技术领域technical field
本发明涉及光学传感的技术领域，尤其涉及一种THZ-SPRi生物传感系统及其负反馈算法。The invention relates to the technical field of optical sensing, in particular to a THZ-SPRi biosensing system and a negative feedback algorithm thereof.
背景技术Background technique
太赫兹波(Tera Hertz，THz)是一种特定波段的电磁辐射，它主要位于微波和红外辐射之间，一般指频率在0.1-10THZ范围的电磁波，波长范围为0.3-3mm，随着超快激光技术不断的成熟和商业化，众多的太赫兹脉冲辐射和探测方法被相继研究出来，由于太赫兹辐射具有宽光谱、窄脉宽、无损性、相干性、惧水性、透视性、指纹吸收谱等诸多特性，确定了它在众多工业、军事和基础研究领域都存在着巨大的发展空间。Terahertz wave (Tera Hertz, THz) is a specific band of electromagnetic radiation, which is mainly located between microwave and infrared radiation. With the continuous maturity and commercialization of laser technology, many terahertz pulsed radiation and detection methods have been researched one after another. Because terahertz radiation has wide spectrum, narrow pulse width, lossless, coherent, fear of water, perspective, and fingerprint absorption spectrum And many other characteristics have determined that it has huge development space in many fields of industry, military affairs and basic research.
SPR传感技术以其免标记、高时间分辨率、非入侵性、高灵敏度等优点已经成为探索分子间相互作用的重要工具，并且被广泛应用于生化分析、药物研发等领域。随着生物技术的发展，人们越来越需要能够同时对多样品经行检测的高通量传感手段。SPRi则是将传感技术与成像技术结合，提高了SPR传感通量，可以实现同时对多样品进行高通量检测。SPRi传感技术已经广泛应用于检测异性亲和力、大分子的动力学结合过程。SPR sensing technology has become an important tool for exploring molecular interactions due to its advantages of label-free, high time resolution, non-invasiveness, and high sensitivity, and has been widely used in biochemical analysis, drug development and other fields. With the development of biotechnology, people increasingly need high-throughput sensing methods that can detect multiple samples at the same time. SPRi combines sensing technology with imaging technology to improve the sensing throughput of SPR and realize high-throughput detection of multiple samples at the same time. SPRi sensing technology has been widely used to detect heterosexual affinity and kinetic binding process of macromolecules.
发明内容Contents of the invention
本发明的主要目的在于提供一种THZ-SPRi生物传感系统及其负反馈算法，运用太赫兹表面等离子共振成像传感技术来实现对生物组织检测，在生物传感方面具有高灵敏、高通量及快速检测等性能，解决了目前SPRi传感技术存在成像速度慢的技术问题。The main purpose of the present invention is to provide a THZ-SPRi biosensing system and its negative feedback algorithm, which uses terahertz surface plasmon resonance imaging sensing technology to realize the detection of biological tissues, and has high sensitivity and high-pass in biosensing. It solves the technical problem of slow imaging speed in the current SPRi sensing technology.
为实现上述目的，本发明第一方面提供一种THZ-SPRi生物传感系统，包括：太赫兹发射模块、传感模块、太赫兹探测模块以及信号显示模块；所述传感模块设置在所述太赫兹发射模块与所述太赫兹探测模块之间，所述太赫兹发射模块包括太赫兹发射器和设置在所述太赫兹发射器与所述传感模块之间的可调滤波器，所述信号显示模块分别与所述太赫兹探测器、所述可调滤波器连接，所述传感模块包括金属膜、生物传感芯片以及棱镜，所述金属膜设置在所述棱镜上，所述生物传感芯片偶联在所述金属膜上，所述太赫兹发射器发射的太赫兹光束从所述棱镜射入所述传感模块，并从所述棱镜折射出来。In order to achieve the above object, the first aspect of the present invention provides a THZ-SPRi biosensing system, including: a terahertz emission module, a sensing module, a terahertz detection module and a signal display module; the sensing module is set on the Between the terahertz transmitting module and the terahertz detecting module, the terahertz transmitting module includes a terahertz transmitter and an adjustable filter arranged between the terahertz transmitter and the sensing module, the The signal display module is respectively connected with the terahertz detector and the tunable filter, the sensing module includes a metal film, a biological sensor chip and a prism, the metal film is arranged on the prism, and the biological The sensor chip is coupled on the metal film, and the terahertz beam emitted by the terahertz emitter enters the sensor module from the prism and is refracted from the prism.
进一步地，所述太赫兹发射模块还包括设置在所述可调滤波器与所述传感模块之间的起偏器，所述太赫兹探测模块包括太赫兹探测器和设置在所述太赫兹探测器与所述传感模块之间的检偏器。Further, the terahertz transmitting module further includes a polarizer arranged between the tunable filter and the sensing module, the terahertz detecting module includes a terahertz detector and a polarizer arranged in the terahertz An analyzer between the detector and the sensing module.
进一步地，所述太赫兹发射模块还包括孔径光阑，所述孔径光阑设置在所述太赫兹发生器与所述可调滤波器之间。Further, the terahertz transmitting module further includes an aperture stop, and the aperture stop is arranged between the terahertz generator and the tunable filter.
进一步地，所述太赫兹发射器与所述孔径光阑之间设置有第一透镜，所述孔径光阑与所述可调滤波器之间设置有所述第一透镜。Further, a first lens is arranged between the terahertz emitter and the aperture stop, and the first lens is arranged between the aperture stop and the tunable filter.
进一步地，所述检偏器与所述太赫兹探测器之间设置有第二透镜，所述检偏器与所述传感模块之间设置有所述第二透镜。Further, a second lens is arranged between the analyzer and the terahertz detector, and the second lens is arranged between the analyzer and the sensing module.
进一步地，所述传感模块还包括设置在所述金属膜上的流通池、与所述流通池连通的注入管以及与所述流通池连接的蠕动泵。Further, the sensing module further includes a flow cell arranged on the metal membrane, an injection pipe connected to the flow cell, and a peristaltic pump connected to the flow cell.
进一步地，本发明第二方面提供一种THZ-SPRi生物传感系统的负反馈算法，包括步骤：Further, the second aspect of the present invention provides a negative feedback algorithm of a THZ-SPRi biosensing system, comprising steps:
S1：设定扫描次数为n，并对所述传感模块进行大范围扫描，获得初始共振波长λ0；S1: set the number of scans as n, and scan the sensing module in a large range to obtain the initial resonance wavelength λ0 ;
S2：选择扫描范围从λ0-x～λ0+x，并对所述传感模块进行扫描；S2: Select the scanning range from λ0 -x to λ0 +x, and scan the sensing module;
S3：判断所述传感模块的折射率是否发生变化，若是，则转至S4，若否，则转至S2；S3: judging whether the refractive index of the sensing module changes, if yes, go to S4, if not, go to S2;
S4：通过变化的折射率确定新的共振波长λi；S4: Determine the new resonance wavelength λi by changing the refractive index;
S5：判断i﹥n是否成立，若成立，转至S6，若不成立，则转至S51；S5: Determine whether i > n is true, if true, go to S6, if not, go to S51;
S51:选择扫描范围从λi-x～λi+x，并对所述传感模块进行扫描；S51: Select the scanning range from λi -x to λi +x, and scan the sensing module;
S52:判断所述传感模块的折射率是否发生变化，若是，则转至S4，若否，则转至S51；S52: judging whether the refractive index of the sensing module changes, if so, then go to S4, if not, then go to S51;
S6：在一系列共振波长λ0～λi中取出最小共振波长设为λmin，取出最大共振波长设为λmax，则得到共振波长的范围为λmin-x～λmax+x。S6: From a series of resonance wavelengths λ0 to λi , take the minimum resonance wavelength as λmin and the maximum resonance wavelength as λmax , then the range of resonance wavelengths is λmin -x to λmax +x.
本发明提供一种THZ-SPRi生物传感系统，有益效果在于：太赫兹发射器发射的太赫兹光束经过棱镜射入传感模块中，并从所述棱镜折射出来；当金属膜上的生物样品和生物传感芯片上修饰的分子相互作用时，会引起传感模块的折射率变化，折射率变化的信号由信号显示模块显示，通过接收到的信号处理对可调滤波器进行负反馈式调制，控制扫描光谱的范围，从而实现快速扫描式生物传感。The invention provides a THZ-SPRi biosensing system, which has the beneficial effect that: the terahertz beam emitted by the terahertz emitter enters the sensing module through a prism, and is refracted from the prism; when the biological sample on the metal film When interacting with the modified molecules on the biosensing chip, it will cause a change in the refractive index of the sensing module. The signal of the refractive index change is displayed by the signal display module, and the adjustable filter is modulated by negative feedback through the received signal processing. , to control the range of the scanning spectrum, thereby realizing fast scanning biosensing.
附图说明Description of drawings
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only These are some embodiments of the present invention. For those skilled in the art, other drawings can also be obtained according to these drawings without creative work.
图1为本发明一种THZ-SPRi生物传感系统的结构示意框图；Fig. 1 is the schematic block diagram of a kind of THZ-SPRi biosensing system of the present invention;
图2为本发明一种THZ-SPRi生物传感系统的负反馈算法的流程示意图。Fig. 2 is a schematic flow chart of a negative feedback algorithm of a THZ-SPRi biosensing system of the present invention.
其中，上述附图包括以下附图标记：Wherein, the above-mentioned accompanying drawings include the following reference signs:
11、太赫兹发射器；12、可调滤波器；13、起偏器；14、孔径光阑；15、第一透镜；21、金属膜；22、棱镜；23、流通池；24、注入管；31、太赫兹探测器；32、检偏器；33、第二透镜；40、信号显示模块。11. Terahertz emitter; 12. Tunable filter; 13. Polarizer; 14. Aperture stop; 15. First lens; 21. Metal film; 22. Prism; 23. Flow cell; 24. Injection tube 31. Terahertz detector; 32. Analyzer; 33. Second lens; 40. Signal display module.
具体实施方式Detailed ways
为使得本发明的发明目的、特征、优点能够更加的明显和易懂，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而非全部实施例。基于本发明中的实施例，本领域技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。In order to make the purpose, features and advantages of the present invention more obvious and understandable, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described The embodiments are only some of the embodiments of the present invention, but not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative efforts belong to the protection scope of the present invention.
请参阅图1，为一种THZ-SPRi生物传感系统，包括：太赫兹发射模块、传感模块、太赫兹探测模块以及信号显示模块40；传感模块设置在太赫兹发射模块与太赫兹探测模块之间，太赫兹发射模块包括太赫兹发射器11和设置在太赫兹发射器11与传感模块之间的可调滤波器12，信号显示模块40分别与太赫兹探测器31、可调滤波器12连接，传感模块包括金属膜21、生物传感芯片以及棱镜22，金属膜21设置在棱镜22上，生物传感芯片偶联在金属膜21上，太赫兹发射器11发射的太赫兹光束从棱镜22射入传感模块，并从棱镜22折射出来。Please refer to Fig. 1, which is a THZ-SPRi biosensing system, including: a terahertz emission module, a sensing module, a terahertz detection module, and a signal display module 40; the sensing module is arranged between the terahertz emission module and the terahertz detection module. Between the modules, the terahertz emission module includes a terahertz emitter 11 and an adjustable filter 12 arranged between the terahertz emitter 11 and the sensing module, and the signal display module 40 is connected with the terahertz detector 31 and the adjustable filter respectively. sensor 12, the sensing module includes a metal film 21, a biosensing chip and a prism 22, the metal film 21 is set on the prism 22, the biosensing chip is coupled to the metal film 21, and the terahertz emitted by the terahertz emitter 11 The light beam enters the sensing module from the prism 22 and is refracted from the prism 22 .
在本发明中，太赫兹发射器11发射的太赫兹光束经过棱镜22射入传感模块中，并从棱镜22折射出来；当金属膜21上的生物样品和生物传感芯片上修饰的分子相互作用时，会引起传感模块的折射率变化，折射率变化的信号由信号显示模块40显示，通过接收到的信号处理对可调滤波器12进行负反馈式调制，控制扫描光谱的范围，从而实现快速扫描式生物传感。本技术方案运用太赫兹表面等离子共振成像传感技术来实现对生物组织检测，减少对生物组织的损坏，在生物传感方面具有高灵敏、高通量及快速检测等性能，解决了目前SPRi传感技术存在成像速度慢的技术问题。In the present invention, the terahertz beam emitted by the terahertz emitter 11 enters the sensing module through the prism 22 and is refracted from the prism 22; when the biological sample on the metal film 21 interacts with the modified molecules on the biosensing chip When it works, it will cause the refractive index of the sensing module to change, and the signal of the refractive index change is displayed by the signal display module 40, and the adjustable filter 12 is subjected to negative feedback modulation through the received signal processing to control the range of the scanning spectrum, thereby Enable fast scanning biosensing. This technical solution uses terahertz surface plasmon resonance imaging sensing technology to realize the detection of biological tissue and reduce the damage to biological tissue. Sensing technology has the technical problem of slow imaging speed.
进一步地，太赫兹发射模块还包括设置在可调滤波器12与传感模块之间的起偏器13，太赫兹探测模块包括太赫兹探测器31和设置在太赫兹探测器31与传感模块之间的检偏器32，通过起偏器13获得偏振光，偏振光在金属膜21上与生物样品发生spri效应，反射出的太赫兹光束由检偏器32检验是否为偏振光，最后被太赫兹探测器31接收。Further, the terahertz transmitting module also includes a polarizer 13 arranged between the adjustable filter 12 and the sensing module, the terahertz detecting module includes a terahertz detector 31 and a terahertz detector 31 arranged between the terahertz detector 31 and the sensing module The polarizer 32 in between is used to obtain polarized light through the polarizer 13. The polarized light has a spri effect on the metal film 21 and the biological sample. The reflected terahertz beam is checked by the polarizer 32 to see whether it is polarized light. Terahertz detector 31 receives.
优选地，太赫兹发射模块还包括孔径光阑14，孔径光阑14设置在太赫兹发生器与可调滤波器12之间，且太赫兹发射器11与孔径光阑14之间设置有第一透镜15，孔径光阑14与可调滤波器12之间设置有第一透镜15；第一透镜15对太赫兹发射器11发出的太赫兹光束进行准直聚焦，孔径光阑14对聚焦后的太赫兹光束再进行空间滤波，经过孔径光阑14滤波后的太赫兹光束再由第一透镜15进一步聚焦后进入可调滤波器12。Preferably, the terahertz emission module further includes an aperture stop 14, the aperture stop 14 is arranged between the terahertz generator and the tunable filter 12, and a first A lens 15, a first lens 15 is arranged between the aperture stop 14 and the adjustable filter 12; the first lens 15 collimates and focuses the terahertz beam emitted by the terahertz transmitter 11, and the aperture stop 14 collimates and focuses the focused terahertz beam The terahertz beam is then spatially filtered, and the terahertz beam filtered by the aperture stop 14 is further focused by the first lens 15 and enters the tunable filter 12 .
同理，检偏器32与太赫兹探测器31之间设置有第二透镜33，检偏器32与传感模块之间设置有第二透镜33，第二透镜33对折射出来的太赫兹光束进行准直聚焦后进入检偏器32。Similarly, a second lens 33 is provided between the analyzer 32 and the terahertz detector 31, and a second lens 33 is provided between the analyzer 32 and the sensing module. After being collimated and focused, it enters the analyzer 32 .
进一步地，传感模块还包括设置在金属膜21上的流通池23、与流通池23连通的注入管24以及与流通池23连接的蠕动泵，生物样品由注入管24注入到流通池23后与金属膜21接触；优选地，采用p625蠕动泵，其具有高稳定性，且可以配合不同的蠕动管来选择流速，蠕动管可选择020号蠕动管。Further, the sensing module also includes a flow cell 23 arranged on the metal membrane 21, an injection tube 24 communicated with the flow cell 23, and a peristaltic pump connected to the flow cell 23, after the biological sample is injected into the flow cell 23 through the injection tube 24 It is in contact with the metal membrane 21; preferably, a p625 peristaltic pump is used, which has high stability and can cooperate with different peristaltic tubes to select the flow rate, and the peristaltic tube can be 020 peristaltic tube.
如图2所示，本发明提供一种THZ-SPRi生物传感系统的负反馈算法，包括步骤：As shown in Figure 2, the present invention provides a kind of negative feedback algorithm of THZ-SPRi biosensing system, comprises steps:
S1：设定扫描次数为n，并对传感模块进行大范围扫描，获得初始共振波长λ0；S1: Set the number of scans as n, and scan the sensor module in a large range to obtain the initial resonance wavelength λ0 ;
S2：选择扫描范围从λ0-x～λ0+x，并对传感模块进行扫描；S2: Select the scanning range from λ0 -x to λ0 +x, and scan the sensing module;
S3：判断传感模块的折射率是否发生变化，若是，则转至S4，若否，则转至S2；S3: Determine whether the refractive index of the sensing module changes, if yes, go to S4, if not, go to S2;
S4：通过变化的折射率确定新的共振波长λi；S4: Determine the new resonance wavelength λi by changing the refractive index;
S5：判断i﹥n是否成立，若成立，转至S6，若不成立，则转至S51；S5: Determine whether i > n is true, if true, go to S6, if not, go to S51;
S51:选择扫描范围从λi-x～λi+x，并对传感模块进行扫描；S51: Select the scan range from λi -x to λi +x, and scan the sensing module;
S52:判断传感模块的折射率是否发生变化，若是，则转至S4，若否，则转至S51；S52: judge whether the refractive index of sensing module changes, if so, then go to S4, if not, then go to S51;
S6：在一系列共振波长λ0～λi中取出最小共振波长设为λmin，取出最大共振波长设为λmax，则得到共振波长的范围为λmin-x～λmax+x。S6: From a series of resonance wavelengths λ0 to λi , take the minimum resonance wavelength as λmin and the maximum resonance wavelength as λmax , then the range of resonance wavelengths is λmin -x to λmax +x.
本技术方案中通过大范围扫描获得初始共振波长，并不断地对共振波长附近波段进行局部扫描，能够保证生物样品发生变化时，共振波长位置始终在扫描范围内，减少了扫描区域，提高了扫描效率。该THZ-SPRi生物传感系统使用了负反馈步长追踪算法，并采用了宽带太赫兹衰减全反射技术，实现了对生物样品折射率检测，改善了现有SPRi成像速度慢的局限性。In this technical solution, the initial resonance wavelength is obtained by scanning in a large range, and the local scanning of the band near the resonance wavelength is continuously performed, which can ensure that when the biological sample changes, the position of the resonance wavelength is always within the scanning range, reducing the scanning area and improving the scanning efficiency. efficiency. The THZ-SPRi biosensing system uses a negative feedback step tracking algorithm and a broadband terahertz attenuated total reflection technology to realize the detection of the refractive index of biological samples and improve the limitation of the existing SPRi imaging speed.
以上为对本发明所提供的一种THZ-SPRi生物传感系统及其负反馈算法的描述，对于本领域的技术人员，依据本发明实施例的思想，在具体实施方式及应用范围上均会有改变之处，综上，本说明书内容不应理解为对本发明的限制。The above is a description of a THZ-SPRi biosensing system and its negative feedback algorithm provided by the present invention. For those skilled in the art, according to the ideas of the embodiments of the present invention, there will be specific implementation methods and application ranges. Changes, in summary, the contents of this specification should not be construed as limiting the present invention.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910870250.3ACN110487745B (en) | 2019-09-16 | 2019-09-16 | THZ-SPRi biosensing system and negative feedback algorithm thereof |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910870250.3ACN110487745B (en) | 2019-09-16 | 2019-09-16 | THZ-SPRi biosensing system and negative feedback algorithm thereof |
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| CN110487745Atrue CN110487745A (en) | 2019-11-22 |
| CN110487745B CN110487745B (en) | 2025-01-17 |
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| CN201910870250.3AActiveCN110487745B (en) | 2019-09-16 | 2019-09-16 | THZ-SPRi biosensing system and negative feedback algorithm thereof |
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| CN114527092A (en)* | 2022-02-21 | 2022-05-24 | 青岛青源峰达太赫兹科技有限公司 | Rapid TDS spectral scanning imaging system optimization method based on delay tracking |
| CN116026760A (en)* | 2022-11-23 | 2023-04-28 | 广东工业大学 | Wavelength type SPR sensing system and method |
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| CN105486665A (en)* | 2016-01-26 | 2016-04-13 | 深圳大学 | SPR detection system and method |
| CN105581773A (en)* | 2014-10-21 | 2016-05-18 | 深圳先进技术研究院 | Terahertz imaging system |
| CN211206242U (en)* | 2019-09-16 | 2020-08-07 | 深圳大学 | A THZ-SPRi Biosensing System |
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| CN103389284A (en)* | 2012-05-09 | 2013-11-13 | 深圳大学 | Surface plasma resonance system and detection method thereof |
| CN105581773A (en)* | 2014-10-21 | 2016-05-18 | 深圳先进技术研究院 | Terahertz imaging system |
| CN105486665A (en)* | 2016-01-26 | 2016-04-13 | 深圳大学 | SPR detection system and method |
| CN211206242U (en)* | 2019-09-16 | 2020-08-07 | 深圳大学 | A THZ-SPRi Biosensing System |
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| 刘立新等: "两维荧光光谱技术及最佳光谱分辨率设计", 深圳大学学报(理工版), vol. 24, no. 03, 31 July 2007 (2007-07-31), pages 252 - 256* |
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114527092A (en)* | 2022-02-21 | 2022-05-24 | 青岛青源峰达太赫兹科技有限公司 | Rapid TDS spectral scanning imaging system optimization method based on delay tracking |
| CN116026760A (en)* | 2022-11-23 | 2023-04-28 | 广东工业大学 | Wavelength type SPR sensing system and method |
| CN116026760B (en)* | 2022-11-23 | 2023-10-31 | 广东工业大学 | Wavelength type SPR sensing system and method |
| Publication number | Publication date |
|---|---|
| CN110487745B (en) | 2025-01-17 |
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