CN102599884A - Laser early cancer diagnosis instrument - Google Patents
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Abstract
本发明公开了一种激光早期癌症诊断仪。它的激光器(1)与光纤耦合器(6)之间的光路上依次置有倍频器(2)、混频器(3)、分频器(4)和滤光片(5);分频器(4)的光路上置有提供采集触发信号的光电转换器(11);传导光纤(7)由入射光纤(71)和接收光纤(72)组成;接收光纤(72)与计算机(12)之间置有用于接收荧光信号的带通滤光片(9)和光电探测器(10);计算机(12)分别与激光器(1)、光电转换器(11)、光电探测器(10)和输出设备(13)电连接,用于控制激光器(1)、对采集到的荧光信号使用时域法进行积分处理,并将其与正常组织的荧光信号比较后的结果送往输出设备(13)显示。它能对多种早期癌症进行有效的诊断。
The invention discloses a laser early cancer diagnosis instrument. A frequency multiplier (2), a frequency mixer (3), a frequency divider (4) and an optical filter (5) are sequentially placed on the optical path between its laser (1) and the fiber coupler (6); The optical path of the frequency converter (4) is equipped with a photoelectric converter (11) that provides an acquisition trigger signal; the conduction optical fiber (7) is made up of an incident optical fiber (71) and a receiving optical fiber (72); the receiving optical fiber (72) is connected to the computer (12 ) are provided with a band-pass filter (9) and a photodetector (10) for receiving fluorescent signals; It is electrically connected with the output device (13), used to control the laser (1), integrate the collected fluorescence signal using the time domain method, and send the result of comparison with the fluorescence signal of normal tissue to the output device (13 )show. It can effectively diagnose many kinds of early cancers.
Description
技术领域 technical field
本发明涉及一种诊断仪,尤其是一种激光早期癌症诊断仪。The invention relates to a diagnostic instrument, in particular to a laser early cancer diagnostic instrument.
背景技术 Background technique
自1984年Alfano等发现利用低功率激光可诱导乳腺、肺组织的自体荧光,以及Richards等用290~600nm波长的激光诱发结肠粘膜组织产生自体荧光以来,很多学者开始了研究利用激光诱导荧光(laser inducedfluorescence,LIF)技术进行光谱分析来诊断早期大肠恶性肿瘤。LIF技术在肠癌早期诊断方面,提出了一种全新的有效诊断途径和方法,在大肠癌及癌前病变的早期诊断方面取得了很大的进展,开创了一种崭新的肿瘤检测方法-光活检术。目前,LIF诊断仪器多由激发光源、传导光纤、光耦合器、多色仪、光学多道分析系统(OMA)和计算机组成,其虽经LIF诊断与组织学诊断的对照验证,其阳性符合率为100%,阴性符合率为94%,为早期诊疗大肠癌提供了较可靠的手段,却也存在着难以克服的不足之处,首先,可诊断的范围太窄,仅能对肠癌进行有效地诊断;其次,因探测到的荧光谱线太弱,不清晰,故对操作人员专业技术水平的要求很高;再次,整套设备造价昂贵,超过100万元人民币,使其的推广应用和产业化难以进行,导致产品推向市场缺乏竞争力。Since Alfano et al. discovered in 1984 that low-power lasers could induce autofluorescence in breast and lung tissues, and Richards et al. used lasers with a wavelength of 290-600 nm to induce autofluorescence in colonic mucosal tissue, many scholars have begun to study the use of laser-induced fluorescence (laser-induced fluorescence). inducedfluorescence (LIF) technology for spectral analysis to diagnose early colorectal malignancies. LIF technology has proposed a new and effective diagnostic approach and method in the early diagnosis of colorectal cancer, and has made great progress in the early diagnosis of colorectal cancer and precancerous lesions, and created a new tumor detection method-light biopsy. At present, LIF diagnostic instruments are mostly composed of excitation light source, conductive optical fiber, optical coupler, polychromator, optical multi-channel analysis system (OMA) and computer. It is 100% and the negative coincidence rate is 94%. It provides a relatively reliable means for early diagnosis and treatment of colorectal cancer, but there are also insurmountable deficiencies. secondly, because the detected fluorescence spectrum line is too weak and unclear, so the professional technical level of the operator is very high; thirdly, the whole set of equipment is expensive, more than 1 million yuan, which makes its popularization and application and industry It is difficult to carry out the transformation, resulting in the lack of competitiveness of products in the market.
发明内容 Contents of the invention
本发明要解决的技术问题为克服现有技术中的不足之处,提供一种诊断范围大、操作简便、价廉物美的激光早期癌症诊断仪。The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art and provide a laser early cancer diagnostic instrument with a large diagnostic range, easy operation, low price and good quality.
为解决本发明的技术问题,所采用的技术方案为:激光早期癌症诊断仪包括激光器、光纤耦合器、传导光纤和计算机,特别是,In order to solve the technical problems of the present invention, the technical solution adopted is: the laser early cancer diagnostic instrument comprises a laser, an optical fiber coupler, a conducting optical fiber and a computer, especially,
所述激光器与光纤耦合器之间的发射光路上依次置有倍频器、混频器、分频器和滤光片,用于输出波长为350~380nm的激光;A frequency multiplier, a frequency mixer, a frequency divider and an optical filter are sequentially arranged on the emission optical path between the laser and the fiber coupler, for outputting laser light with a wavelength of 350-380nm;
所述分频器的发射光路上置有光电转换器,用于提供荧光信号采集的触发信号;A photoelectric converter is placed on the emission optical path of the frequency divider, which is used to provide a trigger signal for fluorescence signal collection;
所述传导光纤由入射光纤和接收光纤组成;The guide fiber is composed of an incident fiber and a receiving fiber;
所述接收光纤与计算机之间的接收光路上置有带通滤光片和光电探测器,用于接收被测物经激光照射后发出的荧光信号;A band-pass filter and a photodetector are placed on the receiving optical path between the receiving optical fiber and the computer for receiving the fluorescent signal emitted by the measured object after being irradiated by laser light;
所述计算机分别与激光器、光电转换器、光电探测器和输出设备电连接,用于控制激光器、对采集到的荧光信号使用时域法进行积分处理,并将其与正常组织的荧光信号比较后的结果送往输出设备显示。The computer is electrically connected to the laser, the photoelectric converter, the photodetector and the output device respectively, and is used to control the laser, integrate and process the collected fluorescence signal using the time domain method, and compare it with the fluorescence signal of normal tissue. The results are sent to the output device for display.
作为激光早期癌症诊断仪的进一步改进,所述的激光器由振荡光路上依次置有的全反镜、调Q晶体、起偏器、激光晶体和输出镜组成,其输出的激光波长为1064nm;所述的激光器输出镜和倍频器之间的发射光路上依次置有与入射光均呈45度角设置的第一反射镜和第二反射镜;所述的倍频器为BBO晶体;所述的混频器为BBO晶体;所述的分频器和滤光片之间的发射光路上依次置有光栏和与入射光呈45度角设置的第三反射镜;所述的第三反射镜上镀有对355nm波长的光全反膜、对532nm和1064nm波长的光增透膜;所述的光电转换器位于分频器分出的波长为532nm或1064nm的发射光路上;所述的接收光纤为两根以上且于入射光纤周边对称设置;所述的滤光片为过滤其他波长光,仅通过350~380nm波长光的滤光片。As a further improvement of the laser early cancer diagnostic instrument, the laser is composed of a total reflection mirror, a Q-switched crystal, a polarizer, a laser crystal, and an output mirror that are sequentially placed on the oscillating optical path, and the output laser wavelength is 1064nm; The first reflector and the second reflector arranged at an angle of 45 degrees to the incident light are arranged successively on the emission optical path between the laser output mirror and the frequency multiplier; the frequency multiplier is a BBO crystal; The frequency mixer is a BBO crystal; the emission light path between the frequency divider and the optical filter is sequentially provided with a light barrier and a third reflector arranged at an angle of 45 degrees with the incident light; the third reflector The mirror is coated with a total reflection film for 355nm wavelength light, and an optical anti-reflection film for 532nm and 1064nm wavelength; the photoelectric converter is located on the emission light path with a wavelength of 532nm or 1064nm separated by the frequency divider; There are more than two receiving optical fibers and they are arranged symmetrically around the incident optical fiber; the optical filter filters other wavelength light and only passes 350-380nm wavelength light.
相对于现有技术的有益效果是,采用激光器与光纤耦合器之间的发射光路上依次置有倍频器、混频器、分频器和滤光片,分频器的发射光路上置有光电转换器,传导光纤由入射光纤和接收光纤组成,且接收光纤与计算机之间的接收光路上置有带通滤光片和光电探测器,以及计算机分别与激光器、光电转换器、光电探测器和输出设备电连接的技术方案,是基于申请人经对大量的实验结果作归一化处理后而得出的:不同的人体正常组织与相应的癌组织具有相似的光谱分布,两者只是在光谱的强度上有所区别。为此,申请人采用先于适宜波段的激光照射被测物--人体组织的同时,对其所产生的自体荧光信号使用时域法进行积分处理,使极微弱的荧光信号经积分处理后被整合成了清晰、明确的荧光波形强度信号,再将其与已知正常组织的荧光信号进行比较,进而得到准确的诊断结果。从而既使本发明诊断的范围大大地扩展了,又极大地降低了操作人员的专业技术水平,并使操作极为简便,还价廉物美,整机的总造价仅约为20万元人民币。Compared with the prior art, the beneficial effect is that a frequency multiplier, a frequency mixer, a frequency divider and an optical filter are sequentially arranged on the emission optical path between the laser and the fiber coupler, and the emission optical path of the frequency divider is equipped with The photoelectric converter, the transmission fiber is composed of the incident fiber and the receiving fiber, and the receiving optical path between the receiving fiber and the computer is equipped with a bandpass filter and a photodetector, and the computer is connected with the laser, the photoelectric converter, and the photodetector respectively. The technical scheme of electrical connection with the output device is based on the applicant's normalization of a large number of experimental results: different human normal tissues and corresponding cancer tissues have similar spectral distributions, and the two are only in the There is a difference in the intensity of the spectrum. For this reason, the applicant irradiates the measured object--human tissue with a laser that is ahead of the appropriate wavelength band, and at the same time integrates the autofluorescence signal generated by it using the time-domain method, so that the extremely weak fluorescence signal is integrated and processed. A clear and unambiguous fluorescent waveform intensity signal is integrated, which is then compared with the fluorescent signal of known normal tissues to obtain accurate diagnostic results. Therefore, the scope of diagnosis of the present invention is greatly expanded, and the technical level of operators is greatly reduced, and the operation is extremely simple, and the price is cheap. The total cost of the whole machine is only about 200,000 yuan.
作为有益效果的进一步体现,一是激光器优选由振荡光路上依次置有的全反镜、调Q晶体、起偏器、激光晶体和输出镜组成,其输出的激光波长优选为1064nm,为准确诊断癌症提供了波段适宜的激光源;二是激光器输出镜和倍频器之间的发射光路上依次优选置有与入射光均呈45度角设置的第一反射镜和第二反射镜,极大地减小了诊断仪的体积;三是倍频器优选为BBO晶体,混频器优选为BBO晶体,不仅工作稳定可靠,还有着通用性强的优点;四是分频器和滤光片之间的发射光路上优选依次置有光栏和与入射光呈45度角设置的第三反射镜,除大大地降低了波长为532nm或1064nm的光的影响之外,还进一步地减小了诊断仪的体积;五是第三反射镜上优选镀有对355nm波长的光全反膜、对532nm和1064nm波长的光增透膜,利于仅为355nm波长的光作为照射人体组织的激光源;六是光电转换器优选位于分频器分出的波长为532nm或1064nm的光路上,便于控制采集被测物经激光照射后发出的自体荧光信号的起始时间的获得;七是接收光纤优选为两根以上且于入射光纤周边对称设置,利于较充分完整地采集自体荧光信号;八是滤光片优选为过滤其他波长光,仅通过350~380nm波长光的滤光片,确保了照射人体组织的激光位于合适的波段内。As a further embodiment of the beneficial effect, one is that the laser is preferably composed of a total reflection mirror, a Q-switched crystal, a polarizer, a laser crystal, and an output mirror that are sequentially placed on the oscillating optical path. Cancer provides a laser source with a suitable wavelength band; the second is that the first reflector and the second reflector that are set at an angle of 45 degrees to the incident light are preferably arranged in sequence on the emission light path between the laser output mirror and the frequency multiplier, which greatly improves the The volume of the diagnostic instrument is reduced; the third is that the frequency multiplier is preferably BBO crystal, and the mixer is preferably BBO crystal, which not only works stably and reliably, but also has the advantage of strong versatility; fourth is the gap between the frequency divider and the filter. It is preferable to place a light barrier and a third mirror set at an angle of 45 degrees to the incident light in sequence on the emission light path of the light emission, which not only greatly reduces the influence of light with a wavelength of 532nm or 1064nm, but also further reduces the diagnostic equipment. The fifth is that the third reflector is preferably coated with a total reflection film for light with a wavelength of 355nm, and an anti-reflection film for light with a wavelength of 532nm and 1064nm, which is beneficial to only light with a wavelength of 355nm as a laser source for irradiating human tissue; six is The photoelectric converter is preferably located on the optical path with a wavelength of 532nm or 1064nm separated by the frequency divider, which is convenient for controlling the acquisition of the starting time of the autofluorescent signal emitted by the measured object after being irradiated by laser light; seven is that the receiving optical fiber is preferably two The above and the symmetrical arrangement around the incident optical fiber are conducive to the collection of autofluorescence signals more fully and completely; eighth, the filter is preferably used to filter other wavelengths of light, and only passes through the filter of 350-380nm wavelength light to ensure that the laser light irradiating human tissues in the appropriate band.
附图说明 Description of drawings
下面结合附图对本发明的优选方式作进一步详细的描述。The preferred modes of the present invention will be further described in detail below in conjunction with the accompanying drawings.
图1是本发明的一种基本结构示意图。Fig. 1 is a kind of basic structure schematic diagram of the present invention.
图2是图1中传导光纤之前光路上的激光器和相关的光学元器件示意图。Fig. 2 is a schematic diagram of the laser and related optical components on the optical path before the optical fiber in Fig. 1 .
图3是图1中的传导光纤的一种基本结构示意图。FIG. 3 is a schematic diagram of a basic structure of the guiding fiber in FIG. 1 .
图4是人体正常肠组织和肠癌组织之间的荧光对比图;图中的横坐标为时间、纵坐标为电压。Fig. 4 is a fluorescence contrast diagram between human normal intestinal tissue and intestinal cancer tissue; the abscissa in the figure is time, and the ordinate is voltage.
图5是人体正常胃组织和胃癌组织之间的荧光对比图;图中的横坐标为时间、纵坐标为电压。Fig. 5 is a fluorescence contrast diagram between human normal gastric tissue and gastric cancer tissue; the abscissa in the figure is time, and the ordinate is voltage.
具体实施方式 Detailed ways
参见图1、图2和图3,激光早期癌症诊断仪由发射光路上依次置有的激光器1、倍频器2、混频器3、分频器4、滤光片5、光纤耦合器6和传导光纤7及光电转换器11,接收光路上置有的带通滤光片9和光电探测器10,以及与计算机12电连接的激光器1、光电转换器11、光电探测器10和输出设备13构成。其中:Referring to Fig. 1, Fig. 2 and Fig. 3, the laser early cancer diagnostic instrument consists of a
激光器1由振荡光路上依次置有的全反镜101、调Q晶体102、起偏器103、激光晶体104和输出镜105组成,其输出的激光波长为1064nm。The
上述激光器1与光纤耦合器6之间的发射光路上依次置有的倍频器2、混频器3、分频器4和滤光片5,是用于输出波长为350~380nm的激光的。A frequency multiplier 2, a frequency mixer 3, a
分频器4的发射光路上置有的光电转换器11,是用于提供荧光信号采集的触发信号的。The
传导光纤7由入射光纤71和接收光纤72组成。The guide fiber 7 is composed of an
接收光纤72与计算机12之间的接收光路上置有的带通滤光片9和光电探测器10,是用于接收被测物8经激光照射后发出的荧光信号的。The band-
计算机12分别与激光器1、光电转换器11、光电探测器10和输出设备13电连接,是用于控制激光器1、对采集到的荧光信号使用时域法进行积分处理,并将其与正常组织的荧光信号比较后的结果送往输出设备13显示的。The
为进一步地优化本发明的性能和减小其体积,激光器1输出镜105和倍频器2之间的发射光路上依次置有与入射光均呈45度角设置的第一反射镜14和第二反射镜15;倍频器2和混频器3均选择为BBO晶体;分频器4和滤光片5之间的发射光路上依次置有光栏16和与入射光呈45度角设置的第三反射镜17;该第三反射镜17上镀有对355nm波长的光全反膜、对532nm和1064nm波长的光增透膜;光电转换器11位于分频器4分出的波长为532nm或1064nm的发射光路上;接收光纤72为两根且于入射光纤71周边对称设置;滤光片5为过滤其他波长光,仅通过350~380nm波长光的滤光片,计算机12为微型计算机;输出设备13为显示器或打印机。In order to further optimize the performance of the present invention and reduce its volume, the first reflection mirror 14 and the second reflector 14 which are arranged at an angle of 45 degrees to the incident light are sequentially placed on the emission optical path between the output mirror 105 of the
使用时,只需将由入射光纤71处导出的激光照射于被测物8--人体组织之上,即可由输出设备13处获得如或近似于图4或图5所示的诊断结果。When in use, only need to irradiate the laser light derived from the
显然,本领域的技术人员可以对本发明的激光早期癌症诊断仪进行各种改动和变型而不脱离本发明的精神和范围。这样,倘若对本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内,则本发明也意图包含这些改动和变型在内。Obviously, those skilled in the art can make various changes and modifications to the laser early cancer diagnostic instrument of the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and equivalent technologies, the present invention also intends to include these modifications and variations.
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