Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Fig. 3 is a flowchart illustrating a method for modifying a surface of a microfluidic chip according to an embodiment of the present invention. As shown in fig. 1, the method comprises the steps of:
step 310: and identifying a micro-channel of the micro-fluidic chip, and taking a plurality of points on the micro-channel as point liquid positions.
This step may be performed by a recognition device, and specifically, the recognition device may include a vision camera and a controller, and the vision camera takes a photograph of the microfluidic chip including the microchannel, and then the controller performs a subsequent recognition and calculation process. For example, the controller may recognize the microfluidic chip in the photograph by, for example, image depth learning, obtain various data, such as size data, of the microfluidic channel on the microfluidic chip, and then select a plurality of points on the microfluidic channel as the point-liquid positions according to the size data, where the plurality of points are a certain position or positions on the microfluidic channel.
Step 320: and (4) dispensing the modified liquid at the liquid dispensing position until the modified liquid covers the surface of the micro-channel.
The step can be realized by a liquid dispensing needle, and the liquid dispensing needle can be controlled by a controller to dispense the modified liquid which just covers the surface of the micro-channel in a mode of a certain volume or a certain time and the like.
The method provided by the embodiment firstly identifies the micro-channel of the micro-fluidic chip by taking a picture, takes a plurality of points on the micro-channel as point-liquid positions, and makes certain modified liquid point out at the point-liquid positions, so that the modified liquid can automatically infiltrate the surface of the whole micro-channel to achieve the purpose of modification. According to the method, only one or a few liquid point positions are selected to fill liquid, the processes of calculating a motion track and carrying out high-frequency liquid according to the calculated motion track are omitted, the precision requirements of micro-channel surface modification on an algorithm and equipment can be effectively reduced, the process is simplified, the production efficiency is improved, and the problems of high equipment precision requirement and high manufacturing cost of micro-fluidic chip surface modification are effectively solved. In addition, the method wets the flow channel by means of free flow of liquid, so that the problem of track deviation caused by a spraying mode is avoided, and the yield is improved.
In an embodiment of the invention, the modifying liquid is a liquid that changes the hydrophilicity of the micro flow channel.
It can be understood by those skilled in the art that the hydrophilic modified liquid has a strong fluidity, i.e., a characteristic of small fluid shear force, and when the method provided by the embodiment of the present invention is used to modify the surface of the micro flow channel, the hydrophilicity of the modified liquid can further promote the free flow of the modified liquid, so that the liquid can infiltrate the whole micro flow channel more quickly and sufficiently, thereby further improving the production efficiency and the yield.
In one embodiment, the identifying the micro-channel on the micro-fluidic chip and taking a plurality of points on the micro-channel as point liquid positions specifically comprises: taking a picture including the micro flow channel; and identifying the micro-channel from the picture, selecting a plurality of points on the micro-channel as point-liquid positions, and calculating the position coordinates of the point-liquid positions. At this moment, the modifying liquid is dispensed at the liquid dispensing position until the modifying liquid covers the surface of the micro-channel, which specifically comprises the following steps: and (4) pointing out the modified liquid to the micro-channel at the position coordinate until the modified liquid covers the surface of the micro-channel.
Specifically, the position coordinates of the point-liquid position may be coordinates located in a three-dimensional space, i.e., coordinates on an XYZ triaxial system. Firstly, a photo including a micro-channel is shot by a visual camera, the micro-channel in the image is identified according to an image identification technology, then one point or a few points on the channel are selected as a point liquid position according to data such as the length, the relative position and the like of the micro-channel, the position information is converted into a coordinate which can be identified by a coordinate system in equipment, and finally, modified liquid is spotted on the micro-channel at the position coordinate through a point liquid needle until the surface of the micro-channel is covered by the modified liquid.
In a preferred embodiment, a point on the microchannel may be selected as the point liquid position, and the coordinate on the horizontal plane may be at or near the midpoint of the microchannel, and the distance from the microchannel in the vertical direction (i.e., the Z-axis) may be smaller than the droplet diameter of the modifying liquid.
That is, by dispensing the liquid to the single point at the middle point or the position close to the middle point of the micro flow channel, the liquid can automatically flow freely and evenly towards the two terminals of the micro flow channel, so that the complexity of calculation can be greatly reduced, the efficiency is improved, and the process of dispensing the liquid at multiple points is further saved. Particularly, when a modifying liquid for changing the hydrophilicity of the micro flow channel is used, the strong fluidity of the modifying liquid can further ensure the smooth operation of the embodiment.
In addition, the distance between the point liquid level and the micro-channel in the vertical direction is smaller than the diameter of the liquid drop of the modified liquid, namely, the distance between the point liquid needle head and the micro-channel is smaller than the diameter of the liquid drop of the modified liquid, so that certain pressure can be provided in the point liquid process, and the waste of the modified liquid is avoided.
In an embodiment of the invention, before dispensing the modified liquid into the micro flow channel, the method further comprises: and driving a liquid dispensing needle for dispensing liquid to move to the position coordinate. This action may be performed by a mobile platform, in particular, the mobile platform may be a multi-axis mobile platform corresponding to a coordinate system, such as an XYZ tri-axis mobile platform.
The XYZ three-axis moving platform can be used for moving a vision camera and/or a point fluid needle in a three-dimensional space. Where the XY axis can be used for movement in the horizontal direction and the Z axis is movement in the vertical direction. For a visual camera, the moving platform can drive the visual camera to move to a micro-channel in the micro-fluidic chip which can be aligned to a target. For the point liquid needle head, the moving platform can be used for driving the point liquid needle head to move to the coordinate position of the preset point liquid position, specifically, the moving platform can drive the point liquid needle head to move in the XY axis direction according to the coordinate of the point liquid position in the horizontal plane, and then drive the point liquid needle head to move in the Z axis direction according to the coordinate of the point liquid position in the vertical direction.
The controller can send the coordinate information to the mobile platform after calculating the position coordinates of the point liquid position, the mobile platform positions the corresponding point liquid position according to the coordinate information, and then drives the point liquid needle head to move to the point liquid position for point liquid. In addition, it should be noted that the position coordinates of the spotting fluid position may be the position coordinates of the spotting fluid that is essential for the spotting fluid needle, or may be the relative position between the mobile platform and the micro channel in the micro fluidic chip, so that when the spotting fluid needle is replaced, the compatibility requirement of the controller for different types of spotting fluid needles can be realized by inputting the parameters of the corresponding spotting fluid needle in the calculation for compensation.
In an embodiment of the invention, before dispensing the modified liquid into the micro flow channel, the method further comprises: acquiring a 3D model of the micro-channel, and calculating the volume of modified liquid required for covering the surface of the micro-channel according to the 3D model; and controlling the liquid dispensing needle to dispense the modified liquid with the volume.
The 3D model may be obtained from a manufacturer, or may be drawn by software such as Solidworks, and then the volume of the modified liquid required to cover the surface of the micro flow channel may be calculated according to the obtained data of the 3D model, for example, the volume of the modified liquid required to cover a layer of water film may be calculated, or the volume of the modified liquid required to cover the entire micro flow channel may be calculated. The calculating step may be performed by the controller, and after calculating the volume of the modified liquid, the controller may output corresponding data to a micro pump connected to the dispensing tip, and the micro pump controls the dispensing of a certain amount of the modified liquid, and the dispensing tip dispenses the liquid at the dispensing position to cover the entire surface of the micro flow channel.
The data output by the controller to the micro pump may be volume data of the modified liquid required to just cover the surface of the micro flow channel, or time data corresponding to the volume data, which is not specifically limited in the present invention.
In an embodiment of the present invention, the modified liquid that is used for controlling the liquid dispensing needle to dispense the volume is specifically: and controlling the liquid dispensing needle to continuously dispense the modified liquid at a uniform speed at the liquid dispensing position and enabling the total dispensed liquid to meet the calculated volume. The method can be realized by a precise micro pump, so that the modified liquid discharged from the liquid dispensing needle maintains fixed pressure and the stability and the high efficiency of the surface modification process are ensured.
Fig. 4 is a flowchart illustrating a method for modifying a surface of a microfluidic chip according to an exemplary embodiment of the present invention, where the following steps in the exemplary embodiment may be controlled and executed by a controller or other computer-based device, and specifically include:
step 410: and obtaining a 3D model of a micro-channel in the micro-fluidic chip.
The 3D model may be obtained from a manufacturer's channel, or may be drawn by mapping software, as long as it can extract various data of the micro channel from the map for subsequent calculations.
Step 420: and calculating the volume of the modified liquid required for covering the surface of the micro-channel according to the 3D model of the micro-channel.
Specifically, the volume of the required modified liquid is calculated by extracting data (such as depth, length and other information) of the micro flow channel according to the model.
Step 430: and controlling the mobile platform to move so as to drive the vision camera to move and shoot the photo comprising the micro-channel.
And controlling the mobile platform to move so that the visual camera can shoot a complete micro-channel photo for subsequent use in calculating the coordinates of the point liquid position on the micro-channel.
Step 440: and identifying the micro-channel, and selecting a point on the micro-channel as a point liquid position.
Specifically, the midpoint position of the micro flow channel can be calculated according to information such as length and relative position, then a point with a distance in the vertical direction from the midpoint position smaller than the droplet diameter of the modified liquid is selected above the midpoint position as the point liquid position, and the position information is converted into a coordinate which can be recognized by a coordinate system in the device and is used as the position coordinate of the point and sent to the mobile platform.
Step 450: and controlling the moving platform to move in the XY axis direction so as to drive the point liquid needle head to move to the point liquid position at the coordinate of the XY axis.
According to the position coordinates received by the moving platform, the moving platform is controlled to move in the XY axis direction, and after data compensation, for example, the point liquid needle head can move to the point liquid position at the coordinates of the XY axis.
Step 460: and controlling the moving platform to move in the Z-axis direction so as to drive the point liquid needle head to move downwards in the Z-axis direction to the coordinate position of the point liquid position in the Z axis.
And controlling the mobile platform to move in the Z-axis direction according to the position coordinates received by the mobile platform, and enabling the point liquid needle head to move to the coordinate position of the point liquid position on the Z axis after data compensation, wherein the Z axis position is the position which is away from the middle point of the micro flow channel and is smaller than the diameter of the liquid drop of the modified liquid.
Step 470: the precision micro-pump is controlled to continuously and uniformly dispense the volume of modifying liquid calculated in step 420.
After the dispensing needle is in place, the controller may control the precision micro-pump to continuously and uniformly dispense the modified liquid, and the dispensing time or the volume of the modified liquid may be adjusted according to the data calculated in step 420.
Step 480: and controlling the precision micro pump to be closed.
And after the liquid adding process is finished, closing the precision micro pump to stop adding the liquid adding needle head to continuously add the modified liquid to the micro flow channel.
Step 490: and controlling the moving platform to move in the Z-axis direction.
The moving platform is controlled to move away from the spotting position in the Z-axis to a safe position and then can continue to move in the XY-axis to return to the initial position.
It should be noted that, this exemplary embodiment is only an example of selecting a midpoint of the micro flow channel, and actually, a point on the micro flow channel near the midpoint may also be selected as the point liquid position, and a few points on the micro flow channel may also be selected as the point liquid positions, which is not limited in this respect.
The steps in the exemplary embodiment can be realized by means of automation without manual intervention, so that the production efficiency is effectively improved, and the production cost and unnecessary waste of human resources are reduced.
The embodiment of the invention also provides equipment for surface modification of the microfluidic chip, which comprises an identification device and a liquid dispensing device. The identification device is used for identifying a micro-channel of the micro-fluidic chip and taking a plurality of points on the micro-channel as point liquid positions. The liquid dispensing device is used for dispensing the modified liquid at the liquid dispensing position until the modified liquid covers the surface of the micro-channel.
In one embodiment, as shown in fig. 5, the recognition device may specifically include a visual camera 510 and a controller 520. The vision camera 510 is used for taking a photo of the microfluidic chip including the microchannel, and may be an industrial camera such as a high-speed camera, a high-definition camera, and the like, and a person skilled in the art may select an appropriate camera type according to needs, and the invention is not particularly limited to the vision camera 510. In this embodiment, because the requirement on the visual camera 510 is low, the visual camera 510 with low accuracy and low cost can be used as much as possible on the basis of ensuring that the shot pictures of the micro-channels in the micro-fluidic chip are clear and recognizable, and the effects of saving cost and reducing technical difficulty can be achieved.
The controller 520 is configured to identify a micro channel from the photo, select a plurality of points on the micro channel as point-liquid positions, and calculate position coordinates of the point-liquid positions. The controller 520 may identify the microfluidic chip in the photo by, for example, deep image learning, to obtain various data, such as size data, of the microfluidic channel on the microfluidic chip, and select a plurality of points on the microfluidic channel as the point-liquid positions according to the size data, where the plurality of points are a certain position or positions on the microfluidic channel.
It should be noted that the position of the controller 520 in fig. 5 is only an example, and the controller 520 may be integrated in the microfluidic surface modification device or an external device, such as a computer, and the present invention is not limited thereto.
The spotting device may include a spotting needle 530, and the spotting needle 530 may be controlled by the controller 520 to spot the modified liquid that just covers the surface of the micro channel to the micro channel at the position coordinates of the spotting position in a certain volume or a certain time.
The device provided by this embodiment first takes a picture by the vision camera 510, then the controller 520 identifies the micro flow channel in the picture, and takes a plurality of points on the micro flow channel as the point liquid positions, and finally the point liquid device makes a certain amount of modified liquid at the point liquid positions, so that the modified liquid can automatically infiltrate into the surface of the whole micro flow channel to achieve the purpose of modification. The device only needs to select one or a few of liquid point positions to fill liquid, the processes of calculating the motion track and carrying out high-frequency liquid according to the calculated motion track are omitted, the complexity of calculation can be greatly reduced, the precision requirements of micro-channel surface modification on an algorithm and the device are effectively reduced, the working procedures are simplified, the production efficiency is improved, and the problems of high precision requirements and high manufacturing cost of the device for micro-fluidic chip surface modification are effectively solved. In addition, the device can be used for modifying the surface of the micro-channel only by depending on the free flow of liquid to infiltrate the channel, so that the problem of track deviation caused by a spraying mode is avoided, and the yield is improved.
In an embodiment of the invention, the modifying liquid is a liquid that changes the hydrophilicity of the micro flow channel.
It can be understood by those skilled in the art that the hydrophilic modified liquid has a strong fluidity, i.e., the fluid shear force is small, and when the device provided by the embodiment of the present invention is used to modify the surface of the micro flow channel, the hydrophilicity of the modified liquid can further promote the free flow of the modified liquid, so that the liquid can infiltrate the whole micro flow channel more quickly and sufficiently, thereby further improving the production efficiency and the yield.
In one embodiment of the present invention, as shown in fig. 5, the apparatus further comprises a moving platform 540 for moving the spotting needle 530 to the position coordinates of the spotting position.
The moving platform 540 may be a multi-axis moving platform corresponding to an in-device coordinate system, such as an XYZ tri-axis moving platform. The XYZ three-axis movement platform 540 can be used for moving the spotting needle 530 and carrying the vision camera 510 to move in a three-dimensional space. Where the XY axis can be used for movement in the horizontal direction and the Z axis is movement in the vertical direction. For the visual camera 510, the moving platform 540 can move the visual camera 510 to a micro channel in the micro fluidic chip that can be aligned to a target. For the liquid dispensing needle 530, the moving platform 540 may be used to drive the liquid dispensing needle 530 to move to the coordinates of the preset liquid dispensing position, specifically, the moving platform 540 may drive the liquid dispensing needle 530 to move in the XY axis direction according to the coordinates of the liquid dispensing position in the horizontal plane, and drive the liquid dispensing needle 530 to move in the Z axis direction according to the coordinates of the liquid dispensing position in the vertical direction.
In this embodiment, after the controller 520 selects the spotting position and calculates the position coordinates of the spotting position, the coordinate information may be sent to the moving platform 540, the moving platform 540 positions the corresponding spotting position according to the coordinate information, and then drives the spotting needle 530 to move to the spotting position for spotting. In addition, it should be noted that the position coordinates of the spotting position may be the position coordinates of the spotting needle 530 for the spotting fluid, or may be the relative positions of the mobile platform 540 and the micro channel in the microfluidic chip, so that when the spotting needle 530 is replaced, the compatibility requirement of the controller 520 for different types of spotting needles 530 can be realized by inputting the corresponding parameters of the spotting needle 530 for compensation in the calculation.
In a preferred embodiment, as shown in fig. 6, the controller 520 selects a point on the microchannel 1 as the point level 2, and the coordinate on the horizontal plane may be located at the midpoint of the microchannel 1 or a position close to the midpoint, and the distance from the microchannel 1 in the vertical direction (i.e., Z axis) may be smaller than the droplet diameter of the modifying liquid.
That is, by dispensing the liquid to the single point at the middle point or the position close to the middle point of the micro flow channel 1, the liquid can automatically flow freely and uniformly to the two terminals of the micro flow channel 1, so that the complexity of calculation can be greatly reduced, the efficiency can be improved, and the process of dispensing the liquid to multiple points can be further saved. Particularly, when a modifying liquid for changing the hydrophilicity of the micro flow channel is used, the strong fluidity of the modifying liquid can further ensure the smooth operation of the embodiment.
In addition, the distance between the spotting position 2 and the micro flow channel 1 in the vertical direction is smaller than the droplet diameter of the modified liquid, that is, the distance between the spotting needle 530 and the micro flow channel 1 is smaller than the droplet diameter of the modified liquid, so that a certain pressure can be provided in the spotting process and the waste of the modified liquid can be avoided.
In one embodiment, the controller 520 is further configured to obtain a 3D model of the micro flow channel 1, and calculate the volume of the modified liquid required to cover the surface of the micro flow channel 1 according to the 3D model. The apparatus further includes a micro pump 550 connected to the spotting needle 530, and after the controller 520 calculates the volume of the modified liquid, it outputs corresponding data to the micro pump 550, and the amount of the modified liquid is spotted by the control of the micro pump 550, and the spotting needle 530 spots the liquid at the spotting position 2 to cover the entire surface of the micro channel under the control of the micro pump 550.
The data outputted from the controller 520 to the micro pump 550 may be volume data of the modified liquid required to cover the surface of the micro flow channel 1, or may be time data corresponding to the volume data, which is not limited in the present invention.
In this embodiment, the controller 520 automatically calculates the volume of the modification liquid required to cover the surface of the micro flow channel according to the acquired 3D model of the micro flow channel, so that the full automation from the acquisition of the 3D model to the completion of the surface modification operation of the micro flow channel in the micro flow control chip is realized, the production efficiency is greatly improved, and the unnecessary labor is reduced.
In a preferred embodiment of the present invention, the micro-pump 550 is a precision micro-pump for continuously tapping the modification liquid from the tapping needle 530 and maintaining the flow rate of the tapped modification liquid uniform. In particular, the precision micropump may be a precision micro syringe pump, such as a continuous precision micro syringe pump, for continuously dispensing the modifying liquid and keeping the dispensed flow rate uniform, so that the dispensed modifying liquid maintains a fixed pressure and guarantees the smoothness and efficiency of the surface modification process.
Those of ordinary skill in the art will appreciate that the various illustrative elements and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware or combinations of computer software and electronic hardware. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the implementation. Skilled artisans may implement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the present invention.
It is clear to those skilled in the art that, for convenience and brevity of description, the specific working processes of the above-described apparatuses, devices and units may refer to the corresponding processes in the foregoing method embodiments, and are not described herein again.
In the several embodiments provided in the present application, it should be understood that the disclosed apparatus, device and method may be implemented in other ways. For example, the above-described apparatus embodiments are merely illustrative, and for example, a division of a unit is merely a logical division, and an actual implementation may have another division, for example, a plurality of units or components may be combined or integrated into another system, or some features may be omitted, or not executed. In addition, the shown or discussed mutual coupling or direct coupling or communication connection may be an indirect coupling or communication connection through some interfaces, devices or units, and may be in an electrical, mechanical or other form.
Units described as separate parts may or may not be physically separate, and parts displayed as units may or may not be physical units, may be located in one place, or may be distributed on a plurality of network units. Some or all of the units can be selected according to actual needs to achieve the purpose of the solution of the embodiment.
In addition, functional units in the embodiments of the present invention may be integrated into one processing unit, or each unit may exist alone physically, or two or more units are integrated into one unit.
The functions, if implemented in the form of software functional units and sold or used as a stand-alone product, may be stored in a computer readable storage medium. Based on such understanding, the technical solution of the present invention may be embodied in the form of a software product, which is stored in a storage medium and includes instructions for causing a computer device (which may be a personal computer, a server, or a network device) to execute all or part of the steps of the method according to the embodiments of the present invention. And the aforementioned storage medium includes: various media capable of storing program check codes, such as a U disk, a removable hard disk, a Read-Only Memory (ROM), a Random Access Memory (RAM), a magnetic disk or an optical disk.
The above description is only for the specific embodiments of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention, and the changes or substitutions should be covered within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.