CN112630195A - Angle modulation type SPR sensor and SPR detection equipment - Google Patents
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Abstract
The invention provides an angle modulation type SPR sensor and SPR detection equipment, the angle modulation type SPR sensor comprises an emitting module, a detection module and a receiving module, the emitting module comprises a light source, the emitting module is used for generating detection light, the detection module comprises a detection pool, a metal layer and a prism, the metal layer is arranged on the detection pool, the prism is arranged on the metal layer, the prism comprises an incident surface, an emergent surface, an attaching surface and at least one reflecting surface, the attaching surface is contacted with the metal layer, the reflecting surface is arranged between the light path of the attaching surface and the incident surface and/or the reflecting surface is arranged between the light path of the attaching surface and the emergent surface, the receiving module comprises a receiver, the detection light emitted by the light source enters the prism through the incident surface and enters the receiver through the emergent surface. The angle modulation type SPR sensor can realize SPR detection without arranging an additional lens or a movable component, the optical path of the angle modulation type SPR sensor is compact, and the angle modulation type SPR sensor is easy to miniaturize.
Description
Technical Field
The invention relates to the field of sensor research, in particular to an angle modulation type SPR sensor and SPR detection equipment.
Background
Surface Plasmon Resonance (SPR) is a physical optical phenomenon, which is an optical technique for characterizing the change of Surface refractive index coefficient, and the SPR technique can be used to observe the Surface phenomena such as the interaction between molecules and the formation of a thin film in real time. Surface Plasmon (SP) refers to an electromagnetic wave that propagates along a surface between a metal and a dielectric. When a metal film of dozens of nanometers exists between the two medium interfaces, the P polarization component of evanescent waves generated by total reflection enters the metal film and interacts with free electrons in the metal film to generate surface plasma, and under the condition that the incident angle or the wavelength is a certain proper value, the surface plasma and the evanescent waves resonate, so that light energy is absorbed, and the energy of reflected light is rapidly reduced.
The SPR detection technique has been widely used in the research fields of life science, biology, pharmacology, analytical chemistry, etc. as a high-precision, label-free, real-time responsive detection means. The SPR detection technology has the characteristics of capability of detecting the interaction between biological molecules in real time, convenience, rapidness, higher resolution than that of the traditional method, no need of marking samples, less sample requirement and the like, is widely applied to the life science fields of proteomics, cell signal conduction, receptor/ligand, antibody/antigen molecule fishing, immune recognition, cancer research, new drug screening and the like, and is used for dynamically monitoring the interaction process of biological molecules such as protein/protein, protein/nucleic acid, new drug molecules/target protein and the like in real time.
The SPR sensor has three coupling modes, namely prism coupling, optical fiber coupling and grating coupling, and the Kretschmann sensor based on the prism coupling mode has the advantages of simple manufacture, convenient use, easy preparation of a sensing chip and the like, so the SPR sensor is widely adopted. The principle of angle modulation is that an angle scanning curve can be obtained by changing the angle between incident light and a normal and measuring the corresponding light intensity under different angles, the angle corresponding to the lowest light intensity point in the angle scanning curve is called as an SPR resonance angle, and the size of the SPR resonance angle is in direct proportion to the change of the surface refractive index coefficient of a measured sample.
In some prior art, the angle modulation may employ a scanning approach. The scanning mode is a mode in which light of a specific wavelength can continuously scan the surface of the sensor chip at fixed angular intervals within a certain angular range, and two structures most commonly used in the scanning mode are a mechanical scanning mode and a galvanometer scanning mode. The mechanical scanning is to change the angle of the incident light relative to the normal line through the motion of the linear motion unit, and the galvanometer scanning mode is to realize the scanning in a certain angle range through the rotation of the galvanometer by taking the galvanometer as an angle driving unit. However, the angle modulation of the scanning method requires a movable component and a corresponding driving module, which makes the SPR sensor based on the scanning method generally have a large volume and is not easy to be miniaturized.
In the prior art, the angle modulation can also adopt a light beam focusing mode, the light beam focusing mode generally uses an LED as a light source, light emitted by the LED becomes a point light source after passing through an aperture diaphragm and then becomes parallel light after passing through a collimating lens, the parallel light is converged on the surface of a metal film at different angles after passing through the diaphragm and a cylindrical lens, and reflected light is converged on a linear array CCD or an area array CCD through a similar light path to realize detection of light signals at different incident angles. However, the beam focusing method requires a lens for collecting incident light or outgoing light, which makes the SPR sensor based on the beam focusing method generally have a large volume and is not easy to be miniaturized.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art. To this end, the present invention proposes an angle modulation SPR sensor and an SPR detection apparatus, which are easy to be miniaturized.
The angle modulation type SPR sensor provided by the invention comprises a transmitting module, a detecting module and a receiving module, the emitting module comprises a light source, the emitting module is used for generating detection light, the detection light is divergent light in a polarization state, the detection module comprises a detection cell, a metal layer and a prism, wherein the metal layer is arranged on the detection cell, the prism is arranged on the metal layer and comprises an incident surface, an emergent surface, a binding surface and at least one reflecting surface, the binding surface is contacted with the metal layer, the reflecting surface is arranged between the binding surface and the light path of the incident surface and/or the reflecting surface is arranged between the binding surface and the light path of the emergent surface, the receiving module comprises a receiver, detection light emitted by the light source passes through the incident surface, the detection light is reflected in the prism, and the detection light enters the receiver through the emergent surface.
According to the SPR sensor of the angle modulation type provided by the present invention, at least the following technical effects are provided: the divergent detection light enters the prism at different angles, and the detection light at different angles irradiates different positions of the metal layer and is reflected to the receiver, so that the angle modulation type SPR detection is realized.
According to some embodiments of the invention, the prism comprises one of the reflecting surfaces, the reflecting surface being disposed between the abutting surface and the exit surface.
According to some embodiments of the invention, the reflective surface is provided with a reflective coating.
According to some embodiments of the invention, the reflective coating is made of an aluminum material.
According to some embodiments of the invention, the light source is an LED light source, and the emission module includes a polarizer.
According to some embodiments of the invention, the receiving module comprises an attenuation sheet through which the detection light enters the receiver.
According to some embodiments of the invention, the receiver employs a line detector.
According to some embodiments of the present invention, an angle modulation-type SPR sensor includes a base on which the transmission module, the detection module, and the reception module are disposed.
According to some embodiments of the invention, the SPR sensor of the angle modulation type includes a pressing block pressing the detection cell toward the prism.
According to the SPR detection apparatus provided by the present invention, the angle modulation-type SPR sensor provided by the present invention is included.
According to the SPR detection device provided by the invention, at least the following technical effects are achieved: by adopting the angle modulation type SPR sensor provided by the invention, the number of parts can be reduced, the volume of SPR detection equipment is reduced, the manufacturing cost of the SPR detection equipment is obviously reduced, and the miniaturization, integration and portable detection application of the SPR detection equipment are facilitated.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 is a schematic optical path diagram of an angle modulation SPR sensor provided in accordance with the present invention;
FIG. 2 is an isometric view of an angle modulation SPR sensor provided in accordance with the present invention;
fig. 3 is a cross-sectional view of an angle modulation-type SPR sensor provided according to the present invention.
Reference numerals:
a light source 11, a polarizing plate 12,
A detection cell 21, a prism 22, a reflective coating 23,
A receiver 31, an attenuation sheet 32,
A base 41 and a pressing block 42.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.
In the description of the present invention, it should be understood that the orientation or positional relationship referred to in the description of the orientation, such as the upper, lower, front, rear, left, right, etc., is based on the orientation or positional relationship shown in the drawings, and is only for convenience of description and simplification of description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention.
In the description of the present invention, the meaning of a plurality of means is one or more, the meaning of a plurality of means is two or more, and larger, smaller, larger, etc. are understood as excluding the number, and larger, smaller, inner, etc. are understood as including the number. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.
In the description of the present invention, unless otherwise explicitly limited, terms such as arrangement, installation, connection and the like should be understood in a broad sense, and those skilled in the art can reasonably determine the specific meanings of the above terms in the present invention in combination with the specific contents of the technical solutions.
The invention provides an angle modulation type SPR sensor, which comprises an emitting module, a detecting module and a receiving module, wherein the emitting module comprises a light source 11, the emitting module is used for generating detection light, and the detection light is divergent light in a polarization state, the detecting module comprises a detecting cell 21, a metal layer and a prism 22, the metal layer is arranged on the detecting cell 21, the prism 22 is arranged on the metal layer, the prism 22 comprises an incident surface, an emergent surface, an adhering surface and at least one reflecting surface, the adhering surface is in contact with the metal layer, the reflecting surface is arranged between the adhering surface and an optical path of the incident surface and/or between the adhering surface and an optical path of the emergent surface, the receiving module comprises a receiver 31, the detection light emitted by the light source 11 passes through the incident surface, the detection light is reflected in the prism 22, and the detection light enters the receiver.
According to the angle modulation type SPR sensor provided by the present invention, by providing a specific optical path structure, divergent detection light is incident on the prism 22 at different angles, the detection light at different angles is irradiated to different positions of the metal layer and reflected to the receiver 31, there is a one-to-one correspondence between the positions of the pixels on which the detection light is incident on the receiver 31 and the incident angles at which the detection light is irradiated to the metal layer, and the intensity of light detected at one pixel position of the receiver 31, that is, the intensity of light corresponding to one incident angle of the detection light, realizes angle modulation type SPR detection, and the angle modulation type SPR sensor does not need to be provided with other lenses or movable members other than the prism 22, and is easy to be miniaturized.
The reflecting surface can adjust the direction of the optical path to turn the detection light in the prism 22, thereby reducing the distance from the optical path starting point to the optical path end point of the angle modulation SPR sensor and facilitating the miniaturization of the angle modulation SPR sensor. The reflecting surface is integrated on the prism 22, and no additional reflecting part is needed, so that the number of parts of the angle modulation type SPR sensor can be reduced.
The detection module may employ a Kretschmann sensor structure with the sample placed between the metal layer and the detection cell 21. The polarized detection light is irradiated onto the metal layer through the prism 22 to excite the surface plasmon resonance phenomenon.
According to some embodiments of the present invention, the prism 22 includes a reflective surface disposed between the abutting surface and the optical path of the exit surface. For example, as shown in fig. 1, the prism 22 is a special prism having a pentagonal prism shape, and the detection light reflected by the metal layer is reflected again by the reflection surface and then emitted from the emission surface. The reflecting surface reflects the detection light, so that the size of the light path in the length direction and the width direction is approximate, and the light path is more compact. In some embodiments, the reflective surface is provided with a reflective plating 23. The reflective plating layer 23 can enhance the reflectance of the reflective surface and reduce the loss of the detection light during reflection. In some embodiments, the reflective coating 23 is made of aluminum.
According to some embodiments of the present invention, the light source 11 is an LED light source and the emission module includes a polarizer 12. As shown in fig. 1 and 3, the polarizing plate 12 is disposed between the light source 11 and the optical path of the prism 22, the LED light source is similar to a point light source, monochromatic divergent light emitted from the LED light source is polarized by the polarizing plate 12, and polarized, divergent detection light enters the prism 22. As shown in fig. 3, the polarizing plate 12 is mounted on the head of the light source 11 by a ferrule, and the light source 11, the polarizing plate 12, and the incident surface are disposed as close as possible, so that the size of the angle modulation SPR sensor is reduced, the length of the optical path is shortened, and excessive dispersion of the detection light is avoided.
According to some embodiments of the invention, the receiving module comprises an attenuation sheet 32, and the detection light enters the receiver 31 through the attenuation sheet 32. The attenuation sheet 32 can proportionally reduce the intensity of the detection light, thereby ensuring that the intensity of the detection light irradiated to the receiver 31 does not exceed the detection range of the receiver 31, and improving the accuracy of the angle modulation type SPR sensor. In some embodiments, the receiver 31 employs a line detector. The line detector may be a line CCD (Charge-Coupled Device) or a photodiode array. The linear array detector and the area array detector can be used for detecting light of the angle modulation type SPR sensor, an imaging area of the linear array detector is a narrow line, and compared with the area array detector, the linear array detector can reduce the cost of the receiver 31 and improve the detection speed.
According to some embodiments of the present invention, the SPR sensor of an angle modulation type includes a base 41, and the transmitting module, the detecting module, and the receiving module are disposed on the base 41. The base 41 stabilizes the relative position relationship between the modules, and makes the SPR sensor portable, and in some embodiments, the modules are fixed on the base 41 by screws, so as to facilitate assembly and disassembly. In some embodiments, the SPR sensor of angle modulation type includes a pressing block 42, the pressing block 42 presses the detection cell 21 to the prism 22, for example, as shown in fig. 3, a positioning slot is formed on the base 41, the prism 22 is positioned on the base 41 through the positioning slot and is pressed and fixed by a screw, the pressing block 42 is mounted on the base 41 through a screw, the pressing block 42 presses the detection cell 21, the pressing force of the pressing block 42 can improve the bonding effect among the detection cell 21, the metal layer and the prism 22, reduce the gap of the contact surface, and improve the accuracy of the SPR sensor of angle modulation type. The pressing force of the pressing block 42 can be adjusted by adjusting the degree of screwing the screw into the base 41.
In some embodiments, the metal layer has a thickness of 50nm, and the metal layer and the prism 22 are coupled together by a matching fluid, which can fill the gap of the contact surface and improve the accuracy of the angle modulation SPR sensor. In some embodiments, the metal layer and the detection cell 21 are sealed by a seal to prevent liquid leakage.
According to the SPR detection apparatus provided by the present invention, the angle modulation-type SPR sensor provided by the present invention is included.
According to the SPR detection apparatus provided by the present invention, by using the angle modulation-type SPR sensor provided by the present invention, SPR detection can be realized without providing a movable member and without providing a lens other than the prism 22, and the SPR detection apparatus can be easily miniaturized.
An angle modulation type SPR sensor provided according to the present invention will be described in detail in one specific embodiment with reference to fig. 1, 2 and 3. It is to be understood that the following description is only exemplary, and not a specific limitation of the invention.
The angle modulation type SPR sensor includes a transmission module, a detection module, a reception module, a base 41, and a pressure block 42, and the transmission module, the detection module, and the reception module are fixedly mounted on the base 41 by screws.
The emitting module comprises a light source 11 and a polaroid 12, the light source 11 adopts an LED light source, the polaroid 12 is arranged at the head of the light source 11 through a clamping sleeve, and the emitting module is used for generating detection light which is divergent light in a polarization state.
Detection module is including detecting the pond 21, the metal level, prism 22, reflection coating 23, the constant head tank has been seted up on the base 41, prism 22 passes through the constant head tank location on base 41, and compress tightly fixedly through the screw, it sets up on prism 22 to detect pond 21, the metal level sets up between detecting pond 21 and prism 22, the thickness of metal level is 50nm, be in the same place through the matching fluid coupling between metal level and the prism 22, seal through the sealing member between metal level and the detection pond 21, briquetting 42 will detect pond 21 and press to prism 22. The prism 22 includes an incident surface, an exit surface, a bonding surface, and a reflecting surface, the bonding surface contacts with the metal layer, the reflecting surface is disposed between the bonding surface and the optical path of the exit surface, the reflective coating 23 is disposed on the reflecting surface, and the reflective coating 23 is made of aluminum material.
The receiving module comprises a receiver 31 and an attenuation sheet 32. The receiver 31 employs a line CCD.
Monochromatic divergent light generated by the LED light source passes through the polarizing plate 12 to form polarized and divergent detection light, which enters the prism 22, the detection light irradiates the bonding surface through the incident surface, the detection light is reflected by the metal layer, and then the detection light is reflected by the reflecting surface, exits the prism 22 through the exit surface, and enters the receiver 31 through the attenuator 32.
According to the SPR sensor of the angle modulation type according to the embodiment of the present invention, at least such functions can be realized by adopting the above design: by setting a specific optical path structure, divergent detection light enters the prism 22 at different angles, the detection light at different angles irradiates different positions of the metal layer and is reflected to the receiver 31, a one-to-one correspondence relationship exists between the positions of pixels on the detection light entering the receiver 31 and the incident angles of the detection light irradiating the metal layer, and the light intensity detected by one pixel position of the receiver 31 corresponds to the light intensity of one incident angle of the detection light, so that the angle modulation type SPR detection is realized.
The reflecting surface can adjust the direction of the optical path to turn the detection light in the prism 22, thereby reducing the distance from the optical path starting point to the optical path end point of the angle modulation type SPR sensor and facilitating the miniaturization of the angle modulation type SPR sensor. The reflecting surface is integrated on the prism 22, and no additional reflecting part is needed, so that the number of parts of the angle modulation type SPR sensor can be reduced.
The reflective plating layer 23 can enhance the reflectance of the reflective surface and reduce the loss of the detection light during reflection. The attenuation sheet 32 can proportionally reduce the intensity of the detection light, thereby ensuring that the intensity of the detection light irradiated to the receiver 31 does not exceed the detection range of the receiver 31, and improving the accuracy of the angle modulation type SPR sensor. The line CCD can reduce the cost of the receiver 31 and can also improve the detection speed.
The pressure of the pressure block 42 can improve the bonding effect among the detection cell 21, the metal layer, and the prism 22, reduce the gap of the contact surface, and improve the accuracy of the angle modulation SPR sensor. The matching fluid can fill gaps of the contact surface, and the accuracy of the angle modulation type SPR sensor is improved. The seal can function to avoid leakage.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an illustrative embodiment," "an example," "a specific example," or "some examples" or the like mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
While embodiments of the invention have been shown and described, it will be understood by those of ordinary skill in the art that: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
Claims (10)
1. An angle modulation type SPR sensor comprising:
an emission module comprising a light source (11) for generating detection light, the detection light being divergent light of a polarization state;
the detection module comprises a detection pool (21), a metal layer and a prism (22), wherein the metal layer is arranged on the detection pool (21), the prism (22) is arranged on the metal layer, the prism (22) comprises an incident surface, an emergent surface, a binding surface and at least one reflecting surface, the binding surface is in contact with the metal layer, and the reflecting surface is arranged between the binding surface and a light path of the incident surface and/or between the binding surface and a light path of the emergent surface;
and the receiving module comprises a receiver (31), the detection light emitted by the light source passes through the incident surface, the detection light is reflected in the prism (22), and the detection light enters the receiver (31) through the emergent surface.
2. The angle modulation-type SPR sensor according to claim 1, wherein: the prism (22) comprises one reflecting surface which is arranged between the binding surface and the light path of the emergent surface.
3. The angle modulation-type SPR sensor according to claim 1 or 2, wherein: the reflecting surface is provided with a reflecting coating (23).
4. The angle modulation-type SPR sensor according to claim 3, wherein: the reflective coating (23) is made of aluminum material.
5. The angle modulation-type SPR sensor according to claim 1, wherein: the light source (11) adopts an LED light source, and the emitting module comprises a polaroid (12).
6. The angle modulation-type SPR sensor according to claim 1, wherein: the receiving module comprises an attenuation sheet (32), and the detection light enters the receiver (31) through the attenuation sheet (32).
7. The angle modulation-type SPR sensor according to claim 1 or 6, wherein: the receiver (31) adopts a linear array detector.
8. The angle modulation-type SPR sensor according to claim 1, wherein: the angle modulation type SPR sensor includes a base (41), and the transmission module, the detection module, and the reception module are provided on the base (41).
9. The angle modulation-type SPR sensor according to claim 8, wherein: the angle modulation type SPR sensor includes a pressure block (42), and the pressure block (42) presses the detection cell (21) against the prism (22).
10. An SPR detection apparatus, comprising: the SPR detection apparatus includes an SPR sensor of an angle modulation type as claimed in any one of claims 1 to 9.
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