Micro-fluidic chip imaging positioning device

Abstract

The utility model discloses a micro-fluidic chip imaging positioning device, and belongs to the technical field of micro-fluidic chip positioning. According to the technical scheme, the system comprises a microcosmic illumination module, a microcosmic imaging module, a chip moving and macroscopic illumination module, a macroscopic imaging module and an optical path multiplexing module; the microscopic illumination module comprises a fly's-eye lens assembly, the fly's-eye lens assembly comprises two fly's-eye lenses, the optical axes of the two fly's-eye lenses are parallel to each other, and the focus of each lens array element in one fly's-eye lens coincides with the center of the lens array element at the corresponding position of the other fly's-eye lens. The micro-fluidic chip clamp is applied to the aspect of micro-fluidic chip imaging positioning, overcomes the defects caused by an existing micro-fluidic chip clamp, solves the technical problems of universality, automation and high precision of micro-fluidic chip positioning, and has the characteristics of rapidness, automation, high precision and universality.

Description

Technical Field

[0001] The present invention belongs to the technical field of microfluidic chip positioning, and in particular relates to a microfluidic chip imaging positioning device. Background Art

[0002] Microfluidic chip technology plays an important role in fields such as chemistry, medicine, and biology due to its small size, low sample volume, low pollution, and high efficiency. In the field of biology, microscopic observation or detection of biological samples in microfluidic chips is generally required, so the fixation and positioning of the chip plays a very important role. The current common method is to design a microfluidic chip fixture or ferrule for the specific chip structure, rely on the hole positioning or edge positioning of the fixture, rely on the flexible material on the fixture (usually an elastic sealing ring, flexible gasket, etc.) to provide clamping force for compression and sealing, and then fix the fixture or ferrule as a whole on the observation platform.

[0003] Chinese patent CN201320465462.1 discloses a rapid positioning device for a microfluidic chip. The main components consist of a three-dimensional platform and a positioning sleeve. The microfluidic chip is inserted into the positioning sleeve and clamped. The sleeve is fixed to a three-dimensional translation stage. The position of the microfluidic chip can be adjusted by controlling the movement of the three-dimensional platform. The advantages of this method are ease of use and rapid positioning.

[0004] However, the method disclosed in the above patent has certain limitations. Specifically: First, the design accuracy and debugging accuracy of the fixture are required to be high. For soft material chips such as PDMS, excessive clamping force will cause serious deformation of the chip, resulting in blockage of the microfluidic channel. Excessive clamping force will cause the chip to leak. For hard material chips such as glass, repeated contact with the fixture will cause small glass slag to accumulate in the fixture, thereby affecting the positioning accuracy. At the same time, in order to adapt to the fixture, high requirements are also placed on the processing accuracy of chips of the same model but different batches. Secondly, different biological samples require the use of microfluidic chips with different structures, but the fixture needs to be designed for each fixed model of microfluidic chip, which is not universal, resulting in low efficiency and high cost. Thirdly, the replacement of the chip requires manual operation due to positioning and clamping, and automation cannot be achieved. Finally, the above positioning method also involves the coupling of the chip fixture and the observation platform. Affected by the structural accuracy, there will be a small position difference each time it is placed, and the uncertainty is very large. Summary of the Invention

[0005] The details of one or more embodiments of the invention are set forth in the following drawings and description to make other features, objects, and advantages of the application more readily apparent.

[0006] The present invention proposes a microfluidic chip imaging positioning device, which solves the disadvantages of existing microfluidic chip fixtures and the technical problems of universality, automation and high precision in microfluidic chip positioning, and has the characteristics of rapidity, automation, high precision and versatility.

[0007] The present invention discloses a microfluidic chip imaging and positioning device, comprising a microscopic illumination module, a microscopic imaging module, a chip movement and macroscopic illumination module, a macroscopic imaging module, and an optical path multiplexing module; the microscopic illumination module comprises a compound eye lens assembly, the compound eye lens assembly comprises two compound eye lenses, the optical axes of the two compound eye lenses are parallel to each other, and the focus of each lens array element in one compound eye lens coincides with the center of the lens array element at the corresponding position of the other compound eye lens; the microscopic imaging module is used to perform infinite microscopic imaging of a sample and provide visualized sample morphology and spatial position; the chip movement and macroscopic illumination module scans and moves the microfluidic chip and provides bright field illumination for macroscopic imaging; the macroscopic imaging module performs macroscopic visual imaging of the entire chip for positioning; and the optical path multiplexing module combines the microscopic illumination module with the macroscopic imaging module.

[0008] In some embodiments, the chip movement and macro-illumination module further includes: a three-dimensional electric scanning platform, a macro-light source, and a microfluidic chip holder; the three-dimensional electric scanning platform moves in the XY direction to move the microfluidic chip forward, backward, left and right for scanning, and moves in the Z direction to perform microscopic focusing of the microfluidic chip; the macro-light source illuminates the microfluidic chip from the side; the microfluidic chip holder is fixed on the three-dimensional electric scanning platform, and a placement area for the microfluidic chip is provided on the microfluidic chip holder; the macro-light source is fixed on the microfluidic chip holder and distributed circumferentially along the microfluidic chip.

[0009] In some embodiments, the microfluidic chip holder further includes: a holder body, a placement area, and a light board; the holder body is fixedly connected to the three-dimensional electric scanning platform; the placement area is opened on the holder body, and the microfluidic chip is fixed in the placement area; the light board is fixedly connected to the holder body and distributed circumferentially along the placement area; the macro light source is a plurality of white light LEDs, and the plurality of white light LEDs are evenly fixed on the light board along the circumference of the placement area.

[0010] In some embodiments, the microfluidic chip support further includes a light board cover that is disposed above the plurality of white light LEDs and is detachably fixedly connected to the light board.

[0011] In some embodiments, the light board is a split structure, including a first light board arranged on one side of the placement area, and a second light board arranged on the other side of the placement area; the light board cover includes a first light board cover fixedly connected to the first light board, and a second light board cover fixedly connected to the second light board.

[0012] In some embodiments, the microscopic illumination module further includes: a microscopic light source, a collimating lens for collimating the divergent light of the microscopic light source into parallel light, a reflecting mirror for making a 90° turn on the light path to compress the volume of the light path, and a condensing lens.

[0013] In some embodiments, the microscopic imaging module includes: a microscopic objective lens, a microscopic imaging lens assembly for focusing the sample image onto a microscopic camera, and a microscopic camera for receiving imaging signals.

[0014] In some embodiments, the macro imaging module includes: a visual imaging lens assembly that focuses the image of the microfluidic chip onto a macro camera, and a macro camera that receives the imaging signal of the microfluidic chip.

[0015] In some embodiments, the optical path multiplexing module further includes: a condenser, a condenser switching assembly, and a dichroic prism; the condenser switching assembly fixes the condenser and controls the condenser to be located at a first position entering the optical path or a second position cutting out the optical path; when the condenser is located at the first position, the condenser is located above the microfluidic chip, the main light of the condenser and the microscopic illumination module are coaxial, and the macroscopic imaging module does not work; when the condenser is located at the second position, the macroscopic imaging module performs macroscopic imaging of the microfluidic chip, and the microscopic illumination module does not work; the dichroic prism is located above the first position, the light of the microscopic illumination module is transmitted through the dichroic prism, and the light reflected back from the microfluidic chip illuminated by the macroscopic light source is reflected through the dichroic prism and enters the visual imaging lens assembly.

[0016] In some embodiments, the microfluidic chip imaging and positioning device further includes a computer control system, which is electrically connected to the microscopic illumination module, the microscopic imaging module, the chip movement and macroscopic illumination module, the macroscopic imaging module, and the optical path multiplexing module.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The present invention provides a microfluidic chip imaging positioning device that can completely replace the traditional chip fixture-based positioning solution. Its advantages are specifically reflected in:

[0019] 1. Strong versatility. It does not require separate design for microfluidic chips with different structures. First, it can be applied to microfluidic chips with different internal structures such as liquid circuits and gas circuits. Secondly, as long as the appearance dimensions of the microfluidic chip within the detection field of view of the macro imaging module are met, it can be directly detected. It has strong versatility and not only avoids the shortcomings of high design and debugging precision of the fixture, but also reduces the requirements for chip precision, thereby reducing costs and improving detection efficiency.

[0020] 2. Improved automation: This device solves the problem that chip fixtures cannot be automated due to positioning and clamping. Through chip bracket structure design, common optical path coupling and other designs, it reserves space for automated equipment operation, and can achieve completely unattended automated positioning and detection.

[0021] 3. Fast and high-precision. This device is based on visual imaging positioning, which avoids the chip fixture installation process. Chip positioning can be completed in seconds, and the efficiency is increased by more than ten times. This device is based on a high-resolution macro camera and combines deep learning algorithm modeling and recognition positioning. The positioning accuracy can reach 1μm, which is significantly improved compared to the mechanical positioning error of 10-100μm. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The drawings described herein are used to provide a further understanding of the present invention and constitute a part of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0023] Figure 1 A schematic structural diagram of a microfluidic chip imaging and positioning device provided in an embodiment of the present invention;

[0024] Figure 2 A schematic diagram of the structure of a microfluidic chip support provided in an embodiment of the present invention;

[0025] Figure 3 A schematic structural diagram of a fly-eye lens assembly provided in an embodiment of the present invention;

[0026] Figure 4 A schematic diagram of the visual imaging positioning process of a microfluidic chip provided by an embodiment of the present invention;

[0027] Figure 5 A schematic diagram of the process of establishing a landmark point or channel recognition model for a microfluidic chip provided by an embodiment of the present invention;

[0028] Figure 6 A schematic diagram of the arrangement of a macro light source on a light board provided by an embodiment of the present invention;

[0029] Figure 7 A simulated diagram of the illumination spot at a sample provided by an embodiment of the present invention;

[0030] Figure 8 This is an imaging effect diagram of a microfluidic chip provided by an embodiment of the present invention;

[0031] Description of the drawings: 101, compound eye lens assembly; 102, microscopic light source; 103, collimating lens; 104, reflecting mirror; 105, condenser lens; 201, three-dimensional electric scanning platform; 202, macroscopic light source;

[0032] 2031, bracket body; 2032, light board; 2033, light board cover;

[0033] 301. Microscope objective lens; 302. Microscopic imaging lens assembly; 303. Microscopic camera; 401. Visual imaging lens assembly; 402. Macroscopic camera; 501. Condenser switching assembly; 502. Beam splitter prism; 60. Computer control system; 70. Microfluidic chip. DETAILED DESCRIPTION

[0034] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is described and illustrated below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention. Based on the embodiments provided by the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work are within the scope of protection of the present invention.

[0035] Obviously, the drawings described below are merely examples or embodiments of the present invention. Those skilled in the art can apply the present invention to other similar scenarios based on these drawings without inventive effort. Furthermore, it is understood that while the effort involved in such a development process may be complex and lengthy, for those skilled in the art related to the disclosure of the present invention, any design, manufacturing, or production changes based on the technical content disclosed in the present invention are merely conventional technical means and should not be construed as an inadequacy of the disclosure of the present invention.

[0036] References to "embodiments" in this disclosure mean that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the disclosure. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described in this disclosure may be combined with other embodiments, unless there is a conflict.

[0037] Unless otherwise defined, technical or scientific terms used in the present invention shall have the ordinary meaning as understood by a person of ordinary skill in the art to which the invention pertains. As used in the present invention, the terms "a," "an," "a kind of," "the," and similar expressions do not limit the number and may refer to the singular or plural. The terms "comprise," "include," "have," and any variations thereof, as used in the present invention, are intended to cover non-exclusive inclusions; for example, a process, method, system, product, or device comprising a series of steps or modules (units) is not limited to the listed steps or units but may also include steps or units not listed, or may include other steps or units inherent to the process, method, product, or device. As used in the present invention, the terms "connect," "connected," "coupled," and similar expressions are not limited to physical or mechanical connections but may include electrical connections, whether direct or indirect. As used in the present invention, "plurality" means two or more. "And / or" describes an association relationship between associated objects, indicating that three relationships may exist. For example, "A and / or B" may mean: A exists alone, A and B exist simultaneously, or B exists alone. The character " / " generally indicates that the objects in the preceding and following relationship are in an "or" relationship. The terms "first", "second", "third", etc. involved in the present invention are only used to distinguish similar objects and do not represent a specific ordering of the objects.

[0038] The present invention provides a microfluidic chip 70 imaging positioning device, such as Figure 1 As shown, it includes a microscopic lighting module, a microscopic imaging module, a chip moving and macroscopic lighting module, a macroscopic imaging module, and an optical path multiplexing module; the microscopic lighting module includes a fly-eye lens assembly 101, as shown Figure 3 As shown, the fly-eye lens assembly 101 includes two fly-eye lenses, the optical axes of which are parallel to each other, and the focal point of each lens array element in one fly-eye lens coincides with the center of the lens array element at the corresponding position in the other fly-eye lens; the microscopic imaging module is used to perform infinite microscopic imaging of the sample, providing visualization of the sample morphology and spatial position; the chip movement and macroscopic illumination module scans and moves the microfluidic chip 70 and provides brightfield illumination for macroscopic imaging; the macroscopic imaging module performs macroscopic visual imaging of the entire chip for positioning. In some embodiments, the microscopic illumination module further includes: a microscopic light source 102, a collimator 103 that collimates the divergent light of the microscopic light source 102 into parallel light, a reflector 104 that makes a 90° turn on the light path to compress the light path volume, and a condenser 105; and the optical path multiplexing module is used to organically combine the microscopic illumination module with the macroscopic imaging module.

[0039] Regarding the microscopic illumination module, it should be noted that the microscopic illumination module provides suitable bright field illumination for microscopic imaging, and includes a microscopic light source 102, which provides a light source for microscopic bright field imaging. The microscopic light source 102 can be a white light LED or a halogen lamp, etc.; a collimator 103, which collimates the divergent light of the light source into parallel light; a compound eye lens assembly 101, which contains two compound eye lenses with completely identical parameters, and whose function is to improve the uniformity and brightness of the illumination; a reflector 104, which is used to make a 90° turn on the light path to compress the volume of the light path; and a condenser 105, which is used to converge the light coming out of the compound eye lens assembly 101 into a uniform square light spot to illuminate the sample area. The microscopic illumination module is one of the core modules of this device, and its main function is to provide high light energy utilization and high uniformity illumination for microscopic imaging. The compound eye lens assembly 101 is the key to achieving the above effect. The optical axes of the two compound eye lenses it contains are parallel to each other, and the focus of each lens array element in the first compound eye lens coincides with the center of the lens array element at the corresponding position of the second lens. The appearance structure of the compound eye lens is as follows: Figure 3 As shown. When the microscopic illumination module is working normally, the light emitted by the microscopic light source 102 is formed into parallel light through the collimator 103. The parallel light passes through the various lens array elements of the first fly-eye lens and is focused to the center of the lens array element at the corresponding position of the second lens array element. The first fly-eye lens divides the wide light beam of illumination into multiple fine light beams of illumination. The uniformity within the range of each fine light beam must be extremely large due to the uniformity of the wide light beam's individual illumination range. Since the entire system is a rotationally symmetrical system, the tiny unevenness of each fine light beam's edge is compensated by the superposition of symmetrical positions, further improving the uniformity of illumination and making effective and uniform use of the light energy within the entire aperture. The second fly-eye lens acts as a field lens, and the light spot coming out of it is focused on the sample through the condenser 105. Each small focused light spot at the sample is illuminated by the light emitted from all points of the light source. At the same time, the light beams emitted from each point on the light source overlap and intersect within the same field of view on the illumination spot. Therefore, all the small light spots converge together to obtain a uniform square light spot to illuminate the sample area, as shown in FIG. Figure 7 shown.

[0040] In some embodiments, the chip movement and macroscopic illumination module further comprises: a three-dimensional electric scanning platform 201, a macroscopic light source 202, and a microfluidic chip 70 holder; the three-dimensional electric scanning platform 201 moves in the XY direction to move the microfluidic chip 70 forward, backward, left, and right for scanning, and moves in the Z direction to perform microscopic focusing on the microfluidic chip 70; the macroscopic light source 202 illuminates the microfluidic chip 70 from the side; the microfluidic chip 70 holder is fixed on the three-dimensional electric scanning platform 201, and a placement area for the microfluidic chip 70 is provided on the microfluidic chip 70 holder; the macroscopic light source 202 is fixed on the microfluidic chip 70 holder and is distributed circumferentially along the microfluidic chip 70. Figure 2As shown, the microfluidic chip 70 support further includes: a support body 2031, a placement area, and a light board 2032; the support body 2031 is fixedly connected to the three-dimensional electric scanning platform 201; the placement area is opened on the support body 2031, and the microfluidic chip 70 is fixed in the placement area; the light board 2032 is fixedly connected to the support body 2031 and is distributed circumferentially along the placement area; the macro light source 202 is a plurality of white light LEDs, such as Figure 6 As shown, a plurality of white light LEDs are evenly fixed on the light board 2032 along the circumference of the placement area.

[0041] The chip movement and macro-illumination module scans and moves the chip, providing suitable brightfield illumination for macroscopic imaging. It includes a three-dimensional motorized scanning platform 201, which uses DC motor control to precisely move the microfluidic chip 70. Movement in the XY directions moves the chip forward, backward, left, and right for scanning, while movement in the Z direction allows for microscopic focusing. The platform's accuracy and resolution can be configured as needed. In this embodiment, the platform's minimum step size is 20nm, and the repeatability during movement is 0.5μm. A macro light source 202 provides light for macroscopic brightfield imaging. The macro light source 202 consists of a series of LEDs evenly distributed around the microfluidic chip 70, illuminating it from the side. A microfluidic chip 70 holder secures the macro light source 202 and provides a placement area for the chip. The biggest difficulty in macroscopic visual imaging positioning of the microfluidic chip 70 is that the microfluidic chip 70 is generally made of a fully transparent material, and to ensure the microscopic imaging effect, the material has a high light transmittance. When the chip is imaged with ordinary coaxial illumination or transmitted illumination, most of the light is transmitted or scattered, and the background will cause great interference, making it impossible to see the fine structure of the chip's internal channels. Even the appearance outline cannot be clearly distinguished from the background. Therefore, the present invention proposes an integrated microfluidic chip 70 bracket design based on side illumination, and its structure is as follows: Figure 2 As shown, it includes a bracket body 2031, a first light board 2032, a second light board 2032, a first light board cover 2033, and a second light board cover 2033. The bracket body 2031 is fastened to the three-dimensional electric scanning platform 201 by screws on one hand, and on the other hand, serves as a carrier of the chip and the macro side lighting source, and reserves space at the upper and lower structures to facilitate the mechanical gripper to clamp and place the chip, so as to achieve full automation; the first light board 2032 and the second light board 2032 are structured as shown in FIG. Figure 6 As shown, a number of white light LEDs are symmetrically distributed on it to evenly illuminate the microfluidic chip 70 from the side. The first light board cover 2033 and the second light board cover 2033 respectively isolate and protect the light board 2032 and decorate it beautifully. The integrated microfluidic chip 70 has a simple structure, small size, and is easy to use. It can meet the needs of automated operation and has strong versatility. Taking a certain microfluidic chip 70 sample as an example, the imaging effect is as follows Figure 8As shown, it can be seen that for the channels in the microfluidic chip 70, the images of the markers and the like are clear and have a high contrast with the background.

[0042] In some embodiments, the microfluidic chip 70 support further includes a light board cover 2033 that is disposed above the plurality of white light LEDs and is detachably fixedly connected to the light board 2032 .

[0043] In some embodiments, the light board 2032 is a split structure, including a first light board 2032 arranged on one side of the placement area, and a second light board 2032 arranged on the other side of the placement area; the light board cover 2033 includes a first light board cover 2033 fixedly connected to the first light board 2032, and a second light board cover 2033 fixedly connected to the second light board 2032.

[0044] In some embodiments, the microscopic imaging module includes: a microscope objective 301, a microscopic imaging lens assembly 302 for focusing the sample image onto a microscopic camera 303, and a microscopic camera 303 for receiving imaging signals. The microscopic imaging module is used to perform infinite microscopic imaging of the sample and provide visualization of the sample morphology and spatial position. It includes a microscope objective 301, which is used to perform microscopic magnification imaging, and is characterized by high magnification (≥50X), high NA (≥0.8), ultra-flat field, and apochromatism; a microscopic imaging lens assembly 302, which is used to focus the sample image onto the microscopic camera 303, and is characterized by wide-field imaging, apochromatism, and achieving diffraction limit over the entire field of view; and a microscopic camera 303, which receives imaging signals and can configure its resolution and field of view parameters as needed.

[0045] In some embodiments, the macro imaging module includes: a visual imaging lens assembly 401 that focuses the image of the microfluidic chip 70 onto a macro camera 402, and a macro camera 402 that receives the imaging signal of the microfluidic chip 70. The macro imaging module is used to perform macroscopic visual imaging of the entire chip for positioning. It includes a visual imaging lens assembly 401 that focuses the chip image onto the macro camera 402. Its characteristics are a large field of view that can cover the entire size of the chip and a long working distance that facilitates common optical path coupling with the micro illumination module; the macro camera 402 receives the chip imaging signal and is characterized by high resolution (20 million pixels and above) that can clearly image the microscopic channels of the microfluidic chip 70 and a large field of view that can clearly image the entire chip field of view.

[0046] In some embodiments, the optical path multiplexing module further includes: a condenser 105, a condenser switching component 501, and a beam splitter prism 502; the condenser switching component 501 fixes the condenser 105 and controls the condenser 105 to be located at a first position entering the optical path or a second position cutting out the optical path; when the condenser 105 is located at the first position, the condenser 105 is located above the microfluidic chip 70, the condenser 105 and the main light of the microscopic illumination module are coaxial, and the macroscopic imaging module does not work; when the condenser 105 is located at the second position, the macroscopic imaging module performs macroscopic imaging of the microfluidic chip 70, and the microscopic illumination module does not work; the beam splitter prism 502 is located above the first position, the light of the microscopic illumination module is transmitted through the beam splitter prism 502, and the light reflected back from the microfluidic chip 70 illuminated by the macroscopic light source 202 is reflected through the beam splitter prism 502 and enters the visual imaging lens assembly 401.

[0047] The function of the optical path multiplexing module is to organically combine the microscopic illumination module and the macroscopic imaging module for optical path multiplexing. This common optical path design greatly reduces the volume and complexity of the overall device, and can realize the functions of the two modules without moving the chip, thereby improving efficiency. The module includes a spectroscopic prism 502, which is used to transmit the light of the microscopic illumination module so that it can be converged into a uniform square light spot by the condenser 105 at the back to illuminate the sample area, and at the same time, the light reflected back from the chip illuminated by the macroscopic light source 202 is reflected into the visual imaging lens assembly 401, which can also be replaced by other spectroscopic elements such as a flat-plate spectrometer and a thin-film spectrometer; a condenser switching assembly 501, on which the condenser 105 is fixed by a flange. The assembly controls the condenser 105 to enter and cut out of the light path. When entering the light path, the condenser 105 and the main light of the microscopic illumination module are coaxial to form a microscopic illumination spot, and the macroscopic imaging module does not work. When cutting out of the light path, the macroscopic imaging module performs macroscopic imaging of the chip, and the microscopic illumination module does not work. Moreover, when the condenser 105 cuts out of the light path, the area above the microfluidic chip 70 becomes larger, which is convenient for the mechanical gripper to clamp and place the chip to achieve full automation. The condenser lens switching assembly 501 can be implemented by a linear motor module, an angle deflection module, a magnetic grating encoder servo, or other mechanisms.

[0048] In some embodiments, the imaging and positioning device of the microfluidic chip 70 further includes a computer control system 60, which is electrically connected to the microscopic illumination module, the microscopic imaging module, the chip movement and macroscopic illumination module, the macroscopic imaging module, and the optical path multiplexing module.

[0049] The computer control system 60 serves as the control and display center for the entire device. It issues control commands and processes through the host computer software. These commands specifically control the on / off and brightness levels of the microscopic and macroscopic light sources 102 and 202; the speed, direction, step size, and distance of the three-dimensional motorized scanning platform 201; the condenser switching assembly 501, which controls the entry and exit of the condenser 105 into the optical path; and the exposure time and white balance of the microscopic and macroscopic cameras 303 and 402. Furthermore, the system is responsible for displaying the sample and chip image plane, and implements methods for positioning the microfluidic chip 70 and measuring samples within the chip, built into the host computer software.

[0050] The method for performing imaging and positioning of the microfluidic chip 70 using the imaging and positioning device of the microfluidic chip 70 is as follows: Figure 4 As shown, the following steps are included:

[0051] Using the macro camera 402 to take a picture of the microfluidic chip 70 and perform distortion correction;

[0052] Identifying the landmarks or channels of the microfluidic chip 70 according to the landmark or channel identification model of the microfluidic chip 70;

[0053] The coordinate transformation is performed according to the calibration matrix to obtain the pixel coordinate set in the coordinates of the micro camera 303, which is the positioning coordinate set of the microfluidic chip 70;

[0054] The coordinates of any position of the microfluidic chip 70 can be obtained according to the positioning coordinate set, and the imaging positioning of the microfluidic chip 70 is completed;

[0055] like Figure 5 As shown, the landmark or channel recognition model of the microfluidic chip 70 is established by the following method:

[0056] Place the distortion correction plate, and use the macro camera 402 to take a photo of the distortion correction plate, and calculate the distortion correction matrix M0 of the macro camera 402 based on the photo;

[0057] After verifying that the distortion correction residual meets the requirements, a macro calibration plate is placed, and the macro camera 402 takes a photo of the macro calibration plate. The photo distortion is corrected according to M0, and then N-point calibration is performed to obtain the transformation matrix M1 between the coordinates of the macro camera 402 and the coordinates of the three-dimensional platform;

[0058] After verifying that the error between the measured value and the predicted value meets the requirements, a microscopic calibration plate is placed, and the microscopic camera 303 takes a photo of the calibration plate. N-point calibration is performed based on the photo to obtain the transformation matrix M2 between the three-dimensional platform coordinates and the microscopic camera 303 coordinates;

[0059] After verifying that the errors between the measured and predicted values ​​meet the requirements, the microfluidic chip 70 is placed and photos of the microfluidic chip 70 are taken using the macro camera 402. This batch of photos is used as a training set for chip recognition. The training set for chip recognition is corrected for distortion according to M0, and a landmark point or channel recognition model for the microfluidic chip 70 is established based on a deep learning algorithm.

[0060] The above imaging positioning method first requires calibration and modeling. Specifically, it includes: 1. Calibration of the coordinate position transformation relationship between the macro camera 402 and the micro camera 303 relative to the three-dimensional electric scanning platform 201; 2. Due to the large field of view of the macro camera 402, it is necessary to perform distortion correction calibration on the macro camera 402; 3. In order to identify the chip for easy positioning, it is necessary to establish a recognition model of the chip landmark points or channels based on the deep learning algorithm. The specific process is as follows Figure 5 The calibration and modeling work is performed after the device is assembled and adjusted, and only needs to be performed once. It is directly built into the host computer software on the computer control system 60 and does not need to be updated as the microfluidic chip 70 changes.

[0061] After calibration and model building, the microfluidic chip 70 can be positioned by visual imaging through the above device. It includes: 1. The macro camera 402 takes a photo of the chip and performs distortion correction; 2. The chip is identified by landmark points or channels according to the model; 3. The coordinate transformation is performed according to the calibration matrix to obtain the pixel coordinate set in the micro camera 303 coordinate, which is the positioning coordinate set of the chip; 4. The coordinates of any position of the chip can be obtained based on the positioning coordinate set, so as to facilitate the imaging, identification, detection, scanning and other tasks of the sample in the chip. The specific process is as follows Figure 4 shown.

[0062] The above-mentioned imaging positioning method and device for the microfluidic chip 70 can completely replace the traditional positioning solution based on a chip fixture. Its advantages are specifically reflected in:

[0063] 1. High versatility. It does not require separate design for microfluidic chips 70 with different structures. First, it can be applied to microfluidic chips 70 with different internal structures such as liquid circuits and gas circuits. Second, as long as the external dimensions of the microfluidic chip 70 within the detection field of view of the macro imaging module are met, it can be directly detected. It has strong versatility and not only avoids the shortcomings of high design and debugging precision of the fixture, but also reduces the chip precision requirements, thereby reducing costs and improving detection efficiency.

[0064] 2. Improved automation: This device solves the problem that chip fixtures cannot be automated due to positioning and clamping. Through chip bracket structure design, common optical path coupling and other designs, it reserves space for automated equipment operation, and can achieve completely unattended automated positioning and detection.

[0065] 3. Fast and high-precision. This device is based on visual imaging positioning, avoiding the chip fixture installation process. Chip positioning can be completed in seconds, increasing efficiency by more than ten times. This device is based on a high-resolution macro camera 402, combined with deep learning algorithm modeling and recognition positioning. The positioning accuracy can reach 1μm, which is significantly improved compared to the mechanical positioning error of 10-100μm.

[0066] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0067] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A microfluidic chip imaging and positioning device, characterized in that: include A microscopic lighting module, the microscopic lighting module includes a fly-eye lens assembly, the fly-eye lens assembly includes two fly-eye lenses, the optical axes of the two fly-eye lenses are parallel to each other, and the focus of each lens array element in one fly-eye lens coincides with the center of the lens array element at the corresponding position of the other fly-eye lens; Microscopic imaging module, used for infinite microscopic imaging of samples, providing visualization of sample morphology and spatial position; The chip movement and macro-illumination module scans and moves the microfluidic chip and provides bright field illumination for macro-imaging; Macro imaging module, which performs macroscopic visual imaging of the entire chip for positioning; and an optical path multiplexing module that combines the microscopic illumination module with the macroscopic imaging module.

2. The microfluidic chip imaging and positioning device according to claim 1, characterized in that: The chip movement and macro illumination module further includes: The three-dimensional motorized scanning platform moves in the XY direction to move the microfluidic chip forward, backward, left, and right for scanning, and moves in the Z direction to perform microscopic focusing of the microfluidic chip; Macro light source, which provides side illumination for the microfluidic chip; The microfluidic chip holder is fixed on the three-dimensional electric scanning platform. A placement area for the microfluidic chip is provided on the microfluidic chip holder. The macro light source is fixed on the microfluidic chip holder and distributed along the circumference of the microfluidic chip.

3. The microfluidic chip imaging and positioning device according to claim 2, characterized in that: The microfluidic chip support further comprises: The bracket body is fixedly connected to the three-dimensional electric scanning platform; A placement area is provided on the support body, and the microfluidic chip is fixed in the placement area; The light panels are fixedly connected to the bracket body and are distributed circumferentially along the placement area; The macro light source is a plurality of white light LEDs, and the plurality of white light LEDs are evenly fixed on the light board along the circumference of the placement area.

4. The microfluidic chip imaging and positioning device according to claim 3, characterized in that: The microfluidic chip support further comprises a light board cover which is arranged above the plurality of white light LEDs and is detachably fixedly connected to the light board.

5. The microfluidic chip imaging and positioning device according to claim 4, characterized in that: The light board is a split structure, including a first light board arranged on one side of the placement area, and a second light board arranged on the other side of the placement area; the light board cover includes a first light board cover fixedly connected to the first light board, and a second light board cover fixedly connected to the second light board.

6. The microfluidic chip imaging and positioning device according to claim 1, characterized in that: The microscopic lighting module further includes: a microscopic light source, a collimating mirror for collimating the divergent light of the microscopic light source into parallel light, a reflecting mirror for making a 90° turn on the light path to compress the volume of the light path, and a condensing mirror.

7. The microfluidic chip imaging and positioning device according to claim 1, characterized in that: The microscopic imaging module includes: a microscope objective lens, a microscopic imaging lens assembly that focuses the sample image onto the microscopic camera, and a microscopic camera that receives imaging signals.

8. The microfluidic chip imaging and positioning device according to claim 1, characterized in that: The macro imaging module includes: a visual imaging lens assembly that focuses the image of the microfluidic chip onto a macro camera, and a macro camera that receives the imaging signal of the microfluidic chip.

9. The microfluidic chip imaging and positioning device according to claim 6, characterized in that: The optical multiplexing module further includes: A condenser switching assembly fixes the condenser and controls the condenser to be located at a first position for entering the light path or a second position for cutting out the light path; when the condenser is in the first position, the condenser is located above the microfluidic chip, the principal light of the condenser and the microscopic illumination module are coaxial, and the macroscopic imaging module does not operate; when the condenser is in the second position, the macroscopic imaging module performs macroscopic imaging of the microfluidic chip, and the microscopic illumination module does not operate; The beam splitter prism is located above the first position. The light from the microscopic illumination module is transmitted through the beam splitter prism, and the light reflected back from the microfluidic chip illuminated by the macroscopic light source is reflected through the beam splitter prism and enters the visual imaging lens assembly.

10. The microfluidic chip imaging and positioning device according to claim 9, characterized in that: The microfluidic chip imaging and positioning device also includes a computer control system, which is electrically connected to the microscopic illumination module, the microscopic imaging module, the chip movement and macroscopic illumination module, the macroscopic imaging module, and the optical path multiplexing module.

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