CN100520394C - Single-channel multi-parameter surface plasms resonance tester - Google Patents
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- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims abstract description 71
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- 239000007788 liquid Substances 0.000 claims description 21
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Abstract
本发明一种单通道多参数表面等离子体谐振(SPR)测试仪属于测试仪器技术领域。该测试仪,包括控制系统、光学系统、机械扫描系统、流通系统及表面等离子体谐振芯片、信号采集处理软件和系统操作控制软件等部分,构成完整的表面等离子体谐振测试系统,其中,机械扫描系统实现角度调制,进行角度和光强信号检测;采用两单元或多单元表面等离子体谐振芯片,待测样品经单通道流过芯片时,可给出对应的双参数或多参数检测结果。本发明的测试仪结构简单,操作简便,可设定参比单元检测或多参数自动化测试,测试数据可靠、精确。
The invention discloses a single-channel multi-parameter surface plasmon resonance (SPR) tester, which belongs to the technical field of test instruments. The tester, including the control system, optical system, mechanical scanning system, circulation system, surface plasmon resonance chip, signal acquisition and processing software, and system operation control software, constitutes a complete surface plasmon resonance testing system. The system realizes angle modulation and detects angle and light intensity signals; using two-unit or multi-unit surface plasmon resonance chips, when the sample to be tested flows through the chip through a single channel, the corresponding double-parameter or multi-parameter detection results can be given. The tester of the invention has simple structure and easy operation, can set reference unit detection or multi-parameter automatic test, and the test data is reliable and accurate.
Description
技术领域 technical field
本发明属于测试仪器技术领域,特别是单通道多参数表面等离子体谐振(SPR)测试仪。The invention belongs to the technical field of test instruments, in particular to a single-channel multi-parameter surface plasmon resonance (SPR) tester.
背景技术 Background technique
目前,单通道表面等离子体谐振(SPR)测试仪每次只测量一个参数,多通道表面等离子体谐振(SPR)测试仪的每个通道也只测量一个参数,造成测试过程复杂,数据量大,耗时且容易出错。At present, the single-channel surface plasmon resonance (SPR) tester only measures one parameter at a time, and each channel of the multi-channel surface plasmon resonance (SPR) tester only measures one parameter, resulting in a complicated test process and a large amount of data. Time consuming and error prone.
发明内容 Contents of the invention
本发明的目的是提出一种新型单通道多参数表面等离子体谐振(SPR)测试仪,该仪器采用两单元芯片、配合相应的光学系统、检测系统和信息处理系统实现双参数检测;或采用多单元芯片及相应的信号采集处理系统,也可以实现单通道多参数测试。The purpose of the present invention is to propose a novel single-channel multi-parameter Surface Plasmon Resonance (SPR) tester, which adopts two unit chips, cooperates with corresponding optical systems, detection systems and information processing systems to realize dual-parameter detection; or adopts multiple The unit chip and the corresponding signal acquisition and processing system can also realize single-channel multi-parameter testing.
为达到上述目的,本发明的技术解决方案是提供一种单通道多参数表面等离子体谐振测试仪,包括控制系统、光学系统、机械扫描系统、流通系统及表面等离子体谐振芯片、信号采集处理软件和系统操作控制软件等部分,构成完整的表面等离子体谐振测试系统,其中,以机械运动扫描结构来实现角度调制,进行角度和光强信号单通道检测;其采用多单元表面等离子体谐振芯片,待测样品经单通道流过芯片时,可给出对应的多参数检测结果。In order to achieve the above object, the technical solution of the present invention is to provide a single-channel multi-parameter surface plasmon resonance tester, including a control system, an optical system, a mechanical scanning system, a circulation system, a surface plasmon resonance chip, and signal acquisition and processing software And the system operation control software and other parts constitute a complete surface plasmon resonance test system, in which, the angle modulation is realized by the mechanical motion scanning structure, and the single-channel detection of the angle and light intensity signal is carried out; it adopts a multi-unit surface plasmon resonance chip, When the sample to be tested flows through the chip through a single channel, the corresponding multi-parameter detection results can be given.
所述的表面等离子体谐振测试仪,其所述流通系统,包括测试池、管路、进液阀、蠕动泵和敏感芯片;其中,光学棱镜下方紧密连接有表面等离子体谐振多单元敏感芯片的金膜,金膜下方紧密连接有测试池;测试池两端设有进液管和出液管,进液管连有进液阀,进液阀设有两进口,一进口与样品管连通,另一进口与载液管连通,载液管上装有蠕动泵;测量池内样品与流通系统表面等离子体谐振多单元敏感芯片接触,给出对应的多参数检测结果。In the surface plasmon resonance tester, the flow system includes a test pool, a pipeline, a liquid inlet valve, a peristaltic pump, and a sensitive chip; wherein, the surface plasmon resonance multi-unit sensitive chip is closely connected under the optical prism. The gold film is closely connected with the test pool under the gold film; the two ends of the test pool are provided with a liquid inlet pipe and a liquid outlet pipe, and the liquid inlet pipe is connected with a liquid inlet valve. The liquid inlet valve has two inlets, one inlet is connected with the sample pipe, The other inlet is connected with the liquid-carrying pipe, and the peristaltic pump is installed on the liquid-carrying pipe; the sample in the measuring cell is in contact with the surface plasmon resonance multi-unit sensitive chip of the circulation system, and the corresponding multi-parameter detection results are given.
所述的表面等离子体谐振测试仪,其所述表面等离子体谐振芯片,为并列式的裸金表面等离子体谐振芯片;多单元表面等离子体谐振芯片,至少是两单元并列式的裸金表面等离子体谐振芯片。In the surface plasmon resonance tester, the surface plasmon resonance chip is a parallel bare gold surface plasmon resonance chip; the multi-unit surface plasmon resonance chip is at least two parallel bare gold surface plasmon resonance chips. Bulk resonator chip.
所述的表面等离子体谐振测试仪,其所述机械扫描系统,包括光学平台、连杆组、滑块、导轨、螺杆、电机、角位移传感器和拉杆,其中,连杆组由四根连杆组成,四根连杆围成菱形,四根连杆可以以连点为轴心转动,其一连点B安装在光学平台上,另一相对的连点A与拉杆连接,拉杆另一端连接滑块;在滑块下有一导轨,滑块可在导轨上移动;滑块另一端接有螺杆,螺杆另一端与电机传动轴动连接,且螺杆另一端端部与角位移传感器连接;In the surface plasmon resonance tester, the mechanical scanning system includes an optical platform, a connecting rod group, a slider, a guide rail, a screw, a motor, an angular displacement sensor and a pull rod, wherein the connecting rod group consists of four connecting rods It is composed of four connecting rods forming a rhombus, and the four connecting rods can rotate around the connecting point as the axis. One connecting point B is installed on the optical table, and the other opposite connecting point A is connected to the tie rod, and the other end of the tie rod is connected to the slider. There is a guide rail under the slider, and the slider can move on the guide rail; the other end of the slider is connected with a screw, the other end of the screw is dynamically connected with the motor transmission shaft, and the other end of the screw is connected with the angular displacement sensor;
光源和阵列光电二极管分别放置在连杆组的连点B两侧的连杆上,位于光学棱镜的入射和反射光路上;光学棱镜、表面等离子体谐振芯片和测量池一起组合在光学平台上。The light source and the array photodiode are respectively placed on the connecting rods on both sides of the connecting point B of the connecting rod group, and are located on the incident and reflected light paths of the optical prism; the optical prism, surface plasmon resonance chip and measuring cell are combined on the optical platform.
所述的表面等离子体谐振测试仪,其所述机械扫描系统,可进行角度测试或在特定角度下的光强测试。In the surface plasmon resonance tester, the mechanical scanning system can perform an angle test or a light intensity test at a specific angle.
所述的表面等离子体谐振测试仪,其所述光源是半导体激光器;阵列光电二极管至少为两单元光电二极管阵列或CCD。In the surface plasmon resonance tester, the light source is a semiconductor laser; the photodiode array is at least a two-unit photodiode array or CCD.
所述的表面等离子体谐振测试仪,其所述光源,通过平行光路系统形成一定面积的光束;双参数测试时,采用的光接收器是两单元光电二极管,多参数测试时,采用的光接收器是多单元光电二极管阵列或CCD。In the surface plasmon resonance tester, the light source forms a light beam of a certain area through a parallel optical path system; during the dual-parameter test, the optical receiver used is a two-unit photodiode; during the multi-parameter test, the light receiver used The detector is a multi-element photodiode array or CCD.
所述的表面等离子体谐振测试仪,其每次测量给出的多参数测量结果,其中一个参数是参比值,与样品测量值进行比对差分,可消除温度和噪声的影响,提高测试可靠性和准确性。In the surface plasmon resonance tester, the multi-parameter measurement results given by each measurement, one of the parameters is a reference value, which is compared and differentiated with the sample measurement value, which can eliminate the influence of temperature and noise, and improve the reliability of the test and accuracy.
所述的表面等离子体谐振测试仪,其控制系统根据运行状态决定机械扫描系统的运行速度和方向,以高精度地调节光束入射角,实现角度扫描;采集信号分为角度和光强两种,当机械运行到极限位置时,控制系统对角度进行校正,并根据运行结果对机械速度自动调整;在每一个可分辨的入射角度,系统都对光强进行检测,检测的采样率和样本数可控,每次运行的结果作为决定下次测量时的参考依据。In the surface plasmon resonance tester, its control system determines the operating speed and direction of the mechanical scanning system according to the operating state, and adjusts the incident angle of the beam with high precision to realize angular scanning; the collected signals are divided into two types: angle and light intensity, When the machine runs to the limit position, the control system corrects the angle, and automatically adjusts the machine speed according to the operation result; at each resolvable incident angle, the system detects the light intensity, and the sampling rate and sample number of detection can be adjusted. Control, the results of each run are used as a reference for determining the next measurement.
本发明的主要特点是在本发明人授权专利:ZL专利号98102366.5的基础上,除保持原表面等离子体谐振测试仪基本结构外,进一步扩展和完善系统。通常采用点光源即可,本发明采用了有一定面积的平行光束,以复盖两单元或多单元芯片,所以本发明系统采用平行光束光源和与芯片对应的两单元或多单元光电二极管以及相应的流动注入系统,并配置两单元或多单元芯片信息采集和处理系统。本发明的测试仪结构简单,操作简便,同时可做多参数自动化测试,且测试数据可靠、精确。The main feature of the present invention is that on the basis of the patent authorized by the inventor: ZL Patent No. 98102366.5, in addition to maintaining the basic structure of the original surface plasmon resonance tester, the system is further expanded and perfected. Generally, a point light source can be used, but the present invention adopts a parallel light beam with a certain area to cover two or more unit chips, so the system of the present invention adopts a parallel light beam light source and two or more unit photodiodes corresponding to the chip and corresponding The flow injection system is equipped with a two-unit or multi-unit chip information collection and processing system. The tester of the invention has simple structure and easy operation, and can do multi-parameter automatic test at the same time, and the test data is reliable and accurate.
附图说明 Description of drawings
图1是本发明单通道多参数表面等离子体谐振(SPR)测试仪的系统结构框图;Fig. 1 is the system structural block diagram of single-channel multi-parameter surface plasmon resonance (SPR) tester of the present invention;
图2是本发明单通道多参数表面等离子体谐振(SPR)测试仪的光学和机械扫描系统结构示意图;Fig. 2 is the optical and mechanical scanning system structural representation of single-channel multi-parameter surface plasmon resonance (SPR) tester of the present invention;
图3是本发明单通道多参数表面等离子体谐振(SPR)测试仪的系统光路和流通系统结构示意图;Fig. 3 is a schematic diagram of the system optical path and flow system structure of the single-channel multi-parameter surface plasmon resonance (SPR) tester of the present invention;
图4是本发明单通道双参数表面等离子体谐振(SPR)测试仪的应用实例测试曲线图。Fig. 4 is a test graph of an application example of a single-channel dual-parameter surface plasmon resonance (SPR) tester of the present invention.
具体实施方式 Detailed ways
本发明装置不仅具有表面等离子体谐振(SPR)生化分析技术特有的:样品无需标记和不需纯化处理、可检测混浊或不透明的样品、可以实时动态检测、入射角范围宽、角度变化分辨率高,适应性强等优点,而且相对于单参数表面等离子体谐振(SPR)测试仪还具有检测灵敏度高、需样品量更少、过程方便快捷、准确可靠、应用范围广和能进行高通量检测等优点,并且,该装置带有配套的流动注入系统,可实现单通道双参数或多参数自动化检测,在生命科学、化学分析、临床诊断、药物筛选、食品安全、环境监控和有关科学研究领域中都可广泛应用。The device of the present invention not only has the unique characteristics of surface plasmon resonance (SPR) biochemical analysis technology: samples do not need to be labeled and purified, can detect turbid or opaque samples, can detect dynamically in real time, have a wide range of incident angles, and have high resolution of angle changes , strong adaptability, etc., and compared with the single-parameter surface plasmon resonance (SPR) tester, it also has high detection sensitivity, less sample volume, convenient and fast process, accurate and reliable, wide application range and high-throughput detection and other advantages, and the device has a supporting flow injection system, which can realize single-channel dual-parameter or multi-parameter automatic detection, and is widely used in life science, chemical analysis, clinical diagnosis, drug screening, food safety, environmental monitoring and related scientific research fields. can be widely applied.
图1是本发明系统结构框图,测试仪的组成包括:光学系统、机械扫描系统、流通系统以及数据采集系统等四个部分,四个部分按标准常规方式连接,并与测试仪控制系统及计算机相联,构成完整的光、机、电一体化系统。Fig. 1 is a block diagram of the system structure of the present invention, and the composition of tester comprises: optical system, mechanical scanning system, circulation system and data collection system etc. four parts, four parts are connected by standard routine, and with tester control system and computer Connected to form a complete optical, mechanical and electrical integration system.
图2是机械扫描系统结构原理示意图。图中,测试仪基座1,光学平台2,连杆组3,滑块4,导轨5,螺杆6,电机7,角位移传感器8,拉杆9,光源10,两(或多)单元阵列光电二极管11,光学棱镜12和测量池13。Fig. 2 is a schematic diagram of the structural principle of the mechanical scanning system. In the figure, tester base 1,
其特征在于,根据表面等离子体谐振(SPR)角调制原理而采用机械扫描结构。这里所说的机械扫描运动结构包括光学平台2、连杆组3、滑块4、导轨5、螺杆6、电机7、角位移传感器8和拉杆9,其中,连杆组3由四根连杆组成,四根连杆围成菱形,四根连杆可以连点为轴心转动,其一连点B安装在光学平台2上,另一相对的连点A与拉杆9连接,拉杆9另一端连接滑块4。在滑块4下有一导轨5,滑块4可在导轨5上移动。滑块4另一端接有螺杆6,螺杆6另一端与电机7动连接,且螺杆6另一端端部与角位移传感器8固接。It is characterized in that a mechanical scanning structure is adopted according to the principle of surface plasmon resonance (SPR) angle modulation. The mechanical scanning motion structure mentioned here includes an
光源10和两(或多)单元阵列光电二极管11分别放置在连杆组3的连点B两侧的连杆上,位于光学棱镜12的入射和反射光路上。光源10是半导体激光器。光学棱镜12、表面等离子体谐振(SPR)芯片和测量池13等一起组合在光学平台2上。The
图3是系统光路、两(或多)单元表面等离子体谐振(SPR)芯片及流通系统结构示意图。其中,光学棱镜12下方紧密连接有表面等离子体谐振两单元敏感芯片21或多单元敏感芯片22的金膜14,金膜14下方紧密连接有测试池13。测试池13两端设有进液管15和出液管16,进液管15连有进液阀17,进液阀17设有两进口,一与样品管18连通,另一与载液管19连通,载液管19上装有蠕动泵20。测量池13内样品与流通系统表面等离子体谐振(SPR)两单元敏感芯片21或多单元敏感芯片22接触。Fig. 3 is a structural schematic diagram of the optical path of the system, two (or more) unit surface plasmon resonance (SPR) chips and the circulation system. Wherein, the
下面结合附图叙述本发明。Describe the present invention below in conjunction with accompanying drawing.
如图1所示,控制系统根据运行状态决定机械扫描运动结构的运行速度和方向,以高精度地调节光束入射角,实现角度扫描;采集信号分为角度和光强两种,当机械运行到极限位置时,控制系统对角度进行校正,并根据运行结果对机械速度自动调整。在每一个可分辨的入射角度,系统都对光强进行检测,检测的采样率和样本数可控。每次运行的结果作为决定下次测量时的参考依据。As shown in Figure 1, the control system determines the operating speed and direction of the mechanical scanning motion structure according to the operating state, and adjusts the incident angle of the beam with high precision to realize angular scanning; the acquisition signal is divided into two types: angle and light intensity. At the limit position, the control system corrects the angle and automatically adjusts the mechanical speed according to the operation result. At each resolvable incident angle, the system detects the light intensity, and the detection sampling rate and number of samples are controllable. The results of each run serve as a reference for determining the next measurement.
图2可知,杠杆机构可以精确地实现微小角位移,而且结构简单。该结构的优点是可实现微小的入射角度变化和较大的变化范围,而且同时对反射光进行了跟踪;系统的灵敏度决定于电机7和角位移传感器8最小可分辨的角位移;系统的精确度主要由螺杆6的制造精度决定,而滑块4的行程长度和连杆的臂长决定测量范围的大小;使用本发明时,待测物是由蠕动泵驱动和阀门控制,通过放置在光学平台2上的测量池13与流通系统表面等离子体谐振(SPR)两单元或多单元敏感芯片接触反应,实现对待测物的检测。It can be seen from Fig. 2 that the lever mechanism can accurately realize the small angular displacement, and the structure is simple. The advantage of this structure is that it can realize a small change in incident angle and a large change range, and at the same time track the reflected light; the sensitivity of the system depends on the minimum resolvable angular displacement of the
图4所示为单通道双参数表面等离子体谐振(SPR)测试仪应用时实测样品曲线图。图中两条曲线中一条(绿线)为参比曲线、一条为样品曲线(红线),将参比值与样品测量值进行比对差分,可消除温度和噪声等外界因素的干扰和影响,进一步提高了测试可靠性和准确性。Fig. 4 is a curve diagram of actual measured samples when a single-channel dual-parameter surface plasmon resonance (SPR) tester is applied. One of the two curves in the figure (green line) is the reference curve and the other is the sample curve (red line). Comparing the reference value with the measured value of the sample can eliminate the interference and influence of external factors such as temperature and noise, and further Improved test reliability and accuracy.
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