WO2022166563A1 - 一种用于监测2-nbdg标记的活体循环肿瘤细胞的装置 - Google Patents

一种用于监测2-nbdg标记的活体循环肿瘤细胞的装置 Download PDF

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WO2022166563A1
WO2022166563A1 PCT/CN2022/072030 CN2022072030W WO2022166563A1 WO 2022166563 A1 WO2022166563 A1 WO 2022166563A1 CN 2022072030 W CN2022072030 W CN 2022072030W WO 2022166563 A1 WO2022166563 A1 WO 2022166563A1
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laser
nbdg
tumor cells
circulating tumor
monitoring
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French (fr)
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魏勋斌
翁小阜
庞恺
顾波波
魏丹
杨章孺
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上海交通大学
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6486Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation

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  • the invention belongs to the technical field of circulating tumor cell detection, and relates to a device for monitoring 2-NBDG-labeled living circulating tumor cells.
  • Circulating Tumor Cells are an important marker of tumor metastasis.
  • CTCs are solid tumor-derived cells detectable in peripheral blood. The occurrence of CTCs is considered to be a prerequisite for the establishment of distant metastasis. The number of CTCs can be used to judge the progress of tumor metastasis, and can also be used as an important indicator for the prognosis judgment of tumor patients, the rapid evaluation of chemotherapy drugs, and tumor recurrence.
  • cancer metastasis is closely related to CTCs, including breast cancer, prostate cancer, melanoma, liver cancer, colon cancer and lung cancer, etc., and many research results have found that CTCs exist in different stages of the tumor. It is closely related to tumor progression, metastasis and recurrence. Therefore, the detection of circulating tumor cells has important scientific significance and clinical application value.
  • CTCs detection techniques can be roughly divided into two types: 1) Immunotype detection: using monoclonal antibodies to directly label and detect tissue-specific proteins of tumors; 2) Molecular type detection: using polymerase chain reaction (polymerase chain reaction) ( Polymerase Chain Reaction, PCR) technology to detect tumor tissue-specific transcripts.
  • polymerase chain reaction Polymerase Chain Reaction, PCR
  • techniques such as density gradient centrifugation and immunomagnetic bead sorting have also been introduced into the detection of CTCs to enrich trace amounts of CTCs in blood, thereby improving the sensitivity of the detection.
  • the above-mentioned CTC enrichment, separation and analysis techniques are all in vitro detection techniques, and the limitation of in vitro detection techniques is that in vitro blood collection is required for detection.
  • the in vitro blood collection process makes circulating tumor cells separate from the living bloodstream environment, and changes in blood parameters and cell physiological environment may lead to changes in circulating tumor cell parameters, resulting in inaccurate test results.
  • the detection sensitivity is limited due to the limited blood collection volume, and it is difficult to frequently draw blood to achieve dynamic monitoring (such as drug efficacy evaluation in the course of tumor chemotherapy).
  • the object of the present invention is to provide a device for monitoring 2-NBDG-labeled living circulating tumor cells, which can realize the monitoring of living circulating tumor cells.
  • a device for monitoring 2-NBDG-labeled living circulating tumor cells comprising:
  • Laser excitation system for generating laser light
  • Laser shaping and focusing system which is used to shape and focus the laser to form a laser slit
  • the fluorescence signal receiving system is used to receive the fluorescence generated by the laser excitation when the living circulating tumor cells labeled with 2-NBDG in the blood vessels flow through the laser slit;
  • the signal analysis system is used for processing and analyzing the fluorescence received by the fluorescence signal receiving system.
  • the laser excitation system includes a laser transmitter.
  • the laser excitation system includes a laser transmitter.
  • the laser excitation system includes at least two laser emitters for generating laser light of at least two wavelengths.
  • the laser light generated by the laser excitation system includes, but is not limited to, one or more of a 488 nm laser, a 532 nm laser, a 561 nm laser, and a 635 nm laser.
  • the laser shaping and focusing system includes one or more of a reflecting mirror, a concave lens, a convex lens, a dichroic mirror or a focusing objective lens. After the laser is focused, a laser slit is formed to cover the human or animal blood vessels.
  • the fluorescent signal receiving system includes a fluorescent receiver.
  • the fluorescent signal receiving system includes a photoelectric conversion device, which converts the fluorescent signal into an electrical signal.
  • the photoelectric conversion device includes a photomultiplier tube.
  • the signal analysis system includes a signal processor.
  • the signal analysis system includes a filter.
  • the signal analysis system uses wavelet filtering, artificial intelligence and other algorithms to denoise the signal and obtain the fluorescence signal of CTCs.
  • the working principle of the present invention is:
  • the present invention injects 2-NBDG into the human or animal blood circulatory system to label CTCs; the laser is shaped and focused to form a laser slit, covering the human body or The blood vessels of animals, when the CTCs labeled with 2-NBDG flow through the laser slit, are excited by the laser to generate fluorescence, and the fluorescence signal receiving system receives the fluorescence, and then in the signal analysis system, the background is removed by artificial intelligence signal processing technology Noise, acquire the fluorescence signal of CTCs, and realize real-time dynamic monitoring of circulating tumor cells in blood vessels.
  • This method provides a new technical means for in vivo monitoring and assessment of clinical tumor metastasis.
  • the present invention has the following characteristics:
  • the present invention can realize the labeling of circulating tumor cells by using 2-deoxyglucose analog (2-NBDG) as a marker of circulating tumor cells.
  • 2-NBDG has no radioactivity, and the metabolism time in the body is 24h, and the cytotoxicity is small. It can provide a new feasible solution for clinical detection of CTCs;
  • the present invention detects living circulating tumor cells, it is not separated from the living blood flow environment, the blood parameters and the cell physiological environment do not change, the circulating tumor cell parameters do not change, and the detection results are more accurate;
  • the present invention When the present invention is used to detect circulating tumor cells in vivo, it is not limited by the amount of blood collection, and the detection sensitivity is improved.
  • Fig. 1 is a schematic diagram of the present invention when detecting 2-NBDG-labeled living circulating tumor cells in blood vessels;
  • Figure 2 is a graph of the fluorescence signal (without signal processing) of the CTCs detected in the application example
  • FIG. 3 is a graph of the fluorescence signal (after signal processing) of the CTCs detected in the application example
  • 1 laser excitation system
  • 2 laser shaping and focusing system
  • 3 laser slit
  • 4 fluorescence signal receiving system
  • 5 signal analysis system
  • 6 fluorescence
  • 7 2-NBDG labeled living circulating tumor cells
  • 8 Blood vessel.
  • a device for monitoring 2-NBDG-labeled living circulating tumor cells includes:
  • Laser excitation system 1 for generating laser light
  • the laser shaping and focusing system 2 is used for shaping and focusing the laser to form a laser slit 3;
  • the fluorescence signal receiving system 4 is used for receiving the fluorescence 6 generated by the laser excitation when the 2-NBDG-labeled living circulating tumor cells 7 in the blood vessel 8 flow through the laser slit 2;
  • the signal analysis system 5 is used for processing and analyzing the fluorescence 6 received by the fluorescence signal receiving system 4 .
  • the method for intelligent monitoring of 2-NBDG-labeled living circulating tumor cells 7 is as follows: 2-NBDG is used as a fluorescent dye to label CTCs, and blood vessels 8 are used as natural sheath flow.
  • the laser slit 3 covers the cross section of the blood vessel 8.
  • the 2-NBDG-labeled living circulating tumor cells 7 flow through the laser slit 3, they are excited by the laser to generate fluorescence 6, and the fluorescence signal receiving system 4 receives the fluorescence 6, and then The background noise is removed by artificial intelligence signal processing technology, and the fluorescence signal of CTCs is obtained, so as to realize the real-time dynamic monitoring of circulating tumor cells in blood vessels.
  • mice After the subcutaneous tumor of tumor cells expressing red fluorescent protein (mCherry) was successfully constructed, the mice were fasted for 1 hour, and 1.6 mg/mL 2-NBDG solution was slowly injected into the mice at a dose of 8 mg/Kg through the tail vein for 1.5 hours. The mice were then placed on the IVFC for detection using 561 nm and 488 nm lasers. The data was continuously monitored for one hour, with every ten minutes as a small node. Finally, after all data were aggregated, the average number of double-positive signals detected per minute was counted, representing the living circulating tumor cells labeled with 2-NBDG in the circulation.
  • 2-NBDG red fluorescent protein
  • FIG. 2 is a graph of the detected fluorescence signal of CTCs (without signal processing)
  • FIG. 3 is a graph of the detected fluorescence signal of CTCs (with signal processing).
  • a device for monitoring 2-NBDG labeled living circulating tumor cells comprising:
  • Laser excitation system 1 for generating laser light
  • the laser shaping and focusing system 2 is used for shaping and focusing the laser to form a laser slit 3;
  • the fluorescence signal receiving system 4 is used for receiving the fluorescence 6 generated by the laser excitation when the 2-NBDG-labeled living circulating tumor cells 7 in the blood vessel 8 flow through the laser slit 2;
  • the signal analysis system 5 is used for processing and analyzing the fluorescence 6 received by the fluorescence signal receiving system 4 .
  • the laser excitation system 1 includes at least two laser transmitters for generating laser light of at least two wavelengths.
  • the lasers generated by the laser excitation system 1 include at least two of 488 nm lasers, 532 nm lasers, 561 nm lasers, and 635 nm lasers.
  • the laser shaping and focusing system 2 includes one or more of a mirror, a concave lens, a convex lens, a dichroic mirror or a focusing objective lens.
  • the fluorescent signal receiving system 4 includes a photoelectric conversion device, and the photoelectric conversion device includes a photomultiplier tube.
  • the signal analysis system 5 includes a signal processor.
  • a device for monitoring 2-NBDG labeled living circulating tumor cells comprising:
  • Laser excitation system 1 for generating laser light
  • the laser shaping and focusing system 2 is used for shaping and focusing the laser to form a laser slit 3;
  • the fluorescence signal receiving system 4 is used for receiving the fluorescence 6 generated by the laser excitation when the 2-NBDG-labeled living circulating tumor cells 7 in the blood vessel 8 flow through the laser slit 2;
  • the signal analysis system 5 is used for processing and analyzing the fluorescence 6 received by the fluorescence signal receiving system 4 .
  • the laser excitation system 1 includes a laser transmitter, and the generated laser is 488 nm laser, 532 nm laser, 561 nm laser or 635 nm laser.
  • the laser shaping and focusing system 2 includes one or more of a mirror, a concave lens, a convex lens, a dichroic mirror or a focusing objective lens.
  • the fluorescent signal receiving system 4 includes a fluorescent receiver.
  • the signal analysis system 5 includes filters.

Abstract

一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,包括:激光激发系统(1),用于产生激光;激光整形聚焦系统(2),用于将激光进行整形聚焦形成激光狭缝(3);荧光信号接收系统(4),用于接收血管(8)中2-NBDG标记的活体循环肿瘤细胞(7)流经激光狭缝(3)时被激光激发产生的荧光(6);信号分析系统(5),用于对荧光信号接收系统(4)接收的荧光(6)进行处理分析。与现有技术相比,能够实现将2-脱氧葡萄糖类似物作为循环肿瘤细胞的标记物对循环肿瘤细胞进行标记,2-NBDG不具有放射性,细胞毒性小,可为临床检测CTCs提供新的可行性方案;在检测活体循环肿瘤细胞时,没有脱离活体血流环境,血液参数及细胞生理环境没有发生变化,循环肿瘤细胞参数不发生变化,检测结果更加准确。

Description

一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置 技术领域
本发明属于循环肿瘤细胞检测技术领域,涉及一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置。
背景技术
循环肿瘤细胞(Circulating Tumor Cells,CTCs)是肿瘤转移的重要标志,CTCs是外周血中可检测到的实体肿瘤来源的细胞,CTCs的发生被认为是建立远处转移的先决条件。CTCs的数目可以用来判断肿瘤的转移进程,也可以作为肿瘤患者的预后判断、化疗药物的快速评估、肿瘤复发等的重要指标。目前临床已经证明了癌症转移与CTCs密切相关的癌症包括乳腺癌、前列腺癌、黑色素瘤、肝癌、结肠癌和肺癌等,并且已有许多研究结果发现CTCs在肿瘤的不同阶段存在,CTCs的数量统计与肿瘤的进展、转移以及复发均有着密切关系。因此,循环肿瘤细胞的检测具有重要的科学意义和临床应用价值。
然而,由于CTCs数目非常稀少,每毫升血液中平均仅存在0-10个CTCs,而血液中含有大量的正常细胞,尤其是白细胞的存在通常会影响最终的结果判读。因此,如何实现在高灵敏度的情况下提高检测的特异性,从大量正常细胞中筛选出目的细胞,是CTCs检测技术发展的必要前提。
目前,用于CTCs检测相对成熟的技术都是基于病人血液样本进行检测的体外技术,即传统CTCs检测技术。所有这些传统CTCs检测技术,可以大致分为两种类型:1)免疫型检测:使用单克隆抗体对肿瘤的组织特异性蛋白进行直接标识检测;2)分子型检测:利用聚合酶链式反应(Polymerase Chain Reaction,PCR)技术对肿瘤组织特异性转录物进行检测。另外,密度梯度离心和免疫磁珠分选等技术也被引入到CTCs的检测中,以对血液中微量的CTCs进行富集,从而提高检测的灵敏度。上述循环肿瘤细胞富集、分离及分析技术均为体外检测技术,而体外检测技术的局限是需要体外采血进行检测。体外采血过程使循环肿瘤细胞脱离了活体血流环境,而血液参数及细胞生理环境发生变化可能会导致循环肿瘤细胞参数发生变化,致使检测结果不准确。此外,由于采血量有限而导致检测灵敏度有限,且难以频繁抽血实现动态监测(如在肿瘤化疗疗程进行中的药效评估)。
发明内容
本发明的目的是提供一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,能够 实现活体循环肿瘤细胞监测。
本发明的目的可以通过以下技术方案来实现:
一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,该装置包括:
激光激发系统,用于产生激光;
激光整形聚焦系统,用于将激光进行整形聚焦形成激光狭缝;
荧光信号接收系统,用于接收血管中2-NBDG标记的活体循环肿瘤细胞流经激光狭缝时被激光激发产生的荧光;
信号分析系统,用于对荧光信号接收系统接收的荧光进行处理分析。
进一步地,所述的激光激发系统包括激光发射器。
进一步地,所述的激光激发系统包括一个激光发射器。
或者,所述的激光激发系统包括至少两个激光发射器,用于产生至少两种波长的激光。
激光激发系统产生的激光包括但不限于488nm激光、532nm激光、561nm激光、635nm激光中的一种或更多种。
进一步地,所述的激光整形聚焦系统包括反射镜、凹透镜、凸透镜、二向色镜或聚焦物镜中的一种或更多种,激光聚焦后形成激光狭缝,覆盖人体或动物血管。
进一步地,所述的荧光信号接收系统包括荧光接收器。
进一步地,所述的荧光信号接收系统包括光电转换器件,将荧光信号转换成电信号。
进一步地,所述的光电转换器件包括光电倍增管。
进一步地,所述的信号分析系统包括信号处理器。
进一步地,所述的信号分析系统包括滤波器。信号分析系统采用小波滤波、人工智能等算法对信号进行去噪,获取CTCs的荧光信号。
本发明的工作原理为:
肿瘤细胞代谢异常于正常细胞,处于葡萄糖高摄取的状态。2-N[7-硝基苯-2-乙二酸,3-4羟氨基](2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino],NBD)标记2-脱氧葡萄糖(2-deoxyglucose,2-DG),即2-NBDG,在被细胞摄取后由于2位氧被取代无法进行后续糖酵解而被滞留在细胞内,在适当波长的激发下能发荧光且不具有放射性,基于2-NBDG的这种特性,本发明将2-NBDG注入人体或者动物血循环系统中对CTCs进行标记;将激光进行整形聚焦形成激光狭缝,覆盖人体或者动物的血管,当被2-NBDG标 记的CTCs流经激光狭缝时,被激光激发,产生荧光,荧光信号接收系统对荧光进行接收,而后在信号分析系统中,通过人工智能信号处理技术去除背景噪声,获取CTCs的荧光信号,实现对血管中循环肿瘤细胞的实时动态监测。该方法为临床肿瘤转移的在体监测和评估提供一个新的技术手段。
与现有技术相比,本发明具有以下特点:
1)本发明能够实现将2-脱氧葡萄糖类似物(2-NBDG)作为循环肿瘤细胞的标记物对循环肿瘤细胞进行标记,2-NBDG不具有放射性,在体内代谢时间为24h,细胞毒性小,可为临床检测CTCs提供新的可行性方案;
2)本发明在检测活体循环肿瘤细胞时,没有脱离活体血流环境,血液参数及细胞生理环境没有发生变化,循环肿瘤细胞参数不发生变化,检测结果更加准确;
3)本发明用于检测活体循环肿瘤细胞时,不受采血量限制,提高了检测灵敏度。
附图说明
图1为本发明在检测血管中2-NBDG标记的活体循环肿瘤细胞时的示意图;
图2为应用例中检测到的CTCs的荧光信号(未经过信号处理)图;
图3为应用例中检测到的CTCs的荧光信号(经过信号处理)图;
图中标记说明:
1—激光激发系统、2—激光整形聚焦系统、3—激光狭缝、4—荧光信号接收系统、5—信号分析系统、6—荧光、7—2-NBDG标记的活体循环肿瘤细胞、8—血管。
具体实施方式
下面结合附图和具体实施例对本发明进行详细说明。本实施例以本发明技术方案为前提进行实施,给出了详细的实施方式和具体的操作过程,但本发明的保护范围不限于下述的实施例。
实施例1:
如图1所示的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,包括:
激光激发系统1,用于产生激光;
激光整形聚焦系统2,用于将激光进行整形聚焦形成激光狭缝3;
荧光信号接收系统4,用于接收血管8中2-NBDG标记的活体循环肿瘤细胞7流经激光狭缝2时被激光激发产生的荧光6;
信号分析系统5,用于对荧光信号接收系统4接收的荧光6进行处理分析。
采用本装置,对2-NBDG标记的活体循环肿瘤细胞7进行智能监测的方法为:将2-NBDG作为荧光染料对CTCs进行标记,将血管8作为天然鞘流,通过对激光光斑整形聚焦形成的激光狭缝3覆盖血管8的横截面,当2-NBDG标记的活体循环肿瘤细胞7流经激光狭缝3时,被激光激发,产生荧光6,荧光信号接收系统4对荧光6进行接收,而后通过人工智能信号处理技术去除背景噪声,获取CTCs的荧光信号,实现对血管8中循环肿瘤细胞的实时动态监测。
应用例:
利用实施例1中的装置,对2-NBDG标记的活体循环肿瘤细胞7进行智能监测,过程如下:
表达红色荧光蛋白(mCherry)的肿瘤细胞皮下瘤构建成功以后,小鼠禁食1小时,1.6mg/mL的2-NBDG溶液按照8mg/Kg的剂量通过尾静脉缓慢注射入小鼠体内,1.5小时后将小鼠放置于IVFC上利用561nm和488nm的激光进行检测。连续监测一个小时的数据,以每十分钟为一次小的节点,最后将所有数据汇总后,统计平均每分钟检测到的双阳信号数目,代表着循环中2-NBDG标记的活体循环肿瘤细胞7。
图2为检测到的CTCs的荧光信号(未经过信号处理)图,图3为检测到的CTCs的荧光信号(经过信号处理)图。
实施例2:
一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,包括:
激光激发系统1,用于产生激光;
激光整形聚焦系统2,用于将激光进行整形聚焦形成激光狭缝3;
荧光信号接收系统4,用于接收血管8中2-NBDG标记的活体循环肿瘤细胞7流经激光狭缝2时被激光激发产生的荧光6;
信号分析系统5,用于对荧光信号接收系统4接收的荧光6进行处理分析。
其中,激光激发系统1包括至少两个激光发射器,用于产生至少两种波长的激光。激光激发系统1产生的激光包括488nm激光、532nm激光、561nm激光、635nm激光中的至少两种。
激光整形聚焦系统2包括反射镜、凹透镜、凸透镜、二向色镜或聚焦物镜中的一种或更多种。
荧光信号接收系统4包括光电转换器件,光电转换器件包括光电倍增管。
信号分析系统5包括信号处理器。
实施例3:
一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,包括:
激光激发系统1,用于产生激光;
激光整形聚焦系统2,用于将激光进行整形聚焦形成激光狭缝3;
荧光信号接收系统4,用于接收血管8中2-NBDG标记的活体循环肿瘤细胞7流经激光狭缝2时被激光激发产生的荧光6;
信号分析系统5,用于对荧光信号接收系统4接收的荧光6进行处理分析。
其中,激光激发系统1包括一个激光发射器,产生的激光为488nm激光、532nm激光、561nm激光或635nm激光。
激光整形聚焦系统2包括反射镜、凹透镜、凸透镜、二向色镜或聚焦物镜中的一种或更多种。
荧光信号接收系统4包括荧光接收器。
信号分析系统5包括滤波器。
上述的对实施例的描述是为便于该技术领域的普通技术人员能理解和使用发明。熟悉本领域技术的人员显然可以容易地对这些实施例做出各种修改,并把在此说明的一般原理应用到其他实施例中而不必经过创造性的劳动。因此,本发明不限于上述实施例,本领域技术人员根据本发明的揭示,不脱离本发明范畴所做出的改进和修改都应该在本发明的保护范围之内。

Claims (10)

  1. 一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,该装置包括:
    激光激发系统(1),用于产生激光;
    激光整形聚焦系统(2),用于将激光进行整形聚焦形成激光狭缝(3);
    荧光信号接收系统(4),用于接收血管(8)中2-NBDG标记的活体循环肿瘤细胞(7)流经激光狭缝(2)时被激光激发产生的荧光(6);
    信号分析系统(5),用于对荧光信号接收系统(4)接收的荧光(6)进行处理分析。
  2. 根据权利要求1所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的激光激发系统(1)包括激光发射器。
  3. 根据权利要求2所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的激光激发系统(1)包括一个激光发射器。
  4. 根据权利要求2所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的激光激发系统(1)包括至少两个激光发射器,用于产生至少两种波长的激光。
  5. 根据权利要求1所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的激光整形聚焦系统(2)包括反射镜、凹透镜、凸透镜、二向色镜或聚焦物镜中的一种或更多种。
  6. 根据权利要求1所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的荧光信号接收系统(4)包括荧光接收器。
  7. 根据权利要求1所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的荧光信号接收系统(4)包括光电转换器件。
  8. 根据权利要求7所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的光电转换器件包括光电倍增管。
  9. 根据权利要求1所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的信号分析系统(5)包括信号处理器。
  10. 根据权利要求1所述的一种用于监测2-NBDG标记的活体循环肿瘤细胞的装置,其特征在于,所述的信号分析系统(5)包括滤波器。
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