WO2016149982A1 - 基于表面等离子共振技术的生物标志物检测方法与系统 - Google Patents

基于表面等离子共振技术的生物标志物检测方法与系统 Download PDF

Info

Publication number
WO2016149982A1
WO2016149982A1 PCT/CN2015/077443 CN2015077443W WO2016149982A1 WO 2016149982 A1 WO2016149982 A1 WO 2016149982A1 CN 2015077443 W CN2015077443 W CN 2015077443W WO 2016149982 A1 WO2016149982 A1 WO 2016149982A1
Authority
WO
WIPO (PCT)
Prior art keywords
light receiving
receiving module
plasmon resonance
surface plasmon
biomarker
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.)
Ceased
Application number
PCT/CN2015/077443
Other languages
English (en)
French (fr)
Inventor
张贯京
陈兴明
葛新科
张少鹏
方静芳
普拉纽克⋅克里斯基捏
古列莎⋅艾琳娜
波达别特⋅伊万
高伟明
梁昊原
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.)
Shenzhen Qianhai AnyCheck Information Technology Co Ltd
E Techno Information Technologies Co Ltd
Bio Tech Academy China Co Ltd
Original Assignee
Shenzhen Qianhai AnyCheck Information Technology Co Ltd
E Techno Information Technologies Co Ltd
Bio Tech Academy China Co Ltd
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 Shenzhen Qianhai AnyCheck Information Technology Co Ltd, E Techno Information Technologies Co Ltd, Bio Tech Academy China Co Ltd filed Critical Shenzhen Qianhai AnyCheck Information Technology Co Ltd
Publication of WO2016149982A1 publication Critical patent/WO2016149982A1/zh
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection

Definitions

  • the present invention relates to the field of biomarker detection, and more particularly to a biomarker detection method and system based on surface plasmon resonance technology.
  • Biomarker refers to a biochemical indicator that can label changes or possible changes in the structure, function, organization, cell and subcellular structure or function of a system, and has a very wide range of uses. Biomarkers can be used for disease diagnosis, for judging disease staging, or for assessing the safety and efficacy of new drugs or new therapies in the target population.
  • Surface plasmon resonance technology SPR (Surface) is commonly used when detecting biomarkers Plasmon Resonance), which uses a physical optical phenomenon caused by total reflection connection of metal film/liquid surface interface to analyze biomolecular interactions, and measures the concentration of biomarkers by infrared light combined with SPR technology.
  • SPR Surface plasmon resonance technology
  • Plasmon Resonance uses a physical optical phenomenon caused by total reflection connection of metal film/liquid surface interface to analyze biomolecular interactions, and measures the concentration of biomarkers by infrared light combined with SPR technology.
  • Surface Plasma The application of resonance technology in biomedicine, and the paper "Application of Surface Plasmon Reson
  • photometry is a more common method, which combines the components of body fluid samples with one or more test reagents in vitro to determine the concentration of analytes multiple times, thereby triggering organisms.
  • a chemical reaction that causes a measurable change in the optical properties of the analyte, which is detected by photometry and utilizes the attenuation of the occurrence of light flow through the optically and/or astigmatic medium, however, this measurement method Affected by the type of the sample itself and the interfering substances it may contain, it is easy to cause systematic errors in the measurement, making the measurement of the concentration of the biomarker inaccurate, and the adjustment of the direction of the optical flow during measurement is difficult to control. It often causes great trouble to the measurer.
  • the present invention provides a method, device and system for detecting biomarkers based on surface plasmon resonance technology for quickly and accurately obtaining biomarker concentration in a test object.
  • the technical solution adopted by the present invention to solve the above technical problem is: a biomarker detection method based on surface plasmon resonance technology, comprising the following steps:
  • the light receiving module receives the reflected light beam, sets an initial position of the received spectrum, and records an initial value of the output electrical signal of the light receiving module.
  • the spectral position adjusting device adjusts the spectral position on the light receiving module of the object to be tested, and moves it to the initial position;
  • the control module calculates the concentration of the biomarker in the detection according to the amount of movement of the spectrum on the light receiving module.
  • the step S0 is further included, and the reflected light beam is collected and then transmitted to the light receiving module.
  • step S00 is further included, and the reflected light beam at the sensor chip is once reflected.
  • a biomarker detection system based on surface plasmon resonance technology includes a light receiving module, a control module, a spectral position adjusting device, and a power module,
  • the light receiving module is electrically connected to the control module for receiving a reflected beam at the sensor chip, and correspondingly outputting an electrical signal, and transmitting the electrical signal to the control module;
  • the spectral position adjusting device is electrically connected to the control module and the power module, and is configured to receive current information of the power module and change a position of a spectrum on the light receiving module, and simultaneously output the current information. Transfer to the control module;
  • the power module is electrically connected to the control module and the spectral position adjusting device for receiving an instruction of the control module, and inputting a current to the spectral position adjusting device according to the instruction;
  • the control module is configured to record electrical signal change information on the light receiving module, and issue a command to the power module, and record current information that the power module sends to the spectral position adjusting device, and output the same to the light receiving module.
  • Signal comparison gives information on the biomarker concentration in the test.
  • the light receiving module includes a first light receiving module, a second light receiving module, and a third light receiving Modules, and the three are set side by side.
  • the biomarker detection system based on surface plasmon resonance technology further includes a concentrating module for transmitting to light The light beam of the receiving module is concentrated.
  • the spectral position adjustment device includes a strip, a mirror, a transmission mechanism, a coil, a magnet and a base, the mirror is disposed on the strip, the transmission mechanism is fixed on the strip at one place, and the other is fixed on the base, and the coil is fixed in the In the transmission mechanism, the magnet is close to the coil, so that after the coil is energized, it can move the strip by the transmission mechanism under the action of the magnet.
  • the transmission mechanism includes racks and gears that mesh with each other, the teeth A strip is secured to the strip and the gear is rotatably secured to the base.
  • the transmission mechanism includes a worm gear and a worm that mesh with each other, and the worm is fixed
  • the worm wheel is rotatably fixed to the base on the slat.
  • a balance device is further disposed on the transmission mechanism, and the balance device and the coil are distributed on both sides of the transmission mechanism. .
  • the spectral position adjusting device further includes a spring, and the strip is supported by the spring.
  • the magnet is a neodymium magnet and has a circular arc shape or a strip shape.
  • the technical effects brought by the invention are: using a biomarker detection method based on surface plasmon resonance technology, using a light receiving module to receive specific spectral information, forming a spectrum, and setting a zero point position, and adjusting the object to be tested on the light receiving module.
  • the spectral position by which the concentration value information of the biomarker in the test object is calculated correspondingly, and the concentration of the biomarker in the test object can be detected conveniently, quickly and accurately; the detection system in the present invention
  • the utility model comprises a control module, a light receiving module, a spectral position adjusting device and a power module, wherein the light receiving module is configured to receive the reflected light beam at the sensing chip, form a spectrum thereon, output an electrical signal, and transmit the electrical signal to the control module
  • the power module receives control of the control module and inputs a current into the spectral position adjusting device.
  • the spectral position adjusting device receives the current of the power module and operates to change the position of the spectrum on the light receiving module, and transmits its own current size information to a control module; the control module records electrical signal change information on the light receiving module And according to the information, an instruction is given to the power module, and the power module is controlled to pass current into the spectral position adjusting device, and the current that the power module sends into the spectral position adjusting device is recorded, and the electrical signal is sent to the optical receiving module.
  • the spectral position adjusting device for detecting the biomarker in the invention passes the force of the coil and the magnet that can be energized, and drives the mirror through the transmission mechanism
  • the movement, thereby adjusting the position of the spectrum on the light receiving module, is simple in structure, low in production cost, and very convenient to use.
  • FIG. 1 is a working principle diagram of a surface plasmon resonance technique according to the present invention.
  • FIG. 2 is a flow chart showing the operation of a method for detecting a biomarker based on surface plasmon resonance technology in the invention
  • FIG. 3 is a flow chart showing the operation of a second embodiment of a biomarker detection method based on surface plasmon resonance technology in the invention.
  • FIG. 4 is a schematic view showing the overall structure of a spectral position adjusting device for biomarker detection in the present invention
  • FIG. 5 is a schematic diagram of a spectrum formed on a light receiving module at a zero position set by a biomarker detecting method based on surface plasmon resonance technology according to the present invention
  • FIG. 6 is a schematic diagram of a spectral position shift that may occur when adjusting a spectral position on a light receiving module in a method for detecting a biomarker based on surface plasmon resonance technology according to the present invention
  • FIG. 7 is a schematic view showing a preferred embodiment of a light receiving module of a biomarker detecting method based on surface plasmon resonance technology according to the present invention.
  • Figure 8 is a schematic view showing the structure of a biomarker detection system based on surface plasmon resonance technology in the present invention.
  • FIG. 1 is a working principle diagram of a surface plasmon resonance technique according to the present invention, which is a prior art, as shown in the figure, a process of detecting a concentration of a biomarker by using a surface plasmon resonance technique, first, setting a flow channel 300 and transmitting
  • the sensing chip 400 is provided with a gold film on the sensing chip 400, and a side portion of the sensing chip 400 with the gold film is located in the flow channel 300, so that the object to be detected flowing into the flow channel 300 can be contacted with
  • the gold film sensor chip 400 when measuring, passes the object to be detected with the biomarker into the flow channel 300, so that the object to be detected is in contact with the sensor chip, and a layer of antibody molecules is modified in advance at the reaction interface.
  • a light beam is emitted from a light source 600, which is irradiated onto the sensor chip 400, and is reflected by the optical detecting unit 700 (the light receiving module is used as an optical detecting unit in the present invention), and is sensed by the optical detecting unit 700.
  • the change of the received beam information obtains the correspondence between the change information and the concentration of the biomarker to be detected, and finally obtains the biomarker concentration value in the object to be detected from the change information.
  • a monochromatic light source such as an infrared beam source can be used, which is effective.
  • the working flow chart of the biomarker detection method based on the surface plasmon resonance technology in the present invention is as shown in FIG. 2, and includes the following steps:
  • the light receiving module receives the reflected light beam, sets an initial position of the received spectrum, and records an initial value of the output electrical signal of the light receiving module.
  • the spectral position adjusting device adjusts the spectral position on the light receiving module of the object to be tested, and moves it to the initial position;
  • the control module calculates the concentration of the biomarker in the detection according to the amount of movement of the spectrum on the light receiving module.
  • FIG. 3 The working flow chart is shown in FIG. 3, and includes the following steps:
  • the light receiving module receives the reflected light beam, sets an initial position of the received spectrum, and records an initial value of the output electrical signal of the light receiving module.
  • the spectral position adjusting device adjusts the spectral position on the light receiving module of the object to be tested, and moves it to the initial position;
  • the control module calculates the concentration of the biomarker in the detection according to the amount of movement of the spectrum on the light receiving module.
  • the invention adopts the surface plasmon resonance technology, firstly adopts a substance not containing the biomarker to be tested, and after receiving the monochromatic beam, receives the polarized light beam by the light receiving module, and sets the initial position to record the output power.
  • the initial value of the signal is used as the initial position value of the spectrum, and then the object to be detected is measured. Since the analyte contains the biomarker, the spectrum of the light receiving module and the position of the dark region thereof are changed, and the corresponding light receiving module is The size of the output electrical signal also changes accordingly. By adjusting the position of the spectrum, the size of the electrical signal outputted by the light receiving module can be the same as that of the initial position.
  • Different adjustment methods can be implemented for the adjustment process of the spectral position. However, there is a one-to-one correspondence between the adjustment amount of each adjustment method and the movement amount of the spectral position, and the concentration of the biomarker in the detection can be calculated.
  • the present invention provides an auxiliary spectral position adjustment device for biomarker detection on the basis of the above, for adjusting the reflected light beam at the optical detection unit 700 (with the light in the present invention)
  • the position on the corresponding module is received to obtain concentration information capable of reflecting the biomarker in the analyte to be detected.
  • the overall structure of the device is shown in FIG. 4, and includes a strip 2, a mirror 3, a spring 4, a gear 7, a coil 9 and a magnet 10.
  • One end of the strip 2 is fixed in an articulated manner, and the other end is fixed to the rack 6.
  • the fixed rack 6 can be arranged as two parts of the fixed connection, one part is a straight section 21 and the other part is a bending section 22, one end of the straight section 21 is fixed by an articulated manner, and the other end is bent and the other end is bent 22 fixedly connected, and the straight line segment 21 is at a certain angle with the horizontal direction (generally at an acute angle), and the mirror 3 is fixed on the straight line segment 21 for reflecting the infrared light when detecting the biomarker, bending The segment 22 is bent at a 90 degree, the horizontal portion thereof is fixedly connected with the straight line segment, and the vertical portion thereof fixes the rack 6.
  • a rack structure can also be provided on the vertical segment, and the rack and the bent portion 22 can be provided.
  • the rack and the bent portion 22 can be provided.
  • a rack provided on the vertical portion of the structure, i.e. made one-piece structure will be more convenient in the production, installation and use.
  • the rack structure on the strip 2 or the fixed rack 6 is in meshing state with the gear 7.
  • the gear 7 When the gear 7 is rotated by an external force, the rack structure or the rack 6 on the strip 2 follows the gear 7 Rotate and rotate to drive the strip 2 to move.
  • a closed coil 9 is attached to the gear 7, which extends 9 out of the body of the gear 7 and extends outwardly a distance, with a fixed magnet 10 placed next to the coil 9. A part of the coil 9 overlaps with the magnet 10, so that when a current is applied to the coil 9, the coil 9 in the closed state forms a closed loop, and when there is current in the closed loop, it is itself charged.
  • the magnetic field generates a magnetic field, and the magnetic field generated by the coil 9 and the magnetic field of the magnet 10 interact with each other. At this time, changing the magnitude/direction of the current flowing into the coil 9 can change the strength of the magnetic field generated by the coil 9 and the direction of the magnetic field. Since the magnitude and direction of the magnetic field generated by the magnet 10 are fixed, when the magnitude and/or direction of the current in the coil 9 is changed, the coil 9 is rotated by the magnetic field of the magnet 10, since the coil 9 is fixed.
  • a spring 4 is attached to the strip 2, and the other end of the spring 4 is fixed to set an initial position so that the spring 4 In this initial position, the entire device is at a zero point, and when it is necessary to adjust the horizontal angle of the mirror 3, the spring force of the spring 4 can be utilized to make the mirror 3 easier to return to the initial position.
  • the above specific process is as follows: when a current is supplied to the coil 9, a magnetic field is generated in the coil, and under the action of the magnet 10, the coil 9 rotates around the shaft 8 under the action of the magnetic field interaction, and the gear 7 also starts to rotate, the strip plate
  • the rack structure on the 2 or the fixedly mounted rack 6 rises/falls under the rotation of the gear 7, thereby driving the strip 2 as a whole to rise/fall, and when the strip 2 starts to rise/fall, it also starts to stretch/
  • the compression spring 4 when the strip 2 and the mirror 3 above it are required to return to the initial position or the desired set position, when the corresponding change in the magnitude or direction of the current flowing into the coil 9, the strip 2 follows When the upper rack structure or the rack 6 is correspondingly moved, the spring 4 can correspondingly provide a contraction force or a tensile force, so that the strip 2 can be more sensitive and quickly restored to the initial with the assistance of the force of the spring 4. Location or desired location.
  • Fig. 4 For the arrangement of the position of the spring 4, reference may be made to Fig. 4, one end of which is fixed to the bent section 22, and the other end is fixed at a corresponding position (for example, a platform or a frame, etc.).
  • one end of the strip 2 is hingedly fixed, and various hinge devices including hinges, hinge balls, and the like can be used here, and the hinge fixing method can be adopted, that is, only the strip 2 can be ensured to be supported around the support point. 1 Rotate with low friction.
  • the shape of the magnet 10 is exemplified in the figure, and the magnet 10 is disposed in the vertical direction (this direction is an intuitive direction in the drawing, and the specific orientation of the object is not limited thereto), and the N pole is set. And the S pole is reasonably distributed, so that the coil 9 can move between the N pole and the S pole of the magnet 10 within the magnetic field of the magnet 10, and it is preferable to use the magnet 10 in order to generate a sufficiently strong magnetic field.
  • the neodymium magnet can obtain a strong magnetic field, so that it can strongly promote the movement of the coil 9 after energization.
  • a balancing device 5 is fixed on the gear 7, and the balancing device 5 is mounted on the gear 7.
  • the position is corresponding to the coil 9, that is, the balance device 5 and the coil 9 are respectively located on both sides of the gear, and the two are at the same level, which play a certain balance between each other.
  • the balancing device 5 is arranged in a coil shape so as to partially extend out of the gear 7, so that the weight of the balancing device 5 can be reduced, and at the same time, the balancing device 5 can also raise the position of the coil 9 under the action of the lever by its own gravity.
  • the fixed end of the strip 2, the fixed end of the spring 4, and the fixing portion of the bracket 11 are all platforms for supporting, for example: A bench-top work platform or a support platform placed on the rack, etc.
  • a rack or casing may be added to secure the entire unit to the frame or casing.
  • the spectral position adjusting device for biomarker detection in the present invention can solve the rotatable fixing manner of the gear 7 on the shaft 8 by using the prior art.
  • the gear 7 can be sleeved outside the bearing. The ring is rotated around the bearing, and then the inner ring of the bearing is fixed on the shaft 8 to fix the shaft 8 on the bracket 11; in addition, the gear 7 can also directly use the bearing gear to directly fix it on the shaft 8.
  • Other existing methods of rotational connection, such as articulation, socketing, etc., which enable the rotational fixation of the gear 7 are within the scope of the present invention.
  • the incident light is the infrared reflected light of the detected object, and the emitted light is the light actually received by the light receiving module 12, and the dark region of the spectrum formed on the light receiving module 12 is required.
  • the magnitude or/and direction of the current flowing into the coil 9 is changed, and the intensity or/and direction of the magnetic field generated by the closed coil 9 also changes with the transmission, such that Since the magnet 10 acts, the coil 9 drives the gear 7 to rotate (the coil 9 is relatively easy to move under the magnetic force of the magnet 10 under the balanced braking action of the balancing device 5), and the gear 7 drives the teeth on the strip 2
  • the strip structure or the rack 6 moves, the strip 2 also starts to move, and the angle of the mirror 3 with the horizontal direction changes with the movement of the strip 2, so that the incident angle of the incident light irradiated onto the mirror 3 changes, correspondingly
  • the exit angle also changes, and the angle at which the emitted light is incident on the light receiving module 12
  • the setting also changes, that is, according to adjusting the magnitude or/and direction of the current flowing into the coil 9, the position of the dark region formed on the light receiving module 12 is controlled correspondingly, through the change of the dark region position and into the coil 9.
  • the change in current obtains the required measurement information.
  • the implementation of the spectral position adjusting device for biomarker detection in the present invention is not limited to the above-described embodiment, for example, the gear 7 in which the movement of the strip 2 is realized and the strip 2 engaged therewith
  • the rack structure or the rack 6 can be integrally replaced by a meshing turbine, a worm or a socket-mounted nut or a screw, and the required changed parts can be modified as needed, for example, a worm or The nut is fixed on the strip 2, and the worm wheel and the screw are fixed on the base.
  • the position of the spring 4 is also not limited to the position shown in the drawing, and it can also be moved to the vicinity of the support point 1, so that the effect of the spring 4 may be better.
  • the incident light rays incident on the mirror 3 are derived from the light beam reflected from the sensor chip 400 in FIG.
  • the spectral position adjusting device for biomarker detection in the present invention is for adjusting the irradiation angle (incident angle and exit angle) of the light beam reflected from the sensor chip 400 on the mirror 3.
  • the present invention first uses a test substance containing a biomarker concentration of a set value (generally zero), and passes it into the flow channel 300 in FIG. 1 at the reaction interface.
  • the antibody molecule is modified on the surface, and the target antigen is not detected in the sample, and the refractive index of the surface medium of the gold film is not changed.
  • the light beam irradiated onto the sensor chip 400 after being refracted by the prism 500 (usually using monochromatic light)
  • the infrared light beam is substantially unchanged after being emitted, and the emitted light is reflected by the mirror 3 and then irradiated to the light receiving module 12 to form a spectrum with a dark region on the light receiving module 12, in which case the light receiving module 12 outputs a light.
  • An electrical signal which is an initial value (zero value). If the dark area position on the light receiving module 12 is shifted, the intensity of the light received thereon changes, and the output of the light receiving module 12 is measured. The change of the electrical signal can be used to know whether the dark region position of the spectrum formed on the light receiving module 12 changes, thereby knowing the presence or absence of the biomarker in the detected substance.
  • the spectrum formed on the light receiving module 12 is as shown in FIG. 5, the initial position can be set, and the intensity of the electrical signal output from the light receiving module 12 is determined as the initial position. Signal strength value.
  • the concentration of the biomarker of the substance to be tested is required, the substance to be detected is introduced into the flow channel 300, and the target antigen in the analyte and the antibody molecule on the reaction interface are combined,
  • the refractive index of the gold film surface medium changes, and correspondingly, the light beam irradiated onto the sensor chip 400 after being refracted by the prism 500 is also changed correspondingly, so that the dark region of the spectrum of the light beam irradiated onto the light receiving module 12 is changed. A change occurs, as shown in FIG. 6, wherein FIG. 6a and FIG.
  • An embodiment of the method for detecting biomarkers in the object to be detected is that when it is detected that the electrical signal outputted on the light receiving module 12 is different from the set initial position, the A current is applied to the coil 9 of the spectral position adjusting device for biomarker detection, so that the coil 9 generates a magnetic field. Under the action of the magnetic field generated by the magnet 10, the coil 9 is forced to rotate and drives the gear 7 to rotate.
  • the rack structure or the rack 6 on the strip 2 that is engaged therewith drives the strip 2 to rotate around its hinged support point 1 to change the angle of the mirror 3 on the strip 2, by adjusting the angle of the mirror 3, Adjusting the angle of the incident light (shown in FIG.
  • the biomarker in the detected substance can be detected. concentration.
  • the light receiving module 12 in the above-described process of adjusting the angle of the mirror 3 to obtain the current in the coil 9 corresponding to the concentration of the biomarker in the object to be detected, as shown in FIG. 6, in the light receiving
  • the position of the dark region of the spectrum formed on the module 12 may occur during the adjustment process as in the direction indicated by a, b, such that the magnitude and/or direction of the current flowing into the coil 9 during the adjustment will It is difficult to determine that, in order to avoid this, the light receiving module 12 can be arranged as shown in FIG. 7 (three of the figures are taken as the first light receiving module 121 and the second light receiving module respectively).
  • the dark area of the spectrum is located on the first light receiving module 121.
  • the electrical signal outputted on the first light receiving module 12 is an initial value.
  • the movement information of the dark area can be known, thereby correspondingly determining the magnitude and/or direction of the current that should be introduced into the coil 9, thereby obtaining a faster adjustment of the dark area to the initial stage.
  • the amount of current in the coil 9 required for the position is known to the concentration of the biomarker in the test.
  • FIG. 8 is a schematic structural diagram of a biomarker detecting system according to the present invention. As shown, it includes a control module 13, a light receiving module 12, a spectral position adjusting device 14, and a power module 15, wherein the light receiving module 12 is used. Receiving the reflected beam at the sensing chip, forming a spectrum thereon, outputting an electrical signal, and transmitting the electrical signal to the control module 13; the power module 15 is controlled by the control module 13 and inputting current to the spectral position adjusting device 14, The spectral position adjusting device 14 receives the current of the power module 15 and operates to change the position of the spectrum on the light receiving module 12 while transmitting its own current size information to the control module 13; the control module 13 records the electrical signal on the light receiving module 12.
  • the information is changed, and an instruction is issued to the power module 15 according to the information, and the power module 15 is controlled to pass a current into the spectral position adjusting device 14, and the current that the power module 15 passes into the spectral position adjusting device is recorded and compared with
  • the electrical signal sent by the light receiving module 12 is compared and calculated to obtain the concentration information of the biomarker in the detected substance.
  • the present invention may additionally provide a concentrating module such that the light beams illuminating the light receiving module 12 are concentrated, so that the light receiving module 12 can receive the light beam better.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

一种基于表面等离子共振技术的生物标志物检测方法、系统和装置，所述检测方法是通过光接收模块接收经过传感芯片处射出的光束，并形成光谱，并通过调整该光谱信息，相应的获取与零点位置对应的变化信息，从而获得检测物的生物标志物的浓度，所述系统包括光接收模块（12）、控制模块（13）、光谱位置调节装置（14）和电源模块（15），用于实现上述方法，所述装置通过可通入电流的线圈（9）带动传动机构运动从而调节镜子的方位，从传感芯片处射出的光束经过镜子反射后照射到光接收模块上。该方法能够方便、快捷的改变检测物中生物标志物的射出光线的光谱位置，获取检测物中生物标志物的有效信息。

Description

基于表面等离子共振技术的生物标志物检测方法与系统
技术领域
本发明涉及生物标志物检测领域，更具体的说涉及基于表面等离子共振技术的生物标志物检测方法及系统。
背景技术
生物标志物（Biomarker）是指可以标记系统、器官、组织、细胞及亚细胞结构或功能的改变或可能发生的改变的生化指标，具有非常广泛的用途。生物标志物可用于疾病诊断、判断疾病分期或者用来评价新药或新疗法在目标人群中的安全性及有效性。在检测生物标志物时，常用到表面等离子共振技术SPR（Surface Plasmon Resonance），即利用金属膜/液面界面光的全反射连接引起的一种物理光学现象来分析生物分子相互作用，并通过红外光结合SPR技术测量生物标志物浓度，具体可参照论文“表面等离子共振技术在生物医学中的应用”，以及论文“表面等离子体共振免疫传感器在蛋白质检测中的应用及其研究进展”—《分析化学》2010年第七期1052-1059。
在生物标志物检测领域，光度测量法是较为常用的方法，其通过在体外将人体的体液标本的分量与一种或多种检验试剂混合，多次确定被分析物的浓度，由此引发生物化学反应，这使得被测物的光学特性发生可测的变化，光度测量法检测并利用光流穿过吸光性的和/或散光性的媒介时的发生的减弱，然而，这种测量方法由于受样本本身的类型和其可能包含的干扰性物质的影响，导致在测量时易发生系统错误，使得对生物标志物的浓度的测量结果不够准确，而且，在测量时光流方向的调节很难掌控，往往给测量者带来极大的困扰。
发明内容
为了解决上述技术问题，本发明提供一种快速、准确获取待测物中生物标志物浓度的基于表面等离子共振技术的生物标志物检测方法、装置及系统。
本发明为解决上述技术问题所采用的技术方案为：基于表面等离子共振技术的生物标志物检测方法，包括以下步骤：
S1、光接收模块接收反射光束，并设定其所接收的光谱的初始位置，记录光接收模块输出电信号的初始值；
S2、光谱位置调节装置调节有待测物时光接收模块上的光谱位置，使其移动至初始位置；
S3、控制模块根据光接收模块上的光谱的移动量计算检测物中生物标志物浓度。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测方法，作为进一步的设置，在步骤S1之前还包括步骤S0、将经过反射后的光束进行聚集，之后将其传送至光接收模块。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测方法，作为进一步的设置，在步骤S0之前，还包括步骤S00、将传感器芯片处的反射光束进行一次反射。
基于表面等离子共振技术的生物标志物检测系统，所述生物标志物检测系统包括光接收模块、控制模块、光谱位置调节装置以及电源模块，
所述的光接收模块，与所述控制模块电连接，用于接收传感芯片处的反射光束，并相应输出电信号，将电信号传送至控制模块；
所述光谱位置调节装置，与所述的控制模块、所述的电源模块电连接，用于接收电源模块的电流信息并改变所述光接收模块上的光谱的位置，同时将所述的电流信息传送至控制模块；
所述的电源模块，与所述的控制模块、所述的光谱位置调节装置电连接，用于接收所述的控制模块的指令，根据所述指令向所述的光谱位置调节装置中输入电流；
所述的控制模块，用于记录光接收模块上的电信号变化信息，并发出指令给电源模块，并记录电源模块向光谱位置调节装置通入的电流信息，将其与光接收模块输出的电信号对比，得出检测物中的生物标志物浓度信息。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，作为针对光接收模块的进一步设置，所述的光接收模块包括第一光接收模块、第二光接收模块以及第三光接收模块，且三者之间并排设置。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，作为进一步的设置，所述的基于表面等离子共振技术的生物标志物检测系统还包括聚光模块，用于将将传输至光接收模块的光束进行聚集。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，作为针对光谱位置调节装置的一种具体的实施方式，所述的光谱位置调节装置包括条板、镜子、传动机构、线圈、磁铁以及底座，所述的镜子设置在条板上，所述的传动机构一处固定在所述的条板上，另一处固定在所述的底座上，所述的线圈固定在所述的传动机构上，所述的磁铁靠近所述线圈，使得向所述线圈中通电后其能够在所述磁铁的作用下通过所述的传动机构带动所述的条板运动。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，作为针对其传动机构的一种可选的实施例，所述的传动机构包括相互啮合的齿条和齿轮，所述的齿条固定在所述的条板上，所述的齿轮可转动的固定在所述的底座上。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，作为针对其传动机构的一种可选的实施例，所述的传动机构包括相互啮合的蜗轮和蜗杆，所述的蜗杆固定在所述的条板上，所述的蜗轮可转动的固定在所述的底座上。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，在所述的传动机构上还设有平衡装置，所述的平衡装置与所述的线圈分布在所述传动机构的两侧。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，所述的光谱位置调节装置还包括弹簧，所述的条板由所述弹簧支撑。
对于本发明中上述的基于表面等离子共振技术的生物标志物检测系统，作为进一步的设置，所述的磁铁为钕磁铁，其形状为圆弧形或条形。
本发明带来的技术效果为：使用基于表面等离子共振技术的生物标志物检测方法，使用光接收模块接收特定光谱信息，形成光谱，并设定零点位置，调整待测物在光接收模块上的光谱位置，通过该调节量对应计算出待测物中的生物标志物的浓度值信息，能够方便、快速、准确的检测出待测物中的生物标志物的浓度；本发明中的检测系统，包括控制模块、光接收模块、光谱位置调节装置和电源模块，其中，光接收模块用于接收传感芯片处的反射光束，其上面形成光谱后，输出电信号，并将电信号传送至控制模块；电源模块接受控制模块的控制，并向光谱位置调节装置中输入电流，光谱位置调节装置接收电源模块的电流并运作改变光接收模块上的光谱的位置，同时将其自身的电流大小信息传递至控制模块；控制模块记录光接收模块上的电信号变化信息，并根据此信息发出指令给电源模块，控制电源模块使其向光谱位置调节装置中通入电流，记录电源模块向光谱位置调节装置中通入的电流，并将其与光接收模块发出的电信号对比计算，得出所检测的物质中的生物标志物的浓度信息；本发明中的用于生物标志物检测的光谱位置调整装置，通过可通电的线圈与磁铁的作用力，并通过传动机构带动镜子运动，从而调节光接收模块上的光谱的位置，结构简单，制作成本低廉，且使用起来非常方便。
附图说明
图1为本发明涉及到的表面等离子共振技术的工作原理图；
图2为发明中的基于表面等离子共振技术的生物标志物检测方法的工作流程图；
图3为发明中的基于表面等离子共振技术的生物标志物检测方法的第二种实施例的工作流程图；
图4为本发明中的用于生物标志物检测的光谱位置调整装置的整体结构示意图；
图5为本发明中的基于表面等离子共振技术的生物标志物检测方法所设定的零点位置时光接收模块上所形成的光谱的示意图；
图6为本发明中的基于表面等离子共振技术的生物标志物检测方法中调节光接收模块上的光谱位置时可能出现的光谱位置移动情况的示意图；
图7为本发明中的基于表面等离子共振技术的生物标志物检测方法的光接收模块的一种较优实施例的示意图；
图8为本发明中的基于表面等离子共振技术的生物标志物检测系统的结构示意图。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，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地描述，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通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。
图1为本发明涉及到的表面等离子共振技术的工作原理图，其为现有技术，如图所示，利用表面等离子共振技术检测生物标志物浓度的过程，首先，设置一个流动通道300和传感芯片400，在传感芯片400上设置一层金膜，并使传感芯片400设有金膜的一面部分位于流动通道300中，使得流入流动通道300内的待检测物能够接触到带有金膜的传感芯片400，测量时，将带有生物标志物的待检测物通入流动通道300，使得待检测物与传感芯片接触，预先在反应界面上修饰一层抗体分子，当目标抗原与抗体识别后，金膜表面介质的折射率发生改变，SPR共振角会随着折射率的改变而改变，折射率的变化又与结合在金属表面的生物大分子质量的变化成正比，共振峰位移的大小将反映固定在金属表面生物分子量的变化，进而实现免疫分析。在图1中，由光源600发出光束，照射到传感芯片400上，经其反射后由光学检测单元700（本发明中将用光接收模块作为光学检测单元）接收，通过光学检测单元700感应其所接收到的光束信息的变化，得出该变化信息与待检测物生物标志物浓度的对应关系，最终从该变化信息中得出待检测物中生物标志物浓度值。对于光源600，可采用单色光源，例如红外线束光源，效果较好。
本发明中的基于表面等离子共振技术的生物标志物检测方法的工作流程图如图2所示，包括以下步骤：
S1、光接收模块接收反射光束，并设定其所接收的光谱的初始位置，记录光接收模块输出电信号的初始值；
S2、光谱位置调节装置调节有待测物时光接收模块上的光谱位置，使其移动至初始位置；
S3、控制模块根据光接收模块上的光谱的移动量计算检测物中生物标志物浓度。
进一步的，本发明还可以对上述过程进行完善，为此，提供第二种更为完善的实施例，其工作流程图如图3所示，包括以下步骤：
S00、将传感器芯片处的反射光束进行一次反射；
S0、将经过反射后的光束进行聚集，之后将其传送至光接收模块；
S1、光接收模块接收反射光束，并设定其所接收的光谱的初始位置，记录光接收模块输出电信号的初始值；
S2、光谱位置调节装置调节有待测物时光接收模块上的光谱位置，使其移动至初始位置；
S3、控制模块根据光接收模块上的光谱的移动量计算检测物中生物标志物浓度。
本发明在表面等离子共振技术的基础上，首先采用不含有待测生物标志物的物质，经单色光束照射后，用光接收模块接收偏振光束，此时设定为初始位置，记录其输出电信号的初始值，作为光谱的初始位置值，之后对待检测物进行测量，因待测物中含有生物标志物，光接收模块上的光谱及其暗区的位置发生改变，相应的光接收模块上所输出的电信号的大小也相应发生变化，通过调节光谱的位置，可使得光接收模块上输出的电信号大小与初始位置时相同，对于光谱位置的调节过程，不同的调节方法都可实现，但每种调节方法的调节量均与光谱位置的移动量存在一一对应关系，可以此计算出检测物中的生物标志物的浓度。
在上述检测过程的原理下，本发明在上述基础上设置一个起辅助作用的用于生物标志物检测的光谱位置调整装置，用于调整反射光线束在光学检测单元700（与本发明中的光接收模块相对应）上的位置，以获取能够反应待检测物中生物标志物的浓度信息。该装置的整体结构示意图如图4所示，包括条板2、镜子3、弹簧4、齿轮7、线圈9和磁铁10，条板2的一端以铰接的方式固定，另一端与齿条6固定连接，在齿条6的旁边设置有一个齿轮7，齿轮7与齿条6处于啮合状态，齿轮7可转动的固定在轴8上，轴8固定在支架11上，为了方便在条板2上固定齿条6，可将条板2设置为固定连接的两部分，一部分为直线段21，另一部分为弯折段22，直线段21的一端采用铰接的方式固定，其另一端与弯折段22固定连接，并使得直线段21与水平方向呈一定的夹角（一般情况下以锐角居多），在直线段21上固定有镜子3，用于反射检测生物标志物时的红外光线，弯折段22呈90度折弯状，其水平部分与直线段固定连接，其竖直部分固定齿条6，当然，也可以在该竖直段上设置齿条结构，将齿条与弯折段22设置成一体结构，相比较而言，在弯折段22的竖直部分上设置齿条结构，即做成一体式的结构在制作、安装以及使用时会更加方便。
条板2上的齿条结构或固定着的齿条6与齿轮7处于啮合状态，当齿轮7在外力的作用下转动时，条板2上的齿条结构或齿条6随着齿轮7的转动而转动，从而带动条板2发生运动。为了控制/调节齿轮7的转动，在齿轮7上固定一个闭合的线圈9，该线圈9要延伸出齿轮7的本体，并向外延伸一段距离，在与线圈9旁边设置一个固定着的磁铁10，线圈9的一部分与磁铁10重叠，这样以来，当向线圈9上通入电流时，处于闭合状态的线圈9形成一个闭合的回路，当这个闭合的回路中有电流通过时，其自身在电磁感应作用下产生磁场，线圈9产生的磁场与磁铁10的磁场相互之间发生作用力，此时，改变通入线圈9中的电流大小/方向可以改变线圈9所产生的磁场强度以及磁场方向，由于磁铁10所产生的磁场的大小和方向是固定的，因此，当改变线圈9中的电流大小和/或方向时，在磁铁10的磁场的作用下，线圈9发生转动，由于线圈9是固定在齿轮7上的，因此，在线圈9开始转动时，齿轮7随着线圈9转动而转动，齿轮7与条板2上的齿条结构或齿条6啮合，因此条板2上的齿条结构或齿条6随着齿轮7的转动而运动（图中为竖直方向运动），最终条板2也会随着线圈9中电流的变化而运动，对于条板2，由于其直线段21是以铰接的方式固定着的，因此，在条板2随着线圈9中通入电流的变化而变化时，条板2的直线段21与水平方向的夹角也将随之而改变，进而，固定在条板2上的镜子3与水平方向的夹角也便随着改变，其上面的反射光线的角度也会随之而改变。
如图4所示，为了进一步提高条板2上的镜子3的水平夹角的调节灵敏度，在条板2上连接一个弹簧4，弹簧4的另一端固定，设定一个初始位置，使得弹簧4在该初始位置时整个装置处于一个零点，当需要调整镜子3的水平夹角时，可借助弹簧4的弹力，使得镜子3更加容易回复至初始位置。上述具体过程表现为：当向线圈9中通入电流，线圈中产生磁场，在磁铁10的作用下，线圈9在磁场交互的作用力下绕轴8转动，同时齿轮7也开始转动，条板2上的齿条结构或固定安装的齿条6在齿轮7的转动下上升/下降，进而带动条板2整体上升/下降，在条板2开始上升/下降时，其同时也开始拉伸/压缩弹簧4，当需使条板2及其上面的镜子3回复至初始位置或所需设定的位置时，当相应的改变通入线圈9中的电流大小或方向，条板2在随着其上面的齿条结构或齿条6相应的运动时，弹簧4能够相应的提供收缩力或拉伸力，使得条板2能够在弹簧4的作用力的协助下更加灵敏、快速的回复至初始位置或所需位置。
对于弹簧4位置的设置，可参照图4，将其一端固定在弯折段22上，另一端固定在相应的位置（例如平台或机架上等）。
在图4中，条板2的一端是铰接固定着的，此处可采用包括合页、铰接球等在内的多种铰接装置及铰接固定方式，即只需确保条板2能够绕支撑点1以较低的摩擦力旋转即可。
如图4中所示，磁铁10的形状以图中为例，在竖直方向（此方向为图中直观方向，具体实物的设置方位并不局限于此）设置磁铁10，并使其N极和其S极合理分布，使得线圈9能够在磁铁10磁场的作用范围内，在磁铁10的N极和S极之间运动，对于磁铁10，为了使其能够产生足够强的磁场，最好使用钕磁铁，可以获得较强的磁场，使其能够强力的促使通电后的线圈9的运动。
进一步的，如图4中所示，为了提高线圈9在齿轮7上的稳定性，并进一步提高线圈9的调节灵敏性，在齿轮7上固定一个平衡装置5，该平衡装置5安装在齿轮7上，其位置要与线圈9对应，即使得平衡装置5和线圈9分别位于齿轮的两侧，并使其二者位于同一水平高度，彼此之间起到一定的平衡作用，在此，可以将平衡装置5设置成线圈状，可以使其部分延伸出齿轮7，这样一来可以减轻平衡装置5的重量，同时，平衡装置5还可以借助自身重力，在杠杆作用下对线圈9的位置高度起到很好的平衡作用，即当线圈9受磁铁10的磁场力向上/下（仅指图中方位，实际方向不限于此）运动时，在平衡装置5的作用下，线圈9只需克服很小的力便可摆脱静止状态进行运动，同样的，当需将线圈9调整至初始位置时，只需克服较小的阻力即可实现，即无需大幅度变动通入线圈9中的电流即可实现对线圈9的位置调整。
对于图4中的轴8，可将其通过支架11进行固定，本发明中，条板2的固定端部、弹簧4的固定端以及支架11的固定处均为具有支撑作用的平台，例如：台式的工作平台或者设置在机架上的支撑平台等，然而，也可以增设一个机架或者外壳，将整套装置固定在机架或外壳上。
本发明中的用于生物标志物检测的光谱位置调整装置，对于齿轮7在轴8上的可转动的固定方式，可采用现有技术进行解决，例如，可采用将齿轮7套在轴承的外圈上，使其可围绕轴承转动，然后将轴承的内圈固定在轴8上，将轴8固定在支架11上；另外，齿轮7也可直接使用轴承齿轮，将其直接固定在轴8上；其它现有的转动连接的方式，如铰接、套接，等等能够实现齿轮7可转动固定的均在本发明的可实施范围之内。
参照图4，以其中的入射光线为所检测的检测物的红外反射光线，以其出射光为光接收模块12实际所接收的光线，当需对光接收模块12上形成的光谱的暗区位置进行调整，以获取进一步关于生物标志物的详细信息时，改变通入线圈9中的电流大小或/和方向，闭合的线圈9所产生的磁场的强度或/和方向也随着发送变化，这样以来，在磁铁10的作用下，线圈9带动齿轮7转动（在平衡装置5的平衡制动作用下线圈9比较容易在磁铁10的磁力作用下运动），进而齿轮7带动条板2上的齿条结构或齿条6运动，条板2也开始运动，镜子3与水平方向的角度随着条板2的运动发生改变，如此以来，照射到镜子3上的入射光的入射角发生变化，相应的，出射角也发生变化，出射光照射到光接收模块12上的角度也发生变化，因此经过检测物反射的红外线在光接收模块12上形成的暗区的位置也会发生改变，即根据调整通入线圈9中电流的大小或/和方向，相应的控制光接收模块12上形成的暗区的位置，通过该暗区位置的改变以及通入线圈9中的电流的改变获得所需的测量信息。
需要特别说明的是，本发明中的用于生物标志物检测的光谱位置调整装置实施并不局限于上述的实施方式，例如，其中实现条板2运动的齿轮7以及与其啮合的条板2上的齿条结构或齿条6，可以由相互啮合的涡轮、蜗杆或者可套接安装的螺母、螺杆进行整体替换，并相应的按需要将所需更改的部位进行修改即可，例如将蜗杆或螺母固定在条板2上，将蜗轮和螺杆固定在底座上即可，对于本领域技术人员以及结合现有的机械领域公知常识的其它领域人员均可十分容易的做出上述变动；而且，本发明中，弹簧4的位置也并不局限于图中所示的位置，还可将其移动至支撑点1附近，这样弹簧4的作用效果可能会更好。
在图4中，照射到镜子3上的入射光线源自于图1中从传感芯片400处反射而来的光束。本发明中的用于生物标志物检测的光谱位置调整装置用于调整从传感芯片400处反射而来的光束在镜子3上的照射角度（入射角和出射角）。
本发明在测量待检测物的生物标志物浓度时，首先使用含有生物标志物浓度为设定值（一般可为零）的检测物，将其通入图1中的流动通道300，在反应界面上修饰一层抗体分子，待检测物中没有目标抗原，金膜表面介质的折射率不会发生改变，此时，经过棱镜500折射后照射到传感芯片400上的光束（一般使用单色光，例如红外光束）出射后基本没有变化，其出射光经过镜子3反射后照射到光接收模块12，在光接收模块12上形成带有暗区的光谱，此种情况下光接收模块12输出一个电信号，该电信号作为一个初始值（零值），若光接收模块12上的暗区位置发生偏移，其上面所接收到的光的强度发生改变，通过测量光接收模块12上输出的电信号的变化，可得知光接收模块12上形成的光谱的暗区位置是否变化，从而得知所检测的物质中的生物标志物的存在与否。
上述零点位置确定后，其在光接收模块12上形成的光谱如图5中所示，可设定该初始位置，并确定从光接收模块12上输出的电信号的强度，作为初始位置的电信号强度值。
上述零点位置确定后，当需要对待测物质的生物标志物浓度进行检测时，将所要检测的物质通入到流动通道300中，由于待检测物中的目标抗原和反应界面上的抗体分子结合，金膜表面介质的折射率发生改变，相应的，经过棱镜500折射后照射到传感芯片400上的光束出射后也相应发生改变，使得照射到光接收模块12上的光束的光谱的暗区位置发生改变，如图6中所示，其中图6a、图6b分别为可能出现的光谱及其暗区在光接收模块12上的移动情况，由于在调节镜子3的过程中，暗区位置在光接收模块12上的移动方向无法得知的不确定性，使得光接收模块12上所接收到的整体的光强发生不同的变化，其所输出的电信号也会发生相应的变化。
本发明中提供的检测上述待检测物中的生物标志物的方法的一种实施例为，当检测到光接收模块12上输出的电信号与设定的初始位置不同时，向图4中的用于生物标志物检测的光谱位置调整装置的线圈9中通入电流，使线圈9产生磁场，在磁铁10所产生的磁场的作用下，线圈9受力旋转，并带动齿轮7转动，齿轮7带动与其啮合的条板2上的齿条结构或齿条6带动条板2以其铰接的支撑点1为中心旋转，从而改变条板2上的镜子3的角度，通过调整镜子3的角度，调节照射到镜子3上的入射光（图4中所示）的角度，从而调整光接收模块12上形成的光谱的暗区的位置，当将暗区位置调整到所设定的零点位置时，记录此时通入线圈9中的电流大小，并将通入线圈9中的电流大小与所检测的物质中的生物标志物的浓度对应起来，即可查出所检测的物质中的生物标志物的浓度。
本发明中，进一步的，在上述的调节镜子3的角度以获取待检测物中生物标志物的浓度对应的通入线圈9中的电流的过程中，如图6中所示的，在光接收模块12上所形成的光谱的暗区的位置在调节过程中可能会出现如其中a、b所示方向的移动，这使得在调节过程中通入线圈9中的电流的大小和/或方向将难以确定，为了避免这种情况，可将光接收模块12设置成如图7中所示的多个（以图中的三个为例，分别为第一光接收模块121、第二光接收模块122和第三光接收模块123），设定位于中间的第一光接收模块121为初始位置所在的模块，即初始位置时，光谱的暗区是位于第一光接收模块121上的，此时第一光接收模块12上输出的电信号为初始值，测量时，当改变通入线圈9中的电流，镜子3的角度发生变化，光谱暗区的位置可能移动至第二光接收模块122或第三光接收模块123，根据获取其上面输出的电信号即可得知暗区的移动信息，从而相应的判断出应该通入线圈9中的电流的大小和/或方向，从而更快的获取将暗区调整至初始位置所需的通入线圈9中的电流大小，得知检测物中生物标志物的浓度。
图8为本发明中的生物标志物检测系统的结构示意图，如图所示，其包括控制模块13、光接收模块12、光谱位置调节装置14和电源模块15，其中，光接收模块12用于接收传感芯片处的反射光束，其上面形成光谱后，输出电信号，并将电信号传送至控制模块13；电源模块15接受控制模块13的控制，并向光谱位置调节装置14中输入电流，光谱位置调节装置14接收电源模块15的电流并运作改变光接收模块12上的光谱的位置，同时将其自身的电流大小信息传递至控制模块13；控制模块13记录光接收模块12上的电信号变化信息，并根据此信息发出指令给电源模块15，控制电源模块15使其向光谱位置调节装置14中通入电流，记录电源模块15向光谱位置调节装置中通入的电流，并将其与光接收模块12发出的电信号对比计算，得出所检测的物质中的生物标志物的浓度信息。
进一步的，本发明还可另外设置聚光模块，使得照射到光接收模块12上的光束得以聚集，使光接收模块12能够更好的接收光束。
上面结合附图对本发明的具体实施方式作了详细说明，但是本发明并不限于上述实施方式，在本领域技术人员所具备的知识范围内，还可以在不脱离本发明宗旨的前提下作出各种变化。

Claims (15)

  1. 基于表面等离子共振技术的生物标志物检测方法，其特征在于：包括以下步骤：
    S1、光接收模块接收反射光束，并设定其所接收的光谱的初始位置，记录光接收模块输出电信号的初始值；
    S2、光谱位置调节装置调节有待测物时光接收模块上的光谱位置，使其移动至初始位置；
    S3、控制模块根据光接收模块上的光谱的移动量计算检测物中生物标志物浓度。
  2. 根据权利要求1中所述的基于表面等离子共振技术的生物标志物检测方法，其特征在于：在步骤S1之前还包括步骤S0、将经过反射后的光束进行聚集，之后将其传送至光接收模块。
  3. 根据权利要求2中所述的基于表面等离子共振技术的生物标志物检测方法，其特征在于：在步骤S0之前，还包括步骤S00、将传感器芯片处的反射光束进行一次反射。
  4. 基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述生物标志物检测系统包括光接收模块、控制模块、光谱位置调节装置以及电源模块，
    所述的光接收模块，与所述控制模块电连接，用于接收传感芯片处的反射光束，并相应输出电信号，将电信号传送至控制模块；
    所述光谱位置调节装置，与所述的控制模块、所述的电源模块电连接，用于接收电源模块的电流信息并改变所述光接收模块上的光谱的位置，同时将所述的电流信息传送至控制模块；
    所述的电源模块，与所述的控制模块、所述的光谱位置调节装置电连接，用于接收所述的控制模块的指令，根据所述指令向所述的光谱位置调节装置中输入电流；
    所述的控制模块，用于记录光接收模块上的电信号变化信息，并发出指令给电源模块，并记录电源模块向光谱位置调节装置通入的电流信息，将其与光接收模块输出的电信号对比，得出检测物中的生物标志物浓度信息。
  5. 根据权利要求4中所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的光接收模块包括第一光接收模块、第二光接收模块以及第三光接收模块。
  6. 根据权利要求5所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的第一光接收模块、第二光接收模块和第三光接收模块并排设置。
  7. 根据权利要求4中所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的基于表面等离子共振技术的生物标志物检测系统还包括聚光模块，用于将将传输至光接收模块的光束进行聚集。
  8. 根据权利要求4中所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的光谱位置调节装置包括条板（2）、镜子（3）、传动机构、线圈（9）、磁铁（10）以及底座（11），所述的镜子（3）设置在条板（2）上，所述的传动机构一处固定在所述的条板（2）上，另一处固定在所述的底座（11）上，所述的线圈（9）固定在所述的传动机构上，所述的磁铁（10）靠近所述线圈（9），使得向所述线圈（9）中通电后其能够在所述磁铁（10）的作用下通过所述的传动机构带动所述的条板（2）运动。
  9. 根据权利要求8所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的传动机构包括相互啮合的齿条（6）和齿轮（7），所述的齿条（6）固定在所述的条板（2）上，所述的齿轮（7）可转动的固定在所述的底座（11）上。
  10. 根据权利要求8所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的传动机构包括相互啮合的蜗轮和蜗杆，所述的蜗杆固定在所述的条板（2）上，所述的蜗轮可转动的固定在所述的底座（11）上。
  11. 根据权利要求9所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：在所述的传动机构上还设有平衡装置（5），所述的平衡装置（5）与所述的线圈（9）分布在所述传动机构的两侧。
  12. 根据权利要求10所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：在所述的传动机构上还设有平衡装置（5），所述的平衡装置（5）与所述的线圈（9）分布在所述传动机构的两侧。
  13. 根据权利要求9所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的光谱位置调节装置还包括弹簧（4），所述的条板（2）由所述弹簧（4）支撑。
  14. 根据权利要求8所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的磁铁（10）为钕磁铁。
  15. 根据权利要求14所述的基于表面等离子共振技术的生物标志物检测系统，其特征在于：所述的磁铁（10）的形状为条形或圆弧形。
PCT/CN2015/077443 2015-03-25 2015-04-24 基于表面等离子共振技术的生物标志物检测方法与系统 Ceased WO2016149982A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201510131569.6A CN104777136B (zh) 2015-03-25 2015-03-25 基于表面等离子共振技术的生物标志物检测方法与系统
CN201510131569.6 2015-03-25

Publications (1)

Publication Number Publication Date
WO2016149982A1 true WO2016149982A1 (zh) 2016-09-29

Family

ID=53618742

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2015/077443 Ceased WO2016149982A1 (zh) 2015-03-25 2015-04-24 基于表面等离子共振技术的生物标志物检测方法与系统

Country Status (2)

Country Link
CN (1) CN104777136B (zh)
WO (1) WO2016149982A1 (zh)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4561023A (en) * 1983-08-16 1985-12-24 Xerox Corporation Dampening system for micro-deflector scanning beam modulator
EP0730241A2 (en) * 1990-05-08 1996-09-04 Symbol Technologies, Inc. Scanning arrangement
JP2000249940A (ja) * 1999-02-24 2000-09-14 Fujikura Ltd 光スイッチ
EP1081529A2 (en) * 1999-08-30 2001-03-07 PSC Scanning, Inc. Reflective dither spring
CN201075777Y (zh) * 2007-08-31 2008-06-18 上海世科嘉车辆技术研发有限公司 后视镜单电机电动角度调节系统
CN101371129A (zh) * 2006-01-19 2009-02-18 香港中文大学 表面等离子体共振传感器以及利用其检测样品的方法
CN101514988A (zh) * 2009-02-26 2009-08-26 中国科学院光电技术研究所 一种葡萄球菌肠毒素探测方法
CN103984091A (zh) * 2013-11-21 2014-08-13 苏州浩创信息科技有限公司 一种扫描器摆镜装置

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9928849D0 (en) * 1999-12-07 2000-02-02 Secr Defence Brit Surface plasmon resonance
BRPI0822092A8 (pt) * 2007-12-20 2016-03-22 Koninklijke Philips Electronics Nv Dispositivo sensor microeletrônico para o exame de partículas alvo, método para o exame das partículas alvo, e, uso do dispositivo sensor microeletrônico
FI20095064A0 (fi) * 2009-01-26 2009-01-26 Wallac Oy Järjestely ja menetelmä optisen mittauslaitteen mittapään ohjaamiseksi
CN104089877B (zh) * 2014-07-10 2016-04-27 上海第二工业大学 一种宽量程范围浊度仪

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4561023A (en) * 1983-08-16 1985-12-24 Xerox Corporation Dampening system for micro-deflector scanning beam modulator
EP0730241A2 (en) * 1990-05-08 1996-09-04 Symbol Technologies, Inc. Scanning arrangement
JP2000249940A (ja) * 1999-02-24 2000-09-14 Fujikura Ltd 光スイッチ
EP1081529A2 (en) * 1999-08-30 2001-03-07 PSC Scanning, Inc. Reflective dither spring
CN101371129A (zh) * 2006-01-19 2009-02-18 香港中文大学 表面等离子体共振传感器以及利用其检测样品的方法
CN201075777Y (zh) * 2007-08-31 2008-06-18 上海世科嘉车辆技术研发有限公司 后视镜单电机电动角度调节系统
CN101514988A (zh) * 2009-02-26 2009-08-26 中国科学院光电技术研究所 一种葡萄球菌肠毒素探测方法
CN103984091A (zh) * 2013-11-21 2014-08-13 苏州浩创信息科技有限公司 一种扫描器摆镜装置

Also Published As

Publication number Publication date
CN104777136A (zh) 2015-07-15
CN104777136B (zh) 2018-06-19

Similar Documents

Publication Publication Date Title
Liu et al. Surface plasmon resonance biosensor based on smart phone platforms
Wang et al. A label-free fiber optic SPR biosensor for specific detection of C-reactive protein
CN104677827B (zh) 一种基于便携式光纤光谱仪的可见近红外漫反射基线信号的扣除装置及其方法
WO2001075420A1 (en) Method and apparatus for detecting mastitis by using visible light and/or near infrared light
CA2748731C (en) An arrangement and a method for controlling a measurement head of an optical measurement instrument
Cierpiak et al. C-reactive protein (CRP) evaluation in human urine using optical sensor supported by machine learning
WO2016149989A1 (zh) 生物标志物检测用光谱位置调节装置
EP1870695A1 (en) Accelerated weathering device with optical slip ring
CN106501219A (zh) 一种便携式多参数表面等离子体谐振生化分析仪
CN109490286A (zh) 用于医院检验科和泌尿科的尿液分析仪
CN120820521B (zh) 一种用于隧道反光玻璃珠的反光性能测试装置
CN103149353B (zh) 多通道试纸盘的定量检测系统及检测方法
CN103698304B (zh) 一种剪式液芯耦合表面等离子体共振成像分析仪
Liu et al. A compact biosensor for binding kinetics analysis of protein–protein interaction
WO2016149981A1 (zh) 基于光反射的生物标志物检测用光谱位置调整装置
CN107356560A (zh) 全反射式斜入射光反射差扫描成像装置及其使用方法
WO2016149980A1 (zh) 变量干预式生物标志物浓度检测方法及装置
CN110132861A (zh) 一种多单元多参数纳米光子学传感特性检测系统及方法
CN104777136B (zh) 基于表面等离子共振技术的生物标志物检测方法与系统
CN215263129U (zh) 一种便携式荧光免疫分析仪机芯
CN209727962U (zh) 一种酶联免疫分析仪
JP2006098368A (ja) 全反射減衰を利用したセンサー
CN103698306B (zh) 一种液芯耦合表面等离子体共振成像分析仪
CN219715240U (zh) 一种平面多角度自动位移透过率检测设备
CN222885630U (zh) 多功能模块化光学实验装置

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15885920

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15885920

Country of ref document: EP

Kind code of ref document: A1