Printing nozzle device, extrusion type organoid 3D printer, communication module and organoid printing method

Abstract

The invention discloses a printing nozzle device, an extrusion type organoid 3D printer, a communication module and an organoid printing method. The printing nozzle device comprises a first propeller assembly, a first temperature control assembly and a first driving assembly. The first propeller assembly is provided with a first liquid guiding end used for guiding out cell ink, and the first temperature control assembly is connected with the first propeller assembly and used for adjusting and controlling the temperature of the cell ink guided out by the first propeller assembly to be within a first preset range. The first driving assembly is connected with the first propeller assembly and used for driving the first propeller assembly to move along a first preset path. And the first driving assembly is configured to enable the first propeller assembly to move towards the direction close to the surface of the receiving carrier until the cell ink guided out of the first liquid guide end is adhered to the surface of the receiving carrier, and then enable the first propeller assembly to move towards the direction away from the surface of the receiving carrier until the cell ink is separated from the first liquid guide end. The printing device is high in efficiency and precision, and can efficiently complete work such as printing of the similar organs.

Description

Technical Field

[0001] The present invention relates to the technical field of organoid manufacturing, and in particular to a printing nozzle device, an extrusion-type organoid 3D printer, a communication module and an organoid printing method. Background Art

[0002] During the preparation of organoids, it is often necessary to prepare droplets of cells and hydrogels such as matrigel through a pipette. The application of high-throughput drug screening, drug sensitivity or regeneration of organoids requires the manufacture of hundreds or thousands of organoids, but manual preparation has problems such as uneven size, high cell consumption, low manufacturing efficiency, and difficult quality control. At the same time, the volume of traditional manual operations is often not less than 5 microliters. How to achieve high-throughput and smaller volume organoid manufacturing with limited samples has become an important challenge in the field. High-activity hydrogel materials such as matrigel that are further suitable for organoid growth have low modulus and temperature-sensitive properties and poor manufacturability. How to effectively manufacture and maintain the high activity and survival of organoids during the manufacturing process is a great challenge. During the extrusion process, adverse factors such as shear force, pressure fluctuations, and fluidity of temperature-sensitive materials may occur, all of which will have a negative impact on the survival rate of cells and subsequent organoids.

[0003] Due to the above problems, the efficiency of organoid manufacturing is greatly limited. Low efficiency, heterogeneity, size and cell control and activity not only increase the cost and time of the experiment, but also greatly affect the smooth progress of subsequent experiments. Summary of the invention

[0004] The main purpose of the present invention is to propose a printing nozzle device, an extrusion-type organoid 3D printer, a communication module and an organoid printing method. The printing nozzle device of the present application has high culture efficiency and high precision, and can efficiently complete tasks such as organoid manufacturing.

[0005] To achieve the above-mentioned object, an embodiment of the first aspect of the present invention provides a printing head device, comprising: A first pusher assembly having a first liquid guide end for guiding out the cell ink; A first temperature control component, connected to the first propeller component, used to adjust and control the temperature of the cell ink exported by the first propeller component to a first preset range; A first driving assembly, connected to the first propeller assembly and used to drive the first propeller assembly to move along a first preset path; Among them, the first driving component is configured to first move the first propeller component toward the direction close to the receiving carrier surface until the cell ink discharged from the first liquid guiding end adheres to the receiving carrier surface, and then move the first propeller component toward the direction away from the receiving carrier surface until the cell ink separates from the first liquid guiding end.

[0006] In some embodiments, the print head device includes an orifice plate, and the orifice plate is provided with a plurality of receiving slots, and the plurality of receiving slots are used to receive the cell ink.

[0007] In some embodiments, a plurality of receiving grooves are evenly spaced and distributed on the orifice plate.

[0008] In some embodiments, the printing nozzle device also includes a second propeller assembly and a second drive assembly, the second propeller assembly has a second liquid conducting end for conducting culture fluid, the second drive assembly is connected to the second propeller assembly, and the second drive assembly drives the second propeller assembly to move along a second preset path to inject the culture fluid into the holding tank.

[0009] In some embodiments, the first drive assembly is configured to be able to drive the first propeller assembly to move in a first direction, and the first drive assembly is configured to be able to drive the first propeller assembly to move in a vertical direction; The second drive assembly is configured to be able to drive the second propeller assembly to move in the first direction, and the second drive assembly is configured to be able to drive the second propeller assembly to move in the vertical direction; The orifice plate is configured to be movable along the second direction, wherein the vertical direction, the first direction and the second direction are perpendicular to each other.

[0010] In some embodiments, the second propeller assembly includes a diverter plate having a plurality of diverter ports, the plurality of diverter ports are all configured as second liquid guiding ends, and the plurality of diverter ports correspond to a plurality of receiving grooves, respectively.

[0011] In some embodiments, the print head device includes a second temperature control component, and the second temperature control component is connected to the orifice plate to adjust the solution in the containing tank to a second preset range.

[0012] In some embodiments, the second temperature control component includes a temperature measuring probe, which is used to detect the temperature of the solution in the containing tank, so that the second temperature control component adjusts the temperature of the solution in the containing tank to a second preset range and a first preset range.

[0013] In some embodiments, the print head device includes a visual monitoring device, which is used to monitor the state of the surface of the receiving carrier in the receiving groove.

[0014] In some embodiments, the first temperature control component includes a water-cooled generator connected to a liquid cooling pipe, and the liquid cooling pipe is suitable for passing a coolant to adjust the temperature of the first thruster component to a first preset range.

[0015] In some embodiments, the first pusher assembly includes a linear pump, the first liquid guiding end is connected to the linear pump, and the linear pump works to make the cell ink flow out from the first liquid guiding end.

[0016] In some embodiments, the first driving assembly is connected to at least two first propeller assemblies, and the first driving assembly is configured to drive each first propeller assembly to move along a first preset path.

[0017] An embodiment of the second aspect of the present invention provides an extrusion-type organoid 3D printer, comprising a print head device according to any one of the aforementioned embodiments, the extrusion-type organoid 3D printer further comprising a shell assembly, the shell assembly having an inner chamber for accommodating the print head device, and the shell assembly sealing the print head device.

[0018] In some embodiments, the housing assembly includes a filter blower, which includes a filter screen and an air guide duct. The filter screen and the air guide duct are suitable for connecting the inner chamber with the external environment to provide a sterile environment for the inner chamber.

[0019] In some embodiments, the housing assembly includes a support unit, the support unit is used to support the print head device, and the support unit is configured as a hollow structure.

[0020] An embodiment of the third aspect of the present invention provides a communication module for use in an extrusion-type organoid 3D printer according to any of the aforementioned embodiments, wherein the communication module comprises a Bluetooth control system configured to at least control a first temperature control component and a second temperature control component.

[0021] An embodiment of the third aspect of the present invention provides an organoid printing method, which is used in an extrusion-type organoid 3D printer according to any of the above embodiments, and the method further includes: Adjusting the temperature of the cell ink in the first thruster assembly to be within a first preset range; Exporting the cell ink to the first liquid-conducting end and adhering to the first liquid-conducting end; driving the first pusher assembly to move until the cell ink contacts the surface of the receiving carrier; The first propeller assembly is driven away from the surface of the receiving carrier, so that the cell ink adhered to the first liquid-conducting end is separated from the first liquid-conducting end and dissolved into the surface of the receiving carrier.

[0022] According to the above embodiments, the beneficial effects of the present invention are: The printing nozzle device of the present invention comprises a first propeller assembly, a first temperature control assembly and a first drive assembly. The first propeller assembly has a first liquid-conducting end for guiding out the cell ink, and the first temperature control assembly is connected to the first propeller assembly, and is used to adjust and control the temperature of the cell ink guided out by the first propeller assembly to a first preset range. The first drive assembly is connected to the first propeller assembly, and is used to drive the first propeller assembly to move along a first preset path. The first drive assembly is configured to first move the first propeller assembly toward a direction close to the surface of a receiving carrier until the cell ink guided out of the first liquid-conducting end adheres to the surface of the receiving carrier, and then move the first propeller assembly toward a direction away from the surface of the receiving carrier until the cell ink is separated from the first liquid-conducting end.

[0023] The present application uses a first driving component to drive a first propeller component to move along a first preset path, so that a droplet of cell ink suspended at the first liquid-conducting end adheres to the liquid surface of the previously-conducted cell ink / the liquid surface of the solution to be reacted. When the first propeller component is away from the surface of the receiving carrier, due to the surface tension and viscosity of the cell ink, the cell ink will gradually detach from the first liquid-conducting end and dissolve into the surface of the receiving carrier.

[0024] Such a design gets rid of the restriction that the cell ink droplets suspended at the first liquid guide end need to accumulate a certain mass before they can fall. Therefore, the propeller assembly of the present application can drip a smaller mass of cell ink onto the surface of the receiving carrier or the previously exported cell ink at one time, that is, the propeller assembly of the present application can export a finer amount of cell ink, that is, the printing nozzle device of the present application has higher precision.

[0025] Furthermore, the first temperature control component is connected to the first propeller component, and is used to adjust the temperature of the cell ink discharged by the first propeller component to a first preset range. This temperature control mechanism ensures that the cell ink is at a suitable temperature before being discharged, which is conducive to the survival and growth of cells.

[0026] In summary, the printing nozzle device of the present application can, on the one hand, discharge a smaller amount of cell ink at a time, and on the other hand, can ensure that the cell ink has sufficient activity when discharged. Therefore, the printing nozzle device of the present application has high culture efficiency and high precision, and can efficiently complete tasks such as organoid manufacturing.

[0027] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0029] Figure 1 This is a schematic diagram of the structure of an extrusion-type organoid 3D printer in one embodiment of the present invention; Figure 2 yes Figure 1 Schematic diagram of the exploded structure of the extrusion organoid 3D printer; Figure 3 yes Figure 2 Enlarged view of point A in the middle; Figure 4 A schematic diagram of the structure of an extrusion-type organoid 3D printer observed from another viewing angle in one embodiment of the present invention; Figure 5 yes Figure 4 Schematic diagram of the cross-sectional structure of the extrusion organoid 3D printer cut by the aa plane; Figure 6 It is a schematic diagram of the structure of the extrusion-type organoid 3D printer after the outer door panel is hidden in one embodiment of the present invention; Figure 7 yes Figure 6 Schematic diagram of the cross-sectional structure of the extrusion organoid 3D printer cut by the bb plane; Figure 8 is a partial structural schematic diagram of a printing nozzle device in one embodiment of the present invention; Fig. 9 From another perspective Figure 8 A schematic diagram of the structure of the printing nozzle device; Fig.10 is a schematic structural diagram of a printing stage unit in one embodiment of the present invention; Fig.11 yes Fig.10 A schematic diagram of the cross-sectional structure of the printing stage unit cut by the cc plane; Fig.12 4 is a flow chart of an organoid printing method according to an embodiment of the present invention.

[0030] Description of Figure Numbers: Shell assembly 10; filter fan 101; high-efficiency filter 102; microscope display screen 103; outer door panel 104; cabinet rear end support 105; machine support unit 106; load-bearing foot cup 107; cabinet lower end support 108; The second propeller assembly 20; the vertical precision screw motor 201; the motor slide block 202; the hydraulic block 203; the liquid injection pump 204; the liquid packaging shell 205; the liquid adding device fixture 206; the microscope 207; the microscope slide 208; Printing stage unit 30; orifice plate holder 301; orifice plate placement platform 302; temperature probe a303; circulating water cooler 304; semiconductor temperature controller 305.

[0031] First propeller assembly 40; vertical precision screw motor 401; motor slider 402; sample spotting block 403; sample spotting injection pump 404; sample spotting package shell 405; sample spotting circulating water cooling generator 406; temperature probe 407; sample spotting device holder 408; A first temperature control component 50; A second temperature control component 60; A first drive assembly 70; A second drive assembly 80; Orifice plate 90; Receiving groove 910.

[0032] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0033] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] It should be noted that if the embodiments of the present invention involve directional indications (such as up, down, left, right, front, back, etc.), the directional indications are only used to explain the relative position relationship, movement status, etc. between the components in a certain specific posture. If the specific posture changes, the directional indication will also change accordingly.

[0035] In addition, if there are descriptions involving "first", "second", etc. in the embodiments of the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features limited to "first" and "second" may explicitly or implicitly include at least one of the features. In addition, if "and / or", "and / or" or "and / or" appears in the full text, its meaning includes three parallel schemes. Taking "A and / or B" as an example, it includes scheme A, or scheme B, or a scheme that satisfies both A and B. In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the ability of ordinary technicians in the field to implement. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0036] The first embodiment of the present application provides a printing head device, referring to Figures 1 to 3 In some embodiments, the print head device includes a first propeller assembly 40, a first temperature control assembly 50 and a first drive assembly 70. The first propeller assembly 40 has a first liquid-conducting end for exporting cell ink, and the first temperature control assembly 50 is connected to the first propeller assembly 40, and is used to adjust the temperature of the cell ink exported by the first propeller assembly 40 to a first preset range. The first drive assembly 70 is connected to the first propeller assembly 40 and is used to drive the first propeller assembly 40 to move along a first preset path. Among them, the first drive assembly 70 is configured to first move the first propeller assembly 40 toward the direction close to the surface of the receiving carrier until the cell ink exported from the first liquid-conducting end adheres to the surface of the receiving carrier, and then move the first propeller assembly 40 toward the direction away from the surface of the receiving carrier until the cell ink is separated from the first liquid-conducting end.

[0037] Further, the print head device is configured such that after the first temperature control component 50 adjusts the first propeller component 40, the first propeller component 40 first exports a certain amount of cell ink, and these certain amounts of cell ink are collected by the collection device of the special outer door panel 104. The first propeller component 40 can drip out the cell ink drop by drop in the form of dispensing. Since the cell ink has a certain viscosity, the cell ink will be suspended at the first liquid guide end when it drips out. If no other measures are taken, only when the quality of the cell ink reaches a certain level, the droplets of cell ink suspended at the first liquid guide end will be separated from the first liquid guide end by gravity and fall into the receiving carrier surface / cell ink. The present application drives the first propeller component 40 to move along the first preset path by making the first drive component 70 so that the droplets of cell ink suspended at the first liquid guide end adhere to the liquid surface of the previously exported cell ink / the liquid surface of the solution to be reacted. When the first pusher assembly 40 is away from the surface of the receiving carrier, due to the surface tension and viscosity of the cell ink, the cell ink will gradually detach from the first liquid-conducting end and dissolve into the surface of the receiving carrier. In other words, the cell ink suspended on the first liquid-conducting end is adsorbed by the previously guided cell ink / solution to be reacted and is torn off from the first liquid-conducting end, that is, the cell ink droplets are extracted from the first liquid-conducting end. By tearing off the cell ink at the first liquid-conducting end, the cell ink droplets are extracted from the first liquid-conducting end.

[0038] Such a design gets rid of the restriction that the cell ink droplets suspended on the first liquid-conducting end need to accumulate a certain mass before they can fall, so the propeller assembly of the present application can drip a smaller mass of cell ink onto the surface of the receiving carrier or the previously derived cell ink at one time, that is, the amount of cell ink that can be derived by the propeller assembly of the present application is more detailed, that is, the precision of the print head device of the present application is higher. For example, the precision of the print head device of the present application can be controlled at 0.1 microliters, that is, the first liquid-conducting end can discharge 0.1 microliters of cell ink.

[0039] Furthermore, the first temperature control component 50 is connected to the first propeller component 40, and is used to adjust the temperature of the cell ink derived from the first propeller component 40 to be within a first preset range. For example, a water-cooling generator is provided inside the first temperature control component 50, and the water-cooling generator is connected to the first propeller component 40 through a liquid cooling pipe to control the temperature of the first propeller component 40. When the cell ink passes through the first propeller component 40, the coolant in the liquid cooling pipe absorbs the heat of the cell ink, so that the temperature of the cell ink is reduced to within the first preset range. This temperature control mechanism ensures that the cell ink is at a suitable temperature before being discharged, which is conducive to the survival and growth of cells.

[0040] In summary, the print head device of the present application can discharge a smaller amount of cell ink at a time, and can ensure that the cell ink has sufficient activity when discharged. Therefore, the print head device of the present application has high culture efficiency and high precision, and can efficiently complete tasks such as organoid manufacturing. Of course, the print head device of the present application can also be used in a variety of application scenarios such as drug screening, screening of different growth and development factors, exploration of cell mechanisms, and manufacturing of multiple tissues.

[0041] It should be noted that, regarding the understanding of the receiving carrier surface, in some embodiments, when the amount of cell ink dripped is small, it does not completely cover the bottom wall of the receiving groove 910 of the orifice plate 90. At this time, the droplet of cell ink suspended at the first liquid conducting end directly contacts the bottom wall of the receiving groove 910. When the first propeller assembly 40 is away from the orifice plate 90, the droplet of cell ink is torn off, separated from the first liquid conducting end, and enters the receiving groove 910; in some embodiments, there is already enough cell ink or other solution in the receiving groove 910. At this time, the droplet of cell ink suspended at the first liquid conducting end contacts the accumulated cell ink page or other solution page. When the first propeller assembly 40 is away from the orifice plate 90, due to the surface tension and viscosity of the originally accumulated cell ink or other solution, the droplet of cell ink suspended at the first liquid conducting end will gradually detach from the first liquid conducting end and dissolve into the receiving carrier surface. The design purpose of the present application is to control the amount of cell ink dispensed by an automated dispensing method. Therefore, regardless of whether the cell ink directly contacts the bottom wall of the containing tank 910 or the surface of the solution, the purpose of the present application can be achieved in accordance with the design principle of the present application. Therefore, the above two embodiments are both within the protection scope of the present application.

[0042] In some embodiments, the first propeller assembly 40 includes a linear pump and a first liquid-conducting end. The linear pump is used to store and squeeze the cell ink, and the first liquid-conducting end is connected to the linear pump. When the linear pump is working, the cell ink is pushed out from the first liquid-conducting end through the reciprocating motion of the internal piston. The design of the first propeller assembly 40 allows precise control of the discharge amount of the cell ink to ensure that the volume of the cell ink discharged each time is consistent. In some embodiments, the parameters of the linear pump of the first propeller assembly 40 can be configured to 100ul, 200ul, 500ul, 1ml, 2ml, 5ml, 10ml, 50ml, 100ml, etc., and the first liquid-conducting end can be a needle, and the diameter of the needle can be 0.1mm, 0.2mm, 0.3mm, 0.5mm.

[0043] The first drive assembly 70 is connected to the first propeller assembly 40, and is composed of a motor and a screw. The motor drives the screw to rotate, and the screw drives the first propeller assembly 40 to move along the first preset path. The first drive assembly 70 drives the first propeller assembly 40 to move, so that the cell ink droplets suspended at the first liquid-conducting end will contact and adhere to the previously derived cell ink liquid surface, and then the first drive assembly 70 drives the first propeller assembly 40 to move away from the previously derived cell ink liquid surface, so that the cell ink droplets previously suspended at the first liquid-conducting end can be smoothly extracted from the first liquid-conducting end. This design avoids droplet residue and can accurately control the volume of cell ink discharged by the first propeller assembly 40.

[0044] Of course, it is understandable that the solution discharged by the first thruster assembly 40 is not limited to cell ink, but can also be cell clusters, hydrogels, DNA, cell spheroids, cell blocks, cell fibers, etc. The corresponding materials are selected according to the actual application. Through the printing nozzle device of the present application, the volume of these materials discharged can be more accurately controlled, that is, the amount of materials participating in the reaction can be more accurately controlled.

[0045] It is understandable that, in some embodiments, the linear pump of the first propeller assembly 40 may be driven in different ways, such as a pneumatic pump or an electric pump, as long as the precise discharge of the cell ink can be achieved.

[0046] It is understandable that the volume of the cell ink droplets discharged by the first liquid-conducting end is determined by the cross-sectional area and lead of the outlet, so in some embodiments, the first liquid-conducting end can be designed into different shapes and sizes to accommodate different types of cell inks and experimental requirements. For example, the first liquid-conducting end can be designed into a slender shape to form small cell ink droplets, or designed into a flat shape to form larger cell ink droplets.

[0047] The motion control of the first propeller assembly 40 by the first drive assembly 70 in order to avoid the residue of droplets at the first liquid-conducting end can be a compensating type or a hovering type. For example, when configured as a compensating type, the first drive assembly 70 continuously drives the first propeller assembly 40 to move away from the cell ink liquid surface, that is, the propeller assembly moves up while dripping liquid, until the last moment, the dripping cell ink is pulled by the cell ink liquid surface and is torn off from the first liquid-conducting end, so as to achieve the effect of accurately controlling the volume of the cell ink. When configured as a hovering type, the first drive assembly 70 only needs to drive the first liquid-conducting end to a preset height. As the cell ink is injected, the liquid level of the cell ink rises. When approaching the preset height, the liquid level of the cell ink will contact the cell ink droplet suspended from the first liquid-conducting end, thereby tearing the drop of cell ink off from the first liquid-conducting end. It can be understood that the volume of the cell ink in the container is determined by the volume of the last drop of cell ink discharged from the first liquid-conducting end. The finer the volume of the last drop of cell ink discharged from the first liquid-conducting end, the finer the volume of the cell ink in the container, that is, the higher the precision. Therefore, whether the compensation type or the suspension type is adopted, it is only necessary to ensure that the last drop of cell ink discharged from the first liquid-conducting end is torn off from the first liquid-conducting end by being adsorbed by the previous cell ink liquid surface, thereby detaching from the first liquid-conducting end.

[0048] In order to accurately control the amount of cell ink in the receiving groove 910, it is necessary to accurately control the height of the first liquid guide end from the cell ink liquid surface. In some embodiments, the height is accurately controlled by a grating ruler to ensure that the accuracy of the print head device can achieve the preset effect.

[0049] In some embodiments, the water-cooled generator in the first temperature control component 50 can use a variety of cooling media, such as water, ethanol or other coolants, to meet the needs of different temperature regulation. The liquid cooling pipe can be designed to be serpentine or spiral to increase the contact area between the coolant and the cell ink and improve the cooling efficiency. In addition, the first temperature control component 50 can also be equipped with a temperature sensor to monitor the temperature of the cell ink in real time to ensure that the temperature is always within the first preset range. In some embodiments, the first preset range is 4 degrees Celsius to 8 degrees Celsius. For example, the temperature can be selected as 4 degrees Celsius, 5 degrees Celsius, 6 degrees Celsius, 7 degrees Celsius, and 8 degrees Celsius.

[0050] The motor of the first drive assembly 70 can be a stepper motor or a servo motor to achieve high-precision motion control. The lead screw can be designed with different pitches to adjust the moving speed and distance of the first propeller assembly 40. The first drive assembly 70 can also be equipped with an encoder to provide real-time feedback of the position information of the first propeller assembly 40 to ensure that it accurately reaches the predetermined position.

[0051] Reference Figure 3 , Figure 6 and Figure 7In some embodiments, the print head device includes an orifice plate 90, and a plurality of receiving slots 910 are provided on the orifice plate 90. The receiving slots 910 are used to receive the cell ink. The design of the orifice plate 90 enables the cell ink to be cultured in multiple independent environments, thereby improving the diversity and efficiency of the experiment.

[0052] The material of the orifice plate 90 can be transparent polystyrene or glass to facilitate observation of cell growth. The surface of the orifice plate 90 can be specially treated, such as hydrophilic treatment or hydrophobic treatment, to improve the adhesion and fluidity of the cell ink. The bottom of the orifice plate 90 can be designed to be flat or concave to meet different experimental requirements.

[0053] It is understood that in some embodiments, the number and arrangement of the receiving slots 910 on the well plate 90 can be adjusted according to the experimental requirements. For example, the well plate 90 can be designed as a 96-well plate 90, a 24-well plate 90 or a 6-well plate 90 to accommodate experiments of different scales. The shape and size of the receiving slots 910 can also be optimized according to the cell type and culture conditions, such as round, square or oval.

[0054] The orifice plate 90 may be equipped with a cover to prevent external contaminants from entering the holding tank 910 and maintain a sterile environment. The cover may be designed to be a breathable material to allow gas exchange but prevent microorganisms from entering. In addition, the orifice plate 90 may also be equipped with a marking system, such as a number or letter mark, to facilitate the experimenter to quickly locate and record the position and content of each holding tank 910.

[0055] The manufacturing process of the orifice plate 90 can be injection molding or blow molding to ensure the dimensional accuracy and surface quality of the orifice plate 90. The edge of the orifice plate 90 can be designed to be wavy or serrated to increase the gripping force and facilitate the operation of the experimenter. The orifice plate 90 can also be equipped with a bracket to maintain its stability on the laboratory table.

[0056] Reference Figure 3 and Figure 7 In some embodiments, the orifice plate 90 includes a plurality of receiving slots 910, which are evenly spaced on the orifice plate 90. The structural design of the orifice plate 90 allows sufficient space between each receiving slot 910 to avoid interference between adjacent receiving slots 910. The uniform distribution of the receiving slots 910 ensures that the cell ink in each receiving slot 910 is cultured under the same conditions, thereby improving the repeatability and accuracy of the experiment. Thus, the print head device of the present application can efficiently and quickly complete the culture work.

[0057] It is understandable that in some embodiments, the number and arrangement of the receiving slots 910 on the orifice plate 90 can be adjusted according to the experimental requirements. For example, the orifice plate 90 can be designed in the form of an array as a 96-well plate 90, a 24-well plate 90, or a 6-well plate 90, or the receiving slots 910 can be configured into multiple concentric circles, spreading out layer by layer. The regular design of the receiving slots 910 on the orifice plate 90 is to facilitate the control of the first drive assembly 70 on the first propeller assembly 40, so that the propeller assembly can quickly respond to the receiving slot 910 that needs to be injected.

[0058] Reference Figures 1 to 3 as well as Figure 6 and Figure 7 In some embodiments, the print head device further includes a second propeller assembly 20 and a second drive assembly 80. The second propeller assembly 20 has a second liquid guide end for guiding out the culture solution, and the second drive assembly 80 is connected to the second propeller assembly 20. The second drive assembly 80 drives the second propeller assembly 20 to move along the second preset path to inject the culture solution into the receiving groove 910 of the orifice plate 90.

[0059] The design of the second propeller assembly 20 is similar to that of the first propeller assembly 40, and includes a liquid storage container and a liquid guide pipe. The liquid storage container is used to store the culture solution, and the liquid guide pipe connects the liquid storage container and the second liquid guide end, and the culture solution is guided out of the second liquid guide end through the operation of the internal pump. The design of the second liquid guide end ensures the accurate discharge of the culture solution, avoiding the situation of excess or deficiency.

[0060] The second driving assembly 80 is composed of a motor and a screw rod. The motor drives the screw rod to rotate, and the screw rod drives the second propeller assembly 20 to move along the second preset path. When the second propeller assembly 20 reaches the predetermined position, the culture liquid is discharged from the second liquid guide end and injected into the receiving groove 910 of the orifice plate 90. This design ensures the accurate distribution of the culture liquid and improves the efficiency and accuracy of the experiment.

[0061] It is understood that in some embodiments, the liquid storage container of the second propeller assembly 20 can be made of different materials, such as stainless steel or plastic, to accommodate different types of culture fluids. The capacity of the liquid storage container can be adjusted according to experimental requirements to meet experiments of different scales. The liquid guide pipe can be designed to have different diameters and lengths to accommodate different flow rates and distances.

[0062] The motor of the second drive assembly 80 can be a stepper motor or a servo motor to achieve high-precision motion control. The screw rod can be designed with different pitches to adjust the moving speed and distance of the second propeller assembly 20. The second drive assembly 80 can also be equipped with an encoder to provide real-time feedback of the position information of the second propeller assembly 20 to ensure that it accurately reaches the predetermined position.

[0063] In some embodiments, the second propeller assembly 20 may further include a diverter plate having a plurality of diverter ports, each of which corresponds to a receiving tank 910. The design of the diverter plate allows the culture fluid to be injected into a plurality of receiving tanks 910 at the same time, thereby improving the efficiency of the experiment. The shape and size of the diverter ports may be optimized according to the size of the receiving tank 910 to ensure uniform distribution of the culture fluid.

[0064] In addition, the second propeller assembly 20 and the second drive assembly 80 can be integrated into one module for easy installation and maintenance. The modular design also allows the user to replace different propeller assemblies and drive assemblies according to experimental requirements, increasing the flexibility and applicability of the device.

[0065] Reference Figures 6 to 9 In some embodiments, the first driving assembly 70 is configured to drive the first propeller assembly 40 to move in a first direction, and the first driving assembly 70 is configured to drive the first propeller assembly 40 to move in a vertical direction. This enables the first propeller assembly 40 to move precisely on a two-dimensional plane, so as to achieve rapid alignment of the first propeller assembly 40 and the receiving groove 910, and precise distribution of the cell ink.

[0066] The second drive assembly 80 is configured to drive the second propeller assembly 20 to move in the first direction, and the second drive assembly 80 is configured to drive the second propeller assembly 20 to move in the vertical direction. The orifice plate 90 is configured to move in the second direction, wherein the vertical direction, the first direction and the second direction are perpendicular to each other.

[0067] Such a structure is in the form of a gantry, which enables the components of the print head device to move along the three directions of x, y, and z, thereby improving the flexibility of the print head device and allowing the first thruster assembly 40, the second thruster assembly 20, and the orifice plate 90 to be aligned more quickly, so the print head device of the present application has a higher working efficiency.

[0068] The first drive assembly 70 and the second drive assembly 80 may include a motor and a screw transmission mechanism. The motor drives the screw to rotate, and the screw drives the first propeller assembly 40 to move along the first direction. The motor may be a stepper motor or a servo motor to achieve high-precision motion control. The pitch of the screw can be adjusted as needed to change the moving speed and distance of the first propeller assembly 40.

[0069] In order to achieve vertical movement, the first drive assembly 70 and the second drive assembly 80 may further include a vertical guide mechanism. The vertical guide mechanism may be a vertical slide rail, and the first propeller assembly 40 is fixed on the slide rail, and the slide block is driven by a motor to move up and down along the slide rail. In this way, the first propeller assembly 40 can move precisely in the vertical direction to adapt to orifice plates 90 of different heights or different experimental requirements.

[0070] It is understood that in some embodiments, the selection of motors can be diversified. In addition to stepper motors and servo motors, DC motors or AC motors can also be used. The motor control method can adopt closed-loop control or open-loop control. Closed-loop control can feedback the position information of the motor in real time through the encoder to ensure high-precision motion control; open-loop control controls the rotation angle of the motor through a preset number of pulses.

[0071] The screw drive mechanism can be designed in different forms, such as ball screw or trapezoidal screw. Ball screw has lower friction resistance and higher transmission efficiency, suitable for high-precision motion control; trapezoidal screw has stronger load-bearing capacity, suitable for large load application scenarios.

[0072] The vertical guide mechanism can adopt different designs, such as linear bearings or linear guides. Linear bearings have low friction resistance and are suitable for high-speed movement; linear guides have high rigidity and stability and are suitable for high-precision positioning.

[0073] In addition, the first drive assembly 70 may also be equipped with a position sensor, such as a photoelectric sensor or a magnetic sensor, for detecting the position of the first thruster assembly 40. These sensors can cooperate with the control system to achieve automatic motion control and improve the intelligence level of the device.

[0074] In some embodiments, the second propeller assembly 20 includes a diverter plate having a plurality of diverter ports, each of which is configured as a second liquid guide end, and each of which corresponds to a plurality of receiving tanks 910. This design allows the second propeller assembly 20 to simultaneously inject the culture solution into a plurality of receiving tanks 910, thereby improving the efficiency of the experiment.

[0075] The material of the manifold can be corrosion-resistant and high-temperature resistant materials, such as stainless steel or polytetrafluoroethylene (PTFE). The surface of the manifold can be smoothed to reduce the residue and contamination of the culture medium. The thickness and shape of the manifold can be designed according to actual needs to ensure uniform distribution of the culture medium.

[0076] The design of each diversion port needs to consider the flow rate and pressure of the culture solution to ensure that the amount of culture solution in each holding tank 910 is consistent. The diameter and spacing of the diversion ports can be optimized according to the size and distribution of the holding tanks 910 to achieve the best distribution effect.

[0077] It is understood that in some embodiments, the structure of the diverter plate can be designed to be detachable for easy cleaning and maintenance. For example, the diverter plate can be designed into multiple independent modules, each module corresponding to a set of receiving slots 910. In this way, the user can replace or clean a specific module as needed without affecting the use of other parts.

[0078] The number and layout of the diverter ports can be adjusted according to the number and arrangement of the receiving slots 910 of the well plate 90. For example, if the well plate 90 is a 96-well plate 90, the diverter plate can be designed to have 96 diverter ports, each of which corresponds to a receiving slot 910. The spacing of the diverter ports can be matched with the spacing of the receiving slots 910 to ensure accurate injection of the culture solution.

[0079] The manifold can also be equipped with a pressure regulating device for regulating the injection pressure of the culture solution. The pressure regulating device can be a regulating valve or a pump. By adjusting the pressure, the flow rate and speed of the culture solution can be controlled to meet different experimental requirements.

[0080] In addition, the flow distribution plate can be equipped with a flow sensor for detecting the flow rate of each flow distribution port. The flow sensor can cooperate with the control system to achieve real-time monitoring and adjustment of the distribution of the culture solution to ensure that the amount of culture solution in each holding tank 910 is consistent. This design not only improves the accuracy of the experiment, but also enhances the reliability of the equipment.

[0081] Reference Figure 6 In some embodiments, the print head device includes a second temperature control component 60, which is connected to the orifice plate 90 and is used to adjust the solution in the receiving tank 910 to a second preset range. The design of the second temperature control component 60 ensures that the cell ink in the orifice plate 90 is cultured at a suitable temperature, thereby improving the survival rate and growth efficiency of the cells.

[0082] The second temperature control component 60 may include a heating element, which may be a resistance heating sheet or a heating wire. The heating element and the cooling element are respectively mounted on the bottom or side of the orifice plate 90, and the heating and cooling powers are adjusted by the control system to maintain the temperature of the solution in the orifice plate 90 within a second preset range. The second preset range may be 32 degrees Celsius to 42 degrees Celsius, such as 33 degrees Celsius, 36 degrees Celsius, 37 degrees Celsius, 39 degrees Celsius, 42 degrees Celsius, preferably 37 degrees Celsius. This range is close to human body temperature and is conducive to maintaining cell activity.

[0083] It is understood that in some embodiments, the heating element of the second temperature control assembly 60 can adopt different heating methods, such as infrared heating, microwave heating or ultrasonic heating, to meet different experimental requirements. The power and distribution of the heating element can be optimized according to the size and shape of the orifice plate 90 to ensure uniform temperature distribution.

[0084] Of course, in some embodiments, in order to adapt to different materials in the receiving tank 910, the second temperature control component 60 can also be a cooling element, and the cooling element can be a semiconductor cooling plate or a water cooling system. The cooling element can use different cooling media, such as water, ethanol or other coolants, to meet the needs of different temperature regulation. The cooling system can be designed for circulating cooling, and the coolant is circulated to the cooling element by a pump to improve the cooling efficiency. In addition, the cooling element can be equipped with a temperature sensor to monitor the temperature of the solution in the orifice plate 90 in real time to ensure that the temperature is always within the second preset range.

[0085] In some embodiments, the second temperature control assembly 60 may also be equipped with a temperature controller, which adjusts the heating and cooling power through a PID algorithm (proportional-integral-differential control) to achieve precise temperature control. The temperature controller may be integrated with a control system, and preset temperatures and control parameters may be set through a user interface to achieve automated operation.

[0086] In addition, the second temperature control assembly 60 can be equipped with a backup power supply to prevent the temperature from being out of control due to a sudden power outage. The backup power supply can automatically switch when the main power supply fails to ensure that the temperature of the solution in the orifice plate 90 is not affected.

[0087] Reference Figure 6 and Fig.11 In some embodiments, the second temperature control component 60 includes a temperature probe, which is used to detect the temperature of the solution in the containing tank 910, so that the second temperature control component 60 adjusts the temperature of the solution in the containing tank 910 to a second preset range. The design of the temperature probe ensures the accuracy and real-time performance of temperature measurement and improves the accuracy of temperature control.

[0088] The temperature probe is installed at the bottom or side of the orifice plate 90, directly contacts the solution in the orifice plate 90, and is connected to the temperature controller through a wire. The temperature probe can be of different types such as thermocouples, thermistors or fiber optic temperature sensors to meet different measurement requirements. Thermocouples have a higher temperature measurement range and response speed, and are suitable for high temperature environments; thermistors have higher sensitivity and stability, and are suitable for normal temperature environments; fiber optic temperature sensors have the advantages of anti-electromagnetic interference and non-contact measurement, and are suitable for special environments.

[0089] It is understood that in some embodiments, the number and position of the temperature probes can be adjusted according to the size of the orifice plate 90 and the number of the receiving slots 910 to ensure uniformity and accuracy of temperature measurement. For example, multiple temperature probes can be installed at different positions of the orifice plate 90, and the control system can collect data from multiple temperature measurement points to calculate the average temperature or the highest / lowest temperature to achieve more accurate temperature control.

[0090] The temperature probe can be equipped with a protective sleeve to prevent impurities or chemicals in the solution from damaging the probe. The protective sleeve can be made of corrosion-resistant and high-temperature resistant materials, such as stainless steel or polytetrafluoroethylene (PTFE). The length and diameter of the protective sleeve can be designed according to actual needs to ensure the normal operation of the temperature probe.

[0091] The connection between the temperature probe and the temperature controller can be wirelessly communicated, such as Bluetooth or Wi-Fi, to reduce the complexity of wiring and increase the flexibility of the equipment. Wireless communication can also achieve remote monitoring and data transmission, making it convenient for users to view and adjust temperature settings in real time.

[0092] In addition, the temperature probe can be equipped with a self-cleaning function, which removes dirt and deposits on the probe surface by periodic vibration or spraying cleaning fluid to ensure the accuracy of temperature measurement. The self-cleaning function can be integrated with the control system to trigger the cleaning operation through preset time intervals or temperature changes, improving the reliability and maintainability of the equipment.

[0093] Reference Fig. 9 In some embodiments, the print head device includes a visual monitoring device, which is used to monitor the state of the solution in the receiving tank 910 in the orifice plate 90. The design of the visual monitoring device ensures that the changes in the cell ink can be observed and recorded in real time during the experiment, thereby improving the accuracy and reliability of the experiment. Specifically, the visual detection device can be a microscope.

[0094] In some embodiments, the visual monitoring device includes a camera and a light source. The camera is installed above the orifice plate 90, and the lens is aimed at each receiving slot 910 in the orifice plate 90 to capture the image of the solution in the receiving slot 910 in real time. The light source can be an LED lamp or a fluorescent lamp, which is installed near the camera to provide sufficient illumination to ensure that the image is clearly visible.

[0095] The camera can be connected to an image processing system, which uses image analysis algorithms to automatically detect and analyze the state of the solution, such as color change, turbidity, cell density, etc. The image processing system can be integrated with the control system to display images and analysis results in real time through the user interface, making it convenient for users to monitor the progress of the experiment.

[0096] It is understood that in some embodiments, the camera can select different types of cameras, such as CCD cameras or CMOS cameras, to adapt to different resolution and frame rate requirements. CCD cameras have higher image quality and stability, and are suitable for high-precision image analysis; CMOS cameras have lower cost and power consumption, and are suitable for large-scale experiments.

[0097] The light source can be of different colors and intensities, such as white light, blue light or ultraviolet light, to suit different cell inks and experimental conditions. The brightness and irradiation angle of the light source can be adjusted according to actual needs to ensure the clarity and contrast of the image.

[0098] The visual monitoring device can also be equipped with an autofocus function, which ensures that the captured image is always clear by adjusting the position of the lens. The autofocus function can be integrated with the control system to achieve automated focusing operation through preset focus points and focus distances.

[0099] In addition, the visual monitoring device can be equipped with an image storage function to save the captured images and videos through a built-in storage device or an external storage device. The image storage function can be integrated with a data management system to transmit image data through a network to achieve remote monitoring and data analysis.

[0100] Reference Fig. 9 In some embodiments, the first temperature control component 50 includes a water-cooled generator connected to a liquid cooling pipe, which is suitable for passing a coolant to adjust the temperature of the first propeller component 40 to a first preset range. The design of the first temperature control component 50 ensures that the cell ink is at a suitable temperature before being discharged, which is conducive to the survival and growth of cells.

[0101] The water-cooled generator includes a coolant tank, a water pump, and a cooling device. The coolant tank is used to store coolant, and the water pump extracts the coolant from the tank and delivers it to the first propeller assembly 40 through a liquid cooling pipe. The cooling device can be a radiator or a refrigerator, which is used to reduce the temperature of the coolant. The coolant contacts the first propeller assembly 40 through the liquid cooling pipe, absorbs the heat of the first propeller assembly 40, and reduces its temperature to within a first preset range.

[0102] It is understood that in some embodiments, different types of coolants can be selected, such as water, ethylene glycol aqueous solution or propylene glycol aqueous solution, to meet different cooling requirements. Water has a higher specific heat capacity and good thermal conductivity, and is suitable for most cooling applications; ethylene glycol aqueous solution and propylene glycol aqueous solution have a lower freezing point and a higher boiling point, and are suitable for low or high temperature environments.

[0103] The liquid cooling pipe can be designed into different shapes and diameters to increase the contact area between the coolant and the first thruster assembly 40 and improve the cooling efficiency. The liquid cooling pipe can be made of corrosion-resistant and high-temperature-resistant materials, such as stainless steel or polytetrafluoroethylene (PTFE), to ensure long-term stable operation.

[0104] The water-cooled generator can be equipped with a temperature sensor to monitor the temperature of the coolant in real time to ensure that the temperature of the coolant is always within the first preset range. The temperature sensor can be integrated with the control system to adjust the speed of the water pump and the power of the cooling device through the PID algorithm (proportional-integral-differential control) to achieve precise temperature control.

[0105] In addition, the water-cooled generator can be equipped with a filter to remove impurities and sediments in the coolant to prevent clogging of the liquid cooling pipes. The filter can be replaced or cleaned regularly to ensure the normal operation of the cooling system.

[0106] The water-cooled generator may also be equipped with a backup power supply to prevent temperature runaway caused by a sudden power outage. The backup power supply may automatically switch when the main power supply fails to ensure that the temperature of the first thruster assembly 40 is not affected. The backup power supply may be integrated with the control system to achieve automated power switching operations through preset switching time and switching conditions.

[0107] Reference Fig. 9 In some embodiments, the first propeller assembly 40 includes a linear pump, the first liquid guide end is connected to the linear pump, and the linear pump works to make the cell ink flow out from the first liquid guide end. The design of the linear pump ensures the accurate discharge of the cell ink, avoids the situation of excess or deficiency, and improves the accuracy and reliability of the experiment.

[0108] The linear pump includes a pump body, a piston and a driving mechanism. A liquid storage chamber is provided inside the pump body. The piston reciprocates in the liquid storage chamber under the action of the driving mechanism. The cell ink is squeezed out of the liquid storage chamber and flows out through the first liquid guide end through the reciprocating motion of the piston. The driving mechanism can be a motor and a screw transmission mechanism. The motor drives the screw to rotate, and the screw drives the piston to move in the liquid storage chamber.

[0109] The liquid storage chamber of the linear pump can be designed with different volumes to accommodate different volumes of cell ink. The material of the liquid storage chamber can be selected from corrosion-resistant and high-temperature resistant materials, such as stainless steel or polytetrafluoroethylene (PTFE), to ensure long-term stable operation. The inlet and outlet of the liquid storage chamber can be equipped with filters to remove impurities and sediments in the cell ink to prevent clogging of the first liquid guide end.

[0110] It is understandable that in some embodiments, the driving mechanism of the linear pump can adopt different driving modes, such as pneumatic drive, hydraulic drive or motor drive, to adapt to different experimental requirements. Pneumatic drive pushes the piston through compressed air, which has a higher response speed and lower cost; hydraulic drive pushes the piston through hydraulic oil, which has higher thrust and stability.

[0111] The piston of the linear pump can be designed in different shapes and sizes to suit different cell inks and experimental conditions. The surface of the piston can be smoothed to reduce friction resistance and improve the efficiency of the pump. The seal of the piston can be made of corrosion-resistant and high-temperature resistant materials such as fluororubber or silicone rubber to ensure long-term stable sealing performance.

[0112] The linear pump can also be equipped with a flow sensor to detect the flow rate of the cell ink. The flow sensor can be integrated with the control system to achieve automated flow control through preset flow thresholds and control parameters. Flow sensors can be of different types, such as turbine flow meters or ultrasonic flow meters, to suit different measurement needs.

[0113] In addition, the linear pump can be equipped with a pressure sensor to detect the pressure of the cell ink. The pressure sensor can be integrated with the control system to achieve automated pressure control through preset pressure thresholds and control parameters. The pressure sensor can be of different types, such as piezoresistive pressure sensor or piezoelectric pressure sensor, to meet different measurement requirements.

[0114] Reference Fig. 9 In some embodiments, the first driving assembly 70 is connected to at least two first propeller assemblies 40, and the first driving assembly 70 is configured to drive each first propeller assembly 40 to move along a first preset path. This design allows multiple first propeller assemblies 40 to work together, thereby improving the discharge efficiency of the cell ink and the flexibility of the experiment.

[0115] The first drive assembly 70 includes a motor and a transmission mechanism. The motor may be a stepper motor or a servo motor, and drives the first propeller assembly 40 to move along the first preset path by driving a transmission mechanism (such as a belt, a gear or a screw). The motor can be controlled by closed-loop control or open-loop control. The closed-loop control uses an encoder to feedback the position information of the motor in real time to ensure high-precision motion control; the open-loop control controls the rotation angle of the motor by a preset number of pulses.

[0116] The first drive assembly 70 may be equipped with a multi-axis motion control system for coordinating the motion of the plurality of first thruster assemblies 40. The multi-axis motion control system may be integrated with the control system, and preset paths and control parameters may be set through a user interface to achieve automated motion control. The multi-axis motion control system may use different control algorithms, such as PID control or fuzzy control, to accommodate different motion requirements.

[0117] It is understood that in some embodiments, the motor of the first drive assembly 70 can be of different types, such as a DC motor or an AC motor, to meet different experimental requirements. A DC motor has a higher response speed and lower cost, and is suitable for high-speed motion; an AC motor has a higher torque and stability, and is suitable for large-load application scenarios.

[0118] The transmission mechanism can be designed in different forms, such as belt drive, gear drive or screw drive. Belt drive has lower friction resistance and higher transmission efficiency, suitable for high-speed movement; gear drive has higher rigidity and stability, suitable for high-precision positioning; screw drive has higher load-bearing capacity and lower wear, suitable for large-load application scenarios.

[0119] The first drive assembly 70 may also be equipped with a position sensor, such as a photoelectric sensor or a magnetic sensor, for detecting the position of the first thruster assembly 40. The position sensor may be integrated with the control system to achieve automatic positioning control through preset position thresholds and control parameters. The position sensor may be of different types, such as a photoelectric switch or a Hall sensor, to meet different detection requirements.

[0120] In addition, the first drive assembly 70 can be equipped with a safety protection device, such as a limit switch or an emergency stop button, to prevent the first thruster assembly 40 from exceeding a preset path or causing an accident. The safety protection device can be integrated with the control system to achieve automated safety control through preset safety thresholds and control parameters. The safety protection device can be of different types, such as a mechanical limit switch or an electronic limit switch, to meet different safety requirements.

[0121] Reference Figures 1 to 11 The embodiment of the second aspect of the present invention provides an extrusion-type organoid 3D printer, comprising any of the above-mentioned print head devices, and the extrusion-type organoid 3D printer further comprises a housing assembly 10. The housing assembly 10 has an inner chamber, which is used to accommodate the print head device to seal the print head device. This design ensures that the print head device works in a sterile environment, improves the purity of the cell ink and culture fluid and the reliability of the experiment.

[0122] The housing assembly 10 includes a housing, an outer door panel 104 and a sealing device. The housing is made of corrosion-resistant and high-temperature-resistant materials, such as stainless steel or polycarbonate, to ensure long-term stable operation. The shape and size of the housing can be designed according to the size and shape of the print head device to provide sufficient space and good sealing performance.

[0123] The outer door panel 104 of the housing assembly 10 can be opened manually or automatically. The manual outer door panel 104 is opened by a handle or a knob, and the automatic outer door panel 104 is opened by a motor and a transmission mechanism. The sealing device of the outer door panel 104 can use a rubber sealing ring or a silicone sealing pad to ensure the sealing performance when the outer door panel 104 is closed. The transparent part of the outer door panel 104 can use a transparent black acrylic material, polycarbonate or glass material to facilitate observation of the experimental conditions in the inner chamber.

[0124] The inner chamber may be equipped with a lighting device and a ventilation device. The lighting device may be an LED lamp or a fluorescent lamp, which provides sufficient light for easy observation and operation. The ventilation device may be a fan or a blower, which circulates the air in the inner chamber through the guide air duct to ensure that the temperature and humidity in the inner chamber are evenly distributed.

[0125] It is understood that in some embodiments, the housing of the housing assembly 10 can be designed as a modular structure for easy disassembly and maintenance. The modular structure allows the user to replace or upgrade different components as needed, such as the outer door panel 104, lighting devices, and ventilation devices, thereby improving the flexibility and maintainability of the device.

[0126] The inner chamber can be equipped with temperature and humidity sensors to monitor the environmental conditions in the inner chamber in real time. The temperature and humidity sensors can be integrated with the control system to achieve automated environmental control through preset temperature and humidity thresholds. The temperature and humidity sensors can be of different types, such as thermocouples, thermistors or humidity sensors, to suit different measurement needs.

[0127] The housing assembly 10 may also be equipped with an emergency vent for quickly exhausting the gas in the inner chamber in an emergency to ensure the safety of the experimenter. The emergency vent may be equipped with a filter to prevent external pollutants from entering the inner chamber. The emergency vent may be integrated with the control system to achieve automated emergency operation through preset emergency conditions.

[0128] Reference Figure 4 and Figure 5 In some embodiments, the housing assembly 10 includes a filter fan 101, which includes a filter screen and a guide air duct, and the filter screen and the guide air duct are suitable for connecting the inner chamber with the external environment to provide a sterile environment for the inner chamber. This design ensures that the air in the inner chamber is always kept sterile, improves the reliability of the experiment, and thus ensures the efficiency of the experiment.

[0129] The filter fan 101 includes a fan, a filter and a guide air duct. The fan can be an axial flow fan or a centrifugal fan, and the external air is introduced into the inner chamber through the guide air duct. The filter can be a HEPA (high efficiency particulate air) filter or a ULPA (ultra-high efficiency particulate air) filter to effectively filter bacteria, viruses and other particulate matter in the air to ensure that the air entering the inner chamber is sterile.

[0130] The guide air duct can be designed in different shapes and sizes to adapt to different internal chamber layouts and air flow requirements. The guide air duct can be made of corrosion-resistant and high-temperature resistant materials, such as stainless steel or polytetrafluoroethylene (PTFE), to ensure long-term stable operation. The inlet and outlet of the guide air duct can be equipped with valve outer door plates 104 to adjust the air flow and pressure to ensure uniform distribution of air flow in the internal chamber.

[0131] It is understandable that in some embodiments, the fan of the filter fan 101 can be of different types, such as a DC fan or an AC fan, to meet different power and speed requirements. A DC fan has a higher response speed and lower cost, and is suitable for a small inner chamber; an AC fan has a higher air volume and stability, and is suitable for a large inner chamber.

[0132] The filter can be equipped with a pre-filter to initially filter large particles in the air and extend the service life of the HEPA or ULPA filter. The pre-filter can be a paper filter or a metal filter, which should be replaced or cleaned regularly to ensure the filtering effect.

[0133] The air duct can be equipped with a pressure sensor to detect the pressure difference between the inner chamber and the outer chamber. The pressure sensor can be integrated with the control system to achieve automatic pressure control through a preset pressure threshold. The pressure sensor can be of different types, such as piezoresistive pressure sensor or piezoelectric pressure sensor, to meet different measurement requirements.

[0134] The filter fan 101 may also be equipped with a temperature sensor for detecting the temperature in the inner chamber. The temperature sensor may be integrated with a control system to achieve automated temperature control through a preset temperature threshold. The temperature sensor may be of different types, such as a thermocouple or a thermistor, to accommodate different measurement requirements.

[0135] In addition, the filter fan 101 can be equipped with an automatic cleaning function to remove dirt and sediment on the filter surface by regular vibration or spraying of cleaning liquid to ensure the filtering effect. The automatic cleaning function can be integrated with the control system to achieve automated cleaning operations through preset time intervals or filtering effects.

[0136] Reference Figure 5In some embodiments, the housing assembly 10 includes a support unit, which is used to support the print head device, and the support unit is configured as a hollow structure. This design ensures that the print head device is firmly placed in the inner chamber, and the hollow structure helps to reduce weight, improve ventilation effect, and enhance the heat dissipation performance of the device.

[0137] In some embodiments, the support unit can form a hollow structure in the form of a base, columns and beams. The base is made of corrosion-resistant and high-temperature resistant materials, such as stainless steel or aluminum alloy, to ensure long-term stable operation. The shape and size of the base can be designed according to the size and shape of the print head device to provide sufficient support area and stability. The columns and beams are made of high-strength materials, such as stainless steel or carbon fiber, to ensure the structural strength and stability of the support unit. The columns and beams can be designed with adjustable heights and angles to accommodate print head devices of different heights and layouts. The connection parts of the columns and beams can be bolted or snap-fitted for easy disassembly and maintenance. The columns and beams can be equipped with shock-absorbing devices, such as rubber pads or springs, to reduce the vibration and noise generated by the equipment during operation and improve the accuracy and reliability of the experiment. The shock-absorbing device can be integrated with the connection part of the support unit to achieve an automated shock-absorbing effect through preset shock-absorbing parameters.

[0138] In some embodiments, the design of the hollow structure can be in a grid, honeycomb or grille shape to ensure good ventilation and heat dissipation. The aperture and spacing of the hollow structure can be adjusted according to actual needs to balance the support strength and ventilation effect. The surface of the hollow structure can be smoothed to reduce the accumulation of dust and pollutants.

[0139] The aperture and spacing of the hollow structure can be designed to be gradual to meet the ventilation and heat dissipation requirements of different parts. For example, the aperture at the bottom can be larger to enhance the heat dissipation effect; the aperture at the top can be smaller to reduce the entry of dust and pollutants. The surface of the hollow structure can be treated with rust prevention, such as spraying anti-corrosion coating, to extend the service life of the equipment.

[0140] It is understood that in some embodiments, the base of the support unit can be designed to be movable, such as equipped with rollers or slide rails, to facilitate the user to move and adjust the position in the laboratory. The rollers can use universal wheels with brakes to ensure the stability of the device when in use. Of course, it is understood that the housing can be equipped with height-adjustable feet to enable the extrusion organoid 3D printer to adapt to a variety of placement scenarios or inclined and rugged placement surfaces.

[0141] In addition, the support unit can be equipped with sensors, such as temperature sensors and humidity sensors, for real-time monitoring of environmental conditions within the chamber. The sensors can be integrated with the control system to achieve automated environmental control through preset temperature and humidity thresholds. The sensors can be of different types, such as thermocouples, thermistors, or humidity sensors, to suit different measurement requirements.

[0142] The third aspect of the present invention provides a communication module for the aforementioned extrusion-type organoid 3D printer, wherein the communication module includes a Bluetooth control system, and the Bluetooth control system is configured to at least control the first temperature control component 50 and the second temperature control component 60. This design allows the user to remotely control and monitor the temperature control component wirelessly, thereby improving the intelligence level and operation convenience of the device.

[0143] The Bluetooth control system includes a Bluetooth module, a microcontroller, and an interface circuit. The Bluetooth module is responsible for wireless communication with external devices (such as smartphones, tablets, or computers), the microcontroller is responsible for processing the received instructions and controlling the temperature control component, and the interface circuit is responsible for connecting the temperature control component and the microcontroller.

[0144] The Bluetooth module can adopt Bluetooth Low Energy (BLE) technology, which has lower power consumption and longer communication distance, and is suitable for long-term wireless communication. The Bluetooth module can support multiple communication protocols, such as SPP (Serial Port Protocol) or GATT (Generic Attribute Profile), to adapt to different application scenarios.

[0145] The microcontroller can use a high-performance embedded processor, such as the ARM Cortex-M series or the STM32 series, which has high processing power and rich peripheral interfaces, and can handle complex control algorithms and data processing tasks. The microcontroller can achieve precise control of the temperature control component through preset control algorithms, such as PID control or fuzzy control.

[0146] The interface circuit may include an analog signal interface and a digital signal interface for connecting the temperature control component and the microcontroller. The analog signal interface may be used to collect the temperature sensor signal of the temperature control component, and the digital signal interface may be used to control the heating and cooling elements of the temperature control component. The interface circuit may be equipped with protection circuits, such as overvoltage protection and overcurrent protection, to prevent damage to the equipment due to electrical faults.

[0147] It is understood that in some embodiments, the Bluetooth control system may be equipped with a user interface, such as a mobile phone application or computer software, through which the user can set the preset temperature and control parameters of the temperature control component and view the operating status and historical data of the temperature control component in real time. The user interface may support multiple languages ​​and operating habits to improve the user experience.

[0148] The Bluetooth control system can be equipped with a data storage function, such as a built-in flash memory or an external SD card, to store the operating data and history of the temperature control components. The data storage function can be integrated with the user interface, through which the user can download and analyze the data and perform statistics and analysis of the experimental results.

[0149] The Bluetooth control system can also be equipped with an alarm function, such as a sound alarm or a light alarm, to alert the user when an abnormality occurs in the temperature control component. The alarm function can be integrated with the control system to achieve automated alarm operation through preset alarm thresholds. The alarm function can support multiple alarm methods, such as local alarm and remote alarm, to improve the safety and reliability of the equipment.

[0150] In addition, Bluetooth control systems can be equipped with security authentication functions, such as password protection or fingerprint recognition, to prevent unauthorized access and operation. Security authentication functions can be integrated with the user interface, and users need to be authenticated before they can control and set up, ensuring the security and confidentiality of the equipment.

[0151] Reference Fig.12 The fourth aspect of the present invention provides an organoid printing method for use in an organoid 3D printer according to any of the above embodiments, the method comprising the following steps: S101: adjusting the temperature of the cell ink in the first pusher assembly 40 to be within a first preset range; S103: exporting the cell ink to the first liquid-conducting end and adhering to the first liquid-conducting end; S105: driving the first propeller assembly 40 to move until the cell ink contacts the surface of the receiving carrier; S107: driving the first propeller assembly 40 away from the surface of the receiving carrier, so that the cell ink adhered to the first liquid-conducting end is separated from the first liquid-conducting end and dissolved into the surface of the receiving carrier.

[0152] Specifically, regarding adjusting the temperature of the cell ink in the first propeller assembly 40 to be within the first preset range, the first temperature control assembly 50 includes a water-cooled generator, which is connected to the first propeller assembly 40 through a liquid cooling pipe. The water-cooled generator generates a coolant, which flows into the first propeller assembly 40 through the liquid cooling pipe, thereby adjusting the temperature of the cell ink in the first propeller assembly 40 to be within the first preset range. The first preset range can be set according to the cell type and experimental requirements, for example, 4 degrees Celsius to 8 degrees Celsius. By accurately controlling the working parameters of the water-cooled generator, such as the coolant flow rate and temperature, the stability and accuracy of the cell ink temperature can be ensured. This helps to maintain cell activity and improve the culture effect.

[0153] Regarding exporting the cell ink to the first liquid-conducting end and adhering to the first liquid-conducting end, the first propeller assembly 40 includes a linear pump, and the first liquid-conducting end is connected to the linear pump. When the linear pump is working, the cell ink is exported from the first liquid-conducting end by pressure. Since the cell ink has a certain viscosity, when the cell ink flows out from the first liquid-conducting end, it will adhere to the surface of the first liquid-conducting end. The working parameters of the linear pump, such as pressure and flow, can be accurately adjusted by the controller to ensure that the export amount and speed of the cell ink meet the experimental requirements. This helps to achieve precise control and uniform distribution of the cell ink.

[0154] Regarding driving the first propeller assembly 40 to move until the cell ink contacts the surface of the receiving carrier, the first drive assembly 70 is connected to the first propeller assembly 40, and the first drive assembly 70 includes a motor and a transmission mechanism. The motor drives the transmission mechanism to move the first propeller assembly 40 along a first preset path. First, the first drive assembly 70 moves the first propeller assembly 40 in a direction close to the surface of the receiving carrier until the first liquid guide end contacts the surface of the receiving carrier. By precisely controlling the speed and stroke of the motor, it can be ensured that the movement trajectory and speed of the first propeller assembly 40 meet the experimental requirements. This helps to achieve rapid contact between the cell ink and the surface of the receiving carrier and improve the culture efficiency.

[0155] Regarding driving the first propeller assembly 40 away from the receiving carrier surface so that the cell ink adhered to the first liquid-conducting end is separated from the first liquid-conducting end and dissolved into the receiving carrier surface, the first driving assembly 70 continues to drive the first propeller assembly 40 to move along the first preset path so that it moves in a direction away from the receiving carrier surface. When the first propeller assembly 40 is away from the receiving carrier surface, due to the surface tension and viscosity of the cell ink, the cell ink will gradually separate from the first liquid-conducting end and dissolve into the receiving carrier surface. Such a design can ensure that the separation process of the cell ink is smooth and complete, avoiding the residue of the cell ink, so the extrusion-type organoid 3D printer of the present application has higher precision.

[0156] For the extrusion organoid 3D printer used in this organoid printing method, refer to Figures 1 to 11 , specifically, refer to Figures 1 to 3 The device is mainly composed of a shell assembly 10, a second pusher assembly 20, a printing stage unit 30, and a first pusher assembly 40.

[0157] The housing assembly 10 in the extrusion-type organoid 3D printer of the present invention is shown in FIG. Figure 4 and Figure 5 The housing assembly 10 includes a filter fan 101, a high-efficiency filter 102, a microscope display screen 103, an outer door panel 104, a cabinet rear end support 105, a machine support unit 106, a load-bearing foot cup 107, and a cabinet lower end support 108.

[0158] The filter fan 101 in the extrusion-type organoid 3D printer of the present invention has a special FFU structure, a guide air duct and an air distribution system design, which can reduce eddy currents, eliminate noise, guide airflow to pass through the filter screen evenly, and can control the wind speed. With the high-efficiency filter screen, a sterile environment of the entire internal environment can be achieved in a short time. The microscope display screen 103 is connected to the microscope through a cable, and the captured video images can be transmitted to the display screen in real time. The outer door panel 104 has two left and right panels, which are made of translucent black acrylic material, and can achieve a semi-transparent effect of the internal structure of the machine. The rear end support 105 plays a supporting role, and there are regular heat dissipation holes in the middle for heat dissipation of the machine. The support units 106 are all hollowed out in the middle to reduce the weight of the machine, and serve as support parts for the components on the machine to ensure the smooth operation of the machine. The load-bearing foot cups 107 are distributed at the four corners of the machine, and the height of the machine operating platform can be adjusted up and down by a small margin. The lower end support 108 of the cabinet is connected to the rear end support 105 of the cabinet, and regular heat dissipation holes are symmetrically distributed in the middle of the cabinet for heat dissipation of the machine.

[0159] The second propeller assembly 20 in the bioreactor of the present invention is Fig. 9 , the second propeller assembly includes a vertical precision screw motor 201, a motor slider 202, a hydraulic block 203, a liquid injection pump 204, a liquid packaging shell 205, a liquid adding device fixture 206, a microscope 207, and a microscope slide 208. The vertical precision screw motor 201 is precisely driven and is responsible for providing power for the liquid adding assembly to move up and down. Including but not limited to transmission in the form of belts, chains, gears, etc. The motor slider 202 is closely matched with the vertical precision screw motor 201, and the screw motor rotates forward and backward to realize the up and down sliding of the slider. One end of the hydraulic block 203 is connected to the liquid injection pump, and the other end is connected to the liquid adding power unit. When it is tightly fitted with the liquid injection pump 204, the downward movement of the hydraulic block 203 will cause the liquid adding material to be squeezed out from the injection needle. The liquid injection pump 204 is composed of a liquid adding push rod, a liquid adding pump shell and an injection needle, and has good airtightness. The size of the liquid injection pump 204 can be adjusted according to the amount of liquid added. The liquid adding package shell 205 serves as a fixing unit for the liquid adding injection pump 204 and plays a supporting role. The liquid adding device fixture 206 serves as a fixing plate of the second thruster assembly 20, on which another set of power units for pressing the liquid adding block 203 is mounted and placed on the back of the fixing plate.

[0160] The microscope 207 in the extrusion-type organoid 3D printer of the present invention can observe the situation of spotting and adding liquid in real time, and provide real-time feedback to the system control unit, so that the individual wells that have not been spotted can be re-spotted. The microscope slide 208 can slide up and down and then be fixed to adjust the imaging format of the microscope 207.

[0161] The first propeller assembly 40 in the bioreactor of the present invention is Fig. 9 The first propeller assembly 40 includes a vertical precision screw motor 401, a motor slider 402, a sample spotting pressure block 403, a sample spotting injection pump 404, a sample spotting packaging shell 405, a sample spotting circulating water cooling generator 406, a temperature probe b407, and a sample spotting device holder 408. The vertical precision screw motor 401 is a precision transmission, responsible for providing power for the sample spotting assembly to move up and down. Including but not limited to transmission in the form of belts, chains, gears, etc. The motor slider 402 is closely matched with the vertical precision screw motor 401, and the screw motor rotates forward and backward to realize the up and down sliding of the slider. The sample spotting pressure block 403 is connected to the sample spotting injection pump at one end and the sample spotting power unit at the other end. When it is closely fitted with the sample spotting injection pump, the downward movement of the sample spotting pressure block 403 will cause the sample spotting material to be squeezed out from the injection needle. The sample spotting injection pump 404 is composed of a sample spotting push rod, a sample spotting pump shell and an injection needle, and has good airtightness. The size of the sample spotting injection pump can be adjusted according to the sample spotting amount. The spotting packaging shell 405 serves as a fixing unit of the spotting injection pump 404, plays a supporting role, and can transfer temperature. The other end of the spotting circulating water-cooled generator 406 is connected to the water pump, and the excess temperature is taken away through water circulation. The temperature probe 407 can detect the temperature of the spotting area in real time. When the predetermined temperature range is reached, the temperature control module will stop working. On the contrary, if it is not in the predetermined temperature range, the temperature control module will start the working mode, and the normal temperature is set at about 4 degrees Celsius to 8 degrees Celsius. The spotting device fixture 408 serves as a fixing plate of the first thruster assembly 40, on which another set of power units of the spotting pressure block 403 are mounted, which are placed on the back of the fixing plate.

[0162] The printing stage unit 30 in the printing platform device of the present invention is referred to Fig.10 and Fig.11 The printing stage unit 30 includes a hole plate holder 301, a hole plate placement platform 302, a temperature probe 303, a circulating water cooler 304, and a semiconductor temperature controller 305. The hole plate holder 301 can place the hole plates 90 of different sizes and hole numbers therein through the surrounding fixed holes to fix the position of each empty space. The hole plate placement platform 302 can be placed with the hole plate holder 301 on the top, and the temperature control module is connected to the bottom. The material has good thermal conductivity and can transmit the temperature of the temperature controller to the hole plate 90 in time. The temperature probe 303 can detect the temperature of the hole plate placement platform 302 in real time. When the predetermined temperature range is reached, the temperature control module will stop working. On the contrary, if it is not in the predetermined temperature range, the temperature control module will start the working mode, and the normal temperature is set at about 37 degrees Celsius. The other end of the circulating water cooler 304 is connected to a water pump to take away the excess temperature through water circulation. The semiconductor temperature controller 305 has cooling at one end and heat generation at the other end. The heat generation surface can fit the hole plate placement platform 302 to transfer temperature.

[0163] The above are only preferred embodiments of the present invention, and are not intended to limit the patent scope of the present invention. All equivalent structural changes made using the contents of the present invention's specification and drawings, or directly / indirectly applied in other related technical fields, are included in the patent protection scope of the present invention.

Claims

1. A printing head device, characterized in that: include: A first pusher assembly having a first liquid guide end for guiding out the cell ink; A first temperature control component, connected to the first propeller component, used to adjust and control the temperature of the cell ink exported by the first propeller component to a first preset range; a first driving assembly, connected to the first propeller assembly and used to drive the first propeller assembly to move along a first preset path; Wherein, the first driving component is configured to first move the first propeller component toward a direction close to the surface of the receiving carrier until the cell ink discharged from the first liquid-conducting end adheres to the surface of the receiving carrier, and then move the first propeller component toward a direction away from the surface of the receiving carrier until the cell ink is separated from the first liquid-conducting end.

2. The print head device according to claim 1, characterized in that: The printing nozzle device comprises an orifice plate, and the orifice plate is provided with a plurality of receiving grooves, and the plurality of receiving grooves are used to receive the cell ink.

3. The print head device according to claim 2, characterized in that: The plurality of accommodating grooves are evenly distributed on the orifice plate.

4. The print head device according to claim 2, characterized in that: The printing nozzle device also includes a second propeller assembly and a second drive assembly, the second propeller assembly has a second liquid conducting end for conducting culture fluid, the second drive assembly is connected to the second propeller assembly, and the second drive assembly drives the second propeller assembly to move along a second preset path to inject the culture fluid into the holding tank.

5. The print head device according to claim 4, characterized in that: The first drive assembly is configured to be able to drive the first propeller assembly to move in a first direction, and the first drive assembly is configured to be able to drive the first propeller assembly to move in a vertical direction; The second drive assembly is configured to be capable of driving the second propeller assembly to move in a first direction, and the second drive assembly is configured to be capable of driving the second propeller assembly to move in a vertical direction; The orifice plate is configured to be movable along a second direction, wherein the first vertical direction, the first direction, and the second direction are perpendicular to each other.

6. The print head device according to claim 4, characterized in that: The second propeller assembly includes a diverter plate having a plurality of diverter ports, the plurality of diverter ports are all configured as the second liquid guiding ends, and the plurality of diverter ports correspond to the plurality of accommodating grooves respectively.

7. The print head device according to claim 2, characterized in that: The printing nozzle device includes a second temperature control component, and the second temperature control component is connected to the orifice plate to adjust the solution in the containing tank to a second preset range.

8. The print head device according to claim 7, characterized in that: The second temperature control component includes a temperature measuring probe, and the temperature measuring probe is used to detect the temperature of the solution in the containing tank, so that the second temperature control component adjusts the temperature of the solution in the containing tank to the second first preset range.

9. The print head device according to claim 2, characterized in that: The print head device comprises a visual monitoring device, and the visual monitoring device is used to monitor the state of the receiving carrier surface in the receiving groove.

10. The print head device according to claim 1, characterized in that: The first temperature control component includes a water-cooled generator, which is connected to a liquid cooling pipe. The liquid cooling pipe is suitable for passing a coolant to adjust the temperature of the first thruster component to the first preset range.

11. The print head device according to claim 1, characterized in that: The first propeller assembly includes a linear pump, the first liquid-conducting end is connected to the linear pump, and the linear pump works to make the cell ink flow out from the first liquid-conducting end.

12. The print head device according to claim 1, characterized in that: The first driving assembly is connected to at least two of the first propeller assemblies, and the first driving assembly is configured to drive each of the first propeller assemblies to move along the first preset path.

13. An extrusion-type organoid 3D printer, characterized in that: include: The printing head device according to any one of claims 1 to 12; The shell assembly has an inner chamber, wherein the inner chamber is used to accommodate the print head device, and the shell assembly seals the print head device.

14. The extrusion-type organoid 3D printer according to claim 13, characterized in that: The housing assembly includes a filter fan, and the filter fan includes a filter screen and a guide air duct. The filter screen and the guide air duct are suitable for connecting the inner chamber with the external environment to provide a sterile environment for the inner chamber.

15. The extrusion-type organoid 3D printer according to claim 13, characterized in that: The housing assembly includes a supporting unit, which is used to support the print head device, and the supporting unit is configured as a hollow structure.

16. A communication module for use in the extrusion-type organoid 3D printer of claim 13, characterized in that: The communication module includes a Bluetooth control system, and the Bluetooth control system is configured to at least control the first temperature control component and the second temperature control component.

17. An organoid printing method, used in the extrusion-type organoid 3D printer according to claim 13, characterized in that: The method comprises: Adjusting the temperature of the cell ink in the first thruster assembly to be within the first preset range; Leading out the cell ink to the first liquid-conducting end and adhering to the first liquid-conducting end; driving the first pusher assembly to move until the cell ink contacts the surface of the receiving carrier; The first propeller assembly is driven away from the surface of the receiving carrier, so that the cell ink adhered to the first liquid-conducting end is separated from the first liquid-conducting end and dissolved into the surface of the receiving carrier.

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