KR102096510B1 - Apparatus and method for 3D bioprinter - Google Patents

Abstract

The present invention relates to a 3D bio-printer device comprising: a material accommodation unit having at least one accommodation portion; a plate unit on which one or more first substrates are seated; a printing unit which sucks a bio-material accommodated in the accommodation portion with a disposable pipette tip replaceable on one side, and prints by dispensing the bio-material using a pre-set program on the first substrate; and a position adjustment unit connected to the printing unit to control the position of the printing unit.

Description

Apparatus and method for 3D bioprinter}

The present invention relates to a 3D bioprinter device and method, and more particularly, to a 3D bioprinter device and method capable of quickly and easily printing complex biological tissues.

3D printer technology is a technology that can produce complex structures in a short time by stacking layers corresponding to drawings made using Computer Aided Design (CAD) without cutting. Recently, this technology has been actively used in industries such as medical, automotive, ship, and footwear beyond prototyping.

On the other hand, with the development of modern medicine, organ transplantation through donors is done for almost all organs, but there is a problem that patients are not benefited from the lack of donors, and artificially produced organs are made of plastic and metal, not cells. There is a problem that biocompatibility is insufficient. Due to these problems, tissue regeneration using bio printing technology has become a major issue. 3D bioprinting technology is a method of manufacturing tissues or organs by stacking a living cell with a desired shape or pattern, such as a stacking method such as a 3D printer.

Conventionally, for three-dimensional bioprinting, methods have been proposed in which cells and a coating material are filled in a chamber or a syringe and controlled by a syringe pump or pneumatically applied, or a coating or laser-based coating using a piezoelectric element. However, the above-described methods have a problem that it is difficult to print complex tissues in fresh conditions because of the nature of biomaterials.

KR 10-2017-0124377 A, 2018.04.05

An object of the present invention is to provide a 3D bio printer apparatus and method capable of quickly and easily printing complex biological tissues through an automated printing unit.

However, these problems are exemplary, and the scope of the present invention is not limited thereby.

In one embodiment of the present invention, a material receiving unit having one or more receiving portions, a plate unit on which one or more first substrates are mounted, and a biomaterial accommodated in the receiving portion while being equipped with a replaceable disposable pipette tip on one side A three-dimensional bio which comprises a printing unit for suctioning and dispensing and printing the biomaterial on a first substrate by a preset program and a position adjusting unit connected to the printing unit to control the position of the printing unit. Provide a printer device.

In one embodiment of the present invention, the material accommodating unit, the plate unit, the printing unit and the chamber unit accommodating the positioning unit therein and disposed above the inside of the chamber unit, at least ultraviolet light on the plate unit It may further include a UV irradiation unit for irradiating.

In one embodiment of the present invention, a pipette tip accommodating portion accommodating a plurality of the disposable pipette tips may be further included.

In one embodiment of the present invention, the second substrate may be seated on the first substrate on which the biomaterial is printed to further include a pressing unit for compressing the height of the biomaterial in a controlled state.

According to an embodiment of the present invention, preparing a biomaterial in a material receiving unit including one or more receiving parts, mounting a replaceable disposable pipette tip on one side of the printing unit, and using the printing unit to the receiving part Inhaling the biomaterial to be accommodated, dispensing and printing the biomaterial on a first substrate to be printed using the printing unit by a preset program, and disposable from the printing unit after the printing is completed It provides a three-dimensional bio-printing method, comprising the step of removing the pipette tip.

In one embodiment of the present invention, the method may further include a step of seating a second substrate on the first substrate on which the biomaterial is printed, and compressing the biomaterial in a controlled state.

Other aspects, features, and advantages other than those described above will become apparent from the following detailed description, claims and drawings for carrying out the invention.

According to an embodiment of the present invention made as described above, through a printing unit that suctions and dispenses biomaterials in a state in which a replaceable disposable pipette tip is mounted, and prints complex biological tissues having various biomaterials quickly and easily Can be printed.

Of course, the scope of the present invention is not limited by these effects.

1 is a perspective view showing a 3D bio printer device according to an embodiment of the present invention.
FIG. 2 is a front view of the 3D bio printer device of FIG. 1.
FIG. 3 is a view for explaining a process of printing using the printing unit of FIG. 1.
4 is a view for explaining a process of seating the second substrate on the first substrate using the pressing unit of FIG. 1.
5 is a flowchart for explaining a 3D bioprinting method according to an embodiment of the present invention.
6 is an image of a structure manufactured through an embodiment of the present invention.

Hereinafter, various embodiments of the present disclosure are described in connection with the accompanying drawings. Various embodiments of the present disclosure may have various modifications and various embodiments, and specific embodiments are illustrated in the drawings and related detailed descriptions are described. However, this is not intended to limit the various embodiments of the present disclosure to specific embodiments, and should be understood to include all modifications and / or equivalents or substitutes included in the spirit and scope of the various embodiments of the present disclosure. In connection with the description of the drawings, similar reference numerals have been used for similar elements.

Expressions such as “comprises” or “can include” that may be used in various embodiments of the present disclosure indicate the existence of a corresponding function, operation, or component disclosed, and additional one or more functions, operations, or The components and the like are not limited. Also, in various embodiments of the present disclosure, terms such as “include” or “have” are intended to indicate that there are features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, It should be understood that one or more other features or numbers, steps, actions, components, parts, or combinations thereof are not excluded in advance.

In various embodiments of the present disclosure, expressions such as “or” include any and all combinations of words listed together. For example, "A or B" may include A, may include B, or may include both A and B.

Expressions such as “first”, “second”, “first”, or “second” used in various embodiments of the present disclosure may modify various elements of various embodiments, but do not limit the elements. Does not. For example, the above expressions do not limit the order and / or importance of the components. The above expressions can be used to distinguish one component from another component. For example, the first user device and the second user device are both user devices and represent different user devices. For example, a first component may be referred to as a second component without departing from the scope of rights of various embodiments of the present disclosure, and similarly, the second component may also be referred to as the first component.

When a component is said to be "connected" to or "connected" to another component, some of the components may or may not be directly connected to the other components, It will be understood that other new components may exist between the other components. On the other hand, when a component is said to be "directly connected" or "directly connected" to another component, it will be understood that no new component exists between the component and the other components. You should be able to.

Terms used in various embodiments of the present disclosure are only used to describe specific specific embodiments, and are not intended to limit various embodiments of the present disclosure. Singular expressions include plural expressions unless the context clearly indicates otherwise.

Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person skilled in the art to which various embodiments of the present disclosure belong.

Terms, such as those defined in a commonly used dictionary, should be interpreted as having meanings consistent with meanings in the context of related technologies, and are ideally or excessively formal unless explicitly defined in various embodiments of the present disclosure. It is not interpreted as meaning.

1 is a perspective view showing a 3D bio printer device 10 according to an embodiment of the present invention, and FIG. 2 is a front view of the 3D bio printer device 10 of FIG. 1. FIG. 3 is a view for explaining a process of printing using the printing unit 130 of FIG. 1, and FIG. 4 is a second substrate (1) on the first substrate S1 using the crimping unit 200 of FIG. 1 S2) is a view for explaining the process of seating.

1 and 2, the 3D bio-printer device 10 according to an embodiment of the present invention includes a chamber unit 101, a material receiving unit 110, a plate unit 120, and a printing unit 130. And a position adjusting unit 140.

The material accommodating unit 110 may include one or more accommodating parts 111. One type of biomaterial may be accommodated in one receiving unit 111. For example, the material accommodating unit 110 may include a plurality of accommodating parts 111 to accommodate a plurality of types of biomaterials. The material accommodating unit 110 is disposed inside the chamber unit 101, and is disposed on a movement path of the printing unit 130, which will be described later, to shorten the printing time.

As used herein, biomaterial refers to a liquid, semi-solid or solid composition comprising a plurality of cells. The biomaterial may have a high cell density or a cell density similar to that of the original cell. As an embodiment, the biomaterial may include a cell solution, a cell-containing gel, a multicellular body or tissue, and additionally include a support material. Alternatively, as another embodiment, the biomaterial may further include a non-cellular material that provides specific biomechanical properties that enable bioprinting.

The biomaterial has a high cell density or a cell density similar to that of the original cell. Cell density of biomaterials may include 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or 95% or more and increments within this range.

In an alternative embodiment, the biomaterial may include a liquid or semi-solid cell solution, cell suspension or cell concentrate. Alternatively, the biomaterial may include a cell solution, suspension, or concentrate liquid or semi-solid (eg, viscous) carrier and a plurality of cells. The carrier can be a cell nutrient medium. The biomaterial may include a semi-solid or solid multicellular aggregate or multicellular body, and a step of preparing a biomaterial by mixing a plurality of cells or cell aggregates with a biocompatible liquid or gel at a predetermined ratio, and compressing the biomaterial It can be prepared by the step of preparing a biomaterial having a desired cell density and viscosity.

Compression of the biomaterial can be achieved by centrifugation, tangential flow filtration ("TFF"), or a combination thereof. In some embodiments, compression of the biomaterial can produce an extrudable composition that allows for the formation of multicellular aggregates or multicellular bodies. In some embodiments, the term “extrudable” means that it can be shaped (eg, under pressure) by forcing through a nozzle or orifice (eg, one or more holes or tubes). In some embodiments, compression of the biomaterial results from growing the cells to an appropriate density. The cell density required for biomaterials will depend on the cell used and the tissue or organ to be produced. In some embodiments, cells of the biomaterial aggregate and / or adhere. In some embodiments, the terms “aggregate,” “aggregated,” and “aggregate” refer to intercellular adhesion properties that bind cells, multicellular aggregates, multicellular bodies and / or layers thereof. In further embodiments, the terms are used interchangeably with the words “fuse”, “fused” and “fusion”. In some embodiments, the biomaterial may further include a support material, cell culture medium, extracellular matrix (or components thereof), cell adhesion agent, cell death inhibitor, anti-apoptotic agent, antioxidant, extruded compound, and combinations thereof. have.

The biomaterial includes any mammalian cell, and the cell can be a vertebrate cell, a mammalian cell, a human cell, or a combination thereof. The type of cell may vary depending on the type of cellular construct, tissue or organ to be produced, and the biomaterial may include one type of cell (also referred to as "homogeneous ink"). In some embodiments, a biomaterial can include one or more types of cells (also referred to as “heterologous ink”).

In one embodiment, the cells are contractile or muscle cells (eg, skeletal muscle cells, cardiomyocytes, smooth muscle cells and myoblasts), connective tissue cells (eg, bone cells, chondrocytes, fibroblasts, and bone forming cells) , Chondrocytes or cells that differentiate into lymphoid tissue), bone marrow cells, endothelial cells, skin cells, epithelial cells, breast cells, vascular cells, blood cells, lymph cells, nerve cells, Schwann cells, gastrointestinal cells, liver cells, pancreatic cells , Lung cells, organ cells, corneal cells, genitourinary cells, kidney cells, regenerative cells, adipocytes, parenchymal tissue cells, epidermal cells, mesothelial cells, stromal cells, undifferentiated cells (eg embryonic cells, stem cells and progenitors) Cells), endoderm-derived cells, mesoderm-derived cells, ectoderm-derived cells, and combinations thereof.

In some embodiments, the cells can be adult differentiated cells. Differentiated cells are cells that have a tissue-specific phenotype consistent with, for example, smooth muscle cells, fibroblasts, or endothelial cells, in which case tissue-specific phenotypes (or potentials to exhibit phenotypes) are used from the time of isolation. Keep until. In other embodiments, the cells are adult undifferentiated cells. Undifferentiated cells are, for example, cells that do not have or have clear tissue-specific traits as smooth muscle cells, fibroblasts or endothelial cells. In some embodiments, undifferentiated cells can include stem cells. Stem cells refer to cells that exhibit growth and self-renewal. Examples of stem cells include, but are not limited to, pluripotent cells, pluripotent cells, multipotent cells, oligopotent cells, monopotent cells and progenitor cells. The stem cells can optionally be embryonic stem cells, adult stem cells, amniotic stem cells and induced pluripotent stem cells. In another embodiment, the cell can be a mixture of adult differentiated cells and adult undifferentiated cells.

In some embodiments, the cells can be immunomodulatory cells. The immunomodulatory cells are selected from mesenchymal stem cells (MSC) or macrophages, or a combination of both. In some embodiments, the mesenchymal stem cells are from bone and / or fat. In some embodiments, macrophages are supplied from tissue and / or blood. In some embodiments, the macrophages are M2-activated macrophages. In some embodiments, M2-activated macrophages isolated from spleen, blood, and / or other tissue sites are added to the biomaterial mixture. In some embodiments, neutral macrophages are activated in vitro prior to addition to the biomaterial mixture. In some embodiments, neutral macrophages are added to the biomaterial mixture incorporating the cytokines required for M2-activation of macrophages. In some embodiments, neutral macrophages are added to a biomaterial mixture containing cells that produce the cytokines required for M2-activation of macrophages. In some embodiments, a mixture of macrophages and MSCs is incorporated into the cell's biomaterial mixture. In some embodiments, parenchymal support cells, such as, but not limited to, fibroblasts are added to the biomaterial mixture to improve the structural properties of the biomaterial.

As used herein, the term “I-biomaterial” includes a proportion of the immunomodulatory cells alc described herein, as well as non-immunoregulatory cells and / or biomaterial supports (which may be present, but are not required). Biomaterial mixture. In some embodiments, the I-biomaterial comprises parenchymal tissue cells; And MSCs, macrophages, or combinations thereof. In some embodiments, the I-biomaterial comprises parenchymal tissue cells; MSC, macrophage, or combinations thereof; And a biomaterial support that is one or more extruded compounds. In some embodiments, the biomaterial support is a hydrogel.

In some embodiments, the biomaterial comprises cell culture medium. The cell culture medium is any suitable medium. In various embodiments, suitable cell culture media include, by way of non-limiting examples, Dulbecco's phosphate buffered saline, Earle's fungus, Hanks fungus, Tyrode's salt, Alsever solution, Gay's fungus solution, Kreb's-Henseleit modified buffer, Kreb's-Ringer bicarbonate buffer, Puck's saline, Dulbecco's modified Eagle's medium, Dulbecco's modified Eagle's medium / nutrient F -12 Ham, Nutrient Mixture F-10 Ham (Ham's F-10), Medium 199, Minimum Essential Medium Eagle, RPMI-1640 Medium, Ames' Medium, BGJb Medium (Fitton-Jackson Modification), Click (Click's ) Medium, CMRL-1066 Medium, Fischer's Medium, Glascow Minimum Essential Medium (GMEM), Iscove's Modified Dulbecco's Medium (IMDM), L-15 Medium (Leibovitz) , McCoy's 5A modified medium, NCTC medium, Swim's S-77 medium, Wee Plymouth (Waymouth) badges, William (William's) may be the medium E or a combination thereof. In some embodiments, the cell culture medium is modified or supplemented. In some embodiments, the cell culture medium further comprises albumin, selenium, transferrin, fetuin, sugar, amino acids, vitamins, growth factors, cytokines, hormones, antibiotics, lipids, lipid carriers, cyclodextrins, or combinations thereof. .

In some embodiments, the biomaterial further comprises an extruded compound (ie, a compound that changes the extrusion properties of the biomaterial). Examples of extruded compounds include gels, hydrogels (including UV crosslinkable hydrogels and thermoreversible hydrogels), surfactant polyols (e.g., Pluronic F-127 or PF-127), thermoreactive polymers, hyaluron Acid salts, alginates, extracellular matrix components (and derivatives thereof), collagen, other biocompatible natural or synthetic polymers, nanofibers, and self-assembled nanofibers.

Gels can also be classified as hydrophobic or hydrophilic. In certain embodiments, the hydrophobic gel substrate is made of colloidal silica, or polyethylene or fatty oil gelled with aluminum soap or zinc soap, and liquid paraffin. Conversely, the base of the hydrophobic gel generally consists of water, glycerol or propylene glycol gelled with a suitable gelling agent (eg, tragacanth, starch, cellulose derivatives, carboxyvinylpolymer and magnesium-aluminum silicate). In certain embodiments, the rheological properties of the compositions or devices disclosed herein are pseudoplastic, plastic, thixotropic or swellable.

 Hydrogels can include those derived from collagen, hyaluronate, fibrin, alginate, agarose, chitosan and combinations thereof. In other embodiments, the hydrogel is a synthetic polymer. In a further embodiment, the hydrogel may include those derived from poly (acrylic acid) and derivatives thereof, poly (ethylene oxide) and copolymers thereof, poly (vinyl alcohol), polyphosphazene and combinations thereof. . In various specific embodiments, the support material is a hydrogel, Novogel ™, agarose, alginate, gelatin, Matrigel®, hyaluronan, poloxamer, peptide hydrogel, poly (isopropyl n-polyacrylic) Amide), polyethylene glycol diacrylate (PEG-DA), hydroxyethyl methacrylate, polydimethylsiloxane, polyacrylamide, poly (lactic acid), silicone, silk, or combinations thereof.

As described above, the biomaterial may include a hydrogel as a compressed compound, and the state of the hydrogel may vary depending on temperature. In other words, since the hydrogel maintains a gel state at a low temperature, the material receiving unit 110 may further include a first temperature control unit (not shown) for printing of a certain shape.

The first temperature control unit (not shown) may adjust the temperature of the entire material receiving unit 110 or may be disposed adjacent to each receiving unit 111 to control the temperature of the receiving unit 111. The first temperature control unit (not shown) may include one or more thermoelectric elements (peltier). Here, the thermoelectric element means a means for controlling the temperature using the Peltier effect. The Peltier effect refers to a phenomenon in which one type of metal is paired with a current to flow, and one contact generates heat and the other contact absorbs heat (cooling).

In detail, the thermoelectric module is used in the form of a module in which n and p-type thermoelectric semiconductors are connected in a series in order to be electrically connected in series and thermally in parallel. That is, in a Γ-type series circuit in which a p-type element and an n-type element are bonded to a metal electrode, when a current is flowed from n-type to p-type so that the electrodes of the pn phase (couple) bission terminals are-and +, respectively, p-type elements The holes in the inside are attracted to the-pole, and the electrons in the n-type element are attracted to the + electrode. At this time, since both holes and electrons have heat from the p-n junction electrode on one side and move to the nutrient branch electrode on the other side, the upper junction is cooled to absorb heat from the surroundings, and the lower nutrient branch releases heat. This phenomenon is called the Peltier effect, and is not only the principle of electronic cooling, but also serves as a heat-pump.

That is, in the Peltier effect, when DC electricity is passed through a circuit made of two different metals having the same shape, heat absorption occurs at one junction and heat generation occurs at the other junction, and when heat is reversed, heat absorption and heat generation reverse. It means a phenomenon. This is a phenomenon in which heat and cooling occur simultaneously on two different cross-sections of metal when an electrical load is applied to two different metals connected to both cross-sections.

l Q p l = αab * Tj * Ｉ = ð * Ｉ

Here, l Qp l = absolute value of heat generated in unit time, αab = a, b relative thermal capacity of two metals according to ambient temperature, ð = αab * Tj = Peltier coefficient, I = current.

In the end, the Peltier effect means the release and absorption of heat that occurs when a current flows through a junction between two different materials. If heat is generated when a current flows in one direction, the Peltier effect is reversible because the current absorbs heat when it flows in the opposite direction. When current flows through the junction, in addition to the Joule heat effect that occurs when current flows through the conductor, heat generation or absorption by the Peltier effect occurs.

The first temperature control unit (not shown) made of the above-described thermoelectric element may control the temperature according to the characteristics of the biomaterial. For example, the first temperature control unit (not shown) may control the first temperature of the receiving unit 111 or the first temperature of the biomaterial to have a range of 2 ° C to 5 ° C. Meanwhile, the material accommodating unit 110 further includes a stirring means (not shown) or a vibration means (not shown) for agitating the biomaterial accommodated in the accommodating part 111 so that the biomaterial is maintained in a uniform state. It might be.

Meanwhile, one or more first substrates S1 may be mounted on the plate unit 120. The first substrate S1 is an area in which biomaterials are printed, and a multiwell plate, a petri plate, a glass slide, and the like can be used. The plate unit 120 supports the one or more first substrates S1 described above, and maintains the material properties of the biomaterial printed on the first substrate S1 or sets the second temperature so as to have predetermined properties. It may include a second temperature control unit (not shown) for adjusting. The second temperature is a temperature required for the printed object, and may be different from the first temperature. For example, the second temperature control unit (not shown) may control the second temperature of the plate unit 120 or the second temperature of the first substrate S1 to have a range of 0 ° C to 50 ° C.

1 to 3, the printing unit 130 sucks the biomaterial accommodated in the accommodating portion 111 in a state in which a disposable pipette M1 is replaceable on one side, and on the first substrate S1 Biomaterials can be dispensed and printed according to a preset program. The printing unit 130 according to an embodiment of the present invention is characterized in that it is not connected to a cartridge storing a biomaterial and discharged, but suctions the biomaterial as necessary and dispenses it. To this end, the printing unit 130 may include a nozzle portion 133 and a body portion 131 that controls pressure for inhalation and dispensing of biomaterial from the nozzle portion 133. In addition, a disposable pipette tip M1 is mounted on one side of the nozzle unit 133, and the printing unit 130 can be used by replacing the disposable pipette tip M1 as necessary. In addition, the body portion 131 can control the discharge amount of the biomaterial.

In a comparative example, when the printing unit is connected to a cartridge storing a biomaterial and discharges it, the entire printing unit must be replaced every time the type of biomaterial is changed. have. However, in the case of an embodiment of the present invention, the printing unit 130 can replace the disposable pipette tip M1 and use the body portion 131 and the nozzle portion 133 as it is, through the above-described configuration, theoretically infinite Printing may be possible using a kind of biomaterial close to.

The 3D bio-printer device 10 according to an embodiment of the present invention may further include a pipette tip accommodating part 160 disposed inside the chamber unit 101. The pipette tip accommodating part 160 accommodates a plurality of disposable pipette tips M1 and is disposed on a movement path of the printing unit 130, and after printing with the first biomaterial, the second biomaterial different from the first biomaterial. Preliminary disposable pipette tips for printing with material can be accommodated. The printing unit 130 may remove the used disposable pipette tip M1 after printing of the first biomaterial, and replace it with a new disposable pipette tip M1.

The position adjustment unit 140 may be connected to the printing unit 130 to control the position of the printing unit 130. The position adjusting unit 140 includes a first linear stage 141 that controls the x-direction movement of the printing unit 130, a second linear stage 143 that controls the y-direction movement, and a third linear that controls the z-direction movement. Stage 142 may be included. The position adjusting unit 140 may precisely control movement of the printing unit 130 in the x-axis, y-axis, and z-axis directions by a preset program.

The 3D bio printer apparatus 10 according to an embodiment of the present invention further includes a control unit 210, and controls a discharge amount or a position of the printing unit 130 by a preset program stored in the control unit 210. The unit 140 can be controlled. Here, the controller (not shown) may include all types of devices capable of processing data, such as a processor. Here, a 'processor' may mean a data processing device embedded in hardware having physically structured circuits, for example, to perform functions represented by codes or instructions included in a program. As an example of such a data processing device embedded in hardware, a microprocessor, a central processing unit (CPU), a processor core, a multiprocessor, and an application-specific integrated ASIC circuit), a field programmable gate array (FPGA), and the like, but the scope of the present invention is not limited thereto. Meanwhile, the control unit 210 may also control the first temperature control unit (not shown) and the second temperature control unit (not shown).

Meanwhile, the chamber unit 101 may have an internal space accommodating the above-described components therein. The chamber unit 101 may further include other components required for printing in addition to the above-described configuration, and at least a part for observing the process of printing inside may be made of a transparent window. The transparent window may be made of glass, plexiglass, acrylic, plastic, or the like. The 3D bio printer apparatus 10 may further include a heap filter, and purify the air inside the chamber unit 101.

The 3D bio printer device 10 may further include an ultraviolet irradiation unit 150 and a compression unit 200.

The ultraviolet irradiation unit 150 is disposed on the inside of the chamber unit 101 and may irradiate ultraviolet rays on at least the plate unit 120. The ultraviolet irradiation unit 150 may include an ultraviolet lamp having a wavelength in the range of 300 nm to 500 nm for UV light curing of biomaterials, as well as an ultraviolet lamp for sterilizing the printing area of the plate unit 120.

The crimping unit 200 may seat the second substrate S2 on the first substrate S1 on which the biomaterial is printed, and compress the biomaterial in a controlled state. The second substrate S2 may have the same configuration as the first substrate S1, but this is not necessary. The second substrate S2 may be mounted on the second substrate receiving unit 170, and as shown in FIG. 4, the compression unit 200 may be the second substrate S2 from the second substrate receiving unit 170. Can be mounted on the first substrate S1. The second substrate S2 may be a flat substrate such as cover glass. Through this, the biomaterial P printed on the first substrate S1 may be controlled in height due to the gravity of the second substrate S2. Alternatively, the crimping unit 200 may control the height of the printed biomaterial P by placing the second substrate S2 on the first substrate S1 and applying a constant pressure to compress it.

On the other hand, although not shown, the three-dimensional bio printer device 10 according to an embodiment of the present invention is disposed on the plate unit 120, pressure control means that can provide a negative pressure or positive pressure to the printed biomaterial ( (Not shown) may be further provided. The pressure control means (not shown) provides a positive pressure or a negative pressure to the biomaterial as needed, so that the material can be transferred and constructed, thereby making it possible to build a complex micro-process.

In addition, the three-dimensional bio printer apparatus 10 according to an embodiment of the present invention is a temperature and humidity control unit 180 for controlling the temperature and humidity inside the chamber unit 101, and a control unit 190 for providing input means to the user ) May be further included. The temperature and humidity control unit 180 may maintain the environment of the chamber unit 101 by adjusting the temperature or humidity inside the chamber unit 101. The chamber unit 101 is provided with a temperature sensor or a humidity sensor for measuring the temperature or humidity of the interior space to check the temperature or humidity described above, and the environment of the interior space of the chamber unit 101 based on the measured value Can keep. The control unit 190 provides an input means and an indicator for checking the temperature or humidity level so that the user can control the operation of the 3D bio-printer device 10, and the input means may be provided as a touch monitor.

5 is a flowchart for explaining a 3D bioprinting method according to an embodiment of the present invention, and FIG. 6 is an image of a structure manufactured through an embodiment of the present invention.

Referring to FIG. 5, in the 3D bioprinting method according to an embodiment of the present invention, first, a biomaterial is prepared in a material accommodating unit 110 including one or more accommodating parts 111 (S100).

The printing unit 130 is equipped with a disposable pipette tip (M1) that is not used on one side (S200). Thereafter, the biomaterial accommodated in the accommodation unit 111 is sucked using the printing unit 130 (S300). The biomaterial is dispensed and printed by a predetermined program on the first substrate S1 to be printed using the printing unit 130 (S400). Here, since the printing unit 130 does not accommodate the biomaterial inside, but dispenses the biomaterial stored therein, as described above, the disposable pipette tip does not need to be replaced according to the biomaterial. M1). Therefore, the disposable pipette tip M1 may be removed from the printing unit 130 after printing is completed (S600).

As another embodiment, when printing is completed on the first substrate S1, the second substrate may be seated on the first substrate S1 to be compressed so that the height of the biomaterial can be controlled (S500). As shown in Figure 6, through the above-described method, it is possible to uniformly control the height of the microstructure, it is possible to secure a sophisticated micro-biostructure.

When printing using a plurality of types of biomaterials, when printing of the first biomaterial is completed, after removing the first disposable pipette tip, a new second disposable pipette tip may be mounted on the printing unit 130. Thereafter, the printing unit 130 may inhale the second biomaterial different from the first biomaterial and repeat the above-described process to print.

As described above, the 3D bio printer apparatus and method according to the embodiments of the present invention have various biomaterials through a printing unit that sucks and dispenses biomaterials while printing with a disposable pipette tip. Complex biological tissues can be printed quickly and easily. In addition, the 3D bio-printer apparatus and method according to embodiments of the present invention can secure a fine micro-biostructure by controlling the level difference of the structure using the second substrate.

As described above, the present invention has been described with reference to the embodiment shown in the drawings, but this is only exemplary, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible therefrom. . Therefore, the true technical protection scope of the present invention should be defined by the technical spirit of the appended claims.

10: 3D bio printer device
101: chamber unit
110: material receiving unit
120: plate unit
130: printing unit
140: position adjustment unit
150: ultraviolet irradiation unit

Claims (6)

A material accommodating unit having at least one accommodating part;
A plate unit on which one or more first substrates are seated;
A printing unit that sucks the biomaterial accommodated in the accommodating portion while mounting a replaceable disposable pipette tip on one side, and dispenses and prints the biomaterial on the first substrate by a predetermined program; And
It includes; a position adjustment unit connected to the printing unit to control the position of the printing unit;
And a pressing unit for mounting a second substrate on the first substrate on which the biomaterial is printed, and compressing the biomaterial in a controlled state. According to claim 1,
A chamber unit accommodating the material accommodating unit, the plate unit, the printing unit and the positioning unit therein; And
And disposed on the upper portion of the chamber unit, the ultraviolet irradiation unit irradiating ultraviolet rays on at least the plate unit. According to claim 1,
A pipette tip accommodating portion for accommodating a plurality of the disposable pipette tips. delete Preparing a biomaterial in a material accommodating unit including at least one accommodating part;
Mounting a replaceable disposable pipette tip on one side of the printing unit;
Inhaling the biomaterial accommodated in the accommodating portion using the printing unit;
Dispensing and printing the biomaterial on a first substrate to be printed using the printing unit by a predetermined program; And
And removing the disposable pipette tip from the printing unit after the printing is completed.
Further comprising the step of placing a second substrate on the first substrate on which the biomaterial is printed and compressing the biomaterial in a controlled state, further comprising a three-dimensional bioprinting method.

delete

Images