A micro-channel type bio-printing device suitable for printing in a liquid environment

Abstract

The application discloses a micro-channel type biological printing device suitable for printing in a liquid environment and relates to the technical field of biological printing.The device comprises a magnetic-assisted precipitation component, and the magnetic-assisted precipitation component comprises a magnetic-assisted precipitation plate.The upper surface of the magnetic-assisted precipitation plate is provided with a containing groove, the containing groove is provided with a micro-fiber collecting groove, and the micro-fiber collecting groove is provided with a plurality of long-strip-shaped magnets.The long-strip-shaped magnets are combined into an Archimedes curve-shaped magnetic-assisted precipitation device.The application can effectively guide the magnetic micro-fiber to form a complex assembly structure in water.The combination mode can make the magnetic-assisted precipitation device be expanded to any shape in the future.A micro-channel printing nozzle, a magnetic-assisted precipitation device, a rotating and translating table and a lateral camera are coupled to form an automatic micro-channel type printing device.The mechanical strength of the printed micro-fiber does not need to be considered, and the printing assembly can be automatically performed according to the shape of the magnetic-assisted precipitation device in the liquid environment.

Description

Technical Field

[0001] This invention relates to the field of bioprinting technology, and in particular to a microfluidic bioprinting device suitable for printing in a liquid environment. Background Technology

[0002] Bioprinting mixes cells, growth factors, and biomaterials to form bio-ink. Using techniques similar to 3D printing, the bio-ink is then stacked layer by layer in an orderly 3D manner to create structures resembling biological tissue. Printed animal cells can be used as food, or human tissue can be printed for tissue transplantation, wound healing, drug testing, and more. Extrusion-based 3D bioprinting is the most mature bioprinting method. It uses a nozzle to extrude bio-ink, forming microfibers (hereinafter referred to as microfibers) that encapsulate cells. The nozzle then moves in three-dimensional space, causing the extruded microfibers to settle in pre-defined locations, forming a 3D printed structure.

[0003] The extruded microfibers are printed to predetermined positions through nozzle movement and gravity deposition, maintaining the shape of the printed structure under the combined action of gravity and adhesion. Therefore, extrusion-based bioprinting is typically performed in air. However, while gravity and adhesion can maintain the printed structure, the microfiber material itself needs to possess a certain structural strength to ensure the printed structure does not deform or collapse. Therefore, extrusion-based bioprinting currently struggles to print materials with very soft mechanical strength. Many biomaterials highly suitable for cell growth, such as decellularized ECM, collagen, and low-concentration gelma, have relatively soft mechanical strength. Printing in liquids provides a low-gravity, low-adhesion printing environment; however, the absence of gravity and adhesion causes the printed microfibers to float in the liquid, resulting in loose and deformed prints. Therefore, finding a way to form specific geometries from extruded, relatively soft microfibers in a liquid environment can solve the current challenge of achieving low-mechanical-strength 3D printing in extrusion-based 3D bioprinting. Summary of the Invention

[0004] To address the above technical problems, this invention provides a microfluidic bioprinting device suitable for printing in a liquid environment. It can automatically print and assemble the microfibers in a liquid environment according to the shape of a magnetically assisted precipitation device without considering the mechanical strength of the printed microfibers.

[0005] To achieve the above objectives, the present invention provides the following solution:

[0006] This invention provides a microfluidic bioprinting device suitable for printing in a liquid environment, including a magnetically assisted precipitation component. The magnetically assisted precipitation component includes a magnetically assisted precipitation plate, the upper surface of which is provided with a receiving groove. A microfiber collection groove is provided in the receiving groove, and multiple elongated magnets are provided in the microfiber collection groove.

[0007] Optionally, a ring is provided at each of the four corners of a virtual rectangle on the magnetically assisted precipitation plate, and the center of the ring corresponds to the top corner of the virtual rectangle.

[0008] Optionally, the ratio of the inner radius to the outer radius of the four rings on the magnetically assisted precipitation plate is different for each other.

[0009] Optionally, the area of ​​the virtual rectangular frame overlaps with the area of ​​the microfiber collection groove by more than 85%.

[0010] Optionally, the ring is black.

[0011] Optionally, within the microfiber collection groove, the polarities of two adjacent elongated magnets are opposite.

[0012] Optionally, the magnetically assisted precipitation component is disposed on a rotary table, the rotary table is disposed on the sliding block of the X-axis translation stage, and the X-axis translation stage is disposed on the sliding block of the Y-axis translation stage; a microchannel type printhead is disposed above the magnetically assisted precipitation component, and the microchannel type printhead is connected to the Z-axis translation stage through a clamping component.

[0013] Optionally, the Y-axis translation stage and the Z-axis translation stage are mounted on the same base.

[0014] Optionally, the microfluidic printhead includes an inner layer needle, a middle layer needle, and an outer layer needle arranged coaxially; the feed ends of the inner layer needle, the middle layer needle, and the outer layer needle are respectively connected to an injection pump through pipelines.

[0015] Optionally, the outer needle tip is provided with a print head at its end, and the end of the print head is set as a pointed tip.

[0016] The present invention achieves the following technical effects compared to the prior art:

[0017] 1. By using multiple elongated magnets arranged in an Archimedes-shaped magnetically assisted sedimentation device, it is possible to effectively guide magnetic microfibers to form complex assemblies in water. This combination method allows the magnetically assisted sedimentation device to be expanded to any shape in the future.

[0018] 2. An automated microfluidic printing device is formed by a microfluidic printhead, coupled with a magnetically assisted precipitation device, a coupled rotating and translational stage, and a coupled lateral camera. It can automatically assemble and print microfibers according to the shape of the magnetically assisted precipitation device in a liquid environment without considering the mechanical strength of the printed microfibers. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is a schematic diagram of the structure of the microfluidic bioprinting device of the present invention, which is applicable to printing in a liquid environment;

[0021] Figure 2 This is a schematic diagram of the magnetically assisted precipitation component in a microfluidic bioprinting device applicable to printing in a liquid environment according to the present invention;

[0022] Figure 3 This is a schematic diagram of the elongated magnet in the microfluidic bioprinting device of the present invention, which is applicable to printing in a liquid environment;

[0023] Figure 4 This is a partially enlarged structural diagram of the microfluidic bioprinting device of the present invention, applicable to printing in a liquid environment;

[0024] Figure 5 This is a schematic diagram of the clamping component in the microfluidic bioprinting device of the present invention, which is applicable to printing in a liquid environment;

[0025] Figure 6 This is a schematic diagram of the printhead structure in the microfluidic bioprinting device of the present invention, which is applicable to printing in a liquid environment.

[0026] Explanation of reference numerals in the attached diagram: 1. X-axis translation stage; 2. Column; 3. Rotary stage; 4. UV light source; 5. Z-axis translation stage; 6. Side camera; 7. Y-axis translation stage; 8. Fixed plate; 9. Clamping component; 10. Microchannel type printhead; 11. Magnetic-assisted sedimentation component; 12. Circular marker A; 13. Circular marker B; 14. Microfiber collection groove; 15. Magnetic-assisted sedimentation plate; 16. Circular marker C; 17. Circular marker D; 18. Long bar magnet; 19. Fastener; 20. Fixing groove; 21. Printhead. Detailed Implementation

[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] like Figures 1 to 6 As shown, this embodiment provides a microfluidic bioprinting device suitable for printing in a liquid environment, including a magnetically assisted precipitation component 11. The magnetically assisted precipitation component 11 includes a magnetically assisted precipitation plate 15. A receiving groove is provided on the upper surface of the magnetically assisted precipitation plate 15. A microfiber collection groove 14 is provided in the receiving groove. A plurality of elongated magnets 18 are provided in the microfiber collection groove 14.

[0029] In this specific embodiment, multiple elongated magnets 18 are assembled to form a specific curved shape. Each elongated magnet 18 is made of neodymium iron boron material, and its radial cross-section is rectangular, with a width of 0.5-2 mm and a height of 1-2 mm. The axial cross-section of the elongated magnet 18 is a wide arc shape, the width of which is consistent with the width of the radial rectangular cross-section, and its curvature value is determined according to the actual design. The elongated magnets 18 are assembled to form a curve with a specific shape, and adjacent magnets along the curve direction have opposite polarities. The distance between adjacent edges of two magnets on two adjacent curves is less than 3 mm. In this specific embodiment, 41 segmented elongated magnets 18 are assembled into a magnetically assisted precipitation device with a wide Archimedean curve shape.

[0030] The magnetically assisted precipitation component 11 is made of a transparent acrylic sheet. The bottom of the microfiber collection tank 14 is machined into a groove with the same Archimedean curve shape as the assembled segmented elongated magnet 18. The groove has a rectangular cross-section, its width being 0.1-0.3 mm larger than the width of the rectangular cross-section of the elongated magnet 18, its height being 1-2 mm higher than the height of the rectangular cross-section, and the depth of the receiving groove is 2-3 mm. The assembled segmented elongated magnet 18 is placed in the microfiber collection tank 14. The bottom edge of the microfiber collection tank 14 is located 1-2 mm from the outer contour of the receiving groove. The depth of the microfiber collection tank 14 is 4-5 mm. Around the outside of the collection tank, there are four circular marker points, namely, circular marker point A12, circular marker point B13, circular marker point C16, and circular marker point D17, which are dyed black. The centers of the four circles are connected by dashed lines to form a rectangular frame, with the four centers located at the four corners of the rectangular frame. The area of ​​the formed rectangular frame overlaps with the area of ​​the collection tank by more than 85%. The radius ratios (inner circle radius / outer circle radius) of the four circular marker points are different. In this specific embodiment, the radius ratio of ring A is 0.25, the radius ratio of ring B is 0.4, the radius ratio of ring C is 0.7, and the radius ratio of ring D is 0.7. The inner circle radius of the four concentric circles is 1mm.

[0031] The magnetically assisted precipitation component 11 is installed in a culture dish with an interference fit, and the culture dish is filled with DMEM solution for cell culture. The culture dish is placed inside the stage of the rotating stage 3. The rotating stage 3 can rotate along its central axis. The rotating stage 3 is mounted on a fixed plate 8 via a column 2, and the fixed plate 8 is then connected to a translation stage that can move linearly in the X and Y directions respectively via bolts. The microfluidic printhead 10 is fixed on the clamping component 9, with the nozzle of the microfluidic printhead 10 perpendicular to the surface of the microfiber collection groove 14. The clamping component 9 is mounted on the Z-axis translation stage 5 via a sleeve. The height of the Z-axis translation stage 5 is adjusted so that the distance in the Z direction from the nozzle of the microfluidic printhead 10 to the magnetically assisted precipitation component 11 is 1-2 mm.

[0032] A typical feature of the microfluidic printhead 10 is its laminar flow effect printing ink, which contains a certain concentration of nano-magnetic particles. In this specific embodiment, the microfluidic printhead 10 is formed by coaxially nesting three needles of different sizes (e.g., the port of needle No. 14 is in the outermost layer, the port of needle No. 18 is in the middle layer, and the port of needle No. 25 is in the innermost layer), and then a transparent tube with a pointed end is fitted onto the end of the largest needle to form the microfluidic printhead 10.

[0033] The side-facing camera 6 is fixed to the L-shaped plate, and the L-shaped plate is fixed to the optical flat plate with bolts. The focal length of the side-facing camera 6 is 2mm. The installation position of the L-shaped plate is adjusted so that the straight-line distance from the camera lens to the microfiber collection groove 14 is about 0.5 meters to obtain the clearest observation effect on the four circular marker points.

[0034] One end of the clamping component 9 is provided with a fixing groove 20, and the fastener 19 is used to make the fixing groove 20 clamp the microchannel type printhead 10.

[0035] Based on the microfluidic bioprinting device suitable for printing in a liquid environment in this embodiment, this embodiment also provides a bioprinting method, the specific steps of which are as follows:

[0036] Step 1: Three injection pumps begin to inject a 2% w / v dextran solution dissolved in DMEM, a 5% w / v GelMA mixture of 0.005 g / mL Fe3O4 magnetic nanoparticles, and a 20% w / v dextran solution dissolved in deionized water into the innermost, middle, and outermost layers of the microchannel printhead 10, respectively.

[0037] Step 2: Start the side camera 6, start the rotary stage 3, X-axis translation stage 1 and Y-axis translation stage 7, and use the camera visual pose estimation method based on four marker points to move one end point (set as: the starting end) of the magnetically assisted precipitation component 11 below the nozzle of the microchannel type printhead 10.

[0038] Step 3: Turn on the UV light source 4 to irradiate the glass tube of the print head 21, and the hollow microfibers begin to be ejected from the nozzle of the print head 21.

[0039] Step 4: Using a visual pose estimation method based on marker points, guide the magnetically assisted precipitation device in the microfiber collection tank 14 to move continuously from the starting end to the end of the Archimedean curve below the nozzle of the print head 21, and then return to the starting end from the end of the curve along the curve direction, repeating back and forth until an Archimedean curve-shaped microfiber assembly structure is formed.

[0040] Step 6: Turn off UV light source 4, printing ends.

[0041] It should be noted that, for those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and that the present invention can be implemented in other specific forms without departing from the spirit or essential characteristics 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. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention, and no reference numerals in the claims should be construed as limiting the scope of the claims.

[0042] This specification uses specific examples to illustrate the principles and implementation methods of the present invention. The descriptions of the above embodiments are only for the purpose of helping to understand the method and core ideas of the present invention. Furthermore, those skilled in the art will recognize that, based on the ideas of the present invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A microfluidic bioprinting device suitable for printing in a liquid environment, characterized in that, The device includes a magnetically assisted precipitation component, comprising a magnetically assisted precipitation plate. The upper surface of the magnetically assisted precipitation plate has a receiving groove, within which a microfiber collecting groove is provided. The microfiber collecting groove contains multiple elongated magnets, which are combined to form an Archimedean curve-shaped magnetically assisted precipitation device. A circular ring is provided at each of the four corners of a virtual rectangular frame on the magnetically assisted precipitation plate, with the center of each ring corresponding to a vertices of the virtual rectangular frame.

2. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 1, characterized in that, The ratio of the inner radius to the outer radius of the four rings on the magnetically assisted precipitation plate is different for each of them.

3. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 1, characterized in that, The area of ​​the virtual rectangular frame overlaps with the area of ​​the microfiber collection channel by more than 85%.

4. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 1, characterized in that, The ring is black.

5. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 1, characterized in that, Inside the microfiber collection tank, the polarities of two adjacent elongated magnets are opposite.

6. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 1, characterized in that, The magnetically assisted precipitation component is mounted on a rotary table, which is mounted on the sliding block of the X-axis translation stage, which is mounted on the sliding block of the Y-axis translation stage. A microchannel type printhead is mounted above the magnetically assisted precipitation component, and the microchannel type printhead is connected to the Z-axis translation stage via a clamping component.

7. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 6, characterized in that, The Y-axis translation stage and the Z-axis translation stage are mounted on the same base.

8. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 6, characterized in that, The microfluidic printhead includes an inner layer needle, a middle layer needle, and an outer layer needle arranged coaxially; the feed ends of the inner layer needle, the middle layer needle, and the outer layer needle are respectively connected to an injection pump through pipelines.

9. The microfluidic bioprinting device suitable for printing in a liquid environment according to claim 8, characterized in that, The outer needle has a printing head at its end, and the end of the printing head is a pointed tip.

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