Biological unit imaging system
By using the combination of nanoparticle layer and piezoelectric platform in the biological unit imaging system, the drift of biological units is compensated in real time, and the impact of cell drift on data analysis in microscopic imaging is solved, achieving more accurate image acquisition.
Patent Information
- Application Number
- CN201811454943.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2018-11-30
- Publication Date
- 2024-12-17
- Estimated Expiration
- 2038-11-30
AI Technical Summary
In microscopic imaging, the drift of biological units has an unnegligible impact on the experimental results, especially in long-term live-cell imaging experiments, where the drift of cells makes image acquisition unstable, affecting the accuracy of data analysis.
A biological unit imaging system is designed, including an image acquisition mechanism and a drift compensation mechanism. By laying a nanoparticle layer on the slide, the drift acquisition module and analysis control module are used to obtain and compensate the drift of the biological unit in real time, and piezoelectricity is used. The platform keeps the biological unit in a constant position.
It effectively eliminates the impact of biological drift phenomenon on image analysis, provides more realistic and accurate biological unit image data, ensuring long-term observation of cells at the same location.
Smart Images

Figure CN109782428B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biological observation technology, and in particular to an observation system for observing biological units. Background Art
[0002] Breakthroughs in life science research rely heavily on the development of advanced instrument technology, and imaging systems are one of the most common and important instruments. With the improvement of optical resolution, sample drift in microscopic imaging will have a significant impact on experimental results, especially in experiments such as three-dimensional reconstruction of nano-sized microstructures and observation of dynamic changes in microstructures within cells, as well as live cell imaging experiments that require long-term recording. For example, when observing the growth and changes of cells for a long time, it is necessary to keep the relative position of the cells unchanged so that the cells are always located at the determined position of the acquired image. However, the drift of cells causes the position of the cells in the image acquired by the camera device to change over time, which is very unfavorable for analyzing cell changes based on image information. In some cases, the cells even shift to areas that the camera device cannot capture, making it impossible for the camera device to capture images with cells. Summary of the invention
[0003] In view of the above technical problems existing in the prior art, an embodiment of the present invention provides a biological unit imaging system.
[0004] In order to solve the above technical problems, the technical solution adopted in the embodiments of the present invention is:
[0005] A biological unit imaging system is used to obtain image information of a biological unit, comprising: an image acquisition mechanism and a drift compensation mechanism; wherein:
[0006] The drift compensation mechanism is used to compensate for the drift of the biological unit so as to keep the biological unit at a constant position;
[0007] The image acquisition mechanism is used to acquire the image of the biological unit after the drift compensation is performed by the drift compensation mechanism.
[0008] Preferably, the biological unit is arranged on a glass slide to form a sample unit, and the upper surface of the glass slide at the lower layer is paved with nanoparticles to form a nanoparticle layer; wherein:
[0009] The drift compensation mechanism obtains the drift amount of the biological unit according to the acquired image change of the nanoparticle layer and compensates for the drift amount.
[0010] Preferably, the drift compensation mechanism comprises:
[0011] A piezoelectric platform, wherein the sample unit is arranged at a hollow position of the piezoelectric platform;
[0012] A drift acquisition module, which is used to obtain image information of the nanoparticle layer in real time;
[0013] The analysis control module is used for analyzing the image information of the nanoparticle layer to calculate the drift of the biological unit, and controlling the piezoelectric platform according to the calculated drift to compensate for the drift of the biological unit.
[0014] Preferably, the drift collection module includes:
[0015] A first light source, which is used to emit light of a first wavelength range capable of imaging the nanoparticle layer toward the sample unit;
[0016] The first camera device receives the light emitted by the first light source to obtain an image of the nanoparticle layer.
[0017] Preferably, the image acquisition mechanism comprises:
[0018] a second light source for emitting light toward the biological unit to visualize the biological unit;
[0019] The second camera device is used to receive the light in the second wavelength range reflected by the biological unit from the light of the second light source to acquire an image of the biological unit.
[0020] Preferably, the wavelength range of the light emitted by the first light source is different from the wavelength range of the light emitted by the second light source.
[0021] Preferably, the first camera device and the second camera device are both located below the piezoelectric platform, and the first camera device and the second camera device separate the light in the first wavelength range and the light in the second wavelength range through a dichroic mirror group to receive corresponding light.
[0022] Preferably, the dichroic mirror group includes a first color mirror and a second color mirror; the first color mirror reflects light in a first wavelength range for receipt by the first camera device, and allows light in a second wavelength range to pass through; the second color mirror reflects light in the second wavelength range for receipt by the second camera device.
[0023] Preferably, the first light source is a mercury lamp disposed below the sample unit.
[0024] Preferably, the second light source is a laser emitter disposed below the piezoelectric platform.
[0025] Compared with the prior art, the beneficial effect of the biological unit imaging system of the present invention is that the present invention eliminates the influence of biological drift on the subsequent image analysis process by adding a drift compensation mechanism, so that researchers can obtain more real and accurate analysis data about the biological unit. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Figure 1 A diagram showing the composition of a biological unit imaging system provided by an embodiment of the present invention.
[0027] Figure 2 Composition diagram of the sample unit.
[0028] Figure 3 This is a comparison chart of different drift amounts in the Z-axis direction captured by the first camera device.
[0029] In the figure:
[0030] 1-first light source; 2-filter; 3-condenser; 4-computer; 5-piezoelectric platform; 6-objective lens; 7-dichroic mirror; 8-imaging lens; 9-first camera device; 10-second light source; 11-dichroic mirror; 13-reflector; 14-second camera device; 15-sample unit; 16-glass slide; 17-nanoparticle layer; 18-biological unit. DETAILED DESCRIPTION
[0031] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention is described in detail below in conjunction with the accompanying drawings and specific implementation methods.
[0032] like Figure 1 As shown, the present invention discloses a biological unit 18 imaging system, which is used to obtain image information of the biological unit 18, such as collecting image information of cells, so as to analyze the cells, such as analyzing the growth process of cells. In order to prevent the biological unit 18 from drifting and affecting the image analysis, the biological unit 18 imaging system is mainly composed of two functional mechanisms. One of the functional mechanisms is an image acquisition mechanism, and the other functional mechanism is a drift compensation mechanism. The image acquisition mechanism is used to collect image information of the biological unit 18 for analysis, and the drift compensation mechanism is used to compensate for the drift generated by the biological unit 18, so that the biological unit 18 is always kept in a constant spatial position when the image is collected, so that the collected image avoids the influence of drift on subsequent image analysis.
[0033] The present invention eliminates the influence of biological drift on the subsequent image analysis process by adding a drift compensation mechanism, so that researchers can obtain more real and accurate analysis data about the biological unit 18.
[0034] A preferred embodiment of the present invention provides a method and type of compensating for the drift of the biological unit 18. In this embodiment, Figure 2 As shown, the biological unit 18 is arranged on the glass slide 16 in a known manner to form the sample unit 15. In this embodiment, nanoparticles are laid on the upper surface of the glass slide 16 to form a nanoparticle layer 17. In this embodiment, it should be noted that the biological unit 18 is actually located on the nanoparticle layer 17, and the movement of the biological unit 18 causes the arrangement of the nanoparticles to change, which causes the image of the nanoparticle layer 17 to change (e.g., Figure 3 ). The drift compensation mechanism disclosed in this embodiment obtains the drift amount of the biological unit 18 according to the image change generated by the nanoparticle layer 17, and the drift compensation mechanism also drives the biological unit 18 (or the glass slide 16) according to the drift amount of the biological unit 18 to compensate for the drift amount. For example, when the biological unit 18 drifts ten nanometers in the positive direction of the X-axis, the drift compensation mechanism will cause the biological unit 18 to move ten nanometers in the negative direction of the X-axis.
[0035] It should be noted that the drift amount of the biological unit 18 refers to the drift amount in space, that is, the drift amount in the three-coordinate directions of XYZ.
[0036] In a preferred embodiment of the present invention, the drift compensation mechanism uses the drift acquisition module to acquire the change image of the nanoparticle layer 17, and uses the analysis control module to analyze the acquired image of the nanoparticle layer 17, and calculates the drift amount of the biological unit 18 based on the analysis result, and compensates the drift amount of the biological unit 18 through the piezoelectric platform 5. When the compensation is completed, the image acquisition mechanism acquires the image of the biological unit 18, so that the acquired image is always an image of the biological unit 18 at the same position.
[0037] A specific imaging system for acquiring an image of the biological unit 18 in the above manner is introduced below.
[0038] like Figure 1 As shown, in the system, the piezoelectric platform 5 opens a hollow portion so that the glass slide 16 is installed on the hollow portion, and a first light source 1 is arranged above the piezoelectric platform 5. Specifically, a mercury lamp is selected as the first light source 1, and a filter 2 is arranged below the mercury lamp. The filter 2 filters the light with a wavelength below 700nm, and a condenser 3 is also arranged below the filter 2. In this way, the light above 700nm is polymerized and irradiated on the glass slide 16 unit, and the light of this wavelength passes through the nanoparticle layer 17.
[0039] An objective lens 6 (the piezoelectric platform 5 is specifically a piezoelectric ceramic platform) is installed at the bottom of the piezoelectric platform 5, and a dichroic mirror 7 is arranged below the objective lens 6, a first camera device 9 is arranged on the left side of the dichroic mirror 7, and an imaging lens 8 is arranged between the dichroic mirror 7 and the first camera device 9. Specifically, a near-infrared camera is selected as the first camera device 9, and the dichroic mirror 7 is used to allow light with a wavelength less than 700nm to pass through, and reflect light with a wavelength greater than 700nm to be directed to the near-infrared camera. In other words, the light with a wavelength of more than 700nm generated by the mercury lamp and passing through the nanoparticle layer 17 is reflected by the dichroic mirror 7 after passing through the objective lens 6, and then received by the near-infrared camera through the imaging lens 8, so that the near-infrared camera can collect an image of the nanoparticle layer 17.
[0040] The microcomputer 4 is selected as the analysis control module, and the analysis control software is installed in the microcomputer 4 and communicates with the near-infrared camera and the piezoelectric platform 5 through the interface. The analysis control software is used to analyze the image collected by the near-infrared camera, and obtain the drift amount of the biological unit 18 by calculating and correcting the image of the nanoparticle layer 17. The analysis control software sends an instruction to the piezoelectric platform 5 according to the calculation result so that the piezoelectric platform 5 moves in the opposite direction by an equal amount to compensate for the drift amount.
[0041] The image acquisition mechanism includes a second light source 10, a second camera device 14 and related lenses. The components in the image acquisition mechanism are arranged in the following manner.
[0042] The second light source 10 is arranged below the piezoelectric platform 5 and on the right side. A laser emitter is selected as the second light source 10. A dichroic mirror 11 tilted toward the laser emitter is arranged below the upper dichroic mirror. The laser emitted by the laser emitter is reflected by the dichroic mirror 11 to form a vertical light. The light passes through the dichroic mirror 7 above and is irradiated on the biological unit 18 through the objective lens 6, so that the biological unit 18 emits light (the light is different from the wavelength of the laser, and its wavelength is less than 700nm). The light emitted by the biological unit 18 (its wavelength is approximately 350-700nm) passes through the objective lens 6 again, passes through the dichroic mirror 7 above (light with a wavelength below 700nm can pass through), and then passes through the dichroic mirror 11 below (light with a wavelength below 700nm can pass through).
[0043] An imaging lens 12 is arranged below the lower dichroic mirror 11, a reflector 13 is arranged below the imaging lens 12, and a second camera device 14 is arranged on one side of the reflector 13. In this way, the light passing through the lower dichroic mirror 11 passes through the imaging lens 12 and then is received by the second camera device 14 through the reflector 13, so that the second camera device 14 captures the image.
[0044] The following is a brief introduction to the workflow of the above system:
[0045] The first camera device 9 collects the image of the nanoparticle layer 17 in real time and transmits the collected image to the computer 4 in real time. The computer 4 obtains the drift amount of the biological unit 18 by analyzing and calculating the image, and sends instructions to the piezoelectric platform 5 at the same time, so that the piezoelectric platform 5 drives the glass slide 16 to move to compensate for the drift amount. When the drift compensation of the biological unit 18 is completed, the second camera device 14 collects images of the static biological unit 18. Then, the first camera device 9 continues to collect data of the nanoparticle layer 17 to continue to send images to the computer 4, and then the above cycle continues, so that the biological unit 18 is always collected by the second camera device 14 at the same position.
[0046] It should state:
[0047] Although the speed of image acquisition is affected by many factors, in fact, the image data of all nanoparticle layers 17 are mainly determined by the data acquisition speed of the near-infrared camera, the response speed of the piezoelectric ceramics in the piezoelectric platform 5, and the data transmission speed of the computer 4 interface. The near-infrared image resolution used in this system is a camera of 2048x1088, the acquisition speed is 49.5fps, and it communicates with the computer 4 through a gigabit network card interface (IEEE 802.3 1000BASE-T, IEEE 802.3af), with a transmission bandwidth of 12bit. The response frequency of the piezoelectric platform 5 when the load is 200g is 530Hz in the X and Y directions (635Hz in the Z direction). Therefore, the speed of this system is mainly determined by the acquisition speed of the near-infrared camera of 49.5fps. If a lower resolution and a smaller imaging area are selected, a faster acquisition speed can be provided. The piezoelectric platform 5 provides two ways to share registers externally, namely TCP / IP protocol and serial port protocol. In order to obtain higher response speed and better stability, the TCP / IP protocol is actually used for communication in this system. There are three main functions of register synchronization: (1) transmitting the accurate position information of the piezoelectric platform 5 to the drift image acquisition module, that is, the computer 4 and the near-infrared camera; (2) calculating the drift amount in the X, Y, and Z directions through the computer 4 program, returning it to the piezoelectric platform 5 in real time through the drift image acquisition module and driving the piezoelectric platform 5 to make corresponding compensation movements; (3) preventing the piezoelectric platform 5 from moving when the drift image acquisition module is not ready, avoiding unexpected downtime and data loss.
[0048] The above embodiments are only exemplary embodiments of the present invention and are not intended to limit the present invention. The protection scope of the present invention is defined by the claims. Those skilled in the art may make various modifications or equivalent substitutions to the present invention within the essence and protection scope of the present invention, and such modifications or equivalent substitutions shall also be deemed to fall within the protection scope of the present invention.
Claims
1. A biological unit imaging system for obtaining image information of a biological unit, characterized in that: include: Image acquisition mechanism and drift compensation mechanism; wherein: The drift compensation mechanism is used to compensate for the drift of the biological unit so as to keep the biological unit at a constant position; The image acquisition mechanism is used to acquire the image of the biological unit after the drift compensation mechanism has performed drift compensation; The biological unit is arranged on a glass slide to form a sample unit, and nanoparticles are laid on the upper surface of the glass slide to form a nanoparticle layer; wherein: The drift compensation mechanism obtains the drift amount of the biological unit according to the acquired image change of the nanoparticle layer and compensates for the drift amount; The drift compensation mechanism comprises: A piezoelectric platform, wherein the sample unit is arranged at a hollow position of the piezoelectric platform; A drift acquisition module, which is used to obtain image information of the nanoparticle layer in real time; An analysis control module, which is used to analyze the image information of the nanoparticle layer to calculate the drift amount of the biological unit, and control the piezoelectric platform according to the calculated drift amount to compensate for the drift amount of the biological unit; The drift collection module includes: A first light source, which is used to emit light of a first wavelength range capable of imaging the nanoparticle layer toward the sample unit; A first camera device, which acquires an image of the nanoparticle layer by receiving light emitted by the first light source; The first light source is a mercury lamp disposed above the sample unit; a filter is disposed below the mercury lamp, the filter can filter light with a wavelength below 700 nm, and a condenser is also disposed below the filter; An objective lens is installed at the bottom of the piezoelectric platform, a dichroic mirror is arranged below the objective lens, the first camera device is arranged on the left side of the dichroic mirror, and an imaging lens is arranged between the dichroic mirror and the first camera device; The drift of the biological unit is the drift in the XYZ three-dimensional coordinate direction in space; The biological unit is located on the nanoparticle layer. The movement of the biological unit causes the arrangement of the nanoparticles to change, causing the image of the nanoparticle layer to change. The changes include: under different offsets from -1000nm to 1000nm in the Z coordinate direction, the image presents different changes in brightness, and the different changes in brightness are at least presented as the difference in the sum of the brightness of the inner and outer rings, and the brightness in the middle changes from high to low.
2. The biological unit imaging system according to claim 1, characterized in that: The image acquisition mechanism comprises: a second light source for emitting light toward the biological unit to image the biological unit; The second camera device is used to receive the light in the second wavelength range reflected by the biological unit from the light of the second light source to acquire an image of the biological unit.
3. The biological unit imaging system according to claim 2, characterized in that: The wavelength range of the light emitted by the first light source is different from the wavelength range of the light emitted by the second light source.
4. The biological unit imaging system according to claim 3, characterized in that: The first camera device and the second camera device are both located below the piezoelectric platform. The first camera device and the second camera device separate the light in the first wavelength range and the light in the second wavelength range through a dichroic mirror group to receive corresponding light.
5. The biological unit imaging system according to claim 4, characterized in that: The dichroic mirror group includes a first color mirror and a second color mirror; the first color mirror reflects light in a first wavelength range for reception by the first camera device and allows light in a second wavelength range to pass through; the second color mirror reflects light in the second wavelength range for reception by the second camera device.
6. The biological unit imaging system according to claim 2, characterized in that: The second light source is a laser emitter disposed below the piezoelectric platform.
Citation Information
Patent Citations
AOTF optical system with image drift compensation
CN102096211A
Digital holography based sample drifting active compensation method and device
CN104568753A
Biological unit imaging system
CN212160221U
Device and Method for Acquiring a Microscopic Image of a Sample Structure
US20130128025A1
Multifocal method and apparatus for stabilization of optical systems
US20180149855A1
