Micro-beam array biochemical sensing device based on CCD image sensor

Abstract

The utility model discloses a micro-beam array biochemical sensing device based on a CCD (Charge Coupled Device) image sensor, which relates to the technical field of biochemical sensing and comprises a semiconductor laser, a multimode optical fiber, a V-shaped groove, a lens group, a micro-beam array, a three-dimensional precision displacement table, the CCD image sensor and digital image processing equipment, the multimode optical fibers are in one-to-one coupling connection with the semiconductor lasers; the V-shaped groove is aligned and fixed with the tail end of each multimode optical fiber and is aligned with the lens group, so that laser emitted by the tail end of each multimode optical fiber is just converged to the tip end of each micro-beam of the micro-beam array arranged on the three-dimensional precision displacement table; the target surface of the CCD image sensor is on the light path of the reflected light of the micro-beam array, and the signal output end of the CCD is connected with the signal input end of the digital image processing device. According to the device, the CCD camera with higher quantum efficiency and lower noise is adopted for signal receiving, the problem of light spot overlapping is successfully solved, time sequence lightening of the array laser set does not need to be controlled, and the detection sensitivity is improved.

Description

Technical Field

[0001] The utility model relates to the technical field of biochemical sensing, in particular to a micro-beam array biochemical sensing device based on a CCD image sensor. Background Art

[0002] Microcantilever biochemical sensing technology based on surface stress detection is an emerging sensing technology. Its principle is: the probe (antigen or antibody) molecule is fixed to one side of the microcantilever (gold-plated layer or non-gold-plated layer) directly or indirectly. When the target molecule in the sample liquid undergoes a specific binding reaction with the modified probe molecule on the surface of the microcantilever, the surface stress of the microcantilever will change, causing the microcantilever to bend and deform. By detecting this deformation process through optical or electrical methods, real-time information of the biochemical reaction can be obtained.

[0003] For example: Chinese utility model patent application number: CN201610027753.0 discloses a micro-cantilever array biochemical sensing device and method based on an optical fiber array, wherein the micro-beam array sensing platform is based on eight semiconductor laser lasers, which illuminate each cantilever in the micro-beam array through multiple beams of single-mode optical fibers, and each laser is lit in turn through timing control; the reflected light spot is irradiated to the position sensitive detector (PSD) target surface through the optical lever optical path, and the signal received by the PSD is transmitted and processed to become the deflection signal of the eight cantilever beams, which is finally stored and displayed in real time.

[0004] However, the above method has the following problems:

[0005] The reflected light spots of different microbeams on the PSD will overlap, which will cause errors in the detection signal. It is necessary to use a time-sequential lighting method to detect the deformation of the microbeam array. However, the time-sequential control of laser lighting will make the laser power unstable, which will cause detection errors in the instrument. Utility Model Content

[0006] The utility model provides a micro-beam array biochemical sensing device based on a CCD image sensor to solve the technical problem that the laser lighting mode of the existing micro-beam array sensing device sequentially controls the laser so that the laser power is unstable, resulting in detection errors in the instrument.

[0007] In order to solve the above problems, the utility model provides a micro-cantilever beam array biochemical sensing device based on a CCD image sensor, comprising: a semiconductor laser, a multimode optical fiber, a V-groove, a lens group, a micro-beam array, a three-dimensional precision displacement stage, a CCD image sensor and a digital image processing device; wherein:

[0008] The plurality of multimode optical fibers are coupled and connected to the plurality of semiconductor lasers in a one-to-one correspondence;

[0009] The V-shaped groove aligns and fixes the end of each multimode optical fiber, and aligns with the lens group, so that the laser emitted from the end of the multimode optical fiber is just focused on the tip of each microbeam of the microbeam array;

[0010] The CCD image sensor is arranged on the optical path of the reflected light of the micro-beam array, and the signal output end of the CCD image sensor is connected to the signal input end of the digital image processing device.

[0011] Preferably, the number of the semiconductor lasers is eight, and the adjustment angle range between the eight semiconductor lasers is 1-4 degrees.

[0012] Preferably, it further comprises a signal generator, wherein the signal generator is used to control the input voltage of the semiconductor laser so as to make the semiconductor laser turn on and off periodically.

[0013] Preferably, it also includes a temperature control device, and the temperature control device includes:

[0014] A first temperature control sheet connected to the semiconductor laser, and the first temperature control sheet is used to stabilize the output of the semiconductor laser;

[0015] The second temperature control sheet is connected to the micro-beam array and is used to adjust the temperature of the micro-beam array so as to adapt the reaction temperature of the micro-beam array for detecting biological molecules and target molecules.

[0016] Preferably, it also includes a microscope observation device installed on one side of the laser incident port of the microbeam array, and the microscope observation device is used to observe the irradiation position of the light spot on each microbeam of the microbeam array.

[0017] Preferably, the V-groove is made by silicon etching, the groove size of the V-groove is suitable for fixing the core of the multimode optical fiber, and the groove center spacing of the V-groove is consistent with the center spacing of each microbeam of the microbeam array.

[0018] Preferably, it also includes a vibration isolation device, which is installed on the optical path between the lens group and the micro-beam array.

[0019] Preferably, it further comprises a computer, wherein a signal input terminal of the computer is connected to a signal output terminal of the digital image processing device.

[0020] Preferably, the micro-beam is rectangular, and the surface of the micro-beam is coated with a biochemical sensitive layer.

[0021] Compared with the prior art, the present invention has significant advantages and beneficial effects, which are specifically embodied in the following aspects:

[0022] The micro-cantilever beam array biochemical sensing device in the utility model is mainly composed of a semiconductor laser, a multimode optical fiber, a V-groove, a lens group, a micro-beam array, a three-dimensional precision displacement stage, a CCD image sensor and a digital image processing device. The laser emitted by the semiconductor laser is led out by a multimode optical fiber, and the core of the multimode optical fiber is fixed in the etched V-groove for positioning; the laser emitted by the semiconductor laser is simultaneously irradiated to the tip of each micro-beam in the micro-beam array from different angles, so that the reflected light spots are projected to different positions of the target surface of the CCD image sensor (charge coupled device) without overlapping, and the light spot signal received by the CCD image sensor is converted into a displacement signal of the micro-beam through digital image correlation processing, and the signal is finally stored and displayed in real time. Among them, the densely packed multi-mode optical fiber coupled with the laser is used as a light source to realize the periodic scanning detection of the micro-beam array by multiple light spots, and there is no mechanical movement during the scanning process, so that the biochemical reaction information on the micro-beam array can be detected with high sensitivity, rapidity, real-time and parallelism; the CCD image sensor is used to record the image before and after the deformation of the micro-beam array, and the deformation amount of the micro-beam is obtained by calculation to realize the deformation detection of the micro-beam. Therefore, the CCD image sensor of this embodiment is arranged on the optical path of the reflected light of the microbeam array, and the signal output end of the CCD image sensor is connected to the signal input end of the digital image processing device. The digital image processing device is used to convert the laser light spot displacement change signal into the bending displacement signal of the corresponding microbeam, thereby realizing real-time monitoring of the biochemical reaction process information on each microbeam. In this way, the microbeam array deformation detection instrument can respond to the deformation of the microbeam in real time and establish the relationship between the deformation and the concentration of the target substance. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a schematic structural diagram of a micro-beam array biochemical sensing device based on a CCD image sensor in an embodiment of the utility model;

[0024] Figure 2 A schematic diagram of the detection optical path between the semiconductor laser, the micro-beam array and the CCD image sensor in the embodiment of the utility model;

[0025] Figure 3 This is a schematic diagram of the detection optical path of the micro-beam array based on CCD in the embodiment of the utility model;

[0026] Figure 4 It is a schematic diagram of the detection principle of the micro-beam array based on CCD in the embodiment of the utility model.

[0027] Description of reference numerals:

[0028] 1- semiconductor laser; 2- multimode optical fiber; 3- V-groove; 4- lens group; 5- microbeam array; 6- three-dimensional precision translation stage; 7- CCD image sensor; 8- digital image processing equipment; 9- microscope observation device; 10- computer; 11- temperature control device; 12- vibration isolation device. DETAILED DESCRIPTION

[0029] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and understandable, the specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0030] In addition, in this article, the directional words such as front, back, top, and bottom involved are defined by the positions of the components in the drawings and the positions of the components relative to each other, just for the sake of clarity and convenience in expressing the technical solution. It should be understood that the use of the directional words should not limit the scope of protection requested by this application.

[0031] In the absence of conflict, the above embodiments and features in the embodiments may be combined with each other.

[0032] like Figure 1-4 As shown, the embodiment of the utility model provides a micro-beam array biochemical sensing device based on a CCD image sensor, the micro-beam array biochemical sensing device comprises a semiconductor laser 1, a multimode optical fiber 2, a V-groove 3, a lens group 4, a micro-beam array 5, a three-dimensional precision displacement stage 6, a CCD image sensor 7 and a digital image processing device 8, wherein:

[0033] The multimode optical fibers 2 are coupled and connected to the semiconductor lasers 1 in a one-to-one correspondence, and the number of the multimode optical fibers 2 is the same as that of the semiconductor lasers 1 and is greater than 2;

[0034] The V-shaped groove 3 aligns and fixes the end of each multimode optical fiber 2, and aligns the lens group 4, so that the laser emitted from the end of the multimode optical fiber 2 is just focused on the tip of each microbeam of the microbeam array 5;

[0035] The CCD image sensor 7 is arranged on the optical path of the reflected light of the micro-beam array 5 , and the signal output end of the CCD image sensor 7 is connected to the signal input end of the digital image processing device 8 .

[0036] As a preferred embodiment of this embodiment, the number of semiconductor lasers is eight, and the adjustment angle range between the eight semiconductor lasers 1 is 1-4 degrees.

[0037] Specifically, see Figure 1 , 2As shown in FIG. 3 , in the embodiment of the utility model, the laser light emitted by the semiconductor laser 1 is led out by a multimode optical fiber 2, and the core of the multimode optical fiber 2 is fixed in the etched V-groove 3 for positioning; the laser light emitted by the eight semiconductor lasers 1 is simultaneously irradiated to the tip of each microbeam in the microbeam array 5 from different angles, so that the reflected light spots are projected onto different positions of the target surface of the CCD image sensor 7 (charge coupled device) without overlapping, and the light spot signal received by the CCD image sensor 7 (charge coupled device) is processed by digital image correlation (DIC), and is converted into displacement signals of eight microbeams with high precision (one-tenth pixel precision, sub-micron level) and high speed (millisecond level), and the signal is finally stored and displayed in real time.

[0038] Since the multiple semiconductor lasers 1 can be controlled to be adjusted to a certain angle so that the reflected light spots can be separated, the timing control adjustment is omitted, and CCD can be used instead of PSD. Because PSD can only accurately detect the center of the PSD target surface, only one light spot can be detected at a time.

[0039] The core components of the micro-beam array biochemical sensing device based on the CCD image sensor in the embodiment of the utility model include: a semiconductor laser 1, a multimode optical fiber 2, an etched V-groove 3, a CCD image sensor 7, a microscope observation device 9, a three-dimensional precision displacement stage 6, a temperature control device 11, a vibration isolation device 12 and a computer 10.

[0040] As a transmission medium for light waves, the characteristics of multimode optical fiber 2 have a very important influence on the transmission of optical signals. Multimode optical fiber 2 has a thick core diameter and a large numerical aperture, which can not only couple more optical power from the light source, but also has cheaper components and is easy to operate.

[0041] At present, multimode optical fiber 2 is widely used not only in conventional communication fields, but also in high-tech fields such as distributed sensors, plasma diagnosis and instrumentation systems, etc., due to its low system cost advantage. In these applications, multimode optical fiber 2 is used to receive the laser emitted by semiconductor laser 1. As a preferred embodiment of the utility model, eight semiconductor lasers 1 are provided, and the lasers of eight semiconductor lasers 1 are simultaneously irradiated to the tips of each micro-beam in micro-beam array 5 from different angles. Therefore, in order to receive the lasers emitted by eight semiconductor lasers 1, it is necessary to consider coupling and connecting multimode optical fiber 2 with semiconductor laser 1 one by one; multimode optical fiber 2 needs to be fixed during use. This embodiment adopts mature positioning and installation technology of V-groove 3 that is easy to mass produce, so that the device manufacturing cost is low, and V-groove 3 is aligned and fixed at the end of each multimode optical fiber 2, and aligned with lens group 4. By adjusting lens group 4, the laser emitted from the end of multimode optical fiber 2 is just converged to the tips of each micro-beam in micro-beam array 5.

[0042] The CCD image sensor 7 is used to record the images before and after the deformation of the microbeam array 5, and the deformation of the microbeam is obtained by calculation to realize the deformation detection of the microbeam. Therefore, the CCD image sensor 7 of this embodiment is arranged on the optical path of the reflected light of the microbeam array 5, and the signal output end of the CCD image sensor 7 is connected to the signal input end of the digital image processing device 8, and the digital image processing device 8 is used to convert the laser light spot displacement change signal into the bending displacement signal of the corresponding microbeam, so as to realize the real-time monitoring of the biochemical reaction process information on each microbeam, so that the deformation detection instrument of the microbeam array 5 can react to the deformation of the microbeam in real time, and can establish the relationship between the deformation and the concentration of the target substance.

[0043] It should be noted here that in traditional technology, the signal received by the position sensitive detector (PSD) can only collect accurate signals in the middle of the concentrated PSD target surface, and PSD is expensive. If you want to use PSD reasonably, you need to rely on timing control to light up eight lasers in sequence. Otherwise, the light spots formed in the central area of ​​the PSD target surface will overlap and the detection signal will be erroneous.

[0044] Compared with the existing microbeam array sensing platform, there is a problem of overlapping reflected light spots of different microbeams on the detector PSD. Since the light spots are difficult to distinguish, a time-sequential lighting method is needed to detect the deformation of the microbeam array. This biochemical sensing device successfully solves the problem of light spot overlap by replacing PSD with CCD and using digital image correlation technology. There is no need to control the sequential lighting of the array laser group, and the real-time position information of different microbeam reflected light spots on the CCD image sensor is accurately obtained, while expanding the dynamic linear detection range.

[0045] In addition, PSD is more expensive and has no obvious advantage in detection sensitivity. In the embodiment of the present invention, the laser spot can be separated by using CCD, which not only reduces the cost and the error caused by power change, but also realizes simultaneous parallel detection.

[0046] Furthermore, the micro-beam array biochemical sensing device also includes a signal generator, which is used to control the input voltage of the semiconductor laser 1 to make the semiconductor laser 1 turn on and off periodically.

[0047] Specifically in the embodiment of the utility model, the semiconductor laser 1 is controlled to periodically turn on and off by a signal generator, so that the laser can periodically scan each microbeam of the microbeam array 5, and the position of the laser spot on the microbeam is adjusted by observation using a microscope.

[0048] Furthermore, in the embodiment of the utility model, the micro-beam array biochemical sensing device further comprises a temperature control device 11, and the temperature control device 11 comprises a first temperature control sheet and a second temperature control sheet, wherein:

[0049] The first temperature control plate is connected to the semiconductor laser 1, and is used to stabilize the output of the semiconductor laser 1; the second temperature control plate is connected to the microbeam array 5, and is used to adjust the temperature of the microbeam array 5, so as to adapt the reaction temperature of the microbeam array 5 to detect biological molecules and target molecules.

[0050] Furthermore, the microbeam array biochemical sensing device in the embodiment of the utility model also includes a microscope observation device 9, which is installed on the laser incident port side of the microbeam array 5 and is used to observe the irradiation position of the light spot on each microbeam of the microbeam array 5.

[0051] Furthermore, the V-groove 3 is made by silicon etching, the groove size of the V-groove 3 is suitable for fixing the core of the multimode optical fiber 2, and the groove center spacing of the V-groove 3 is consistent with the center spacing of each microbeam of the microbeam array 5.

[0052] Specifically in the embodiments of the present utility model, the V-groove 3 is generally composed of an optical fiber upper fixing block and an optical fiber lower fixing substrate, wherein a smaller size is selected as the optical fiber upper fixing block, and a larger size is selected as the optical fiber lower fixing substrate, a bare optical fiber of a multimode optical fiber 2 is placed in the V-groove 3 of the optical fiber lower fixing substrate, and then the optical fiber upper fixing block is placed on it and pressed tightly, and glue is applied to the joint between the optical fiber upper fixing block and the optical fiber lower fixing substrate for pre-fixing, and then the bare optical fiber is removed to complete the production of the V-groove 3 positioning structure.

[0053] Furthermore, the microbeam array biochemical sensing device in the embodiment of the utility model also includes a vibration isolation device 12, which is installed on the optical path between the semiconductor laser 1 and the microbeam array 5. Considering that the vibration isolation effect of the optical platform will directly affect the stability of the reflector and the subsequent laser. When the vibration isolation device 12 is installed near the optical platform, the vibration isolation device 12 can control the jitter amplitude of the laser to less than 20μrad (about 4"), which is beneficial to the effect of laser targeting.

[0054] Furthermore, the micro-beam array biochemical sensing device in the embodiment of the utility model further includes a computer 10, and the signal input end of the computer 10 is connected to the signal output end of the digital image processing device 8. In this way, the signal processed by the digital image processing device 8 can be recorded and saved in real time in the computer 10.

[0055] The specific working process of the microbeam array biochemical sensing device based on CCD image sensor is as follows:

[0056] First, a plurality of multimode optical fibers 2 are coupled one-to-one with a corresponding number of semiconductor lasers 1, and the ends of the multimode optical fibers 2 are aligned and fixed in V-shaped grooves 3 having the same spacing as the beam spacing of the micro-beam array 5. The laser light emitted from the ends of the multimode optical fibers 2 is converged to the tip of the micro-beam of the micro-beam array 5 through the lens group 4.

[0057] Multiple semiconductor lasers 1 are directed toward the lens group 4 at an angle of 1-4 degrees, and then irradiate corresponding numbers of corresponding micro-beams;

[0058] The CCD image sensor 7 receives the laser spot displacement change signal amplified by the optical lever principle, and is reflected to the target surface of the CCD image sensor 7 by the corresponding micro-beam until all lasers are observed to be distinguishable;

[0059] In this step, the laser incident angle can be adjusted so that the laser spots do not overlap. For example, eight lasers are directed at the lens at an angle of 1-4 degrees, and then irradiated to eight microbeams. The lasers can be distinguished by being reflected by the microbeams to the CCD target surface. In order to achieve the effect of non-overlapping reflected lasers, not only can the incident laser angles be different, but also some equipment (such as a rotating lens) can be set to keep the eight incident lasers deviated at the same time, so that the reflected lasers can also be distinguished.

[0060] The laser spot displacement change signal is converted into a bending displacement signal of the corresponding micro-beam by using the digital image processing device 8, so as to realize real-time monitoring of the biochemical reaction process information on each micro-beam.

[0061] Although the utility model is disclosed as above, the protection scope of the utility model is not limited thereto. Those skilled in the art may make various changes and modifications without departing from the spirit and scope of the disclosure, and these changes and modifications will fall within the protection scope of the utility model.

Claims

1. A microbeam array biochemical sensing device based on a CCD image sensor, characterized in that: include: Semiconductor laser, multimode optical fiber, V-groove, lens group, micro beam array, three-dimensional precision translation stage, CCD image sensor and digital image processing equipment; Among them: The plurality of multimode optical fibers are coupled and connected to the plurality of semiconductor lasers in a one-to-one correspondence; The V-shaped groove aligns and fixes the end of each multimode optical fiber, and aligns with the lens group, so that the laser emitted from the end of the multimode optical fiber is just focused on the tip of each microbeam of the microbeam array; The CCD image sensor is arranged on the optical path of the reflected light of the micro-beam array, and the signal output end of the CCD image sensor is connected to the signal input end of the digital image processing device.

2. The microbeam array biochemical sensing device based on CCD image sensor according to claim 1 is characterized in that: The number of the semiconductor lasers is eight, and the adjustment angle range between the eight semiconductor lasers is 1-4 degrees.

3. The microbeam array biochemical sensing device based on CCD image sensor according to claim 1, characterized in that: It also includes a signal generator, which is used to control the input voltage of the semiconductor laser to make the semiconductor laser turn on and off periodically.

4. The microbeam array biochemical sensing device based on a CCD image sensor according to claim 1, characterized in that: Also included is a temperature control device, the temperature control device comprising: A first temperature control sheet connected to the semiconductor laser, and the first temperature control sheet is used to stabilize the output of the semiconductor laser; The second temperature control sheet is connected to the micro-beam array and is used to adjust the temperature of the micro-beam array so as to adapt the reaction temperature of the micro-beam array for detecting biological molecules and target molecules.

5. The microbeam array biochemical sensing device based on CCD image sensor according to claim 1, characterized in that: It also includes a microscope observation device, which is installed on one side of the laser incident port of the micro-beam array, and the microscope observation device is used to observe the irradiation position of the light spot on each micro-beam of the micro-beam array.

6. The microbeam array biochemical sensing device based on CCD image sensor according to claim 1, characterized in that: The V-groove is made by silicon etching, the groove size of the V-groove is suitable for fixing the core of the multimode optical fiber, and the groove center spacing of the V-groove is consistent with the center spacing of each microbeam of the microbeam array.

7. The microbeam array biochemical sensing device based on a CCD image sensor according to claim 6, characterized in that: It also includes a vibration isolation device, which is installed on the optical path between the lens group and the micro-beam array.

8. The micro-beam array biochemical sensing device based on CCD image sensor according to claim 7, characterized in that: It also includes a computer, wherein a signal input terminal of the computer is connected to a signal output terminal of the digital image processing device.

9. The micro-beam array biochemical sensing device based on a CCD image sensor according to claim 1, characterized in that: The micro-beam is rectangular, and the surface of the micro-beam is coated with a biochemical sensitive layer.

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