System for realizing operation of photoelectric tweezers

Abstract

The invention relates to the technical field of photoelectric tweezers, in particular to a system for achieving operation of the photoelectric tweezers. According to the technical scheme, the system comprises a camera, an imaging barrel lens, a beam combiner, a projection system, a fluorescence module, an objective lens turntable, an electric XYZ platform, a signal generation system and a control module, the camera captures a microscopic objective lens imaging light beam through the imaging barrel lens, and the beam combiner is used for projecting a microscopic light beam and reflecting a projection light beam; the projection system is composed of an LED light source, an array reflector set and the like and projects controllable light spots under an objective lens. The fluorescent module switches a bright field mode and a fluorescent mode; the objective lens turntable automatically switches multiplying power; the electric XYZ platform is used for fixing and positioning a biological chip; the signal generation system outputs an electric signal of the control chip; the control module is divided into a camera control part, a projection part and a motor part to cooperatively complete photoelectric tweezer operation. The photoelectric tweezers operation and the fluorescence operation are completed by one system, and the photoelectric tweezers operation and the fluorescence operation are controlled through a proper control process.

Description

Technical Field

[0001] The present invention relates to the technical field of photoelectric tweezers, and in particular to a system for realizing photoelectric tweezers operation. Background Art

[0002] The photoelectric tweezers system is a technology that uses light irradiation to capture, manipulate and measure microscopic particles (such as atoms, molecules, cells, etc.). The photoelectric tweezers system can be used to capture and manipulate cells, viruses, bacteria, as well as organelles and cell components within cells. It allows the operator to operate without touching the sample, thereby reducing damage and contamination to the sample. Photoelectric tweezers technology can be combined with microfluidics technology to achieve high-throughput target sorting, separation and processing. This integrated system can be used in fields such as cell screening, drug delivery and biosensing. Traditional photoelectric tweezers systems require signal generators, projection light sources, microscopes and other structures, and the degree of integration is not high. The existence of these devices alone leads to the following problems:

[0003] High system complexity: Traditional systems require multiple devices to operate together, involving functional modules such as microscope imaging, spot projection and signal control, and the linkage between modules is complex;

[0004] Difficult operation: Users need to control multiple devices separately, such as focusing of the microscope system, adjustment of the light projection path, and setting of electrical signals, which increases the operation burden and time cost;

[0005] Low integration: Traditional optoelectronic tweezers systems usually rely on the physical connection of independent devices, lack a unified control interface between devices, and are difficult to meet the high-throughput and automated requirements of modern biological experiments.

[0006] With the development of life sciences and biotechnology, the demand for precise manipulation of microscopic particles is increasing. For example, application fields such as cell screening, drug delivery, and biosensing require that photoelectric tweezers technology can improve efficiency while reducing the risk of damage and contamination to samples. Therefore, it is urgent to develop a highly integrated, easy-to-operate, and powerful photoelectric tweezers system.

[0007] To this end, we propose a system to implement photoelectric tweezers operation to solve the existing problems. Summary of the invention

[0008] The purpose of the present invention is to provide a system for realizing photoelectric tweezers operation in view of the problems existing in the background technology.

[0009] To achieve the above-mentioned purpose, the present invention provides the following technical solutions: a system for realizing photoelectric tweezers operation, comprising a camera, an imaging tube lens, a beam combiner, a projection system, a fluorescence module, an objective lens turntable, an electric XYZ platform, a signal generation system and a control module, wherein the camera is used to capture an imaging beam of a microscope system, the imaging tube lens is used to image an object under a microscope objective lens to the camera, and the beam combiner is used to project a microscope imaging beam and reflect the projection beam;

[0010] The projection system includes an LED light source, a collimating lens group, a compound eye lens, a lens group, a reflector, an array reflector group, a prism and a projection tube lens, and its function is to generate a projection light beam, and its projection surface coincides with the photographed surface of the microscope. By controlling the projection of the projection system, a bright spot can be generated in any area under the objective lens, and a controllable light spot can be projected under the microscope objective lens;

[0011] The fluorescence module is used to generate a bright field illumination beam and a fluorescence beam. The objective lens turret is driven by a motor. Objective lenses of different magnifications are installed on the objective lens turret to achieve automatic switching of the objective lenses. In general photoelectric tweezers operations, 4X, 10X, and 20X objective lenses are commonly used.

[0012] The electric XYZ platform is used to fix the biochip and realize the three-dimensional precise positioning of the chip, wherein the XY movement is used to take pictures of different parts of the biochip or operate the photoelectric tweezers, and the Z movement is used to find the appropriate focal plane of the objective lens;

[0013] The biochip is used to carry samples, and microscopic imaging and photoelectric tweezers operation are achieved through an electric XYZ platform. The signal generating system is connected to the biochip through a wire, and outputs a sine wave or square wave signal with an amplitude less than V and a frequency less than MHz. The control module includes a control module and a control module, which are respectively used for camera image processing, projection system control, and precise control of the electric XYZ platform, objective lens turntable and signal generating system. The two control modules are connected through a communication interface.

[0014] Preferably, the array reflector group in the projection system has two reflection directions, ON and OFF. Through the control of the system, the light in the ON reflection direction is reflected to the subsequent microscope system, and the light in the OFF reflection direction is reflected to a specific position to extinguish.

[0015] Preferably, the control module adjusts the Z-axis position of the electric XYZ platform through an automatic focusing algorithm to focus the system, and generates a light spot projection path through an image recognition algorithm to complete the photoelectric tweezers operation of the target cell.

[0016] Preferably, the fluorescence module realizes switching between bright field and fluorescence modes through motor control, and can adjust the fluorescence intensity and the exposure time of the camera.

[0017] Preferably, the electric XYZ platform positions the focal plane of the objective lens turntable by controlling the Z axis, and realizes imaging and operation of different areas of the biochip by moving the XY axis.

[0018] Preferably, the control module sends the generated spot image to the projection system at a specific frequency via an HDMI interface to achieve dynamic photoelectric tweezers operation.

[0019] Preferably, the signal generating system can adjust the frequency, amplitude and waveform type of the output waveform in real time to meet different experimental requirements.

[0020] Preferably, the LED light source of the projection system is monochromatic light, the collimating lens group is used to convert the emitted light beam into a parallel light beam, the compound eye lens is used to split the light beam into a number of small light beams, the lens group is a lens group composed of two lenses, and its function is to image each small unit onto the surface of the array reflector group, the reflector is used to fold the light path, the prism is used to fold the light path, and the projection tube lens is used to project the light emitted by the array reflector group onto the objective lens at a suitable magnification.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The present invention proposes a system for realizing photoelectric tweezers operation. The system significantly improves the operation efficiency and applicability through multi-module integrated design and precise control. The beneficial effects thereof include:

[0023] Highly integrated design: The system integrates microscope imaging, spot projection, fluorescence detection and signal generation functions, and centralizes the traditional scattered equipment. Through two control modules, various parts of the system are controlled, and one system completes the photoelectric tweezers operation and fluorescence operation. Through appropriate control processes, the control of the photoelectric tweezers operation and the control of the fluorescence operation are realized;

[0024] Modular control: The system uses two independent control modules to realize the precise operation of camera image processing, light projection control, and electric XYZ stage and signal generation system respectively. The modules can achieve efficient collaboration through the communication interface.

[0025] Easy to operate: Using autofocus algorithm and image recognition technology, the system can quickly locate target cells and generate light spot paths, reducing the user's operating burden and improving the automation of the experiment;

[0026] Versatility: The system supports seamless switching between photoelectric tweezers operation and fluorescence detection functions, and can be widely used in cell capture, manipulation, separation, drug screening, biosensing and other fields;

[0027] Precise control and efficient experiments: The electric XYZ platform supports three-dimensional precise positioning. Combined with dynamic spot projection and adjustable electrical signal application, it can achieve high-precision control and rapid experiments on target cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is the system optical path diagram of the present invention;

[0029] Figure 2 The optical path diagram of the projection system of the present invention;

[0030] Figure 3 It is the principle diagram of the control part of the present invention;

[0031] Figure 4 It is a control flow chart of the photoelectric tweezers operating system of the present invention;

[0032] Figure 5 This is a flow chart of fluorescence photography of the system of the present invention.

[0033] Reference numerals:

[0034] 101. Camera; 102. Imaging tube lens; 103. Beam combiner; 104. Projection system; 105. Fluorescence module; 106. Objective lens turntable; 107. Electric XYZ platform; 108. Biochip; 109. Signal generation system; 201. LED light source; 202. Collimating lens group; 203. Compound eye lens; 204. Lens group; 205. Reflector; 206. Array reflector group; 207. Prism; 208. Projection tube lens. DETAILED DESCRIPTION

[0035] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] Embodiment 1

[0037] like Figure 1-Figure 5 As shown, a system for realizing photoelectric tweezers operation proposed by the present invention includes a camera 101, an imaging tube lens 102, a beam combiner 103, a projection system 104, a fluorescence module 105, an objective lens turntable 106, an electric XYZ platform 107, a signal generation system 109 and a control module, wherein the camera 101 is used to capture a microscopic imaging light beam, the imaging tube lens 102 is used to image the object under the microscope objective lens to the camera 101, the beam combiner 103 is used to project the microscopic imaging light beam and reflect the projection light beam, and the projection system 104 can project a controllable light spot under the microscope objective lens;

[0038] The fluorescence module 105 is used to generate a bright field illumination beam and a fluorescence beam. The fluorescence module 105 realizes the switching between the bright field and fluorescence modes through motor control, and can adjust the fluorescence intensity and the exposure time of the camera 101;

[0039] The objective lens turret 106 is driven by a motor and is equipped with objective lenses of multiple magnifications to achieve automatic switching of the objective lenses. The electric XYZ platform 107 is used to fix the biochip 108 to achieve three-dimensional precise positioning of the chip. The electric XYZ platform 107 positions the focal plane of the objective lens turret 106 by controlling the Z axis, and realizes imaging and operation of different areas of the biochip 108 by moving the XY axis.

[0040] The biochip 108 is used to carry samples, and microscopic imaging and photoelectric tweezers operation are achieved through the electric XYZ platform 107. The signal generating system 109 is connected to the biochip 108 through wires, and outputs a sine wave or square wave signal with an amplitude less than 30V and a frequency less than 5MHz. The signal generating system 109 can adjust the frequency, amplitude and waveform type of the output waveform in real time to meet different experimental requirements.

[0041] The projection system 104 includes an LED light source 201, a collimating lens group 202, a fly-eye lens 203, a lens group 204, a reflector 205, an array reflector group 206, a prism 207 and a projection tube lens 208. The LED light source 201 of the projection system 104 is monochromatic light. The collimating lens group 202 is used to convert the light beam emitted by 201 into a parallel light beam. The fly-eye lens 203 is used to split the light beam into a plurality of small light beams. The lens group 204 is a lens group composed of two lenses, and its function is to image each small unit of 203 onto the surface of the array reflector group 206. The reflector 205 is used to fold the light path.

[0042] The array reflector group 206 has two reflection directions, ON and OFF. Through the control of the system, the light in the ON reflection direction is reflected to the subsequent microscopic system, and the light in the OFF reflection direction is reflected to a specific position to be extinguished;

[0043] The function of the prism 207 is to fold the light path, and the function of the projection tube lens 208 is to project the light emitted by the array reflector group 206 to the objective lens at a suitable magnification;

[0044] The control module includes a control module 1 and a control module 2, which are respectively used for image processing of the camera 101, control of the projection system 104, and precise control of the electric XYZ platform 107, the objective lens turntable 106 and the signal generation system 109. The two control modules are connected through a communication interface. The control module sends the generated spot image to the projection system 104 at a specific frequency through the HDMI interface to realize dynamic photoelectric tweezers operation. The control module adjusts the Z-axis position of the electric XYZ platform 107 through an automatic focusing algorithm to focus the system, and generates a spot projection path through an image recognition algorithm to complete the photoelectric tweezers operation of the target cell.

[0045] The functions of the two parts are different. The control module 1 mainly communicates with the camera 101 through the USB3.0 interface, sets the parameters of the camera 101 and receives the image of the camera 101, performs relevant image processing, and communicates with the projection module through the USB and HDMI interfaces, sets the brightness of the projection module, generates a projection image through image recognition, and transmits it to the projection module through HDMI.

[0046] The main functions of the control module 2 are to control the position of the XYZ motor, control the objective lens rotation motor, select the appropriate objective lens gear, control the signal generating module and read its status to control the waveform and frequency amplitude of its output, control the gear and fluorescence intensity of the fluorescence module 105, and the control module 1 and the control module 2 communicate through the USB port.

[0047] Embodiment 2

[0048] like Figure 1-Figure 5 As shown, the system for realizing photoelectric tweezers operation proposed by the present invention executes the following process during the photoelectric tweezers operation:

[0049] First, the chip to be controlled is loaded onto the XYZ platform, and the XYZ platform is driven by the control module 2 to adjust the chip position to within the field of view of the objective lens. The control module 1 starts the autofocus algorithm, adjusts the Z axis of the XYZ platform, finds the best focus plane, focuses the optical system, and ensures that the target area of ​​the sample is clearly imaged to the camera 101;

[0050] The control module 1 is used to process the sample image collected by the camera 101, and the position and boundary of the target cell are identified by the image algorithm. According to the identification result, the control module 1 calculates the pixel area to be illuminated, and generates the path of the circled light spot by path planning;

[0051] The control module 1 sends the projection image data to the array reflector group 206 of the projection system through the HDMI interface. The projection system 104 accurately projects the light spot to the target cell area by controlling the prism 207 and the projection tube lens 208.

[0052] The control module 2 drives the signal generation system 109 to generate an electrical signal of a specific frequency and amplitude, which is applied to the upper and lower electrodes of the biochip 108 through a wire, and the light spot position and signal frequency are adjusted to capture and manipulate the target cells to complete the operation;

[0053] The image is sent to the projection module at a certain frequency via HDMI, so that the cells move with the light spot, completing the photoelectric tweezers operation;

[0054] The control process of fluorescence detection and shooting is as follows:

[0055] First, the chip is loaded on the XYZ platform, and then the Z axis is adjusted while the system is focused using the automatic focusing algorithm of the image captured by the camera 101;

[0056] The control module 2 drives the motor of the fluorescence module 105, switches to the designated fluorescence filter position, and adjusts the fluorescence brightness to achieve the best effect of fluorescence photography, and then photographs the fluorescence;

[0057] Setting the exposure time of the camera 101 to adapt to the fluorescence brightness to ensure clear capture of the fluorescence signal of the target sample;

[0058] The camera 101 is started to capture sample images in bright field and fluorescence modes respectively, and the data are saved in real time for subsequent analysis.

[0059] The control module 1 synthesizes and analyzes the collected microscopic image and fluorescent image, identifies the operation effect of the target area, records the light spot path, signal parameters and cell movement trajectory as experimental data, adjusts the light spot projection path or signal parameters according to the analysis results, and repeats the photoelectric tweezers operation until the expected experimental goal is achieved.

[0060] The above-mentioned specific embodiments are only several preferred embodiments of the present invention. Based on the technical solutions of the present invention and the relevant inspirations of the above-mentioned embodiments, those skilled in the art can make various alternative improvements and combinations to the above-mentioned specific embodiments.

[0061] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

Claims

1. A system for implementing photoelectric tweezers operation, comprising a camera (101), an imaging tube lens (102), a beam combiner (103), a projection system (104), a fluorescence module (105), an objective lens turret (106), an electric XYZ platform (107), a signal generation system (109) and a control module, characterized in that: The camera (101) is used to capture a microscopic imaging light beam, the imaging tube lens (102) is used to image the object under the microscope objective lens onto the camera (101), the beam combiner (103) is used to project the microscopic imaging light beam and reflect the projection light beam, the projection system (104) comprises an LED light source (201), a collimating lens group (202), a compound eye lens (203), a lens group (204), a reflector (205), an array reflector group (206), a prism (207) and a projection tube lens (208), and can project a controllable light spot under the microscope objective lens, the fluorescence module (105) is used to generate a bright field illumination light beam and a fluorescence light beam, the objective lens turntable (106) is driven by a motor, and is equipped with objective lenses of multiple magnifications, so as to realize the objective lens The electric XYZ platform (107) is used to fix the biochip (108) to achieve three-dimensional precise positioning of the chip. The biochip (108) is used to carry samples. Microscopic imaging and photoelectric tweezers operation are achieved through the electric XYZ platform (107). The signal generation system (109) is connected to the biochip (108) through a wire and outputs a sine wave or square wave signal with an amplitude less than 30V and a frequency less than 5MHz. The control module includes a control module 1 and a control module 2, which are respectively used for camera (101) image processing, projection system (104) control, and electric XYZ platform (107), objective lens turntable (106) and signal generation system (109) precise control. The two control modules are connected through a communication interface.

2. A system for implementing photoelectric tweezers operation according to claim 1, characterized in that: The array reflector group (206) in the projection system (104) has two reflection directions, ON and OFF. Through the control of the system, the light in the ON reflection direction is reflected to the subsequent microscope system, and the light in the OFF reflection direction is reflected to a specific position to be extinguished.

3. A system for implementing photoelectric tweezers operation according to claim 1, characterized in that: The control module adjusts the Z-axis position of the electric XYZ platform (107) through an automatic focusing algorithm to focus the system, and generates a light spot projection path through an image recognition algorithm to complete the photoelectric tweezers operation of the target cell.

4. A system for implementing photoelectric tweezers operation according to claim 1, characterized in that: The fluorescence module (105) realizes the switching between bright field and fluorescence modes through motor control, and can adjust the fluorescence intensity and the exposure time of the camera (101).

5. A system for implementing photoelectric tweezers operation according to claim 1, characterized in that: The electric XYZ platform (107) positions the focal plane of the objective lens turntable (106) by controlling the Z axis, and realizes imaging and operation of different areas of the biochip (108) by moving the XY axis.

6. A system for implementing photoelectric tweezers operation according to claim 1, characterized in that: The control module sends the generated light spot image to the projection system (104) at a specific frequency via the HDMI interface, thereby realizing dynamic photoelectric tweezers operation.

7. A system for implementing photoelectric tweezers operation according to claim 1, characterized in that: The signal generating system (109) can adjust the frequency, amplitude and waveform type of the output waveform in real time to meet different experimental requirements.

8. A system for implementing photoelectric tweezers operation according to claim 2, characterized in that: The LED light source (201) of the projection system (104) is monochromatic light, the collimating lens group (202) is used to convert the light beam emitted by 201 into a parallel light beam, the compound eye lens (203) is used to split the light beam into a plurality of small light beams, the lens group (204) is a lens group composed of two lenses, and is used to image each small unit of 203 onto the surface of the array reflector group (206), the reflector (205) is used to fold the light path, the prism (207) is used to fold the light path, and the projection tube lens (208) is used to project the light emitted by the array reflector group (206) onto the objective lens at a suitable magnification.

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