a time-varying digital signal. The steady state acquisition module performs integral acquisition of the electrical signal output by the high sensitivity detector 54, wherein the electrical signal integration time corresponding to the fluorescence of each wavelength should be greater than 100ms.
And the fluorescence life fitting module performs convolution fitting analysis on the digital signal obtained in the transient acquisition module. Specifically, the convolution fitting algorithm adopted in this embodiment is as follows:
Figure BDA0003895305970000061
Figure BDA0003895305970000062
Figure BDA0003895305970000063
wherein t and t' are both time, G (t) is a response function of the system, w is response characteristic time, and the time width of the response function is described and is determined by the pulse width of the exciting light, the bandwidth of the detector and the bandwidth of the data acquisition unit; f (t) is a function describing the excitation and decay of fluorescence, where r Characteristic time of fluorescence rising edge, A 0 And t 0 Coordinate translation of fluorescence intensity and time. k is the number of actual fluorescence decay processes, which is generally equal to 2 or 3 for autofluorescence of breast tissue and breast tumors, determined by the composition of the fluorophore substance of the test object, A i And τ i The amplitude and lifetime of the corresponding fluorescence decay process, respectively. Fitting with f (tThe influence of system response broadening can be removed, and the accurate autofluorescence lifetime can be obtained.
Finally, the average fluorescence lifetime τ is calculated from the following formula:
Figure BDA0003895305970000064
the mean fluorescence lifetime τ can be used as a fluorescence lifetime parameter for comparing and discriminating normal tissues and tumor tissues, and the fluorescence lifetime is referred to as the mean fluorescence lifetime τ hereinafter.
The light intensity numerical value processing module is used for calculating the digital signals obtained by the steady-state acquisition module so as to realize the discrimination of the tissues to be detected. In this embodiment, the fluorescence signals passing through the four filter channels are set to have light intensity I in the order of the wavelengths from low to high 1 、I 2 、I 3 、I 4 And by the formula R = (I) 2 +I 3 )/(I 1 +I 4 ) And calculating the R value. Selecting 0.95 as a threshold line, and judging the tissue to be detected as a normal mammary tissue when the R value is obviously greater than 0.95; when the R value is obviously less than 0.95, the tissue to be detected can be judged to be breast tumor tissue; for the tissue with the R value close to 0.95, the comparison result of the fluorescence lifetime and the typical fluorescence lifetime of normal mammary tissue is combined for judging.
The following are examples of the detection of breast tumor tissue and normal breast tissue by the breast tumor detection system.
Please refer to fig. 3, which shows the results of fluorescence lifetime detection and convolution fitting for breast tumor tissue and normal breast tissue respectively by using the system of this embodiment. The k value of the convolution fitting algorithm is 2, the autofluorescence lifetime generated by the obtained breast tumor tissue is 2.66ns, the autofluorescence lifetime generated by the normal breast tissue is 4.05ns, and obvious difference exists between the autofluorescence lifetime generated by the normal breast tissue and the autofluorescence lifetime generated by the normal breast tissue, so that the detection system has sufficient time resolution and sensitivity, and can meet the requirement of measuring the fluorescence lifetime of the breast tissue and the breast cancer tissue.
Please refer to fig. 4, which shows the detection results of the autofluorescence generated by the system for breast tumor tissue and normal breast tissue at wavelengths of 400nm, 420nm, 430nm, and 465nm. Wherein the light intensity of the two tissues on the selected characteristic wavelength has larger difference, so that the breast tumor tissue and the normal tissue can be discriminated according to the light intensity difference of the fluorescence signal generated by the tissue to be detected on the four wavelengths.
Please refer to fig. 5, which is a result of R values obtained by using the system to perform fluorescence intensity acquisition of the four characteristic wavelengths on 16 tissue samples (including 8 breast tumor tissue samples and 8 normal breast tissue samples) and further calculating the light intensities. Wherein, the R values of all tumor tissues are less than 0.95, and the R values of all normal breast tissues are greater than 0.95, so 0.95 can be selected as the threshold line for judging the breast tumor tissue and the normal breast tissue.
The invention determines the wavelength of the excitation light suitable for discriminating between the breast tumor tissue and the normal breast tissue, and the wavelength of the excitation light can enable the life and the intensity of the fluorescence signals of the breast tumor tissue and the normal breast tissue to have larger difference so as to be easier to detect. In addition, the invention adopts a hundred-picosecond-level excitation light source, a broadband avalanche photodiode with response time of subnanosecond level and a data collector with high bandwidth, high sampling rate and high storage depth to cooperate for fluorescence life detection, and eliminates errors in the system by using a convolution fitting method, thereby realizing the high-precision fluorescence life detection effect by using the cost far lower than that of the prior technical scheme, and being more beneficial to popularization and application in clinical detection. Furthermore, the fluorescence signal enters the transient detection unit and the steady detection unit simultaneously by utilizing the spectroscope, so that the synchronous detection of the fluorescence service life and the fluorescence light intensity can be realized, and compared with the method in the prior art, the method needs to carry out detection of the transient detection unit and the steady detection unit successively, the detection time is saved. Furthermore, compared with the prior art that the intensity of the fluorescence signal needs to be detected by using equipment such as a grating spectrometer and the like, the system selects wavelengths of 400nm, 420nm, 430nm and 465nm as characteristic wavelengths for detecting the fluorescence intensity, and an R value calculated by the respective light intensity values is used as a reference standard for screening the breast tumor tissue and the normal breast tissue, so that the cost is lower, the implementation is easier, and the result is more suitable for being used as a reference for screening the breast tumor tissue. In addition, the technical scheme of the invention is also suitable for detecting and screening the cancer metastasis of the axillary lymph node tissue.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that various changes and modifications can be made by those skilled in the art without departing from the spirit of the invention, and these changes and modifications are all within the scope of the invention.

Claims (10)

1. An autofluorescence-based breast tumor detection system, comprising: the device comprises an excitation light source, a light conduction unit, a transient detection unit and a data acquisition and processing unit; wherein the excitation light source generates ultraviolet excitation light with the pulse width of hundred picoseconds and the repetition frequency of kilohertz; the light conduction unit transmits the excitation light to irradiate the tissue to be detected, and an autofluorescence signal generated by the excited tissue to be detected is transmitted to the transient detection unit through the light conduction unit; the transient state detection unit comprises a high-speed response detector with response time in a subnanosecond level, and the high-speed response detector converts the fluorescent signal returned by the light conduction unit into an electric signal; the data acquisition and processing unit comprises a data acquisition unit and a fluorescence life fitting module, wherein the bandwidth of the data acquisition unit is at least 1GHz, the sampling rate is at least 4GS/s, the storage depth is at least 1Mpts, and the data acquisition and processing unit converts the electric signal output by the high-speed response detector into a digital signal; and the fluorescence fitting module performs convolution fitting processing on the digital signal to obtain the fluorescence lifetime of the autofluorescence signal.
2. The detection system of claim 1, wherein the convolution fitting process is formulated as:
Figure FDA0003895305960000011
wherein
Figure FDA0003895305960000012
Figure FDA0003895305960000013
In the formula, t and t' are both time, B is a normalization factor of a Gaussian response function, w is the response characteristic time of the system, and tau r Characteristic time of fluorescence rising edge, A 0 And t 0 The coordinate translation amounts of fluorescence intensity and time, respectively, k is the number of fluorescence decay processes, A i And τ i The amplitude and lifetime of the corresponding fluorescence decay process, respectively;
the average fluorescence lifetime τ is calculated from the following formula:
Figure FDA0003895305960000014
3. the detection system of claim 2, wherein: the excitation light source comprises a laser and a collimating mirror, wherein the laser is used for generating laser, and the collimating mirror is arranged on a light path of the laser.
4. The detection system according to claim 3, wherein the light conducting unit comprises a dichroic mirror, a first fiber coupling mirror, an optical fiber and a second fiber coupling mirror, wherein the dichroic mirror has a high reflectivity for the excitation light and a high transmittance for the autofluorescence light, is disposed on an optical path of the excitation light and reflects the excitation light into the first fiber coupling mirror, and two ends of the optical fiber are connected to the first fiber coupling mirror and the second fiber coupling mirror, respectively.
5. The detection system according to claim 4, wherein the collimating mirror, the first fiber coupling mirror and the second fiber coupling mirror are quartz lenses, and the optical fiber is an ultraviolet optical fiber.
6. The detection system according to any one of claims 1 to 5, further comprising a spectroscope and a steady-state detection unit, wherein the spectroscope is disposed on an optical path of the autofluorescence signal output by the light conduction unit, and divides the fluorescence signal into a transient path and a steady-state path, and allows the fluorescence signal of the transient path to enter the transient detection unit and the fluorescence signal of the steady-state path to enter the steady-state detection unit; the steady state detection unit comprises a fluorescence signal multi-channel band-pass filter device and a high-sensitivity detector which are sequentially arranged on a steady state circuit, wherein the multi-channel band-pass filter device comprises at least two filter channels, and each filter channel can enable a fluorescence signal in a specific wavelength range to pass through; the high-sensitivity detector converts the light intensity of the fluorescent signals passing through different filtering channels into electric signals respectively; and the data acquisition unit is also used for carrying out integral acquisition on the electric signals output by the high-sensitivity detector to obtain fluorescence signal intensity values in different wavelength ranges.
7. A detection system according to claim 6, characterised in that the multi-channel band-pass filter means comprises four filter channels having a bandwidth of 10nm and centre wavelengths of 400nm, 420nm, 430nm and 465nm respectively.
8. The inspection system of claim 7, wherein the multi-channel bandpass filter is a roller-type bandpass filter stack including a roller frame and 10nm bandpass filters with center wavelengths of 400nm, 420nm, 430nm, and 465nm, respectively.
9. The detection system according to claim 8, wherein the excitation light wavelength is 355nm.
10. According to the rightThe detection system of claim 9, wherein the data acquisition and processing unit further comprises a light intensity value processing module for processing the fluorescence signal intensity values obtained by the data acquisition unit in different wavelength ranges according to formula (I) 2 +I 3 )/(I 1 +I 4 ) Performing an operation of formula I 1 、I 2 、I 3 、I 4 And sequentially obtaining the fluorescence signal intensity values of the filtering channels with the central wavelengths of 400nm, 420nm, 430nm and 465nm.
CN202211271879.4A 2022-10-18 2022-10-18 Mammary gland tumor detection system based on autofluorescence Active CN115607110B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211271879.4A CN115607110B (en) 2022-10-18 2022-10-18 Mammary gland tumor detection system based on autofluorescence

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211271879.4A CN115607110B (en) 2022-10-18 2022-10-18 Mammary gland tumor detection system based on autofluorescence

Publications (2)

Publication Number Publication Date
CN115607110A true CN115607110A (en) 2023-01-17
CN115607110B CN115607110B (en) 2023-11-21

Family

ID=84863492

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202211271879.4A Active CN115607110B (en) 2022-10-18 2022-10-18 Mammary gland tumor detection system based on autofluorescence

Country Status (1)

Country Link
CN (1) CN115607110B (en)

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6426505B1 (en) * 2000-01-19 2002-07-30 University Of Maryland Biotechnology Institute Phase-modulation fluorometer and method for measuring nanosecond lifetimes using a lock-in amplifier
CN1362048A (en) * 2002-01-24 2002-08-07 华南师范大学 Visible light induced delayed lighting no-damage tumor imaging method and equipment
US20040073119A1 (en) * 2001-03-01 2004-04-15 Mary-Ann Mycek Fluorescence lifetime spectrometer (fls) and methods of detecting diseased tissues
EP1584918A2 (en) * 2004-04-07 2005-10-12 Europhoton GmbH, Gesellschaft für optische Sensorik Method and device for fluorescence lifetime imaging nanoscopy
CN1808101A (en) * 2004-12-15 2006-07-26 中国科学院上海应用物理研究所 Fluorescence detection method for DNA and kit thereof
US20070156036A1 (en) * 2004-06-17 2007-07-05 The Regents Of The University Of Californa Time-resolved non-invasive optometric device for detecting diabetes
US20080212867A1 (en) * 2007-03-02 2008-09-04 Provenzano Paolo P Use of Endogenous Fluorescence to Identify Invading Metastatic Breast Tumor Cells
US20120276578A1 (en) * 2010-10-27 2012-11-01 Chiara Stringari Phasor Method to Fluorescence Lifetime Microscopy to Discriminate Metabolic State of Cells in Living Tissue
CN104614353A (en) * 2015-01-28 2015-05-13 中国科学院半导体研究所 Two channel-based multi-spectrum fluorescent imaging microscopic system and method
CN106092996A (en) * 2016-08-03 2016-11-09 复旦大学 A kind of cancer diagnosis system based on the autofluorescence life-span
CN106383102A (en) * 2016-09-05 2017-02-08 广东工业大学 Method and system for measuring fluorescence lifetime
US20170250518A1 (en) * 2008-01-19 2017-08-31 Nkt Photonics A/S Variable Repetition Rate Supercontinuum Pulses
CN109211871A (en) * 2018-11-26 2019-01-15 深圳大学 A kind of stimulated emission depletion fluorescence lifetime super-resolution imaging device
WO2021204858A1 (en) * 2020-04-10 2021-10-14 Humanitas Mirasole S.P.A. Method for quantitative imaging of the metabolic status of a lesion
CN114624217A (en) * 2022-03-11 2022-06-14 桂林电子科技大学 System for detecting skin cancer lesion degree based on multispectral fluorescence lifetime

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6426505B1 (en) * 2000-01-19 2002-07-30 University Of Maryland Biotechnology Institute Phase-modulation fluorometer and method for measuring nanosecond lifetimes using a lock-in amplifier
US20040073119A1 (en) * 2001-03-01 2004-04-15 Mary-Ann Mycek Fluorescence lifetime spectrometer (fls) and methods of detecting diseased tissues
CN1362048A (en) * 2002-01-24 2002-08-07 华南师范大学 Visible light induced delayed lighting no-damage tumor imaging method and equipment
EP1584918A2 (en) * 2004-04-07 2005-10-12 Europhoton GmbH, Gesellschaft für optische Sensorik Method and device for fluorescence lifetime imaging nanoscopy
US20070156036A1 (en) * 2004-06-17 2007-07-05 The Regents Of The University Of Californa Time-resolved non-invasive optometric device for detecting diabetes
CN1808101A (en) * 2004-12-15 2006-07-26 中国科学院上海应用物理研究所 Fluorescence detection method for DNA and kit thereof
US20080212867A1 (en) * 2007-03-02 2008-09-04 Provenzano Paolo P Use of Endogenous Fluorescence to Identify Invading Metastatic Breast Tumor Cells
US20170250518A1 (en) * 2008-01-19 2017-08-31 Nkt Photonics A/S Variable Repetition Rate Supercontinuum Pulses
US20120276578A1 (en) * 2010-10-27 2012-11-01 Chiara Stringari Phasor Method to Fluorescence Lifetime Microscopy to Discriminate Metabolic State of Cells in Living Tissue
CN104614353A (en) * 2015-01-28 2015-05-13 中国科学院半导体研究所 Two channel-based multi-spectrum fluorescent imaging microscopic system and method
CN106092996A (en) * 2016-08-03 2016-11-09 复旦大学 A kind of cancer diagnosis system based on the autofluorescence life-span
CN106383102A (en) * 2016-09-05 2017-02-08 广东工业大学 Method and system for measuring fluorescence lifetime
CN109211871A (en) * 2018-11-26 2019-01-15 深圳大学 A kind of stimulated emission depletion fluorescence lifetime super-resolution imaging device
WO2021204858A1 (en) * 2020-04-10 2021-10-14 Humanitas Mirasole S.P.A. Method for quantitative imaging of the metabolic status of a lesion
CN114624217A (en) * 2022-03-11 2022-06-14 桂林电子科技大学 System for detecting skin cancer lesion degree based on multispectral fluorescence lifetime

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ZHANG WEI,等: "A time-domain fluorescence diffusion optical tomography system for breast tumor diagnosis", 《CONFERENCE ON OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE IX》, pages 1 - 11 *
杨乾乾: "荧光寿命成像在皮肤癌诊断中的应用研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, no. 5, pages 1 - 70 *

Also Published As

Publication number Publication date
CN115607110B (en) 2023-11-21

Similar Documents

Publication Publication Date Title
James et al. Excitation pulse‐shape mimic technique for improving picosecond‐laser‐excited time‐correlated single‐photon counting deconvolutions
CN111060516B (en) Multi-channel in-situ detection device and method for subsurface defects of optical element
WO2013116760A1 (en) Optical analysis of emissions from stimulated liquids
CN110108677B (en) Biological delay luminescence detection system
CN108088832A (en) A kind of single light source CARS spectral devices and the method for detecting Raman active medium
CN201795862U (en) Ultraviolet-visible and fluorescence combined spectrometer
CN101995387A (en) Multi-functional ultraviolet-visible spectrometer
CN108051413A (en) A kind of light activated photoluminescence spectra measuring system of pulse
CN103592277A (en) High-precision fluorescent lifetime measuring device
CN114460061A (en) Time-gated Raman spectrum system and Raman spectrum correction method
Holtom Artifacts and diagnostics in fast fluorescence measurements
CN214096364U (en) Raman probe based on double compound eye lens set
CN107121208A (en) The data acquisition device and lifetime of excited state measuring method of lifetime of excited state measurement based on frequency counting card
CN106680260B (en) A kind of portable coherent antistockes Raman spectroscopy instrument
CN112505016A (en) Compact portable multi-wavelength in-situ Raman detector and detection method thereof
Prenna et al. Methodological and instrumentational aspects of cytofluorometry
CN115607110B (en) Mammary gland tumor detection system based on autofluorescence
CN112113939A (en) Fluorescence lifetime imaging method and device based on spectral technology
US20070139652A1 (en) Fiber optical assembly for fluorescence spectrometry
CN115046987B (en) Time-gated Raman spectrum system and time synchronization compensation method thereof
Vickers et al. Time-resolved fluorescence with an optical-fiber probe
CN108007906B (en) Long afterglow material phosphorescence excitation spectrum measurement system and method
CN108152252B (en) Integral femtosecond time resolution fluorescence life measuring spectrometer
Näther et al. Temporal and spectral separation of singlet oxygen luminescence from near infrared emitting photosensitizers
Bowman et al. A single photon timing instrument that covers a broad temporal range in the reversed timing configuration

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant