3D printing platforms, systems, and devices

Abstract

A 3D printing platform is described that includes a stereolithography 3D printing device that utilizes a static optical assembly and a procedural modeling application that represents 3D scenes as signed distance functions. Structures such as bioreactors that can be printed using such a platform, as well as their features and uses, are also described.

Description

[Technical Field]

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 969,434, filed February 3, 2020, and U.S. Provisional Patent Application No. 63 / 010,405, filed April 15, 2020, each of which is incorporated herein by reference in its entirety. [Background technology]

[0002] A crystalline lattice can be a unit (e.g., a symmetric unit) that can contain one-dimensional or multi-dimensional patterns, and when repeated at given intervals (e.g., regular intervals), can create structures, such as crystallographic structures. Such structures have been widely studied in various areas of science and technology.

[0003] In the field of 3D printing, stereolithography (SLA) works by projecting light onto a photosensitive resin contained in a printing bath. The projected light can initiate a polymerization reaction, which can produce a cross-linked polymer structure that can adhere to the printing stage. Summary of the Invention

[0004] Modeling and / or creating objects using crystallographic structures can be time-consuming. Furthermore, depending on the number of crystals involved in a scene, visualizing such scenes using techniques such as mesh-based renderers and / or human manipulation can be very difficult. In many cases, such techniques may require modeling tools that provide adequate functionality to users. In some cases, exploring such complex scenes using traditional geometry-based modeling tools can be computationally expensive and time-consuming, and in some cases, even infeasible.

[0005] Procedural geometry can be an alternative to traditional geometry-based modeling and can involve describing one or more scenes using one or more algorithms as an alternative to or in combination with lists of geometric primitives. Within some areas of computer graphics, procedural modeling can have applications as an alternative or supplement to geometry-based approaches. In some instances, modeling tools such as AutoCAD, SolidWorks, or Inventors can use procedural modeling to generate certain types of geometric shapes. However, for practical reasons, existing tools may not be geared toward efficiently visualizing or manipulating geometry as a function; instead, in most cases, existing tools can convert an implicit representation of a geometry into a list of vertices. In many cases, such approaches can at least partially negate or negate the potential benefits of procedural modeling approaches. Such advantages of the procedural modeling approach may include the ability to efficiently visualize scenes, including large and detailed scenes, and / or the ability to store such visualizations using less disk space, in some cases using only a few bytes of disk space.

[0006] In one aspect, a procedural modeling suite is described herein that offers numerous advantages, such as the ability to visualize and manipulate crystallographic structures composed of countless crystalline lattices at an infinite level of detail. By utilizing storage space, the modeling suite also offers a novel and compact approach to storing these complex scenes in files of only a few kilobytes, instead of wasting terabytes of space to store the geometry of just one scene. In some cases, the procedural modeling suite described herein sends instructions to one or more 3D printing devices so that the modeled structures can be physically realized, benefiting many areas of science and technology.

[0007] In another aspect, described herein is a 3D printing technology that includes improvements to SLA, particularly Digital Light Processing (DLP)-based SLA. In DLP-based SLA, the projection pattern is delivered by a digital mask. A first layer is projected for a predefined time, and once the polymerized layer is attached to the print stage, the print stage moves upward along the Z axis and a second layer is projected. This layer is then attached to the previous layer. Subsequent projections of layers generate a 3D geometry.

[0008] In some embodiments, the DLP-based SLA described herein enables pixel-based modulation and management of light and is suitable for fabricating micrometer-sized structures. Important micrometer-sized structures include, but are not limited to, structures with periodically spatially distributed crystallographic geometries to form crystalline lattices. In some cases, such structures are porous structures, and in further examples, such structures are microfluidic structures. In particular, the 3D printing techniques described herein are suitable for printing continuous-flow microbioreactors at commercial scales and dimensions, such as those disclosed in U.S. Patent Application No. 62 / 743,974 and International Application No. PCT / US19 / 55231, both of which are incorporated by reference in their entireties.

[0009] A major limitation faced in these efforts includes the inability of commercially available SLA technologies (e.g., LCD-, laser-, and DLP-based) to achieve the resolution required for many microstructures. LCD and laser technologies fall short of the required resolution due to pixel size or laser spot size, respectively. Furthermore, commercially available SLA-DLP-based technologies can reach the required resolution only for printing low "hole volume" parts.

[0010] Maintaining high resolution in the 3D printing of large-sized parts is particularly challenging. One approach to printing large parts while maintaining high resolution is known as scanning projection stereolithography. Scanning projection stereolithography is based on the use of a gantry that allows scrolling of a projector under the printing fluid reservoir. With scanning projection stereolithography, the main limitations include mechanical noise being translated into the printing process, resulting in printing errors in the range of the printing resolution, and also slowing down the printing speed of the process due to large distance displacement of the projector across the printing area.

[0011] One continuous 3D printing technique is known as Continuous Liquid Interface Production (CLIP), but with CLIP, the printing volume is small and it is not possible to print large structures. To overcome these limitations of existing approaches, a 3D printing technique based on a static optical setup is proposed for printing large structures with high resolution.

[0012] Accordingly, in one aspect, a stereolithography 3D printing device is disclosed herein, the stereolithography 3D printing device comprising: a light engine configured to project a luxbeam comprising a plurality of pixels along a Z-axis; at least one collimation lens configured to collimate the luxbeam; a microlens array (MLA) configured to focus the collimated luxbeam into a smaller diameter final beam, where each pixel of the luxbeam is subdivided into a plurality of subpixels to increase the resolution of the final beam; and a microdiaphragm array (MDA) configured to reduce noise and crosstalk between lenses of the MLA. The 3D printing device includes: a static optical assembly including a light engine, a collimation lens, an MLA, at least one projection lens, and a movable stage configured to translate one or more of the at least one projection lens in the XY plane; a static optical assembly, wherein a distance along the Z axis between the light engine, a collimation lens, an MLA, the at least one projection lens, and the movable stage of the static optical assembly is fixed; a printing fluid reservoir including a print stage movable on the Z axis; and control circuitry configured to control at least the light engine, the movable stage, and the print stage to achieve stereolithography 3D printing. In some embodiments, the light engine includes a UV (ultraviolet) projector and / or a deep UV projector. In various embodiments, the light engine has an operating wavelength between 370 nm and 415 nm. In certain embodiments, the light engine has an operating wavelength of about 405 nm. In other specific embodiments, the light engine has an operating wavelength of about 380 nm. In some embodiments, the light engine is a first light engine configured to project a first operating wavelength, and the 3D printing device further includes a second light engine configured to project a second operating wavelength. In a further embodiment, the second light engine operates in parallel with the first light engine, and the second operating wavelength is selected to inhibit polymerization of the photocurable resin in the printing fluid reservoir.In some embodiments, the light engine comprises a digital micromirror device (DMD). In various further embodiments, the DMD has a resolution of about 2560 pixels by about 1600 pixels. In some embodiments, the light engine comprises a liquid crystal on silicon (LCoS) device. In various further embodiments, the LCoS device has a resolution of about 4096 pixels by about 2400 pixels. In certain embodiments, the light engine has a light-generating area of ​​about 90 mm by about 50 mm. In other specific embodiments, the light engine has a light-generating area of ​​about 140 mm by about 90 mm. In some embodiments, the 3D printing device comprises a system of collimation lenses. In further embodiments, the system of collimation lenses comprises between two and six collimation lenses. In some embodiments, the movable stage comprises a piezoelectric mechanism configured to translate one or more of the at least one projection lens in the XY plane. In further embodiments, the piezoelectric mechanism translates one or more of the at least one projection lens in the XY plane with nanometer resolution. In further embodiments, the stage has a translation range of at least 50 μm on the X axis and at least 50 μm on the Y axis. In still further embodiments, the stage has a translation range of approximately 100 μm on the X axis and approximately 100 μm on the Y axis. In some embodiments, the stage has a translation resolution of a subpixel length or less. In various embodiments, the MLA comprises a biconvex array, a biconcave array, a uniconvex array, a uniconcave array, or a combination thereof. In certain further embodiments, the MLA comprises a monolithic biconvex array. In some embodiments, the MLA comprises a planar substrate and a plurality of microlenses on each of the two largest opposing sides of the substrate plane. In various further embodiments, the planar substrate is borosilicate glass or etched glass, and the plurality of microlenses is polymer or glass.In certain embodiments, the MDA is positioned between the planar substrate and one of the microlenses of the MLA. In some embodiments, the 3D printing device includes multiple MDAs, for example, two, three, or four MDAs. In various embodiments, the MDA has a diaphragm aperture size of 10 μm to 15 μm. In various embodiments, the MLA subdivides each pixel of the Lux beam into between 4 and 7498 subpixels. In further various embodiments, the MLA subdivides each pixel of the Lux beam into between 4 and 100 subpixels. In certain embodiments, the MLA subdivides each pixel of the Lux beam into 9 subpixels. In other specific embodiments, the MLA subdivides each pixel of the Lux beam into 25 subpixels. In other specific embodiments, the MLA subdivides each pixel of the Lux beam into 49 subpixels. In some embodiments, at least one projection lens magnifies the final print area. In alternative embodiments, the at least one projection lens reduces the final printing area. In some embodiments, the final printing area is at least two times the light generation area of ​​the light engine. In further embodiments, the final printing area is at least four times the light generation area of ​​the light engine. In some embodiments, the control circuitry is configured to control at least the light engine, the movable stage, and the print stage to achieve stereolithography 3D printing in a semi-continuous, substantially continuous, or continuous pattern. In some embodiments, the control circuitry is configured to control the print stage to move at a predefined constant velocity in the Z axis. In some embodiments, the control circuitry is configured to control the movable stage to translate one or more projection lenses of the at least one projection lens in the XY plane to scan the Lux beam in the predefined pattern. In further embodiments, the predefined pattern comprises a spiral pattern. In some embodiments, the predefined pattern comprises a continuous space-filling curve.In further embodiments, the predefined pattern comprises a Sierpinski curve. In certain non-limiting embodiments, the control circuitry is configured to control at least the light engine, the movable stage, and the print stage to achieve stereolithographic 3D printing of porous structures comprising periodically spatially distributed gyroid geometries. In some embodiments, the 3D printing device further comprises a robotic gantry configured to scroll the static optical assembly in the XY plane relative to the printing fluid vat. In further embodiments, the control circuitry is further configured to control the robotic gantry. In some embodiments, the control circuitry is configured to control the print stage to achieve bottom-up stereolithographic 3D printing. In an alternative embodiment, the control circuitry is configured to control the print stage to achieve top-down stereolithographic 3D printing. In some embodiments, the printing fluid vat comprises a multi-phase photocurable resin. In some embodiments, the 3D printing device is configured for sterile 3D printing, and the printing fluid vat comprises a sterile photocurable resin.

[0013] In another aspect, disclosed herein is a computer-implemented system including at least one processor, a memory, and instructions executable by the at least one processor to create a procedural modeling application, the procedural modeling application including: a presentation module configured to represent the scene as a signed distance function and render the scene by utilizing ray marching, the presentation module including: a scene library including one or more procedural objects (POs); a scene editor that allows a user to add one or more POs to the scene and create a constructive solid geometry (CSG) tree for the scene; a procedural object (PO) editor that allows a user to edit properties of each PO added to the scene; a simulation editor that allows a user to configure one or more simulations of the scene; and a print editor that allows a user to configure the scene for printing; a simulation module configured to perform one or more simulations in the scene; and a print module configured to generate a queue of slice files and send the slice files to a 3D printer. In some embodiments, the presentation module allows a user to add a PO to a scene by dragging a PO from a scene library and dropping the PO into a viewport. In some embodiments, the presentation module allows a user to save an edited PO to the scene library. In some embodiments, one or more POs comprise a crystallography unit. In further embodiments, the presentation module allows a user to duplicate a crystallography unit to form a crystal lattice in a scene. In some embodiments, properties of a PO include links for connecting to one or more adjacent POs and conduits connecting the links.In some embodiments, the signed distance function includes a mathematical equation that represents the entire crystal lattice. In certain non-limiting embodiments, the crystallography unit comprises a gyroid. In further certain non-limiting embodiments, the crystal lattice comprises a periodically spatially distributed gyroid geometry. In some embodiments, the signed distance function does not include a list of geometric primitives. In various embodiments, the one or more simulations include one or more of a microfluidics simulation, a computational fluid dynamics (CFD) simulation, use of a lattice Boltzmann method (LBM) combined with a signed distance function to solve a CFD simulation, or a combination thereof. In some embodiments, the one or more simulations include visualization of one or more features of the simulation. In various embodiments, the print editor allows a user to configure one or more of a surface profile, a printer run order, layer thicknesses, a Lux beam exposure time, and a pixel resolution. In some embodiments, performance of the procedural modeling application does not degrade with increasing scene size or scene detail. In some embodiments, the at least one processor comprises a plurality of graphics processing units (GPUs). In some embodiments, the at least one processor comprises a cloud computing platform.

[0014] In another aspect, disclosed herein is a non-transitory computer-readable storage medium encoded with instructions executable by at least one processor for creating a procedural modeling application, the procedural modeling application including: a graphical user interface (GUI) with a viewport; a presentation module configured to render the scene by representing the scene as a signed distance function and utilizing ray marching, the presentation module including: a scene library including one or more procedural objects (POs); a scene editor that allows a user to add one or more POs to the scene and creates a constructive solid geometry (CSG) tree for the scene; a procedural object (PO) editor that allows a user to edit properties of each PO added to the scene; a simulation editor that allows a user to configure one or more simulations of the scene; and a print editor that allows a user to configure the scene for printing; a simulation module configured to perform one or more simulations of the scene; and a print module configured to generate a queue of slice files and send the slice files to a 3D printer. In some embodiments, the presentation module allows a user to drag a PO from a scene library and drop the PO into a viewport to add the PO to a scene. In some embodiments, the presentation module allows a user to save an edited PO to the scene library. In some embodiments, one or more POs comprise a crystallography unit. In further embodiments, the presentation module allows a user to duplicate a crystallography unit to form a crystal lattice in the scene. In some embodiments, the properties of the PO include links for connecting the PO to one or more adjacent POs and conduits connecting the links. In some embodiments, the signed distance function includes a mathematical equation that represents the entire crystal lattice. In certain non-limiting embodiments, the crystallography unit comprises a gyroid.In further specific, non-limiting embodiments, the crystal lattice comprises periodically spatially distributed gyroid geometries. In some embodiments, the signed distance function does not include a list of geometric primitives. In various embodiments, the one or more simulations include one or more of a microfluidics simulation, a computational fluid dynamics (CFD) simulation, using a lattice Boltzmann method (LBM) in combination with a signed distance function to solve a CFD simulation, or a combination thereof. In some embodiments, the one or more simulations include visualization of one or more features of the simulation. In various embodiments, the print editor allows a user to configure one or more of a surface profile, a printer run order, a layer thickness, a Lux beam exposure time, and a pixel resolution. In some embodiments, performance of the procedural modeling application does not degrade with increasing scene size or scene detail. In some embodiments, the at least one processor comprises multiple graphics processing units (GPUs). In some embodiments, the at least one processor comprises a cloud computing platform.

[0015] In another aspect, a computer-implemented method for procedural modeling is disclosed herein, the method including providing a procedural modeling application, the procedural modeling application including: a scene library including one or more procedural objects (POs); a scene editor that allows a user to add one or more POs to a scene and creates a constructive solid geometry (CSG) tree for the scene; a procedural object (PO) editor that allows a user to edit properties of each PO added to the scene; a simulation editor that allows a user to configure one or more simulations of the scene; and a print editor that allows a user to configure the scene for printing; representing the scene as a signed distance function; rendering the scene by utilizing ray marching; performing one or more simulations in the scene; generating a queue of slice files; and sending the slice files to a 3D printer. In some embodiments, a presentation module allows a user to drag a PO from the scene library and drop the PO into a viewport to add the PO to the scene. In some embodiments, the presentation module allows a user to save an edited PO to the scene library. In some embodiments, one or more POs comprise crystallography units. In further embodiments, the presentation module allows a user to replicate crystallography units to form a crystal lattice within the scene. In some embodiments, the properties of the POs include links for connecting to one or more adjacent POs and conduits connecting the links. In some embodiments, the signed distance function includes a mathematical equation representing the entire crystal lattice. In certain non-limiting embodiments, the crystallography units comprise gyroids. In further certain non-limiting embodiments, the crystal lattice comprises periodically spatially distributed gyroid geometries. In some embodiments, the signed distance function does not include a list of geometric primitives.In various embodiments, the one or more simulations include one or more of a microfluidics simulation, a computational fluid dynamics (CFD) simulation, using a lattice Boltzmann method (LBM) in combination with a signed distance function to solve a CFD simulation, or a combination thereof. In some embodiments, the one or more simulations include visualization of one or more features of the simulation. In various embodiments, a print editor allows a user to configure one or more of a surface profile, a printer run order, layer thicknesses, a Lux beam exposure time, and a pixel resolution.

[0016] In another aspect, disclosed herein is a method for fabricating a 3D object comprising a plurality of repeating units, the method including providing a procedural modeling application that enables a user to at least: add one or more crystallography units to a 3D scene; replicate the one or more crystallography units to form a crystal lattice within the scene; and configure links to connect the replicated crystallography units and conduits connecting the links; create a constructive solid geometry (CSG) tree for the scene; represent the 3D scene as a signed distance function; render the scene by utilizing ray marching; generate a queue of slice files; and send the slice files to a 3D printing device, such as a stereolithography 3D printing device. In some embodiments, the crystallography units are spatially distributed periodically to form the crystal lattice. In various embodiments, the procedural modeling application further allows a user to perform at least one of: selecting one or more crystallographic units from a scene library; editing properties of each crystallographic unit added to the scene; configuring one or more simulations of the scene; and configuring the scene for 3D printing. In some embodiments, the method further includes performing one or more simulations within the scene. In further embodiments, the one or more simulations include a microfluidics simulation. In other embodiments, the one or more simulations include a computational fluid dynamics (CFD) simulation. In still other embodiments, the one or more simulations include using a lattice Boltzmann method (LBM) in combination with a signed distance function to solve the CFD simulation. In some embodiments, the one or more simulations include visualization of one or more features of the simulation.In some embodiments, the signed distance function includes a mathematical equation that represents the entire crystal lattice. In some embodiments, the signed distance function does not include a list of geometric primitives. In some embodiments, the crystallographic units are densely repeated in the crystal lattice. In certain non-limiting embodiments, the 3D object comprises a bioreactor.

[0017] In another aspect, a method for fabricating a bioreactor is disclosed herein, the method including providing a procedural modeling application that enables a user to add a plurality of mini-modules to a 3D scene and assemble the plurality of mini-modules into a macrostructure to create the bioreactor; creating a constructive solid geometry (CSG) tree for the scene; representing the 3D scene as a signed distance function; rendering the scene by utilizing ray marching; generating a queue of slice files; and sending the slice files to a stereolithography 3D printing device. In some embodiments, one or more of the mini-modules are double gyroids (DG) or modified DG. In some embodiments, the mini-modules are arranged in multiple layers within the macrostructure. In further embodiments, the multiple layers are assembled into a first matrix and a second matrix, where the second matrix occupies the free space within the first matrix, and the first matrix and the second matrix occupy the same volume, have no contact points, and maintain a constant minimum distance. In some embodiments, the 3D scene and slice files are configured for a printing surface of up to about 320 mm x 320 mm. In some embodiments, the cubic mm volume of the 3D scene contains up to about 14 mini-modules. In some embodiments, the printing volume of the bioreactor is up to about 102,400,000 cubic mm. In some embodiments, the printing volume of the bioreactor contains up to about 1,496,704,035 mini-modules. In some embodiments, one or more of the mini-modules comprise channels, the channels having diameters of about 8 μm to about 2000 μm. In various embodiments, each mini-module has an edge length of about 40 μm to about 9797 μm. In various embodiments, each mini-module has an edge length of about 68417 to about 9.4×10 11 has a volume of cubic millimeters

[0018] In another aspect, a bioreactor is disclosed herein, the bioreactor comprising: a plurality of volumes, each volume comprising a crystallography unit symmetrically repeated in a three-dimensional crystal lattice, each three-dimensional crystal lattice functionalized and fluidly interconnected to provide at least one microchannel or chamber; an inoculation microchannel configured to receive a plurality of cells into the bioreactor; a harvest microchannel configured to receive a plurality of cells or derivatives thereof from the bioreactor; a first channel system comprising at least one microchannel formed by at least one microchannel or chamber in one or more of the plurality of volumes; and a second channel system comprising at least one microchannel formed by at least one microchannel or chamber in one or more of the plurality of volumes; the first channel system and the second channel system providing separate inputs to the bioreactor. In some embodiments, the bioreactor is a bubble-free bioreactor. In some embodiments, the bioreactor produces a continuous laminar flow of a medium. In some embodiments, the bioreactor produces a continuous laminar flow of a gas. In some embodiments, the bioreactor has a spherical topology. In further embodiments, the multiple volumes are arranged in concentric layers at various distances from the center of the spherical topology. In various embodiments, the bioreactor comprises 3, 4, 5, 6, 7, 8, 9, or 10 volumes. In certain embodiments, the bioreactor comprises 8 volumes. In some embodiments, the crystallography unit comprises a double gyroid structure or a modified double gyroid structure. In some embodiments, the inoculation channel delivers the multiple cells to the central volume of the bioreactor. In some embodiments, the first channel system is a liquid medium system fluidly connected to the inoculation microchannel and the harvest microchannel. In further embodiments, the medium system further comprises at least one medium intake microchannel. In further embodiments, the bioreactor further comprises a liquid medium input device configured to allow liquid medium to flow into each medium intake microchannel.In further embodiments, the media system is configured to provide uniform media distribution. In some embodiments, the plurality of volumes comprises one or more volumes functionalized for cell culture. In certain embodiments, the plurality of volumes comprises four volumes functionalized for cell culture. In some embodiments, the second channel system is a gas system. In further embodiments, the gas system further comprises at least one gas intake microchannel. In further embodiments, the gas system fluidly connects the at least one gas intake microchannel to the exterior of the bioreactor. In further embodiments, the bioreactor further comprises a gas input device configured to introduce a gas composition into each gas intake microchannel. In further embodiments, the gas system is configured to provide uniform gas distribution. In some embodiments, the plurality of volumes comprises one or more volumes functionalized for gas distribution and comprising a gas distribution chamber. In certain embodiments, the plurality of volumes comprises five volumes functionalized for gas distribution and comprising a gas distribution chamber. In some embodiments, the media system and the gas system are non-overlapping systems separated by one or more porous membranes. In some embodiments, the plurality of volumes comprises a collection layer in fluid communication with the collection microchannel and comprising a collection chamber. In some embodiments, the bioreactor further comprises an outer layer. In some embodiments, the plurality of volumes comprises one or more transition layers between volumes of different functionalization, and the crystallography unit comprises transition crystals.

[0019] In another aspect, disclosed herein is a method of growing a plurality of cells or derivatives thereof, the method comprising providing a bioreactor, the bioreactor comprising a crystallography unit, each volume of which is symmetrically repeated in a three-dimensional crystal lattice, each three-dimensional crystal lattice being functionalized and fluidly interconnected to provide at least one microchannel or chamber; an inoculation microchannel configured to receive a first plurality of cells into the bioreactor; a harvest microchannel configured to receive a second plurality of cells or a bio-product from the bioreactor; and a microchannel formed by at least one microchannel or chamber in one or more of the plurality of volumes. The method includes providing a first channel system including at least one microchannel; and a second channel system including at least one microchannel formed by at least one microchannel or chamber in one or more of the multiple volumes, the first channel system and the second channel system providing separate inputs to the bioreactor; and directing a first plurality of cells to the inoculation microchannel, wherein the plurality of cells flows from the inoculation microchannel through at least one microchannel or chamber in the multiple volumes, and the first plurality of cells undergoes cell growth to produce a second plurality of cells. In some embodiments, the method further includes harvesting the second plurality of cells or a subpopulation thereof from the harvest microchannel. In some embodiments, the second plurality of cells or a subpopulation thereof produces a bioproduct. In some embodiments, the method further includes harvesting the bioproduct from the harvest channel. In some embodiments, the bioproduct is a protein, an antibody, a small molecule, and / or a metabolite. In some embodiments, the first plurality of cells comprises prokaryotic cells. In some embodiments, the first plurality of cells comprises eukaryotic cells. In various embodiments, the plurality of cells is selected from the group consisting of bacterial cells, fungal cells, yeast cells, algal cells, plant cells, avian cells, mammalian cells, and any combination thereof. In some embodiments, the bioreactor is a bubble-free bioreactor.In some embodiments, the bioreactor produces a continuous laminar flow of medium. In some embodiments, the bioreactor produces a continuous laminar flow of gas. In some embodiments, the bioreactor has a spherical topology. In further embodiments, multiple volumes are arranged in concentric layers at various distances from the center of the spherical topology. In various embodiments, the bioreactor includes 3, 4, 5, 6, 7, 8, 9, or 10 volumes. In certain embodiments, the bioreactor includes 8 volumes. In some embodiments, the crystallography unit includes a double gyroid structure or a modified double gyroid structure. In some embodiments, the inoculation channel delivers a plurality of cells to a central volume of the bioreactor. In some embodiments, the first channel system is a liquid medium system fluidly connected to the inoculation microchannel and the harvest microchannel. In further embodiments, the medium system further includes at least one medium intake microchannel. In further embodiments, the bioreactor further includes a liquid medium input device configured to direct liquid medium into each medium intake microchannel. In further embodiments, the medium system is configured to provide uniform distribution of medium. In some embodiments, the plurality of volumes comprises one or more volumes functionalized for cell culture. In certain embodiments, the plurality of volumes comprises four volumes functionalized for cell culture. In some embodiments, the second channel system is a gas system. In further embodiments, the gas system further comprises at least one gas intake microchannel. In further embodiments, the gas system fluidly connects the at least one gas intake microchannel and the exterior of the bioreactor. In further embodiments, the bioreactor further comprises a gas input device configured to flow a gas composition into each gas intake microchannel. In further embodiments, the gas system is configured to provide uniform distribution of gas. In some embodiments, the plurality of volumes comprises one or more volumes functionalized for gas distribution and comprising a gas distribution chamber.In certain embodiments, the plurality of volumes comprises five volumes functionalized for gas distribution and comprising gas distribution chambers. In some embodiments, the media system and the gas system are non-overlapping systems separated by one or more porous membranes. In some embodiments, the plurality of volumes comprises a collection layer in fluid communication with the collection microchannel and comprising a collection chamber. In some embodiments, the bioreactor further comprises an outer layer. In some embodiments, the plurality of volumes comprises one or more transition layers between differently functionalized volumes, and the crystallography unit comprises transition crystals.

[0020] In another aspect, disclosed herein is a computer-implemented system for creating a procedural modeling application, comprising at least one processor, a memory, and instructions executable by the at least one processor, the procedural modeling application including: an interface that enables a user to define at least one volume within a scene; identify crystallographic units for the at least one volume; identify symmetries for the crystallographic units; and edit properties of the crystallographic units; replicate the identified crystallographic units according to the identified symmetries to generate a three-dimensional crystal lattice, the three-dimensional crystal lattice being functionalized and fluidly interconnected to provide at least one microchannel or chamber; represent the scene as a signed distance function; and render the scene; a simulation editor that enables a user to configure one or more simulations of the scene; a simulation module that is configured to perform one or more simulations within the scene; a print editor that enables a user to configure the scene for printing; and a print module that is configured to generate a queue of slice files and send the slice files to a 3D printer. In some embodiments, the interface further allows a user to configure one or more microchannels within at least one volume. In some embodiments, at least one microchannel or chamber comprises a fluidly continuous liquid or gas transport system. In some embodiments, the characteristics of the crystallography units include links connecting one or more adjacent crystallography units and conduits connecting the links. In some embodiments, the signed distance function comprises a mathematical equation representing the entire crystal lattice. In some embodiments, the crystallography units comprise a gyroid. In further embodiments, the crystal lattice comprises periodically spatially distributed gyroid geometries.In some embodiments, the procedural modeling application further includes a deep learning algorithm trained to predict transition volumes between volumes of different functionalizations and transition crystallographic units for the transition volumes. In some embodiments, the algorithm includes one or more neural networks (NNs). In various further embodiments, the one or more NNs include one or more generative adversarial networks (GaNs) or one or more variational autoencoders (VAEs). In some embodiments, the one or more simulations include finite element analysis (FEA). In some embodiments, the one or more simulations evaluate microfluidic continuity of at least one microchannel or chamber. In some embodiments, the signed distance function does not include a list of geometric primitives. In some embodiments, performance of the procedural modeling application does not degrade with increasing scene size or scene detail. In some embodiments, the at least one processor includes multiple graphics processing units (GPUs). In some embodiments, the at least one processor comprises a cloud computing platform.

[0021] A better understanding of the features and advantages of the present subject matter will be achieved by reference to the following detailed description and accompanying drawings that set forth illustrative embodiments. [Brief explanation of the drawings]

[0022] [Figure 1] FIG. 1 shows an example of a crystallographic structure with a 3D geometry; in this case, a three-dimensional pattern formed by unit cells that are repeated at regular intervals. [Figure 2]Rasterization Pipeline: A non-limiting schematic diagram of a rasterization pipeline that starts with a 3D mesh and includes performing vertex processing, rasterization, raster operations, and fragment processing to produce an image output, in this case. [Figure 3] Ray tracing method; in this case, a non-limiting schematic diagram of the ray tracing method, which involves casting rays from the camera origin to find what part of the scene each ray covers. [Figure 4] Flowchart; in this case, a non-limiting example of a flowchart illustrating the ray-marching pipeline used to fully represent a procedural environment from a single mathematical equation such as a signed distance function. [Figure 5] FIG. 1 illustrates a non-limiting example of a ray marching method used to render a 3D scene; in this case, rays are cast from a virtual camera viewing the 3D scene, and for each ray, the technique involves marching in the direction of the ray and, at each step, evaluating a mathematical equation that represents the scene to calculate how far the ray is from the closest point on the surface. [Figure 6] FIG. 1 illustrates a non-limiting example of a ray marching method used to render a 3D scene; in this case, rays are cast from a virtual camera viewing the 3D scene, and for each ray, the technique involves marching in the direction of the ray and, at each step, evaluating a mathematical equation that represents the scene to calculate how far the ray is from the closest point on the surface. [Figure 7] FIG. 1 illustrates a non-limiting example of a ray marching method used to render a 3D scene; in this case, rays are cast from a virtual camera viewing the 3D scene, and for each ray, the technique involves marching in the direction of the ray and, at each step, evaluating a mathematical equation that represents the scene to calculate how far the ray is from the closest point on the surface. [Figure 8]A non-limiting platform architecture diagram; in this case, a platform architecture diagram that includes a software suite with a present module, save module, simulation module, and print module used by model and simulation designers, a 3D printer device, and a cloud computing system. [Figure 9] FIG. 1 illustrates a non-limiting example of a graphic user interface (GUI) overview for a procedural modeling application; in this case, a GUI overview including a central viewport, a window displaying a CSG tree representation of the current scene, a scene library containing procedural objects, and a window displaying the properties of the currently selected procedural object. [Figure 10] FIG. 10 illustrates a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI that allows a user to select a procedural object, and interface elements are provided for the user to edit the properties of the procedural object. [Figure 11] FIG. 1 shows a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI that allows a user to select a texture, where formatting and previews are provided. [Figure 12] FIG. 10 illustrates a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI that allows a user to drag a procedural object from a scene library, drop the procedural object into a procedural object editor, and begin editing the properties of the procedural object. [Figure 13]FIG. 1 illustrates a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI that allows a user to observe editable properties of a selected procedural object (e.g., a cubic crystal) shown in a viewport and create multiple crystal cells from the cubic crystal. [Figure 14] FIG. 10 illustrates a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI that allows a user to set links for each face of a cubic crystal procedural object and set positions for the links on the faces, for example to form a gyroid. [Figure 15] FIG. 1 shows a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI that allows a user to save an edited procedural object (a gyroid unit cell) to a scene library. [Figure 16] FIG. 10 illustrates a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI that allows a user to identify saved procedural objects within a scene library, where the edited procedural object (a gyroid unit cell) inherits properties from the procedural object from which it was created, and where the GUI also allows a user to duplicate the procedural object to form a crystal lattice, such as a gyroid lattice. [Figure 17] FIG. 1 illustrates a non-limiting example of a flowchart showing the process by which a user interacts with an application that creates, edits, and saves procedural objects, in this case from previously created objects. [Figure 18] FIG. 1 shows a non-limiting example of a flowchart illustrating a process for a user to interact with an application, in this case to create and edit new procedural objects. [Figure 19]FIG. 1 shows a non-limiting example of a schematic diagram of a crystalline unit cell; in this case, a schematic diagram showing the nomenclature of crystalline unit cell features such as faces, links, and conduits. [Figure 20] FIG. 1 shows a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI showing the setup of a simulation to be carried out within a 3D scene model. [Figure 21] FIG. 1 shows a non-limiting example of a GUI for a procedural modeling application; in this case, a GUI showing the results of a simulation performed within a 3D scene model. [Figure 22] Architectural Diagram; in this case, a non-limiting example of an architecture diagram for a slicer and printer synchronization module. [Figure 23] Schematic structural diagram for a 3D printer device; in this case, a non-limiting example of a schematic structural diagram for a 3D printer device including a Lux beam generating element, a collimator lens, a monolithic MLA, and a series of projection lenses, one of which is linked by a piezoelectric stage. [Figure 24] FIG. 10 shows a non-limiting example of a diagram of the piezoelectric stage movement of the projection lens and its effect on the Lux beam scan path; in this case, the scan path demonstrates a semi-continuous brick printing process with a spiral pattern. [Figure 25A] 1 is a diagram of a non-limiting example showing piezoelectric stage movement of a projection lens and its effect on a Lux beam; in this case, XY plane pixel displacement of the Lux beam within a pixel field. [Figure 25B] 1 is a diagram of a non-limiting example showing piezoelectric stage movement of a projection lens and its effect on a Lux beam; in this case, XY plane pixel displacement of the Lux beam within a pixel field. [Figure 25C]1 is a diagram of a non-limiting example showing piezoelectric stage movement of a projection lens and its effect on a Lux beam; in this case, XY plane pixel displacement of the Lux beam within a pixel field. [Figure 26] FIG. 1 shows a non-limiting example of a diagram illustrating a brick printing process; in this case, an object being printed by a semi-continuous brick printing process. [Figure 27] 1 shows a non-limiting example of a schematic structural diagram for a 3D printer device; in this case, including a light engine, a collimator, a monolithic MLA, a piezoelectric element, a series of projection lenses, a reservoir window, a volume of photocurable (e.g., light-curable) resin, and a print bed, as well as guides and threaded rods capable of producing a print result. [Figure 28] FIG. 1 illustrates a non-limiting example of a light engine for a 3D printing device. [Figure 29] FIG. 1 illustrates a non-limiting example of an amplitude modulation element for a 3D printing device. [Figure 30A] FIG. 1 shows a non-limiting example of a microlens; in this case, a single biconvex microlens. [Figure 30B] 1 shows a non-limiting example of a structural diagram of an MLA; in this case, an MLA comprising a planar substrate and an array of microlenses applied to the largest opposing planar surfaces of each of the substrates. [Figure 30C] FIG. 1 shows a non-limiting example of an optical diagram of an MLA; in this case, an optical diagram including the light path through a first array of microlenses, a substrate, and a second array of microlenses. [Figure 31] FIG. 1 illustrates a non-limiting example of a piezoelectric stage for a 3D printing device. [Figure 32]FIG. 1 illustrates a non-limiting example of a processing (e.g., computing) device; in this case, a device having one or more processors, memory, storage, and a network interface. [Figure 33A] FIG. 1 shows an example of a mini-module in an example schema for assembling mini-modules into a macro-structure. [Figure 33B] FIG. 10 shows an example of assembling mini-modules into an example three-dimensional matrix in an example schema for assembling mini-modules into a macrostructure. [Figure 33C] FIG. 1 shows an example of a three-dimensional matrix in an example schema for assembling mini-modules into a macrostructure. [Figure 33D] FIG. 1 shows an example layer of a three-dimensional matrix in an example schema for assembling mini-modules into a macrostructure. [Figure 33E] FIG. 1 shows an example assembly comprising multiple three-dimensional layers in an example schema for the assembly of mini-modules into a macrostructure. [Figure 33F] FIG. 1 shows an example assembly comprising multiple three-dimensional layers in an example schema for the assembly of mini-modules into a macrostructure. [Figure 34A] 1A-1C show examples of layer assemblies of various shapes, for example, square and square-like assembly shapes. [Figure 34B] 1A-1C show examples of layer assemblies of various shapes, for example, square and square-like assembly shapes. [Figure 34C] 1A-1C show examples of layer assemblies of various shapes, for example, square and square-like assembly shapes. [Figure 34D] 1A-1C show examples of layer assemblies of various shapes, for example, square and square-like assembly shapes. [Figure 33E] 1A-1C show examples of layer assemblies of various shapes, for example, square and square-like assembly shapes. [Figure 33F]1A-1C show examples of layer assemblies of various shapes, for example, square and square-like assembly shapes. [Figure 35A] FIG. 10 illustrates an example of a module layer connected to an example supply circuit. [Figure 35B] FIG. 10 illustrates an example of a module layer connected to an example supply circuit. [Figure 35C] FIG. 10 illustrates an example of a module layer connected to an example supply circuit. [Figure 35D] FIG. 10 illustrates an example of a module layer connected to an example supply circuit. [Figure 35E] FIG. 10 illustrates an example of a module layer connected to an example supply circuit. [Figure 35F] FIG. 10 illustrates an example of a module layer connected to an example supply circuit. [Figure 36] FIG. 1 illustrates example layers for a hollow pyramid shape. [Figure 37A] FIG. 1 provides an example of growth for a hollow pyramid shape. [Figure 37B] FIG. 1 provides an example of growth for a hollow pyramid shape. [Figure 38] FIG. 10 shows an external feed circuit for a hollow pyramid shape. [Figure 39] FIG. 1 is a diagram showing an example of a lamellar macrostructure. [Figure 40] FIG. 1 shows an example of a lamellar macrostructure with a supply circuit. [Figure 41] FIG. 1 illustrates an example macro structure. [Figure 42] FIG. 1 illustrates an example supply and collection arrangement. [Figure 43A] FIG. 10 shows an overview of an example connection system including a connector between a cell chip module and a fluid source. [Figure 43B] FIG. 1 shows a schematic of an example connection system with input and output needles. [Figure 43C] FIG. 1 illustrates an example connection made by an example connection system. [Figure 43D]10A-10C illustrate an example embodiment of a connection system having needles that penetrate chambers in an example cell chip module. [Figure 43E] 10A-10C illustrate an example connection system having a needle that penetrates the second chamber. [Figure 44] FIG. 1 shows a schema for an example method of cell growth, storage, environmental optimization, and scale-up production. [Figure 45] FIG. 1 shows the cubic growth rate of a spherical structure with respect to its radius. [Figure 46A] 1 is a cross-sectional view of an example sphere bioreactor and its components. [Figure 46B] 1 is a cross-sectional view of an example sphere bioreactor and its components. [Figure 47] FIG. 1 shows an example of an example sphere bioreactor. [Figure 48] FIG. 1 shows an example of the internal mini-modules or building blocks of an example bioreactor and the internal components such as channels, conduits, and chambers configured for fluid flow within the bioreactor. [Figure 49] FIG. 1 illustrates a mathematical representation of a structure in accordance with the method and system of the present disclosure. [Figure 50] 1A-1C illustrate mathematical and geometric representations of structures in accordance with the methods and systems of the present disclosure. [Figure 51A] 1A-1C illustrate example structures such as shapes or mini-modules that can be constructed according to the methods of the present disclosure. [Figure 51B] 1A-1C illustrate example structures such as shapes or mini-modules that can be constructed according to the methods of the present disclosure. [Figure 52] FIG. 1 illustrates an example 3D sphere macrostructure and its voxelized representation. [Figure 53] 1A-1C illustrate the structure of several example connectors provided herein. [Figure 54] FIG. 1 illustrates an example 3D printer optics configuration with a micro-diaphragm array and a micro-lens array. [Figure 55A]FIG. 1 is a diagram of an example of a 3D printer device including a secondary wavelength generator. [Figure 55B] FIG. 1 is a diagram of an example of a 3D printer device including a secondary wavelength generator. [Figure 56A] FIG. 10 is an example diagram of a 3D printer device including a coating on the liquid reservoir window. [Figure 56B] FIG. 10 is an example diagram of a 3D printer device including a coating on the liquid reservoir window. [Figure 57A] FIG. 1 illustrates the printing process for an example 3D printed bioreactor. [Figure 57B] FIG. 10 shows a digital rendering of the 3D printed bioreactor and cross-sectional views as a function of location height. [Figure 58] FIG. 1 shows an example 3D printer device and printed bioreactor. DETAILED DESCRIPTION OF THE INVENTION

[0023] Systems, methods, and devices for printing objects are provided herein. The systems, devices, and methods may include devices and methods for 3D printing objects.

[0024] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this subject matter belongs. As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Any reference herein to "or" is intended to encompass "and / or" unless stated otherwise.

[0025] Whenever the terms "at least," "greater than," or "greater than or equal to" are associated with the first number in a series of two or more numbers, the term "at least," "greater than," or "greater than or equal to" applies to each and every number in the series. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0026] Whenever the terms "no more than," "less than," or "less than or equal to" follow the first number in a series of two or more numbers, the terms "no more than," "less than," or "less than or equal to" apply to each of the numbers in the series. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0027] As used herein, the term "unit cell" generally refers to the smallest repeating unit having a perfectly symmetrical crystallographic structure (see, for example, 105 in Figure 1).

[0028] As used herein, the term "crystal lattice" generally refers to a unit having a three-dimensional pattern that, when repeated, creates a crystallographic structure (see, for example, 110 in Figure 1).

[0029] As used herein, the term "gyroid" generally refers to a connected, periodic, minimal surface that does not contain straight lines. Such surfaces can have mathematically infinite connections. In some instances, gyroids are unique, important, embedded members of a related family of Schwarz P and D surfaces with a bond angle of association of approximately 38.01°. Gyroids can be configured as single gyroids or double gyroids. Double gyroids can be oriented and configured for specific applications in microfluidic devices. Double gyroids can be constructed by balancing geometric aspects related to the hydrodynamic performance observed in minimodules and macrostructures (e.g., macroshapes), such as double gyroid crystallographic structures and space groups. Gyroids or double gyroids can be implemented in a variety of crystallographic structures.

[0030] As used herein, the term "production bioreactor" or "bioreactor" generally refers to a bioreactor device suitable for scaling the production of cells and / or products produced by the cells. A production bioreactor may include one or more channels or other openings for inputting cells and providing liquid media, gas compositions, and other cellular environmental factors, as well as one or more channels for harvesting cells and / or products produced by the cells.

[0031] As used herein, the term "culture media formulator" generally refers to a component or device that mixes ingredients for use as a culture medium for growing cells.

[0032] As used herein, the term "minimodule" generally refers to segments of a bioreactor that can be interconnected and assembled into a larger structure (e.g., a macrostructure or shape) to constitute at least a portion or the entire bioreactor.

[0033] As used herein, the term "gyroid" generally refers to a connected, periodic, minimal surface that does not contain straight lines. Such surfaces can have mathematically infinite connections. In some instances, gyroids are unique, important, embedded members of a related family of Schwarzian P and D surfaces with bond angles of approximately 38.01°. Gyroids can be configured as single gyroids or double gyroids. Double gyroids can be oriented and configured for specific applications in microfluidic devices. Double gyroids can be constructed by balancing geometric aspects related to the hydrodynamic performance observed in minimodules and macrostructures (e.g., macroshapes), such as double gyroid crystallographic structure and space group. Gyroids or double gyroids can be implemented in a variety of crystallographic structures.

[0034] As used herein, the term "bubble-free" generally refers to a bioreactor or other device that has substantially laminar or laminar fluid flow, such that there are no or substantially no air bubbles. Bubble-free bioreactors generally do not have mixing elements, such as moving blades, fins, propellers, or the like, that can generate air bubbles in the fluid.

[0035] Devices and systems for 3D printing are provided herein. The device can comprise a stereolithography 3D printing device. Methods of using such devices for applications such as 3D printing are also provided. The stereolithography device can comprise an optical assembly. The optical assembly can be a static optical assembly. Alternatively, in some examples, the optical assembly can be a dynamic optical assembly. The device can further comprise a light engine, which can be configured to project one or more beams. The beam can include or be a Lux beam. The beam (e.g., a Lux beam) can comprise one or more pixels. The one or more pixels can comprise multiple pixels. The one or more pixels can be located along an axis (e.g., the Z axis).

[0036] The device and / or optical assembly may further include one or more lenses. The one or more lenses may include a collimation lens. The lens (e.g., the collimation lens) may be configured to collimate the Lux beam. In some examples, the optical assembly may include a microlens array (MLA). The MLA may be configured to converge the collimated Lux ​​beam into a modified beam, which may have a smaller diameter compared to the Lux beam. In some cases, the modified beam may be the final beam. Alternatively, the modified beam may not be the final beam; for example, the modified beam may be an intermediate beam, and more beams may be further generated. In some examples, one or more pixels of the Lux beam (e.g., each pixel of the Lux beam) may be split into multiple subpixels, which may increase the resolution of the modified beam and / or the final beam.

[0037] The device may further comprise a micro-diaphragm array (MDA), which may be configured to reduce noise and / or crosstalk between lenses of the MLA.

[0038] The device may further include at least one projection lens and a movable stage that may be configured to translate one or more of the at least one projection lens within a plane. The plane may be a two-dimensional (2D) plane, such as a plane in space. The 2D plane may be a plane between two axes in space. The space may be a multidimensional space, such as a three-dimensional (3D) space. For example, the plane may be a plane between an X axis and a Y axis (e.g., an XY plane). Alternatively, the plane may be an XZ plane or a YZ plane. The plane may be defined by two vectors, each of which may be parallel to two axes in space. For example, the plane may be an XY plane, and the distance between the light engine, collimation lens, MLA, at least one projection lens, and movable stage of the optical assembly along the Z axis (or any other axis perpendicular to the plane) may be fixed. Alternatively, in some cases, the distance may not be fixed and may be subject to change over time.

[0039] The device may further include a printing fluid reservoir. The printing fluid reservoir may include a printing stage. In some examples, the printing stage may be fixed. In some examples, the printing stage may be movable. The printing stage may be configured to move in any direction or along any axis in space. The movement of the stage may be defined in Cartesian, polar, spherical, or any other coordinate system. In some examples, the printing stage may be configured to move (e.g., be movable) along an X-axis, a Y-axis, and / or a Z-axis in 3D space in a Cartesian coordinate system. In some examples, the stage may move along more than one axis. In some examples, the stage may be configured to rotate and / or move in a polar or spherical coordinate system in an angular direction or in a radial direction of a circle.

[0040] A device, such as a printing fluid reservoir of a device, can further include control circuitry that can be configured to control one or more device components, such as a light engine, a movable stage, and / or a printing stage, to achieve a given goal, such as printing an object, such as by stereolithography 3D printing.

[0041] In some examples, computer systems and computer-implemented systems and methods are also described herein, which may include one or more processors and one or more memories. The computer systems may include instructions executable by at least one processor and capable of creating applications. The applications may include modeling, such as procedural modeling.

[0042] The procedural modeling application can include a graphic user interface (GUI). The graphic user interface can include a viewport. Methods and systems, such as procedural modeling applications, can further include a presentation module. The presentation module can be configured to present a scene. In some examples, the scene can be represented as a signed distance function, and the scene can be rendered using ray marching.

[0043] The presentation module may include a scene library. The scene library may include one or more procedural objects (POs). The presentation module may further include a scene editor. The scene editor may enable a user to add one or more POs to a scene and / or create a constructive geometry (e.g., a constructive solid geometry (CSG)) tree for the scene. The presentation module may further include a procedural object (PO) editor, which may enable a user to edit properties of POs that may be added to the scene. The presentation module may further include a simulation editor, which may enable a user to configure one or more simulations of the scene. The presentation module may further include a print editor, which may enable a user to configure the scene for printing.

[0044] The methods and systems, e.g., the presentation module, can further include a simulation module. The simulation module can be configured to perform one or more simulations. The simulations can be performed on a scene. The methods and systems, e.g., the presentation module, can further include a printing module. The printing module can be configured to generate a queue of slice files and send the slice files to a 3D printer. The 3D printer can comprise or be a device or system provided elsewhere herein or another device or system.

[0045] Provided herein is a non-transitory computer-readable storage medium that may be encoded with instructions that may be executable by at least one processor to, for example, create a procedural modeling application.

[0046] The procedural modeling application may include a graphic user interface (GUI). The GUI may include a viewport and a presentation module. The presentation module may be configured to represent a scene, for example, as a signed distance function and may render the scene by utilizing ray marching. The presentation module may include a scene library.

[0047] The scene library can include one or more procedural objects (POs). The presentation module can further include a scene editor that can enable a user to add one or more POs to a scene and / or create constructive geometry, such as a constructive solid geometry (CSG) tree, for the scene. The presentation module can include a procedural object (PO) editor that can enable a user to edit properties of each PO added to the scene, a simulation editor that can enable a user to configure one or more simulations of the scene, a print editor that can enable a user to configure the scene for printing, a simulation module that can be configured to perform one or more simulations of the scene, and a print module that can be configured to generate a queue of slice files and send the slice files to a device, such as a 3D printer. The 3D printer can be a device or system provided elsewhere herein or another device or system.

[0048] A computer-implemented method for procedural modeling is provided herein. The computer-implemented method for procedural modeling can include providing a procedural modeling application. The procedural modeling application can include a scene library. The scene library can include one or more procedural objects (POs). The procedural modeling application can further include a scene editor that can enable a user to add one or more POs to a scene and / or create geometry, such as a constructive solid geometry (CSG) tree, for the scene. The procedural modeling application can further include a procedural object (PO) editor that can enable a user to edit the properties of the POs, for example, each PO added to the scene. The procedural modeling application can further include a simulation editor. The simulation editor can enable a user to configure one or more simulations of the scene. The procedural modeling application may include a print editor that may enable a user to compose a scene for printing, represent the scene as a signed distance function, render the scene by utilizing ray marching, perform one or more simulations within the scene, generate a queue of slice files, and / or send the slice files to a 3D printer, which may be a device or system provided elsewhere herein or another device or system.

[0049] Methods for fabricating multidimensional objects, such as 2D or 3D objects, are provided herein. In some cases, the multidimensional object (e.g., a 3D object) can comprise one or more units. In some examples, the one or more units can comprise multiple units or a plurality of units. In some examples, the units include or are repeated or repeating units. The method can include providing a procedural modeling application. The procedural modeling application can be a procedural modeling application provided elsewhere herein or another procedural modeling application. The procedural modeling application can be configured to perform one or more functions. In some examples, the functions can be performed at the request of a user, who can provide input or instructions to the application. Alternatively, artificial intelligence, machine learning, or other techniques can be used to perform one or more functions.

[0050] In some examples, the procedural modeling application may be configured to add one or more units to a scene. The scene may be a multidimensional scene. A scene (e.g., a multidimensional scene) may include any number of dimensions, e.g., 1, 2, 3, 4, 5, 6, 7, or more. In some examples, the units may be crystallographic units. For example, crystallographic units may be added to a scene (e.g., a 3D scene). The method may further include replicating one or more units (e.g., crystallographic units) to form a structure. The structure may comprise or be a lattice. For example, the structure may include a crystal lattice within the scene. The method may further include constructing links and / or connections that may connect the units (e.g., the replicated crystallographic units). The structure may further comprise one or more conduits. The conduits may connect the links. The method may include creating a constructive solid geometry (CSG) tree for the scene. The method may further include representing the 3D scene as a signed distance function, rendering the scene by utilizing ray marching, generating a queue of slice files, and / or transmitting the slice files to a device, such as a 3D printing device, such as a stereolithography 3D printing device. The device may comprise any device provided elsewhere herein, other devices, or combinations thereof.

[0051] When visualizing and manipulating any virtual scene, something of interest may be a representation of one or more geometric shapes contained in the scene or any structure within the scene. Examples of approaches that may be adopted to address this problem include using explicit and / or implicit representations.

[0052] In some examples, in an explicit representation, a geometric shape may be stored as a list of geometric primitives. The geometric primitives may include geometric primitives of any shape and with any dimension. For example, the geometric primitives may include points, triangles, polygons, or other geometric primitives. The geometric primitives may include one or more dimensions, for example, 1, 2, 3, 4, 5, 6, 7, or more dimensions. In some examples, the geometric primitives may include n dimensions, where n is an integer between 0 and infinity in n-dimensional space.

[0053] In some cases, explicit representations may not require transformations to extract a 3D representable model for printing and may allow, for example, local manipulation of the model vertex by vertex. In some cases, explicit representations may include drawbacks. Examples of drawbacks of explicit representations may include a fixed maximum level of detail established by the distribution of vertices, loss of intrinsic information of the geometry, which in some cases may only be represented by a list of a small number of geometric primitives, difficulties associated with performing global operations, and a lack of provision for a compact data representation of the complete scene. For example, in some cases, the data representation of the complete scene may not be compact, e.g., may occupy a large amount of space in memory. Examples of widely used explicit representations may include geometric primitives such as polygons and / or triangles. In some cases, surfaces may be divided or subdivided and rendered, for example, using rasterization.

[0054] In an implicit representation, geometry may be stored as a mathematical function or equation that may be specified over a manifold. An implicit representation may benefit from mechanisms to extract information needed for printing purposes and may facilitate local or global manipulation of the model. An implicit representation may include several advantages. For example, an implicit representation may not fix a given level of detail and may offer the possibility of obtaining an infinite level of detail. An implicit representation may not cause the inherent information of the geometry to be lost. It may be advantageous to perform global manipulations in an implicit representation. In some instances, the data may be compact, e.g., occupy less disk space compared to an explicit representation approach.

[0055] Marching Cubes / Tetrahedra: This technique consists in converting the implicit representation of the entire scene into its explicit representation. This technique is not suitable for large scenes because, after the conversion, it loses the data compactness of the implicit representation.

[0056] Rasterization: This technique has been widely used in real-time computer graphics over the past decade because its good performance and versatility are sufficient to achieve good visual results. Rendering has a runtime complexity that is typically linear in the number of triangles that need to be rendered, while the space-time complexity of the problem is linear in the number of vertices needed to represent the entire scene.

[0057] Referring to FIG. 2, an example of a rasterization pipeline is provided. In this example, the rasterization pipeline begins with a 3D mesh 205. In a first example vertex processing step 210, a host program fills the API's vertex buffer memory with an array of vertices. These vertices are typically defined in global coordinates; therefore, they are transformed into camera space coordinates. The vertices can now be projected into screen coordinates. This transformation goes from 3D camera space coordinates to 2D screen system coordinates. In this example, the vertices are now interpreted as 2D triangles in screen space 215. In a second example rasterization step 220, the triangles are converted into pixel fragments 225. In a third example raster manipulation step 230, the fragments are colored according to the desired lighting technique(s) and optionally texture filtering to produce colored fragments 235. Finally, in this example, a fragment processing step 240 results in a final image output 245.

[0058] This process, sometimes called the "graphics pipeline," is typically implemented in hardware but may be manipulated by intermediate steps called "shaders." Over the past 20 years, the graphics pipeline has been refined to maximize the number of triangles available for rendering. Rasterization, in particular, has significant performance considerations in that the execution time complexity of the algorithm is linear with respect to the number of vertices, since all of the vertices must be examined to produce the final image. It should be noted that this can be reduced to a logarithmic order of complexity by using AABBs to sort the elements in the scene; even so, the time complexity is still strongly bound to the number of elements in the scene. Therefore, the algorithm does not scale well. Nevertheless, this method has gained popularity due to its ease of parallelization using GPUs.

[0059] Ray Tracing (Ray Casting): In the approach described herein, in some examples, ray tracing is utilized as a method of rendering that has key advantages over rasterization. Modern GPUs have evolved to become the highly programmable parallel floating processors they are today. This new paradigm, in which multiple threads run simultaneously on multiple data sources (MTMD processors), has opened the door to new opportunities for the well-known traditional ray casting rendering technique.

[0060] 3, an example ray tracing diagram is provided. Unlike a rasterization pipeline, this method starts with pixels in a raster image 310 to find what part of the scene each ray / pixel covers and then shoots its rays along the camera view frustum 305. Some rays may hit 320 objects in the scene 315, and some may miss 325.

[0061] Referring to Figure 4, an example of a ray marching method is provided. In this example, for each pixel in the scene, a ray is traced 405 through the scene, typically by using a BVH. Further, in this example, if the ray intersects 415 with any object, a hit 420 is calculated and saved. After traversing the entire structure 410, the algorithm evaluates 425 whether the ray hits 435 or not 430 the surface; if so, a color is calculated or an additional ray is cast from the desired location.

[0062] Ray tracing and crystal lattices A lattice is an ordered array of points that describes the arrangement of particles that form a crystal. This order in the arrangement of particles gives it useful properties that are beneficial for improving the execution time of rendering techniques.

[0063] Ray Marching This technique involves determining the intersection of an orthographic projection of the entire scene with a single plane. Typically, a 3D printer only requires a limited set of layers, usually just one layer. Once the printing process begins, one layer can be updated at a time; therefore, there is no need to store the entire representation of the scene before starting the printing process. Implicit representations using signed distance functions (SDFs) are well suited to these tasks due to the simplicity of extracting the intersection of a 3D scene with a plane.

[0064] This technique can be similar to ray casting, but can be used to generate entire procedural environments completely from a single mathematical equation. The idea is to modify both the abstract representation of the scene and the rendering technique to combine them in a way that can better handle both space and runtime complexities. The scene is now represented as a mathematical function, such as an SDF. Since a crystal lattice consists of an ordered arrangement of particles, it is not impossible to find such a function. An SDF takes a point in space and calculates how far that point is from a surface.

[0065] Example: The following function describes a circle in two dimensions:

[0066] / / params:

[0067] / / p: any point in 3D space

[0068] / / c: center of the sphere

[0069] / / r: radius of the sphere

[0070] float sphere_distance(in vec3 p, in vec3 c, float r)

[0071] {

[0072] return length(pc)-r;

[0073] }

[0074] To render a scene, the technique shoots out rays from a virtual camera that views the scene (see, e.g., Figure 5). For each pixel of the raster image, the technique marches along the direction of the ray (see, e.g., Figure 6), and at each step, evaluates the SDF to calculate how far the pixel is from the closest point on the surface (see, e.g., Figure 7).

[0075] Ray marching gives significant performance improvements. With ray marching, the entire scene is represented as a single mathematical equation, so the runtime complexity does not depend on the number of objects in the scene, but on the complexity of the SDF computation. An analysis of the spatial complexity shows that the scene can be described by a single mathematical function. It is clear that there is no need to discretize the scene by vertices. This gives the possibility to dramatically reduce the space required to store the scene, while preserving the details of the original geometry inherited by the mathematical functions.

[0076] These performance improvements are amplified when modeling crystal lattices composed of ordered repetitions of the same unit cell structure. To achieve the necessary amount of repetition, in some instances the rendering suite described herein does not specify each unit cell position individually; instead, in such instances, a mathematical equation is found to represent the entire crystal structure.

[0077] Procedural Modeling Applications 8, in a particular embodiment, a procedural modeling application has an architecture including a present module, a save module, a print module, and a simulation module. In this embodiment, the application architecture is also in operative communication with a cloud computing system and at least one 3D printing device, such as a 3D printing device described herein.

[0078] 8, in this embodiment, the presentation module includes a suite of tools configured for use by a model designer user. Non-limiting examples of tools configured for use by a model designer user include a scene library, a procedural object (PO) editor, and a scene editor. In this embodiment, the scene editor allows the user to access the features of the print editor and the simulation editor.

[0079] In some examples, a presentation module of a procedural modeling application includes a scene library. In further examples, the scene library includes one or more POs available for addition to a scene. In various examples, the POs in the scene library include POs that are premade and provided by the application, newly created by the user, created by the user by editing the properties of other POs, loaded from an external source, and the like. In certain embodiments, a user optionally adds a PO to a scene by dragging an icon representing a PO from the scene library and dropping the icon into a viewport or other feature of the presentation module representing the scene.

[0080] In some examples, the presentation module of the procedural modeling application includes a PO editor. In further examples, the PO editor allows for the creation and editing of PO files for each PO. In further examples, the PO editor provides features that allow a user to edit one or more properties of each PO in the scene library and / or each PO added to a scene. Non-limiting examples of editable PO properties include type, scale, position, links connecting one or more adjacent POs (including the type, scale, shape, and position of each link), conduits connecting the links (including the type, scale, shape, path, and position of each conduit), and replication properties such as the number of replications, replication pattern, replication density, and the like.

[0081] In some examples, the presentation module of the procedural modeling application includes a scene editor. In a further example, the scene editor enables creation and editing of a project file for the scene. In yet a further example, the scene editor provides features that enable a user to add one or more POs to the scene. In still a further example, the scene editor creates a constructive solid geometry (CSG) tree for the scene and updates the CSG tree as the scene is constructed and revised. In certain embodiments, the scene editor provides features that enable a user to replicate crystallographic units with precisely specified scales, patterns, densities, etc. to form crystal lattices within the scene.

[0082] In some examples, the procedural modeling application includes a save module. In further examples, the PO file(s) are referenced by a project file, and the project file is referenced by a print file. In further examples, the PO file(s), project file(s), and / or print file(s) are stored by the save module in a project database that is in communication with a local file system that enables file searching, retrieval, and similar functions.

[0083] Still referring to FIG. 8 , in this embodiment, the presentation module also includes tools configured for use by a simulation designer user, who may be the same user as the model designer user or a different user, and the procedural modeling application includes a simulation module. A non-limiting example of a tool configured for use by the simulation designer user includes a simulation editor. In a further example, the simulation editor provides features that allow a user to configure one or more simulations of a scene. In yet a further example, the simulation editor generates and maintains simulation input files, which, along with scene and project information, are ingested by the simulation module to perform simulations utilizing cloud computing resources.

[0084] Many types of simulations are suitable for use in the procedural modeling applications described herein. Suitable simulations include, by way of non-limiting example, microfluidics simulations, computational fluid dynamics (CFD) simulations, and the Lattice Boltzmann Method (LBM) combined with a signed distance function to solve CFD simulations. In certain examples, the simulation module provides visualization of one or more characteristics of the simulation, such as performance characteristics.

[0085] Still referring to FIG. 8 , in this embodiment, the presentation module includes a print editor, and the procedural modeling application includes a print module. In some examples, the print editor enables creation and editing of print files for a scene. In further examples, the print editor provides features that enable a user to configure a scene for printing. In still further examples, the print editor provides features that enable a user to configure, by way of non-limiting examples, surface profile(s), printer run order, layer thickness(es), lux beam exposure time(s), and pixel resolution(s). In some examples, the print module, via a slicer, takes print files and other information from the print editor along with simulation information to produce slice files. In further examples, a file server provides slice files to a cache that is internal or external to one or more 3D printing devices. An example slicer / printer synchronization architecture is provided in FIG. 22.

[0086] Graphic User Interface In some instances, a procedural modeling application includes a GUI that presents elements and features that allow one or more users to access the application's functions.

[0087] Referring to FIG. 9, in certain embodiments, the procedural modeling application described herein includes a GUI that includes a central viewport, a window displaying a CSG tree representation of the current scene, a scene library containing procedural objects, and a window displaying the properties of the currently selected procedural object.

[0088] In some examples, the procedural modeling applications described herein include a GUI that allows a user to access functions that allow a user to select a procedural object, where interface elements are for the user to edit properties of the procedural object (see, e.g., FIG. 10); that allows a user to select a texture, where a format and preview are provided (see, e.g., FIG. 11); that allows a user to drag a procedural object from a scene library and drop the procedural object into a procedural object editor to begin editing properties of the procedural object (see, e.g., FIG. 12); and that allows a user to observe editable properties of the selected procedural object (e.g., a cubic crystal) shown in a viewport. Non-limiting examples include allowing a user to create multiple crystal cells from a cubic crystal (see, e.g., FIG. 13); allowing a user to set links for each face of a cubic crystal procedural object and set positions for the links on the faces, e.g., to form a gyroid (see, e.g., FIG. 14); allowing a user to save an edited procedural object (gyroid unit cell) to a scene library (see, e.g., FIG. 15); and allowing a user to identify the saved procedural object in the scene library, where the edited object (gyroid unit cell) inherits properties from the procedural object from which it was created; and the GUI also allows a user to duplicate the procedural object to form a crystal lattice, such as a gyroid lattice (see, e.g., FIG. 16).

[0089] 19, a schematic diagram of a crystal unit cell is provided, including nomenclature. The nomenclature shown in the diagram includes the terms "face" 1910, "symmetrical face" 1920, "link" 1915, and "conduit" 1905.

[0090] In various further examples, the procedural modeling applications described herein include a GUI that allows a user to access multiple simulation functions, including, by way of non-limiting example, allowing a user to set up a simulation to be performed on a 3D scene model (see, e.g., FIG. 20) and allowing a user to observe the results of a simulation to be performed on a 3D scene model (see, e.g., FIG. 21).

[0091] Example Process Referring to FIG. 17 , in a particular embodiment, a process is provided for a user to interact with an application to create, edit, and save procedural objects from previously created objects. In this embodiment, the user selects a PO, in this case a cubic crystal PO, from the scene library 1705. Next, the user selects the PO by right-clicking on the PO and selects “Duplicate” from the options menu 1710. As a result, a new cubic crystal PO is added to the scene library 1715. The user then selects the new PO 1720 and can rename the new PO to a “gyroid lattice” 1725. Next, the user can set multiple links for each pair of symmetry planes on the PO 1730, and similarly, can set multiple conduits 1735. Finally, in this example process, the user uses conduits to connect groups of links from different planes to complete fluid connectivity within the lattice 1740.

[0092] Similarly, with reference to Figure 18, in a particular embodiment, a process is provided for a user to interact with an application to create and edit new procedural objects. In this embodiment, the user begins the process by dragging a PO from a scene library 1805. The user then drops the PO into a location 1810. If the location is not valid, the user must start again.

[0093] Continuing with FIG. 18, if the location is valid and the user drops the PO into the editor viewport, the new PO is added to the scene library 1815. The user can then select the new PO 1820, and the default property explorer shows the PO's variables 1825. The user can select a random variable 1830 and optionally change the variable value 1835. If the value is acceptable, the value is changed 1840.

[0094] Continuing with FIG. 18, if the location is valid and the user has not dropped a PO into the editor viewport, a new node is added to the scene's CSG tree 1845 and the new PO is added to the scene library 1850. The user can then select the new node 1855 and the property explorer shows the node variables 1860. The user can select a random variable 1865 and optionally change the variable value 1870. If the value is acceptable, the value is changed 1875 and the change is made visible in the viewport 1880.

[0095] 3D printing device In some examples, the 3D printing devices described herein include a static optical assembly. In further examples, the static optical assembly includes: a light engine configured to project a Lux beam including a plurality of pixels along the Z axis; at least one collimation lens configured to collimate the Lux beam; a microlens array (MLA) configured to focus the collimated Lux ​​beam into a final beam with a smaller diameter, where each pixel of the Lux beam is subdivided into a plurality of subpixels to increase the resolution of the final beam; a microdiaphragm array (MDA) configured to reduce noise and crosstalk between lenses of the MLA; at least one projection lens; and a movable stage configured to translate one or more of the at least one projection lens in the XY plane. In further examples, with respect to the static optical assembly, the distance along the Z axis between the light engine, collimation lens, MLA, at least one projection lens, and movable stage of the static optical assembly is substantially fixed or is fixed.

[0096] Referring to FIG. 23 , in a specific embodiment, a stereolithography 3D printing device includes a frame structure that supports other components of the device and defines a Z-axis. In this embodiment, the 3D printing device further includes a static optical assembly. Starting from the bottom of the device along the Z-axis and proceeding toward the top, the static optical assembly includes a Lux beam generator, a collimator, a monolithic MLA, a piezoelectric stage, and at least one projection lens. Further, in this embodiment, a stepper motor drives a threaded rod that adjusts the position of a printing fluid reservoir comprising the print stage on the Z-axis. Other components include linear guides, ball screws, control electronics, etc. Finally, in this embodiment, the static optical assembly is configured to project a pixel field onto the print stage.

[0097] Slicer / Printer Synchronization Architecture In some examples, the procedural modeling application communicates print instructions to one or more 3D printing devices via a single slicer / printer synchronization device, multiple slicer / printer synchronization devices, or a slicer / printer synchronization pipeline. Many hardware and / or software architectures are suitable for generating and managing queues of slice files that instruct, for example, a stereolithography 3D printing device. In some examples, the procedural modeling application described herein communicates print instructions to a single 3D printing device. In other examples, the procedural modeling application described herein communicates print instructions to multiple 3D printing devices, serially or in parallel. In further examples, the multiple 3D printing devices can include, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, or more 3D printing devices, including increments therein.

[0098] Referring to FIG. 22 , in a specific embodiment, the slicer / printer synchronization architecture includes a print editor 2205 in a presentation module of a procedural modeling application. In this embodiment, the print editor 2205 generates and maintains a print file 2210 that is sent to a slicer 2215. The slicer 2215 generates a slice queue 2220, which is sent to a file server 2225 for cooperation with a 3D printer 2230 via a “last slice signal.” Additionally, in this embodiment, the printer 2230 generates a “slice continued signal” that is sent through a synchronization gate 2230, which generates an “iteration signal” to form a feedback loop for the slicer 2215. In various examples, the slicer 2215 and / or the file server 2225 can be separate devices, can be combined with each other, and / or can be integrated into the 3D printer 2230.

[0099] Semi-continuous printing: brick printing process In some examples, the 3D printing devices described herein include control circuitry configured to control at least the light engine, the movable stage, and the print stage to achieve stereolithography 3D printing. In further examples, the control circuitry is configured to control the print stage to move at a predetermined constant velocity on the Z axis. In further examples, the control circuitry is configured to control the movable stage to translate one or more of the at least one projection lens in the XY plane.

[0100] In various examples, the 3D printing devices described herein include control circuitry configured to control at least a light engine, a movable stage, and a print stage to achieve stereolithographic 3D printing in a semi-continuous, substantially continuous, or continuous pattern. In certain examples, the 3D printing devices described herein are configured to perform a semi-continuous printing process. In further examples, the semi-continuous printing process includes a brick printing process.

[0101] In some examples, the control circuitry is configured to control the movable stage to translate one or more of the at least one projection lens in the XY plane to scan the Lux beam in a predefined pattern. Many patterns are suitable for scanning the Lux beam, including, but not limited to, row-by-row patterns, column-by-column patterns, cross-hatch patterns, and patterns dependent on the geometry of the 3D object / scene to be printed. In some examples, the predefined pattern includes a continuous space-filling curve. In a further example, the predefined pattern includes a Sierpinski curve. In some examples, the predefined pattern is a substantially spiral pattern or a spiral pattern.

[0102] The printing process, in some instances, is based on multiple technological points. One point, in such instances, is the movement of a piezoelectric stage in the XY plane for scanning a light beam under a printing fluid reservoir. Another point, in such instances, is the frames per second (fps) of the projected image. Yet another point, in such instances, is the movement of the printing stage at a predefined constant velocity along the Z axis.

[0103] In a particular example, the process involves scanning the light beam in a spiral, as shown in FIG. 24. In a further particular example, the exposure time for every frame is determined by the amount of subpixels included in the print area. As a non-limiting example, if the amount of subpixels is 9, the first frame would be exposed for 1 / 9 of the time in the resin that all frames must be exposed to, the second frame would be exposed for 2 / 9 of the time, and so on, until it ends with the last frame. In such an example, this process is repeated for every pixel to be illuminated. In some examples, the scanning of the illumination pattern is delivered by a piezoelectric stage that moves in the XY plane by, as a non-limiting example, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more microns on either side. In this example, the described scanning takes advantage of the continuous printing approach and is capable of "writing" across the resin with very high resolution in a static setup. In some examples, the printing fluid reservoir has an underlying material that is semi-permeable and / or substantially permeable to oxygen. In such examples, the permeability of the printing fluid reservoir to oxygen allows for inhibition of the polymerization reaction. Figure 24 shows piezoelectric movement in a spiraling path.

[0104] Figure 25A shows neutral positioning of the piezoelectric stage in the XY plane with no pixel displacement due to optical scanning. Figure 25B shows rightward positioning of the piezoelectric stage in the XY plane to produce leftward pixel displacement due to optical scanning. Figure 25C shows leftward positioning of the piezoelectric stage in the XY plane to produce rightward pixel displacement due to optical scanning. Figure 26 shows a series of steps during an example brick printing process.

[0105] Example 3D Printing Device Embodiments Referring to FIG. 27 , in a specific embodiment, light coming from a light engine 2701 is projected onto a collimator 2702. After entering the collimator, the light reaches a monolithic MLA 2703, which focuses the collimated beam, resulting in a final beam with a smaller diameter. This is the main pillar for the resolution increase of the static optical setup described herein in an off-the-shelf embodiment. The area of ​​one pixel here can be subdivided, for example, into 9, 25, or 49 subpixels, or even up to 7498 subpixels, and any increment between 4 and 7498, depending on the desired printing resolution. Once the light beam is focused by the MLA 2703, optical scanning is performed by moving the lens in the XY plane by a piezoelectric stage 2704. The piezoelectric stage 2704 allows for scanning the light beam over a larger area. All subpixels are magnified in diameter and projected onto a reservoir window 2706 within the scanned area by a series of three projection lenses 2705. This alignment and magnification is produced by the projection lenses 2705, which are located after the MLA 2703 in the light path. In this example embodiment, the final printed area is estimated to be approximately four times the initial area of ​​90 mm x 85 mm. The printing reservoir contains a photocurable resin 2707. A printed result, such as a 3D object, is produced layer by layer on the print bed 2709 as the photocurable resin 2707 is activated by UV light from the light engine and the print bed 2709 advances upward on guides 2710 by threaded rods 2711 driven by stepper motors.

[0106] Light Engine In some examples, the 3D printing devices described herein include a light engine. In some examples, the light engine is a UV light source based on digital micromirror device (DMD) technology. In other examples, the light engine is a UV light source based on liquid crystal on silicon (LCoS) technology. In some examples, the light engine includes a UV projector and / or a deep UV projector. In some examples, the light engine has an operating wavelength of about 350, 355, 360, 365, 370, 375, 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, 440, 445, or 450 nm, including increments therein. In some examples, the light engine has an operating wavelength selected to initiate polymerization of a photocurable resin in a printing fluid bath.

[0107] The first example light engine approach described herein is based on DMD technology. In some examples, this approach utilizes an industrial UV projector (Luxbeam) operating at an operating wavelength of 405 nm or 380 nm. The light engine illuminates a light path leading to a liquid bath containing a photosensitive resin. In a further example of this approach, spatial modulation of the light is performed by a DMD, an electromechanical device based on an array of aluminum-based micrometer-sized mirrors. Light is projected onto tiny mirrors by a UV LED and reflected from actuated mirrors. Each mirror has two states: "on" and "off." When the mirror is on, it can reflect incident light. Each tiny mirror represents one pixel. In some examples of this approach, the pixel pitch of the DMD is 5.4 μm. In some examples, the light engine has a working distance of 177.8 mm with a corresponding pixel pitch, e.g., 35 μm, and a 90 x 50 mm 2 In one embodiment, the Lux beam has a resolution of 2560 x 1600 pixels and a power output of 7 W. In some examples, the irradiance of the Lux beam at the working distance is 150 mW / cm. 2Figure 28 shows a non-limiting example of a suitable Lux beam.

[0108] The second example light engine approach described herein is based on LCoS technology. In some examples, the LCoS is responsible for spatial light modulation (amplitude-based). In further examples, the LCoS has an LCD panel on top and a mirror on the back. The LCD enables pixels where incident light hits the back mirror and is reflected down to the liquid reservoir toward the optical path. In one example, the pixel pitch of the LCoS can be 3.5 μm and can have a resolution of 4K×2K (4096×2400) pixels. Figure 29 shows an example of a suitable LCoS.

[0109] In some examples, the 3D printing devices described herein include a first light engine configured to project a first operating wavelength and a second light engine configured to project a second operating wavelength. In some examples, the second light engine operates in parallel with the first light engine, and the second operating wavelength is selected to inhibit polymerization of the photocurable resin in the printing fluid reservoir. In some examples, the second light engine projects an image that is complementary and inverse to the image projected by the first light engine to increase the fidelity and accuracy of the printed object.

[0110] Collimator In some examples, the 3D printing devices described herein include a collimator. In some examples, the collimator includes one or more collimation lenses. A collimator is one or more optical lenses that convert an incoming diverging beam into a parallel beam. A Lux beam has an uncollimated light beam. Light beam collimation is necessary to ensure a homogeneous distribution of light irradiation. Many optical configurations of collimation lenses are suitable. In some examples, the collimator includes one collimation lens. In other examples, the collimator includes multiple collimation lenses. In some examples, the multiple collimation lenses include, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more collimation lenses arranged in a collimation lens assembly or system.

[0111] Microlens Array (MLA) In some examples, the 3D printing devices described herein comprise an MLA. In some examples, the MLA is an optical device comprising a square-packaged array of micrometer-sized lenses (see, for example, FIG. 30A). The MLA can be positioned within the light engine, in front of the light engine, or after the light engine. Many types of microlenses are suitable for the MLA, dictating the nature of the array. By way of non-limiting example, the MLA comprises a biconvex array, a biconcave array, a uniconvex array, a uniconcave array, or a combination thereof. In certain embodiments, the MLA comprises a monolithic biconvex array.

[0112] 30B, in a particular embodiment, the MLA comprises a planar substrate with a first array of microlenses MLA1 affixed to one side and a second array of microlenses MLA2 affixed to the opposite side. In this embodiment, a polymer layer is also positioned on either side of the substrate, between the substrate and each of the arrays of microlenses. Similarly, in this particular embodiment, an MDA is positioned between the substrate and one of the arrays of microlenses (e.g., MLA2).

[0113] Many materials are suitable for the substrate, including, but not limited to, borosilicate glass, etched glass, or a combination thereof. Similarly, many materials are suitable for the microlenses, including, but not limited to, polymer, glass (e.g., BOROFLOAT® float borosilicate glass or other highly transparent glass capable of withstanding thermal stress), or a combination thereof. In certain embodiments, the main substrate is made of borosilicate and the microlenses are made of a polymer material.

[0114] Referring to FIG. 30C, in certain embodiments, the path of each light beam through opposing lenses of the MLA focuses each pixel of the Lux beam.

[0115] In various examples, the MLA subdivides each pixel of the Lux beam into between 4 and 7498 subpixels. For example, in various examples, the MLA subdivides each pixel of the Lux beam into approximately 4, 8, 32, 64, 128, 256, 512, 1024, 2048, 4098, or more subpixels, including increments therein.

[0116] In a specific example embodiment, the MLA comprises a monolithic biconvex array of microlenses, each with a 30 μm pitch. In this specific embodiment, the dimensions of the MLA are L: 139.12 mm, W: 88.24 mm, and H: 1.1 mm. Furthermore, in this embodiment, the radius of curvature (ROC) is estimated to be 130 μm, and the sagittal height is 1.5 μm. Finally, in this example, the MLA subdivides each pixel of the Lux beam into 9, 25, or 49 subpixels.

[0117] Micro Diaphragm Array (MDA) In some embodiments, the 3D printing devices described herein include one or more MDAs. In further examples, the one or more MDAs are configured to reduce noise and crosstalk between light beams passing through the lenses of the MLA. In such examples, the microdiaphragms of the one or more MDAs are numbered and aligned to correspond to the microlenses of the MLA. In some examples, each microdiaphragm of the one or more MDAs has an aperture size of about 5, 10, 15, 20, 25, 30, or more μm, including increments therein. In other examples, each microdiaphragm of the one or more MDAs has an aperture size of about 30, 35, 30, 15, 10, 5, or less μm, including increments therein. Reducing the aperture size of the microdiaphragms of the one or more MDAs can increase contrast and provide higher resolution printing. However, reducing the aperture size of the microdiaphragms of one or more MDAs can subsequently reduce the amount of energy provided to the resin for polymerization. Thus, in some examples, each microdiaphragm of one or more MDAs has an aperture size of about 5-10, 5-15, 5-20, 5-25, 5-30, 10-15, 10-20, 10-25, 10-30, 15-20, 15-25, 15-30, 20-25, 20-30, or 25-30 μm. In one example, each microdiaphragm of one or more MDAs has an aperture size of about 10-15 μm.

[0118] In some examples, the 3D printing devices described herein include one MDA. In some examples, the 3D printing devices described herein include multiple MDAs. The 3D printing devices described herein suitably include two, three, four, or more MDAs. Many locations within the static optical assembly are suitable for an MDA. By way of non-limiting example, an MDA may be positioned within the MLA and / or elsewhere within the assembly. In some examples, an MDA may be positioned between the planar substrate of the MLA and one or both of the MLA's microlenses. In some examples, the MDA and MLA may be disposed adjacent to each other. In some examples, the MDA and MLA may be disposed adjacent to each other and adjacent to the LCoS. In another example, the MDA and MLA may be disposed in the lath beam path at a location remote from the LCoS. In another example, the 3D printing device includes at least one MDA but does not include an MLA. In another example, the 3D printing device includes at least one MDA and a crystal configured to focus the collimated Lux ​​beam. The crystal can be a glass substrate, such as BOROFLOAT® 33 borosilicate glass, that has a wide operating temperature range and high transmittance at the wavelengths used.

[0119] FIG. 54 shows an example 3D printer optics configuration with an MDA and an MLA. The 3D printer optics can include a light engine 5401 configured to generate one or more light beams (e.g., UV light beams). The light beams generated by the light engine 5401 are directed to a polarized beam splitter (PBS) 5402. The PBS 5402 can direct the light to a wave plate (e.g., a quarter-wave plate) 5403. The optics can further include an MDA 5404 and an MLA 5406 disposed between the wave plate 5403 and the LCoS 5406. In one example, an MLA 5405 can be disposed between the MDA 5404 and the LCoS 5406. The light beam can pass through the wave plate 5403, MDA 5404, and MLA 5405, reflect off the back surface of the LCoS 5406, and return through the MLA 5405, MDA 5404, and wave plate 5403 as multiple discrete beams of light. Upon contacting the PBS 5402, the light beam can be reflected at angles of incidence of at least approximately 45, 60, 90, and 135 degrees. In one example, the light is reflected by the PBS 5402 at an angle of approximately 90 degrees. The reflected light can pass through one or more projection lenses 5407 to generate microspots 5409 on the sides of the printing fluid reservoir window 5408. The microspots 5409 can enable polymerization of resin disposed in contact with or adjacent to the printing fluid reservoir window 5408.

[0120] Movable stage In some examples, the 3D printing devices described herein include a movable stage. In further examples, the movable stage, e.g., a piezoelectric movable stage, has an operating principle based on the piezoelectric effect. In some examples, the movable stage is configured to translate one or more projection lenses in the XY plane with nanometer resolution to scan the Lux beam across the printing area.

[0121] Many ranges of motion are suitable for the movable stages described herein. By way of non-limiting example, suitable ranges of motion include distances in the X direction of approximately 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 μm, or greater, including increments therein. By way of non-limiting example, suitable ranges of motion include distances in the Y direction of approximately 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 μm, or greater, including increments therein. In some examples, the movable stage is a piezoelectric stage and has a range of motion in X of 100 μm and a range of motion in Y of 100 μm. In a further particular example, the working frequency is in the kHz range.

[0122] Many motion increments are suitable for the movable stages described herein. By way of non-limiting example, suitable motion increments include distances in the X direction of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 nm, or greater, including increments therein. By way of further non-limiting example, suitable motion increments include distances in the X direction of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 μm, or greater, including increments therein. By way of non-limiting example, suitable ranges of movement include distances in the Y direction of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 nm, or more, including increments therein. By way of further non-limiting example, suitable movement increments include distances in the Y direction of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 μm, or more, including increments therein.

[0123] In some examples, the movable stage has a translational resolution in the X direction, the Y direction, or both the X and Y directions that is equal to or less than the sub-pixel length into which each pixel of the light engine is divided.

[0124] FIG. 31 shows a non-limiting example of a suitable piezoelectric stage.

[0125] Projection lens In some examples, the 3D printing devices described herein include one or more projection lenses. In further examples, the 3D printing devices described herein include one projection lens. In some examples, the 3D printing devices described herein include multiple projection lenses, including, but not limited to, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more projection lenses. In such examples, the projection lenses may be arranged into a projection lens assembly or system.

[0126] In some examples, the one or more projection lenses are concentric setups of lenses whose primary purpose is to shape the final configuration of the light beam to ensure good energy distribution and beam spatial quality in the printing fluid reservoir. The projection lenses are configured with aspheric lenses designed to adjust to the quality requirements of a specific printing resolution. In some examples, the one or more projection lenses enlarge the final printing area. In some examples, the one or more projection lenses enlarge the final printing area by approximately 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, 10x, 20x, 30x, 40x, 50x, 60x, 70x, 80x, 90x, 100x, or more, including increments therein, of the light-generating area of ​​the light engine. In some examples, the one or more projection lenses reduce the final printing area.

[0127] printing liquid tank In some examples, the 3D printing devices described herein include a printing fluid vat. In some examples, the vat is a container of photosensitive resin utilized in a stereolithography 3D printing process. In some examples, the material beneath the vat is permeable or semi-permeable to oxygen to enable photopolymerization quenching. In some examples, the printing fluid vat is configured for sterile 3D printing, and the photocurable resin is maintained in a sterile state. The printing fluid vat can include one or more optically transparent surfaces (e.g., vat windows). The one or more optically transparent surfaces can allow transmission of a lux beam from a light engine through a portion of the printing fluid vat to polymerize the photocurable resin. Non-limiting examples of optically transparent surfaces (e.g., vat windows) include glass or optically transparent polymers, such as, for example, cyclic olefin copolymers.

[0128] Second Wave Generator In some examples, the 3D printing device includes a second wave generator. The second wave generator can be disposed adjacent to an edge of the optically transparent surface of the printing fluid reservoir (e.g., disposed adjacent to an edge of the reservoir glass). The second wave generator can project a light beam into the edge of the optically transparent surface of the reservoir (e.g., a reservoir window), causing the light beam to undergo total internal reflection within and along the long dimension of the optically transparent surface. The total internal reflection can generate an evanescent field that propagates outside of and through resin disposed adjacent to the optically transparent surface. The evanescent field can reduce, substantially prevent, or prevent polymerization of a photocurable resin disposed adjacent to or in contact with the surface of the printing fluid reservoir to reduce or prevent adhesion of the polymerized resin to the surface of the printing fluid reservoir window. The evanescent field can reduce or prevent polymerization within about 10, 20, 30, 50, 75, 100, 125, 150, 200, or more nanometers of the surface of the printing fluid reservoir window. In one example, the evanescent field reduces or prevents polymerization within about 100 nm of the optically transparent surface of the printing fluid reservoir. The air incidence angle and critical refraction angle at which a wavelength of light is projected into an optically transparent surface (e.g., the reservoir window) and reflected internally to enable total internal reflection can be determined by Equations 1 and 2.

[0129]

number

[0130]

number

[0131] where n R is the refractive index of the resin, and n G is the refractive index of an optically transparent surface (e.g., a bath window), and n Ais the refractive index of air. The wavelength of the light beam can be any wavelength of light that reduces or prevents polymerization. For example, the wavelength of the light beam can be a UV wavelength (e.g., about 350 to about 450 nm) or a red wavelength (e.g., about 600 to 650 nm). The wavelength of the light beam can be at least about 350, 355, 360, 365, 370, 375, 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, 440, 445, or 450 nm, including increments therein. The wavelength of the light beam can be at least about 575, 580, 585, 590, 595, 600, 605, 610, 615, 620, 625, 630, 635, 640, 645, 650, 655, 660, 665, 670, 675, or longer, including increments therein. In one example, the wavelength of the light beam can be about 375 nm to 400 nm. In another example, the wavelength of the second light beam can be about 600 nm to 650 nm. The wavelength of the light beam can be longer or shorter than, but not equal to, the wavelength used to polymerize the resin.

[0132] Figures 55A and 55B show diagrams of an example 3D printer device including a second wavelength generator. Referring to Figure 55A, light 5501 coming from the light engine is projected onto a collimator 5502. After entering the collimator, the light reaches an MLA 5503, which focuses the collimated beam, resulting in one or more beams with smaller diameters. Once the light beam is focused by the MLA 5503, optical scanning is performed by moving the lens in the XY plane using a piezoelectric stage 5504. The piezoelectric stage 5504 allows the light beam to be scanned over a larger area. All subpixels are magnified in diameter and projected onto a reservoir window 5506 within the scanned area by a series of three projection lenses 5505. This alignment and magnification is produced by the projection lenses 5505, which are located after the MLA 5503 in the light path. The printing reservoir contains a photocurable resin 5507. A printed result 5508, such as a 3D object, is produced layer by layer on the print bed 5509 as the photocurable resin 5507 is activated by UV light from the light engine and the print bed 5509 is advanced upward on guides 5510 by threaded rods 5511 driven by stepper motors. The 3D printing device includes a secondary wave generator 5512 configured to project a light beam 5513 through the long dimension of the vat window 5506. Figure 55B shows a close-up view of the interface between the secondary wave generator 5512 and the vat window 5506. The light beam 5513 projected through the long dimension of the vat window 5506 undergoes total internal reflection, generating an evanescent field that reduces or prevents polymerization of resin in contact with or adjacent to the surface of the vat window 5506. The light source for the light beam 5513 can be an LED or a laser. The second wave generator may include one or more lenses configured to shape or direct light to enable total internal reflection of the light beam 5513.

[0133] Printing tank coating In some examples, the 3D printing device can include one or more coatings disposed on the reservoir window or other surfaces of the printing reservoir to reduce, substantially prevent, or prevent adhesion of polymerized resin to the reservoir window. The coating can be any coating type that inhibits polymerization at the interface or otherwise includes anti-adhesion properties. In one example, the coating is a mesoporous coating. The mesoporous coating can include one or more base materials, such as, but not limited to, metal oxides, silica, organosilica, carbon, metal-organic frameworks, zeolites, or any combination thereof. The coating can be applied using sol-gel chemistry, physical deposition techniques, dip coating, spin coating, or any other coating process.

[0134] The coating can have any thickness useful for reducing or preventing adhesion of the polymerized resin. For example, the coating can have a thickness of at least about 5, 10, 25, 50, 75, 100, 125, 150, 175, 200, or more nm. The coating can have a thickness of about 5-10, 5-25, 5-50, 5-75, 5-100, 5-125, 5-150, 5-175, 5-200, 10-25, 10-50, 10-75, 10-100, 10-125, 10-150, 10-175, 10-200, 25-50, 25-75, 25-100, 25-125, 25-150, 25-175, 25-200, 50-75, 5 The coating can have a thickness of 0-100, 50-125, 50-150, 50-175, 50-200, 75-100, 75-125, 75-150, 75-175, 75-200, 100-125, 100-150, 100-175, 100-200, 125-150, 125-175, 125-200, 150-175, 150-200, or 175-200 nm. In one example, the coating has a thickness of about 25-100 nm. The coating can have pores with diameters of about 2-50 nm. The inter-pore distance can vary from about 5-10, 5-15, or 5-20 nm. In one example, the inter-pore distance ranges from 5-20 nm. The coating can have a contact angle of at least about 10, 15, 20, 25, 30, 40, 50, or 60 degrees. In one example, the coating has a contact angle of at least about 25 degrees.

[0135] Figures 56A and 56B show diagrams of an example 3D printer device including a coating on a reservoir window. Referring to Figure 56A, light coming from a light engine 5601 is projected onto a collimator 5602. After entering the collimator, the light reaches an MLA 5603, which focuses the collimated beam, resulting in one or more beams with smaller diameters. Once the light beam is focused by the MLA 5603, optical scanning is performed by moving the lens in the XY plane using a piezoelectric stage 5604. The piezoelectric stage 5604 allows the light beam to be scanned over a larger area. All subpixels are magnified in diameter and projected onto a reservoir window 5606 within the scanned area by a series of three projection lenses 5605. This alignment and magnification is produced by the projection lenses 5605, which are located after the MLA 5603 in the light path. The printing reservoir contains a photocurable resin 5607. A print result 5608, such as a 3D object, is produced layer by layer on the print bed 5609 as the photocurable resin 5607 is activated by UV light from the light engine and the print bed 5609 is advanced upward on guides 5610 by threaded rods 5611 driven by stepper motors. The 3D printing device includes a coating 5612 disposed on the surface of the reservoir window 5606. Figure 56B shows a close-up view of the interface of the coating 5612 and the reservoir window 5606. The coating 5612 is disposed on the surface of the reservoir window 5606 that contacts the resin. The coating can reduce or prevent polymerized resin from adhering to the surface of the reservoir window 5606.

[0136] Printing bed (stage) In some examples, the 3D printing devices described herein include a print bed. In some examples, a photocurable resin is photopolymerized on the surface of the print stage. The print stage is articulated to move in the Z-axis under the control of circuitry to accomplish the printing process. For example, the print stage can be assembled on a guide rod and mounted to a threaded rod driven by a stepper motor. In some examples, the 3D printing devices described herein utilize a bottom-up printing approach, and the print stage moves correspondingly in the Z-axis. In some examples, the 3D printing devices described herein utilize a top-down printing approach, and the print stage moves correspondingly in the Z-axis.

[0137] Example 3D Objects / Scenes The platforms, systems, and devices provided herein (collectively "printer systems") are applicable to printing porous structures based on periodically spatially distributed crystallographic geometries. In one example, a printer system is used to generate such structures. In some examples, the crystallographic geometries can include or be crystal lattices based on unit cells. The unit cells can have a shape. The shape of the unit cells can be any shape, such as those described elsewhere herein. In one example, the shape of the unit cells can include a gyroid, a double gyroid, or a modified gyroid or modified double gyroid. For 3D printing, a gyroid can be a suitable geometry in some cases because the gyroid is freestanding, avoiding the need for external supports for the creation of 3D objects containing the structures. In some instances, the porous structure comprises channels with diameters ranging from 150 μm to 600 μm, and an intermembrane space (e.g., material separating two independent circuits) ranging from 200 μm to 400 μm at its thinnest point. In such instances, to achieve a sufficient level of detail, 15 μm voxels on each edge are required to ensure smooth termination at the 300 μm size level of the structure. The smaller the voxels, the smoother the surface will be on the macroscale.

[0138] The printer systems provided herein may also be applicable to printing bioreactors. In some examples, the printer systems are used to generate bioreactors, such as miniature bioreactors. In some examples, the bioreactors are composed of multiple mini-modules. Each mini-module can have a shape, and the mini-modules can be arranged, i.e., printed, into a macrostructure. Examples of such bioreactors with various macrostructures and mini-modules are also provided herein. The bioreactors provided herein include various macrostructures, various mini-modules of different shapes, and various features detailed elsewhere herein. Methods of manufacturing and using such bioreactors are also provided herein.

[0139] In some examples, the printer system herein can produce, for example, mini-modules of a defined size, such that one or both channels of the structure (e.g., a mini-module and / or multiple mini-modules combined into a macrostructure, such as a bioreactor or layer of a bioreactor) accommodate a stream of objects of a set size (e.g., a stream of biological organisms and cells). In one embodiment, at least one of the channels of the structure is constructed to limit the number of cells flowing through the channel at any one point, e.g., the flow of single cells, but not multiple cells flowing together. In some examples, the channel diameter is slightly larger than a single cell, e.g., the channel is about 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% wider than the diameter of a single cell, including increments therein. In some examples, the cells are between about 0.5 μm and about 100 μm. In some examples, the cells are prokaryotic cells and single cells between about 0.5 μm and about 5 μm. In some cases, the cells are microorganisms such as bacteria, yeast, fungi, etc., and the cells are between about 0.5 μm and about 30 μm, or between about 3 μm and about 30 μm. In some cases, the cells are eukaryotic cells, and the single cells are between about 10 μm and about 100 μm, or between about 10 μm and about 30 μm.

[0140] In some examples, mini-modules can be printed to have channel diameters of about 8 μm to about 2000 μm. In some examples, mini-modules are printed to have edges of 40 μm to 9797 μm. In the examples herein, mini-modules are printed to have edges of about 68417 to 9.4×10 11 It is printed to have a volume of cubic millimeters.

[0141] In some examples, the mini-module can have a regular cubic wrap structure with its edges of length "L." L can be related to the sweep diameter. In some examples, L is equal to 2 / 3 of the sweep diameter of the microchannel times the square root of 2 times the square root of 3. The total surface and volume of the microchannel corresponding to the liquid component can be equal to the corresponding dimension of the gas component when the radii of both components are the same within the mini-module. In some examples, the radii of the components can be different. In some examples, when both radii are equal, the microchannel radius can be no greater than 0.7 times the sweep radius. The shortest distance between two mini-modules on two different faces is equal to the square root of the sweep radius times 2 minus the sum of the radii of each component channel.

[0142] In some instances, the area of ​​a first channel with a DG can be equal to the area of ​​a second channel within the DG, and the area of ​​the matrix phase is the sum of the areas of the first and second channels. The distance between the matrix phase separating the channels and the center of each channel is constant.

[0143] In some examples, the printer system can print a series of mini-modules within a macrostructure. In some examples, the mini-modules are modified double gyroids (DGs) that are assembled into a macrostructure to create a 3D object, such as a bioreactor. In some examples, the mini-modules can be arranged in layers within the macrostructure. An assembly of interconnected mini-modules with identical orientation is called a "layer." The layers can be arranged, for example, in a rhomboidal fashion, such that in some examples, when the same number of modules are connected in a selected direction, the resulting growth is not proportional; thus, the growth of the layers is irregular relative to one another. In some examples, the layers are arranged in a square or other fashion such that the resulting growth is proportional.

[0144] In some examples, an assembly of layers of mini-modules ("first matrix") can be co-located with a second assembly of layers of mini-modules ("second matrix"), where the second matrix occupies the free space left by the first matrix, the matrices occupying the same volume having no contact points and maintaining a certain minimum distance.

[0145] In some instances, mini-modules can be assembled into hollow pyramid macrostructures. In some instances, hollow pyramid macrostructures can create hollow pyramid bioreactors, as provided elsewhere herein. The hollow pyramids can have a hollow center of a certain volume and increasing cross-sections. In some instances, the hollow pyramids have increasing volumes between layers (which is the number of mini-modules added between one layer and the next in the flow direction), ordered by (i) an alternating growth between their outer edges and (ii) an increasing internal perimeter (i.e., the circumference of the internal hollow center). For example, if N is the number of modules on one of the outer edges of the hollow pyramid, n is the number of mini-modules that make up one of the inner edges of the hollow pyramid, and N = (8; 8) in one layer, then n = (4; 4). This logic is repeated alternately and clockwise (taking into account the flow direction) between the outer edges of the pyramid in each layer. The result is a stepped pyramid whose steps form a faceted spiral: the inner periphery also has spiral growth, but at a lower frequency than the outer periphery, and the growth direction for the inner periphery is opposite to that of the outer periphery.

[0146] In some examples, methods and systems for generating lamellar macrostructures (e.g., other systems such as 3D printing devices, hardware, software, and any methods, systems, or materials provided elsewhere herein) are provided herein. In some examples, the lamellar macrostructures can be used as lamellar bioreactors. In some examples, the bioreactors use lamellar macrostructures composed of multiple mini-modules. The mini-modules can be DG or can have other shapes. The lamellar macrostructures have increasing cross-sections composed of constant-thickness sheets and mini-modules. The constant-thickness sheets allow uniform access of materials into the bioreactor, such as from a feed circuit. The volume increase between layers (which is the number of modules added between one layer and the next in the flow direction) can be determined by the bioreactor and can be ordered by alternating growth between the shortest edges of the sheets. In the lamellar macrostructures, there can be one or more sheets, for example, 2, 3, 4, 5, 6, 7, 8, or more than 8 sheets, arranged side by side. The space between each sheet can be used to place a supply circuit or part of a supply circuit that supplies the modules within the sheet.

[0147] In some examples, the methods and systems provided herein can be used to create trees, such as chessboard macrostructures. The chessboard macrostructure can create a chessboard bioreactor. In some examples, mini-modules of any shape (e.g., DG or any other mini-module shape provided elsewhere herein) can be assembled into a chessboard macrostructure having at least one hollow column of constant cross section that vertically intersects the layers of mini-modules. In some examples, the chessboard macrostructure has one, two, three, four, or more than four such columns. The columns can be used to provide areas for transporting liquid media and other substances through channels that follow the vertical columns.

[0148] In some examples, the 3D printing systems and methods provided herein, such as printer systems, can provide the capacity for continuous printable surfaces with high resolution, such as for building bioreactors using macrostructures with repeating mini-modules. In some examples, the printing surface can be up to approximately 320 mm x 320 mm. In some examples, the printing surface is up to approximately 320 mm x 320 mm, and each 1 x 1 x 1 mm saturated cube of printing area holds up to approximately 14,616 mini-modules (e.g., DG or modified DG, etc.). In some examples, the printing volume is up to 320 mm x 320 mm x 1000 mm (X, Y, Z coordinates of the printing volume), and the printing volume holds up to approximately 1,496,704,035 mini-modules or less. Nevertheless, in many examples, 3D printing methods, devices, and systems are used to create bioreactors, and such 3D printing methods, devices, and systems can be used to create any object, such as any 3D object. Likewise, while in many instances reaction vessels such as bioreactors are made using the 3D printing systems and methods described herein, such bioreactors may be made using other methods in other instances.

[0149] Provided herein are methods for constructing 3D objects using techniques such as 3D printing, which may include using methods and systems provided elsewhere herein. In some examples, the methods and / or systems provided herein can be used to construct 3D structures, which may have a variety of applications. In some cases, the 3D structure constructed or manufactured may comprise units or modules, such as parts, components, sections, or subunits, which may be assembled to create a structure or object. As an example, the 3D object may be a reaction vessel or a bioreactor. The bioreactor may be according to any of the bioreactors provided elsewhere herein. The bioreactor may comprise one or more mini-modules. The bioreactor mini-modules may be assembled to create a macrostructure. The macrostructure may be a bioreactor macrostructure provided herein.

[0150] In some examples, in the methods of the present disclosure, a space can be mathematically described by a continuous and / or ordered matrix. The matrix can include any number of dimensions, such as 1, 2, 3, 4, 5, 6, 7, 8, or more. In one example, the matrix can be a 3D matrix. The space can be a 3D space. In some cases, the matrix can be continuous and ordered, such as a continuous and ordered three-dimensional (3D) matrix. The matrix can define the boundaries of available spaces into which elements can be placed to function the space according to the requirements of the space they occupy. The methods can be implemented using a computer. Computer systems that can be used to implement the methods of the present disclosure are provided herein. In some examples, the methods can include computer-implemented methods, such as software, code, or a set of instructions, for implementing the methods described herein. Such methods may be described in further detail elsewhere herein.

[0151] In some cases, the mini-modules can be assembled into structures (e.g., macro-structures) that provide targeted control of media and gas flow and distribution within the structure (e.g., a bioreactor). In other examples, the same approach can be implemented to create multiple parts, units, components, modules, or mini-modules to build structures other than reactors or bioreactors. The 3D objects, structures, or modules created using the methods or systems provided herein can have a variety of applications.

[0152] In some examples, the mini-modules can have a certain shape or structure. The shape or structure can include any shape or structure provided elsewhere herein. In one example, the shape or structure of the mini-modules can include a modified double gyroid (DG), which can be assembled into a macrostructure to create the production bioreactors provided herein. Figures 33A-33F illustrate an assembly that begins with a first mini-module (e.g., a DG) and assembles additional mini-modules such that the geometry is repeated to form a three-dimensional (3D) matrix whose growth can be limited to two of the three possible dimensions. The connection point of one mini-module to another mini-module can be referred to as a "mouth." This first assembly of interconnected mini-modules that can be identically oriented is referred to as a "layer." The layers can be arranged, for example, in a rhomboid, so that in some examples, when the same number of modules are connected in a selected direction, the resulting growth is not proportional, and thus the growth of the layers is irregular relative to each other. In some instances, the layers can be arranged in a square or other manner so that the resulting growth is proportional. Figures 37A-37F show an example of layer assembly and growth. Layer assembly and growth can occur in any direction.

[0153] A mini-module can be a building block of a larger structure, which can be a bioreactor. A mini-module can be constructed by assembling multiple smaller units, such as unit cells, which can be voxels that can be used to define a space or a structure within a space. A unit cell can have a shape. The shape of a mini-module can include any shape, such as any geometric shape, and any size. A mini-module can be a crystallographic cell that can be used to order or define a space. For example, a space or its features can be defined, structured, or shaped by the presence or absence of unit cells or their positions in the space. For example, in a given area of ​​space, a high density of instance unit cells or voxels can be provided to define or create a solid object. For example, a large number of unit cells or voxels can be located within a small area, and therefore the area can be defined or recognized by a user, entity, software, machine, or artificial intelligence (AI) as a solid structure, such as a wall, that is densely packed with unit cells or voxels and has a given thickness. In another example, unit cells may be sparse in a given area. In such cases, unit cells or voxels may be assembled to create hollow spaces, substantially empty spaces, channels, holes, or the like. For example, multiple unit cells of appropriate shape may be assembled to create mini-modules or building blocks, such as conduits or hollow chambers, such as the hollow chamber of a bioreactor (e.g., chamber 4840). Methods for constructing such structures are provided herein. Methods for constructing such structures may be implemented by a computer system, such as software components provided herein, AI, machine learning, other computer-implemented methods, and any combination thereof. In some examples, a computer-implemented method may provide a set of instructions (e.g., executable instructions) that can be used by a device provided herein to 3D print a given structure, such as a bioreactor provided herein.

[0154] A mini-module can be constructed by assembling multiple smaller units, such as voxels or unit cells. In some examples, a mini-module can be composed of crystallographic cells, which can be used to define and / or order a space, such as a 3D space, according to the methods of the present disclosure. The shape of the unit cell can belong to a given class. Examples of unit cell or crystallographic cell classes can include primitive, body-centered, face-centered, side-centered, other classes, and combinations thereof. Examples of unit cell shapes can include cubic, spherical, rectangular, pyramidal, gyroid, double-gyroid, triclinic, monoclinic, orthorhombic, trigonal, hexagonal, or any other geometric shape. The shape of the unit cell can include a Bravais lattice. The Bravais lattice can have any of the shapes provided herein. Examples of Bravais lattices and unit cell or crystallographic cell shapes are provided in Table 1.1. The unit cells can be used as voxels to order or generate space and create mini-modules.

[0155] [Table 1]

[0156] A crystallography cell or unit cell can contain one or more elements, in some examples, a finite number of elements. An element can be a set of coordinates that can be given a meaning. Examples of an element can include a point, an axis, a proper axis, a non-proper axis, a center, a plane, or another element. In some examples, an assembly of unit cells and elements can form a structure such as a macrostructure or a mini-module. In one example, such an assembly can form a hollow cylinder that can be configured to allow the flow of a fluid, such as a gas or liquid. For example, an assembly of unit cells, elements, and / or combinations thereof can create a channel, a conduit, a chamber, or another mini-module or building block of a bioreactor described herein, such as a channel (e.g., channel 4820, 4810, or any other channel provided elsewhere herein). In some examples, an assembly of unit cells and elements can form a solid structure, such as a solid wall, a solid block, or another structure.

[0157] In some cases, the arrangement of elements within unit cells (e.g., within crystallographic cells or within crystals) can be important to minimize or avoid, to the extent possible, potential disruptions of functional continuity within possible volumes or structures created by the assembly of such unit cells and / or elements. In some examples, the arrangement of unit cells and / or elements can be implemented by example mathematical instructions, equations, or formulations, which can include mathematical functions, mathematical operations, and / or mathematical operators. Examples of such mathematical operators can be symmetry operators.

[0158] A mathematical operator may generally be referred to as a mapping or function that can operate on elements of a first space (e.g., a 3D space) to yield elements of another space. In some cases, the second space may be the same as the first space. The operator may include a linear map that can operate on a vector space. In some cases, the operator may preserve properties of the spaces and / or elements, such as their continuity. The operator may be a linear operator, a bounded operator, or another type of operator. Examples of operators that may be performed on elements include a translation operator, a rotation operator, an inverse operator, a reflection operator, and an identity operator. An example operator that may be used to implement the methods of the present disclosure may be a symmetry operator.

[0159] In some examples, bioreactor mini-modules can have double gyroid or modified double gyroid geometries. A double gyroid (DG) can comprise two gyroids and include two intergrown, non-overlapping domains. A modified double gyroid (DG) can include two intergrown, non-overlapping domains that may be bounded by two constant-mean-curvature (CMC) surfaces separated by a matrix phase. A modified double gyroid structure can include minor modifications to the connections of an unmodified double gyroid to tailor the structure to a given macrostructure or function. Modifications can include blocking a portion of the connection or intersection (e.g., "mouth"), modifying the diameter of one or both phase channels of the structure, or completely or partially removing any of the phase channels present in the DG structure. A DG or modified DG can include a first gyroid structure intertwined with a second gyroid structure. The two channels can be separated, for example, by a porous membrane.

[0160] In one example, in the bioreactors provided herein, disconnected connectors of units (e.g., mini-modules) on the edge of each layer can be used to connect the layer to other functions, such as inputs for media flow or gas, and outputs for spent media (e.g., harvest layer 4610 and / or harvest channel 4696), spent gas (e.g., gas intake channel, gas harvest channel, not shown), and cells or bio-products produced by the cells. In some cases, the output of cells or bio-products produced by the cells can be the same as or different from the output of spent media.

[0161] In some examples, an assembly of a layer of mini-modules (a "first matrix") can be co-located with a second assembly of a layer of mini-modules (a "second matrix"), where the second matrix can occupy the free space left by the first matrix, and matrices occupying the same volume cannot have contact points and can maintain a certain minimum distance. In further examples, higher-order assembly of a layer of mini-modules can be achieved by co-locating one or more subsequent matrices (e.g., a second matrix, a third matrix, a fourth matrix, a fifth matrix, etc.) with an initial matrix, where the one or more subsequent matrices occupy the free space left by the initial matrix, and matrices occupying the same volume cannot have contact points and can maintain a certain minimum distance. Example assemblies of two matrices are shown in Figures 34A-34F. Figure 34A shows an example of a portion of a double gyroid inscribed within a cube. Figure 34B shows an orthogonal view and cutaway view of the structure in Figure 34A. Figures 34C and 34D show examples of growth direction of the second layer relative to the first layer. Figure 34E shows an example of volume subtracted from the pyramid and counterclockwise growth. Figure 34F shows an example of clockwise growth of the macrostructure along the vertical axis of the hollow pyramid.

[0162] Macro Structure Example Hollow Pyramid Macro Structure In some examples, the mini-modules can be assembled into hollow pyramid macrostructures. The hollow pyramid macrostructures can have a hollow center of a certain volume and an increasing cross section. Using the hollow pyramid macrostructure, the supply circuit can supply both the outer and inner peripheries. For the construction of hollow pyramids, the matrix can have an initial layer that can be linked to a distributor and a layer that can then be connected to a collector. The number of upper mice of the initial layer, starting from the lower mouse of the layer that connects to the collector, is set M=2. n Thus, the connecting channels or trees can branch in balanced pairs. The trees can be the distribution structure (input) and collection (output) of the bioreactor. In some cases, the bioreactor can be bubble-free. At both the input and output of the bioreactor and / or its modules, the channels can range from a single channel to multiple channels, e.g., 2 nThe layers can transition or branch into channels. The increase in volume between layers (which is the number of mini-modules added between one layer and the next in the flow direction) can be determined by the bioreactor and can be ordered by (i) growth in an alternating sense between its outer edges and (ii) growth in its inner perimeter (i.e., around the internal hollow center). For example, if N is the number of modules at one of the outer edges of a hollow pyramid, n is the number of mini-modules that make up one of the inner edges of the hollow pyramid, and N = (8; 8) in one layer, then n = (4; 4) (see, e.g., Figure 36). This logic can be repeated in an alternating and clockwise sense (taking into account the flow direction) between the outer edges of the pyramid in each layer. The result can be a stepped pyramid whose steps form a faceted spiral. In some instances, the inner periphery may have a spiral growth, in some cases with a lower frequency than the outer periphery, and the growth direction for the inner periphery may be opposite to that of the outer periphery (see Figures 37A and 37B). In some instances, the interaction of the inner and outer spirals with the flow direction may result in vortex-type motion of the flowing medium within the hollow pyramidal structure.

[0163] In some examples, the feed system of a bioreactor can be connected to the bioreactor through one or more channels, such as subchannels. The subchannels of the feed circuit can surround one or more layers within the bioreactor at example distances (e.g., equal distances) on each side of a given layer. The subchannels can connect as edges of layers in one or more mouths of a mini-module. An example set of connections is shown in Figures 36A-36F.

[0164] In some examples, the feed circuit can connect to the bioreactor at 1, 2, 3, 4, 5, 6, 7, 8, or more than 8 points. In one example, the feed circuit can feed a hollow pyramid macrostructure bioreactor, and the feed circuit can have a division of five subchannels. One or more of these subchannels extend inside the pyramid internal channel, and the remaining channels provide subchannels parallel to the edges of each layer (external channels). Pressure and flow balance in the feed circuit can be maintained through balancing of the external and / or internal channels of the feed system. An example feed circuit for a hollow pyramid shape is shown in FIG. 38.

[0165] Lamellar macrostructure In some instances, the macrostructure of the bioreactor can be a lamella. In some instances, a supply system can be connected to the bioreactor through one or more subchannels. The subchannels of the supply circuit can surround one or more layers within the bioreactor at equal distances on each side of a given layer. The subchannels can connect as edges of layers in one or more mouths of the mini-module. A set of example connections is shown in Figures 35A-35F.

[0166] In some examples, the bioreactor can use a lamellar macrostructure composed of mini-modules. Such mini-modules can have any shape or configuration. The shape or configuration can be in accordance with the shapes or configurations provided elsewhere herein, such as DG or other shapes. The lamellar macrostructure can have an increasing cross-section composed of constant-thickness sheets and mini-modules. The constant-thickness sheets allow for uniform or homogeneous access of materials from the supply circuit. The volume increase between layers (the number of modules added between one layer and the next in the flow direction) can be determined by the bioreactor and can be ordered by alternating mean growth between the shortest edges of the sheets (see, for example, Figure 39). In the lamellar macrostructure, there can be one or more sheets, e.g., 2, 3, 4, 5, 6, 7, 8, or more than 8 sheets, which can be arranged side by side or in different configurations. The space between each sheet can be used to place a supply circuit or part thereof, which can supply modules within the sheet (see, for example, Figure 40).

[0167] Chess Macro Structure In some examples, the mini-modules can be assembled into a wooden chess macrostructure that can have at least one hollow column of constant cross-section that can intersect the layers of mini-modules (e.g., vertically or in another direction). In some examples, the wooden chess macrostructure can have one, two, three, four, or more than four such columns. The columns can be used to provide areas for transporting liquid media and other substances through channels and / or other features that follow the vertical columns. Collection of spent media, gases, cells, and bioproducts can occur on one, more than, or all of the exterior surfaces of the structure, which can be driven by a pressure difference between the center and face of the column or using another technique or force. An example wooden chess macrostructure is shown in FIG. 41, and an example supply and collection arrangement is shown in FIG. 42.

[0168] Sphere Macrostructure In some examples, the mini-modules can be assembled into a sphere macrostructure. The sphere structure can be used to create a sphere bioreactor. An example of using multiple mini-modules to build a sphere macrostructure is shown in Figure 52. Multiple mini-modules 5210 are assembled into a 3D sphere macrostructure shape.

[0169] Examples of sphere bioreactors are shown in Figures 46A, 46B, and 47 and are described in further detail elsewhere herein.

[0170] Connected Systems The modules can be connected, coupled, or in fluid communication by one or more connection systems. Figures 43A and 43B show an example connection system that can include a connector between a cell chip module and a fluid source or fluid collection module. The connector can include a support and a set of hollow needles that can allow for the entry and exit of fluids and / or fluids containing cells. In some examples, the connector connects to a first module, such as a cell chip module, through the needles. The cell chip module can be a cell chip module described elsewhere herein. The needles can be arranged in sets, such that each set of needles includes a needle for fluid input and another needle for fluid output from the cell chip module. One end of the needles can be used to enter a chamber or channel in the cell chip module, and the other end of the needles can be connected to a fluid source, a collection device, or another module.

[0171] In some examples, a set of needles can include at least one input needle and one output needle. In some examples, there can be multiple sets of needles. Each set of needles can be directed to a separate chamber and / or separate channel to which fluid can be directed for input or removed for output.

[0172] In some examples, the bioreactor systems provided herein can include one or more modules. The one or more modules can include a cell chip module, a sandbox bioreactor, a production bioreactor, and / or more modules. The device can further include one or more connectors that can connect the modules to each other or to external pieces, devices, sources, modules, etc. For example, a connector can connect a cell chip module to one or more sources of fluids, such as culture media, nutritional supplements, chemical inputs, trypsin, wash / buffer solutions that can be used to supply fluids to the cell chip module and, optionally, remove spent fluids. In some examples, a connector can connect a cell chip module to a second module, such as a sandbox bioreactor, or a production bioreactor, such as for transferring cells from one module to another.

[0173] In one example, the connection system can further include a wash chamber, so that the needle can be washed and / or sterilized before entering a module, such as a cell chip module. In one example, the wash chamber can include one or more chambers (e.g., separate chambers) at one end of the cell chip module. In some examples, the wash chamber(s) can be bounded on a first end by a septum, which can contain the wash chamber from the environment, through which the needle can be pierced into the wash chamber from one end. In some examples, the wash chamber can be bounded on a second end by a safety film or other boundary that can contain a cleaning or sterilization fluid (or gas) within the wash chamber. A connector in such examples can be connected at the other end of the needle to a fluid source, such as one having a cleaning or sterilant and wash solution(s).

[0174] On the other side of the safety film or boundary, there can be a channel. Once cleaned and sterilized, the needle can be placed into the chamber through the safety film or boundary. The channel can be a culture media channel that flows culture media from the needle to other locations within the cell chip. The channel can be a cell collection channel, from which cells present within the chip (such as cells growing and proliferating within the chip) can then be directed into the channel and then through the needle to a separate module or collection component. The channel can be a waste channel, through which spent media can be directed and removed from the chip.

[0175] Figure 43C shows examples of connections made by the connector system to components including culture media, sterilant, and to waste collection and sandbox modules. Connecting tubes or channels connect from the connector system, and in some cases, valves can be utilized to direct fluids from the connector to the appropriate source, collector, or module.

[0176] Figure 43D shows an example of a connection system with needles penetrating a first chamber in a cell chip module, such as for cleaning and sterilization or other purposes, and shows an example of a connection system during a cleaning process with fluid flow from a component containing sterile fluid to a sterile chamber in the cell chip, with one set of needles for removing used sterile fluid.

[0177] Figure 43E shows an example of a connection system with needles penetrating the second chamber after cleaning and sterilization. The first set of needles (left) can be positioned so that the input needles enter the culture media channel / chamber, allowing new culture media to flow into the cell chip module. The middle set of needles can be positioned so that one needle is positioned to output spent media and culture waste from the channel in the cell chip module. The third set of needles (right) can be positioned so that only the output needle enters the chamber / channel and is positioned to output media and cells from the cell chip module.

[0178] Materials for constructing bioreactor modules and other printed objects The systems, components, and modules described herein can be made from a variety of materials, and such materials can be adjusted depending on the cell growth and the cellular environment used. In some examples, the components and modules, or portions thereof, are made by 3D printing using the printing systems described herein. Printing can use commercially available resins and infrared (UV) curable biocompatible polymers. In some examples, the biomaterial used can include a combination of three subcomponents: a biocompatible polymer, a photoinitiator, and a UV absorber.

[0179] Example resins include, but are not limited to, polycaprolactone (PCL), polyethylene glycol (PEG), PEG-diacrylate (PEGDA), polyglycolic acid (PGA), polylactic acid (PLA), polylactic-co-glycolic acid, polypropylene fumarate (PPF), polyurethane (PU), polyvinyl alcohol (PVA), silk, poly(glycerol sebacate) acrylate (PGSA), epoxy-based resins, natural polymer-based resins, bioceramic-based resins, alginate-based resins, GelMA-based resins, nanocomposite-based resins, bioinks, and cellulose-based resins.

[0180] Computer Systems Referring to FIG. 32, a block diagram illustrating an example machine is shown that includes at least one processor 3200 (e.g., a processing or computing system) within which a set of instructions may be executed to cause the device to implement or perform any one or more of the aspects and / or methods for static code scheduling of the present disclosure.

[0181] The processing device 3200 may include one or more processors 3201, memory 3203, and storage 3208, which communicate with each other and with other components via a bus 3240. The bus 3240 may also be linked to a display 3232, one or more input devices 3233 (which may include, for example, a keypad, keyboard, mouse, stylus, etc.), one or more output devices 3234, one or more storage devices 3235, and various tangible storage media 3236. All of these elements may interface to the bus 3240 directly or through one or more interfaces or adapters. For example, the various tangible storage media 3236 may interface to the bus 3240 through a storage media interface 3226. The processing device 3200 may have any suitable physical form, including, but not limited to, one or more integrated circuits (ICs), a printed circuit board (PCB), a mobile portable device (such as a cell phone or PDA), a laptop or notebook computer, a distributed computer system, a computing grid, or a server.

[0182] The processing device 3200 includes one or more processor(s) 3201 (e.g., a central processing unit (CPU), a general purpose graphics processing unit (GPGPU), or a quantum processing unit (QPU)) that perform functions. The processor(s) 3201 optionally include a cache memory unit 3202 for temporary local storage of instructions, data, or computer addresses. The processor(s) 3201 are configured to support the execution of computer-readable instructions. The processing device 3200 can provide the functionality for the components shown in FIG. 32 as a result of the processor(s) 3201 executing non-transitory processor-executable instructions embodied in one or more tangible computer-readable storage media, such as memory 3203, storage 3208, storage device 3235, and / or storage medium 3236. The computer-readable medium can store software capable of implementing the methods of the present disclosure, and the processor(s) 3201 can execute the software. The memory 3203 can read the software from one or more other computer-readable media (such as mass storage device(s) 3235, 3236) or from one or more other sources through an appropriate interface, such as the network interface 3220. The software can cause the processor(s) 3201 to perform one or more processes or one or more steps of one or more processes described or illustrated herein. Performing such a process or step can include defining data structures stored in the memory 3203 and modifying the data structures as directed by the software.

[0183] The memory 3203 may include various components (e.g., machine-readable media) including, but not limited to, random access memory components (e.g., random access memory (RAM) 3204) (e.g., static RAM (SRAM), dynamic RAM (DRAM), ferroelectric random access memory (FRAM), phase-change random access memory (PRAM), etc.), read-only memory components (e.g., read-only memory (ROM) 3205), and any combination thereof. The ROM 3205 may act to communicate data and instructions unidirectionally to the processor(s) 3201, and the RAM 3204 may act to communicate data and instructions bidirectionally with the processor(s) 3201. The ROM 3205 and RAM 3204 may include any suitable tangible computer-readable media described below. In one example, a basic input / output system 3206 (BIOS), containing the basic routines that help to transfer information between elements within processing device 3200 , such as during start-up, may be stored in memory 3203 .

[0184] Persistent storage 3208 is bidirectionally connected to processor(s) 3201, optionally through storage control unit 3207. Persistent storage 3208 provides additional data storage capacity and may include any suitable tangible computer-readable medium described herein. Storage 3208 may be used to store operating system 3209, executable(s) 3210, data 3211, applications 3212 (application programs), and the like. Storage 3208 may also include an optical disk drive, a solid-state memory device (e.g., a flash-based system), or any combination of the above. Information in storage 3208 may be incorporated as virtual memory in memory 3203, where appropriate.

[0185] In one example, storage device(s) 3235 may be removably interfaced to processing device 3200 via storage device interface 3225 (e.g., via an external port connector (not shown)). In particular, storage device(s) 3235 and associated machine-readable media may provide non-volatile and / or volatile storage of machine-readable instructions, data structures, program modules, and / or other data for processing device 3200. In one example, software may reside, completely or partially, within the machine-readable media on storage device(s) 3235. In another example, software may reside, completely or partially, within processor(s) 3201.

[0186] Bus 3240 connects various subsystems. References herein to a bus can, where appropriate, include one or more digital signal lines that serve a common function. Bus 3240 can be any of several types of bus structures including, but not limited to, a memory bus, a memory controller, a peripheral bus, a local bus, and any combination thereof, using any of a variety of bus architectures. By way of example and not limitation, such architectures include an Industry Standard Architecture (ISA) bus, an Enhanced ISA (EISA) bus, a Micro Channel Architecture (MCA) bus, a Video Electronics Standards Association local bus (VLB), a Peripheral Component Interconnect (PCI) bus, a PCI-Express (PCI-X) bus, an Accelerated Graphics Port (AGP) bus, a HyperTransport (HTX) bus, a serial advanced technology attachment (SATA) bus, and any combination thereof.

[0187] The processing device 3200 may also include input device(s) 3233. In one example, a user of the processing device 3200 can input commands and / or other information into the processing device 3200 via the input device(s) 3233. Examples of the input device(s) 3233 include, but are not limited to, an alphanumeric input device (e.g., a keyboard), a pointing device (e.g., a mouse or touchpad), a touchpad, a touchscreen, a multi-touch screen, a joystick, a stylus, a gamepad, an audio input device (e.g., a microphone, a voice response system, etc.), an optical scanner, a video or still image capture device (e.g., a camera), and any combination thereof. In some examples, the input device is a Kinect, Leap Motion, or the like. Input device(s) 3233 may be interfaced to bus 3240 via any of a variety of input interfaces 3223 (e.g., input interface 3223), including, but not limited to, serial, parallel, game port, USB, FIREWIRE, THUNDERBOLT, or any combination of the above.

[0188] In some examples, when the processing device 3200 is connected to the network 3230, it can communicate with other devices connected to the network 3230, including, among other things, mobile devices and enterprise systems, distributed computing systems, cloud storage systems, cloud computing systems, and the like. Communications to / from the processing device 3200 can be transmitted through the network interface 3220. For example, the network interface 3220 can receive incoming communications (such as requests or responses from other devices) from the network 3230 in the form of one or more packets (such as Internet Protocol (IP) packets), and the processing device 3200 can store the incoming communications in memory 3203 for processing. The processing device 3200 can similarly store outgoing communications (such as requests or responses to other devices) in the form of one or more packets in memory 3203 and transmit them from the network interface 3220 to the network 3230. The processor(s) 3201 can access these communication packets stored in memory 3203 for processing.

[0189] Examples of network interface 3220 include, but are not limited to, a network interface card, a modem, and any combination thereof. Examples of network 3230 or network segment 3230 include, but are not limited to, a distributed computing system, a cloud computing system, a wide area network (WAN) (e.g., the Internet, an enterprise network), a local area network (LAN) (e.g., a network associated with an office, building, campus, or other relatively small geographic space), a telephone network, a direct connection between two computing devices, a peer-to-peer network, and any combination thereof. Networks such as network 3230 can use wired and / or wireless communication modes. In general, any network topology can be used.

[0190] Information and data may be displayed through a display 3232. Examples of the display 3232 include, but are not limited to, a cathode ray tube (CRT), a liquid crystal display (LCD), a thin film transistor liquid crystal display (TFT-LCD), an organic liquid crystal display (OLCD) such as a passive-matrix OLED (PMOLED) or an active-matrix OLED (AMOLED) display, a plasma display, and any combination thereof. The display 3232 may be interfaced to other devices, such as the processor(s) 3201, memory 3203, and persistent storage 3208, as well as input device(s) 3233, via a bus 3240. The display 3232 is linked to the bus 3240 via a video interface 3222, and the transport of data between the display 3232 and the bus 3240 may be controlled by a graphics control 3221. In some examples, the display is a video projector. In some examples, the display is a head-mounted display (HMD) such as a VR headset. In some examples, suitable VR headsets include, by way of non-limiting example, HTC Vive, Oculus Rift, Samsung Gear VR, Microsoft HoloLens, Razer OSVR, FOVE VR, Zeiss VR One, Avegant Glyph, Freefly VR headsets, and the like. In some examples, the display is a combination of devices as disclosed herein.

[0191] In addition to the display 3232, the processing device 3200 may include one or more other peripheral output devices 3234, including, but not limited to, audio speakers, printers, storage devices, and any combination thereof. Such peripheral output devices may be connected to the bus 3240 via an output interface 3224. Examples of the output interface 3224 include, but are not limited to, a serial port, a parallel connection, a USB port, a FIREWIRE port, a THUNDERBOLT port, and any combination thereof.

[0192] Additionally or alternatively, processing device 3200 may provide functionality as a result of hardwired or otherwise embodied logic in circuitry that can operate in place of or in conjunction with software to perform one or more processes, or one or more steps of one or more processes, described or illustrated herein. References to software in this disclosure may encompass logic, and references to logic may encompass software. Furthermore, references to computer-readable media may encompass, where appropriate, circuitry (such as an IC) that stores software for execution, circuitry that embodies logic for execution, or both. This disclosure encompasses any appropriate combination of hardware, software, or both.

[0193] Those skilled in the art will appreciate that the various illustrative logical blocks, modules, circuits, and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or a combination of both. To clearly illustrate this interchangeability of hardware and software, the various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality.

[0194] The various illustrative logic blocks, modules, and circuits described in connection with the embodiments disclosed herein may be implemented or performed using a general-purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general-purpose processor may be a microprocessor, but in the alternative, the processor may be any conventional processor, controller, microcontroller, or state machine. A processor may also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, multiple microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0195] The steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in a software module executed by one or more processor(s), or in a combination of the two. A software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, a hard disk, a removable disk, a CD-ROM, or any other form of storage medium known in the art. An example storage medium is coupled to the processor such that the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium may be integral to the processor. The processor and the storage medium may reside in an ASIC. The ASIC may reside in a user terminal. In the alternative, the processor and the storage medium may reside as discrete components in a user terminal.

[0196] According to the description herein, suitable processing devices include, by way of non-limiting example, server computers, desktop computers, laptop computers, notebook computers, sub-notebook computers, netbook computers, netpad computers, handheld computers, Internet appliances, mobile smartphones, and tablet computers.

[0197] In some embodiments, the processing device includes an operating system configured to execute executable instructions. An operating system is software, including, for example, programs and data, that manages the device's hardware and provides services for the execution of applications. Those skilled in the art will recognize that suitable server operating systems include, by way of non-limiting examples, FreeBSD, OpenBSD, NetBSD®, Linux, Apple® Mac OS X Server®, Oracle® Solaris®, Windows Server®, and Novell® NetWare®. Those skilled in the art will recognize that suitable personal computer operating systems include, by way of non-limiting examples, UNIX-like operating systems such as Microsoft® Windows®, Apple® Mac OS X®, UNIX®, and GNU / Linux®. In some examples, the operating system is provided by cloud computing. Those skilled in the art will similarly recognize that suitable mobile smartphone operating systems include, by way of non-limiting examples, Nokia® Symbian® OS, Apple® iOS®, Research In Motion® BlackBerry® OS, Google® Android®, Microsoft® Windows Phone® OS, Microsoft® Windows Mobile® OS, Linux®, and Palm® WebOS®.

[0198] Non-transitory computer-readable storage medium In some examples, the platforms, systems, media, and methods disclosed herein include one or more non-transitory computer-readable storage media encoded with a program including instructions executable by an operating system of a networked computing device. In some examples, the computer-readable storage medium is a tangible component of the computing device. In some examples, the computer-readable storage medium is optionally removable from the computing device. In some examples, the computer-readable storage medium includes, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, solid-state memories, magnetic disk drives, magnetic tape drives, optical disk drives, distributed computing systems including cloud computing systems and services, and the like. In some cases, the programs and instructions are encoded on the medium permanently, substantially permanently, semi-permanently, or non-transitoryly.

[0199] Executable Instructions In some examples, the platforms, systems, media, and methods disclosed herein include at least one set of executable instructions (e.g., computer program, computer application) or their use. A computer program includes a sequence of instructions written to perform specified tasks and executable by one or more processor(s) of a computing device's CPU. Computer-readable instructions may be implemented as program modules, such as functions, objects, application programming interfaces (APIs), computing data structures, and the like, that perform particular tasks or implement particular abstract data types. In light of the disclosure provided herein, those skilled in the art will recognize that computer programs may be written in a variety of languages ​​and versions.

[0200] The functionality of the computer-readable instructions may be combined or distributed as desired in various environments. In some examples, a computer program may include one sequence of instructions. In some examples, a computer program may include multiple sequences of instructions. In some examples, a computer program may be provided from one location. In some examples, a computer program may be provided from multiple locations. In some examples, a computer program may include one or more software modules. In some examples, a computer program may comprise, in part or in whole, one or more web applications, one or more mobile applications, one or more standalone applications, one or more web browser plug-ins, extensions, add-ins, or add-ons, or a combination thereof. The functionality of the computer-readable instructions may include methods for constructing spaces using multiple mini-modules and methods for constructing structures such as bioreactors, which are described in more detail elsewhere herein.

[0201] Web Applications In some examples, the computer program includes a web application. In light of the disclosure provided herein, those skilled in the art will recognize that a web application, in some examples, utilizes one or more software frameworks and one or more database systems. In some examples, the web application is created on a software framework such as Microsoft® .NET or Ruby on Rails (RoR). In some examples, the web application utilizes one or more database systems, including, by way of non-limiting examples, relational, non-relational, object-oriented, associative, XML, and document-oriented database systems. In some examples, suitable relational database systems include, by way of non-limiting examples, Microsoft® SQL Server, mySQL™, and Oracle®. Those skilled in the art will also recognize that a web application, in some examples, can be written in one or more versions of one or more languages. A web application can be written in one or more markup languages, presentation specification languages, client-side scripting languages, server-side coding languages, database query languages, or combinations thereof. In some instances, web applications are written to some extent in a markup language such as Hypertext Markup Language (HTML), Extensible Hypertext Markup Language (XHTML), or Extensible Markup Language (XML). In some instances, web applications are written to some extent in a presentation specification language such as Cascading Style Sheets (CSS).In some examples, web applications are written to some extent in a client-side scripting language such as Asynchronous JavaScript and XML (AJAX), Flash® ActionScript, JavaScript, or Silverlight®. In some examples, web applications are written to some extent in a server-side coding language such as Active Server Pages (ASP), ColdFusion®, Perl, Java™, JavaServer Pages (JSP), Hypertext Preprocessor (PHP), Python™, Ruby, Tcl, Smalltalk, WebDNA®, or Groovy. In some examples, web applications are written to some extent in a database query language such as Structured Query Language (SQL). In some examples, web applications integrate with enterprise server products such as IBM® Lotus Domino®. In some examples, web applications include a media player component. In various further examples, the media player element utilizes one or more of many suitable multimedia technologies, including, by way of non-limiting examples, Adobe® Flash®, HTML 5, Apple® QuickTime®, Microsoft® Silverlight®, Java™, and Unity®.

[0202] Mobile Applications In some examples, the computer program comprises a mobile application provided to the mobile computing device. In some examples, the mobile application is provided to the mobile computing device when the mobile computing device is manufactured. In some examples, the mobile application is provided to the mobile computing device over a computer network as described herein.

[0203] Given the disclosure provided herein, mobile applications are created using techniques known to those skilled in the art using hardware, languages, and development environments known in the art. Those skilled in the art will recognize that mobile applications can be written in a number of languages. Suitable programming languages ​​include, by way of non-limiting examples, C, C++, C#, Objective-C, Java™, JavaScript, Pascal, Object Pascal, Python™, Ruby, VB.NET, WML, and XHTML / HTML with or without CSS, or combinations thereof.

[0204] Suitable mobile application development environments are available from several sources. Commercially available development environments include, but are not limited to, Airplay SDK, alcheMo, Appcelerator®, Celsius, Bedrock, Flash Lite, .NET Compact Framework, Rhomobile, and WorkLight Mobile Platform. Other development environments are available free of charge and include, but are not limited to, Lazarus, MobiFlex, MoSync, and Phonegap. Similarly, mobile device manufacturers distribute software developer kits, but are not limited to, iPhone and iPad (iOS) SDK, Android™ SDK, BlackBerry® SDK, BREW SDK, Palm® OS SDK, Symbian SDK, webOS SDK, and Windows Mobile SDK.

[0205] Those skilled in the art will recognize that several commercial forums are available for the distribution of mobile applications, including, by way of non-limiting examples, the Apple® App Store, Google® Play, Chrome WebStore, BlackBerry® App World, App Store for Palm devices, App Catalog for webOS, Windows® Marketplace for Mobile, Ovi Store for Nokia® devices, and Samsung® apps.

[0206] Standalone Applications In some examples, a computer program includes a standalone application, which is a program that runs as an independent computer process and is not an add-on, e.g., a plug-in, to an existing process. Those skilled in the art will recognize that standalone applications are often compiled. A compiler is a computer program or programs that convert source code written in a programming language into binary object code, such as assembly language or machine code. Suitable compiled programming languages ​​include, by way of non-limiting examples, C, C++, Objective-C, COBOL, Delphi, Eiffel, Java™, Lisp, Python™, Visual Basic, and VB .NET, or combinations thereof. Compilation is often performed at least in part to create an executable program. In some examples, a computer program includes one or more compiled executable applications.

[0207] Software Module In some examples, the platforms, systems, media, and methods disclosed herein include software, server, and / or database modules, or the use thereof. In light of the disclosure provided herein, software modules are created by techniques known by those skilled in the art using machines, software, and languages ​​known in the art. The software modules disclosed herein are implemented in multiple ways. In some examples, a software module includes a file, a section of code, a programming object, a programming structure, or a combination thereof. In further various examples, a software module includes multiple files, multiple sections of code, multiple programming objects, multiple programming structures, or a combination thereof. In some examples, one or more software modules include, by way of non-limiting examples, a web application, a mobile application, and a standalone application. In some examples, a software module is within one computer program or application. In some examples, a software module is within two or more computer programs or applications. In some examples, a software module is hosted on one machine. In some examples, a software module is hosted on two or more machines. In some examples, the software modules are hosted on a distributed computing platform, such as a cloud computing platform. In some examples, the software modules are hosted on one or more machines in one location. In other examples, the software modules are hosted on one or more machines in two or more locations.

[0208] Database In some examples, the platforms, systems, media, and methods disclosed herein include one or more databases or their use. Given the disclosure provided herein, those skilled in the art will recognize that many databases are suitable for storing and retrieving procedural objects, 3D scenes, signed distance functions, rendering, printing, and 3D object information. In some examples, suitable databases include, by way of non-limiting examples, relational databases, non-relational databases, object-oriented databases, object databases, entity-relationship model databases, associative databases, XML databases, and document-oriented databases. Further non-limiting examples include SQL, PostgreSQL, MySQL, Oracle, DB2, Sybase, and MongoDB. In some examples, the database is internet-based. In some examples, the database is web-based. In some examples, the database is cloud computing-based. In certain embodiments, the database is a distributed database. In some examples, the database is based on one or more local computer storage devices.

[0209] Bioreactor and method for making bioreactor The devices and systems provided herein, such as devices and systems for 3D printing, can be used to build multidimensional (e.g., 3D) structures of any shape or type that can perform any function. In some examples, the methods and systems provided herein can be used to make bioreactors. Such bioreactors, their structure, design, morphology, applications, and methods for their manufacture and use are also provided herein.

[0210] In some examples, reaction vessels, such as bioreactors, and methods for manufacturing such reaction vessels are provided herein. In some examples, systems including reaction vessels are provided. The reaction vessels can include or be reactors. The reaction vessels and / or reactors can be configured to perform any suitable reaction or process. In some examples, the reactors can perform chemical reactions to produce chemicals. In some examples, the reactors can synthesize biomaterials. The biomaterials can include or be cells, organelles, nuclei, cellular components such as DNA, any intracellular components or materials, and / or any combination thereof. In some examples, the reaction vessel or reactor can include or be a bioreactor. The system including a bioreactor can be similar to the system provided in Application No. PCT / US19 / 55231, which is incorporated herein by reference in its entirety for all purposes.

[0211] A method for generating a reaction vessel, such as a bioreactor, can include providing a procedural modeling application. The procedural modeling application can be according to a procedural modeling application provided elsewhere herein, another application, or any combination thereof. In some examples, a method for generating a reaction vessel, such as a bioreactor, can include performing a function. The application can be configured to perform the function in response to a request or input from a user or independently of a user. For example, performing the function using the procedural modeling application can include artificial intelligence (AI) and / or machine learning implications. In some examples, performing the function can include adding multiple units to a scene. The units can be according to any unit provided elsewhere herein. In some examples, the units can include modules or mini-modules. For example, a mini-module can be added to a scene. The scene can be any scene described elsewhere herein. In some examples, the scene can be a 3D scene. For example, a mini-module can be added to a 3D scene.

[0212] In some examples, a method for generating a reaction vessel, such as a bioreactor, using, for example, a procedural modeling application, can further include assembling multiple units (e.g., mini-modules) into a structure to create a reaction vessel or reactor (e.g., a bioreactor). The method can further include creating a constructive solid geometry (CSG) tree for the scene, representing the scene (3D scene) as a signed distance function, rendering the scene by utilizing ray marching, generating a queue of slice files, and sending the slice files to a stereolithography 3D printing device or another device. The device (e.g., a 3D printing device or system) can comprise or be any device or system provided elsewhere herein, another device, and / or any combination thereof.

[0213] Provided herein are reaction vessels, such as bioreactors, that can be made and used in accordance with the methods of the present disclosure. In some instances, the reaction vessels (e.g., bioreactors) provided herein can include or be systems, components, for producing and maintaining cells, and for producing and isolating cells and products produced by the cells. Methods for making and using such systems are also provided herein. The systems, components, and methods can provide flexibility in tailoring production for different types of cells, different types of cellular environments, and different types of molecules to be produced. The systems, components, and their methods of manufacture and use can also provide flexibility in scale. For example, the systems, components, and methods described herein can provide for production scale-up without changing or substantially changing bench-scale growth conditions.

[0214] In some instances, the bioreactors provided herein can be used to grow cells. Bioreactors can be of any size or scale. In some instances, the bioreactors can be micro-bioreactor scale, whereby the systems can be configured as benchtop bioreactors capable of growing and producing cells and / or cell products in both small and large quantities. The systems and methods of use are advantageous in their scalability, flexibility, and resource conservation.

[0215] In some instances, the bioreactors provided herein may be bubble-free bioreactors. In some cases, the reactor or process performed in the bioreactor may benefit from or require a procedure for homogenizing the medium inside the reactor. In some cases, mixing or the equivalent of mixing may be required or beneficial to homogenize the reactor contents within a given area. Traditionally, in some cases, conventional reactors, mixing approaches such as propellers or bubbles are used to provide homogenization within the reactor. Such mixing can create turbulence within the bioreactor that can effect homogenization and can increase the rates of mass transfer, heat transfer, and fluid movement in the reactor's interior regions. However, in many cases, turbulence may not be appropriate or optimal. Turbulence inside the reactor may make it more difficult to precisely control conditions. Therefore, in some cases, avoiding mixing, bubbles, and / or propellers may be beneficial. Provided herein are bioreactors capable of and / or configured to perform their functions without the inherent need for propellers or gas or mixing methods that can create turbulence within the bioreactor. For example, bubbles and turbulence can be avoided within the bioreactor. In some examples, the bioreactors provided herein include laminar flow therein throughout a process (e.g., a process or reaction performed by the bioreactor, such as cell growth). The internal and external structures, topologies, and features provided elsewhere herein can enable the manufacture and use of bioreactors that can perform their intended functions using laminar flow and may not require bubbles or turbulence for homogenization. In some examples, homogenized laminar flow of gas and / or liquid streams can be provided within the reactor.

[0216] In some examples, a reaction vessel (e.g., a bioreactor) can include interconnected bioreactor components, such as modules or micromodules, that can perform processes or reactions, individually or in combination, such as to produce or grow cells or perform other functions. The cells can be any type of cell. Examples of cells can include bacterial cells, fungal cells, yeast cells, eukaryotic cells, plant cells, or algal cells. The cells can be recombinant cells.

[0217] In some examples, the reaction vessel or bioreactor can include or be a production bioreactor module or production layer (e.g., production layer 4694 shown in FIG. 47). The production bioreactor or production layer 4696 of the bioreactor can provide an environment for scale-up growth and production of cells and / or bio-products from cells or other biological species.

[0218] Reaction vessels provided herein, such as bioreactors (e.g., bioreactor 4700 or any other bioreactor provided elsewhere herein), can comprise multi-dimensional structures, such as 3D structures, which can comprise one or more (e.g., multiple) mini-modules. A bioreactor can include 1, 2, 4, 6, 8, 10, or more mini-modules, including increments therein. The mini-modules can create one or more (e.g., series) of channels and chambers for cell growth and movement, and for the flow of liquid media, gases, and bio-products.

[0219] The mini-modules of the production bioreactor can comprise shapes such as geometric shapes. Such geometric shapes can include gyroids. The gyroids can include or be implemented in a variety of shapes and / or configurations. In some instances, the shapes and / or configurations can comprise crystallographic structures.

[0220] In some examples, the mini-modules can have shapes such as double gyroids, modified double gyroids, or any shape that can be described as a triply periodic minimal surface (TPMS). Surfaces of this type can form lattice systems that can grow in any direction or across any dimension of any coordinate system. For example, the lattice can grow on one or more axes of a Cartesian coordinate system, such as X, Y, and / or Z. In some examples, the growth can occur periodically.

[0221] In some cases, a TPMS can be free of self-intersections and can divide a given volume into two (or more) independent sub-volumes. A self-intersection can comprise a surface with a single normal vector for a point, which can define the surface. If a surface divides a volume and circumscribes two independent and congruent sub-volumes, the surface is called a balanced surface. In some examples, a TPMS can be described by elementary patches or asymmetric units from which the entire surface can be constructed by its symmetry elements.

[0222] In some examples, the mini-modules can be fluidly connected (eg, interconnected) to one another so that gases, medium, and / or by-products can flow from one mini-module to another.

[0223] In some examples, the mini-modules of the production bioreactor have a shape. The shape can be any shape, such as any geometric representation. The shapes of the mini-modules can be provided elsewhere herein, such as in Table 1.1. In some cases, the shape can further include modifications or transitions. For example, modifications can be to the shape of the mini-module, to its connections, and / or both. The shape modifications or transitions can be minor or major. The modifications or transitions can adapt the structure or shape (e.g., of the mini-module) to a given macrostructure or function. In some examples, the modifications can include blocking a portion of a connection or intersection (e.g., a "mouth"), modifying the diameter of one or more channels of the structure, or completely or otherwise changing the shape.

[0224] In one example, the shape of the bioreactor mini-module can comprise or be a double gyroid or modified double gyroid shape. A double gyroid (DG) shape can include two gyroids and / or two intergrown, non-overlapping domains. A modified double gyroid (DG) shape can include two intergrown, non-overlapping domains that may be bounded by two constant mean curvature (CMC) surfaces separated by a matrix phase. For example, a modified double gyroid structure can include modifications to the connections of an unmodified double gyroid to tailor the structure to a given macrostructure or function. The modifications can be minor or major. In some examples, the modifications can include blocking a portion of a connection or intersection (e.g., a "mouth"), modifying the diameter of one or both phase channels of the structure, or completely or partially removing any of the phase channels present in the DG structure. A DG or modified DG can include a first gyroid structure intertwined with a second gyroid structure. The two channels can be separated by a porous membrane (matrix phase). The matrix phase allows gas molecules to diffuse in a manner that can be based, at least in part, on a specific pressure and gas composition. When the microchannel radii of both the liquid and gas components are equal, the matrix phase surface can be equal to their sum. Two CMC surfaces can create two continuous channels when multiple DGs are interconnected (e.g., interdigitated). These two channels can create two non-overlapping channels for the flow of liquid medium and / or gas. The porous membrane can provide a surface on which specific cell types can attach and grow. In some instances, one channel can provide liquid medium throughout the production bioreactor. In some instances, both channels can provide liquid. In some instances, one channel can provide liquid medium and another channel can provide gas to the production bioreactor.In some instances, the diameter of the microchannels of the mini-modules can be varied to suit particular cell types, production needs and characteristics, and the like.

[0225] In some examples, the mini-module can have a regular cubic wrap structure with its edges of length "L." L can be related to the swept diameter. In some examples, L can be equal to 2 / 3 of the swept diameter of the microchannel times the square root of 2 times the square root of 3. The total surface and volume of the microchannel corresponding to the liquid component can be equal to the corresponding dimension of the gas component when the radii of both components are the same within the mini-module. In some examples, the radii of the components can be different. In some examples, when both radii are equal, the microchannel radius can be no greater than 0.7 times the swept radius. In some examples, the shortest distance between two mini-modules on two different faces can be substantially equal to the square root of the swept radius times 2 minus the sum of the radii of each component channel.

[0226] In some examples, the area of ​​a first channel having a DG shape can be equal to the area of ​​a second channel within the DG, and the area of ​​the matrix phase can be the sum of the area of ​​the first channel and the area of ​​the second channel.

[0227] In some instances, for example in a DG geometry, the distance between the matrix phase separating the channels and the center of each channel can be constant.

[0228] The rate at which media and gas flow through a production layer (e.g., production layer 4696, or any other production layer of a production bioreactor provided anywhere herein) in any geometry bioreactor (e.g., a bioreactor having a DG geometry or another geometry provided elsewhere herein) can be determined by various factors, such as the selected cell type and cell density and the stress conditions created on the cells. The rate at which gas diffuses through the matrix and into the liquid medium can be determined by various factors, such as the gas composition and gas pressure in the gas channels formed by the structure, and the membrane thickness and materials selected to fabricate the channels and surrounding areas. Gas flow rates and operating pressures can be related to the culture cell density. In some instances, the gas flow rate can be equal to the volume of gas component per minute. In some instances, the gas flow rate can be about 2, 3, 5, or 10 times or more the volume of gas component per minute. In some instances, the operating pressure can range from about 1 atmosphere (atm) to 5 atm. In some examples, the operating pressure can be above atmospheric pressure, such as about 1 atm, 2 atm, 3 atm, 4 atm, 5 atm, or more.

[0229] The shape of the bioreactor mini-module can be configured to provide certain characteristics. Each shape can include example advantages. For example, an example advantage of the DG shape can be the reduction of gravity, which may provide uneven exposure to media and gas exchange in other structures. The DG shape can create three-dimensional (3D) laminar flow, thereby averaging out variations in the distance of any one cell to the structure walls and providing more consistent and uniform exposure among the cell population. Furthermore, the DG shape can help avoid stagnant areas of liquid or gas where flow may not occur or may be blocked. This can enable the use of higher throughput through bioreactors with lower velocities, resulting in lower shear stress on the cells. This can avoid turbulence within the bioreactor. This can make it possible to achieve homogenization while using laminar flow within the bioreactor.

[0230] In some instances, the average fluid velocity in the channels of a bioreactor (e.g., a DG bioreactor) can be greater than or equal to about 1 μm / sec, 3 μm / sec, 5 μm / sec, 10 μm / sec, 15 μm / sec, 20 μm / sec, 50 μm / sec, 100 μm / sec, 200 μm / sec, or greater. For example, a DG structure can provide adequate and optimized diffusion of media and gases compared to some other bioreactor systems. In some instances, the velocity of liquid media flowing through channels in a DG can be greater than the free-fall velocity of cells flowing through the same channels.

[0231] The mini-module DG structure can provide increased surface area over many other geometry options, which can provide surface area for cell growth as well as improvements in liquid media flow, mixing, and gas exchange. When L equals L1, the surface of each component can be written as Y = 3258.6.XE(-1), where Y is square millimeters per microliter and X is equal to the radius defined by L1.

[0232] In some examples, the mini-module structures of the bioreactor (e.g., structures having a DG structure or any of the shapes provided elsewhere herein) can be mated together into a macrostructure or macroshape that constitutes the production bioreactor. The macrostructure or macroshape can include any shape, any geometry, any geometric representation, any size, and / or any combination thereof. In some examples, the macrostructure can be a cube, a pyramid, a sphere, a cylinder, a multidimensional geometric shape, and / or any combination thereof. As an example, the macrostructure can be a hollow pyramid, a lamellar pyramid, a chessboard arrangement, a log, a sphere, or a different shape.

[0233] In some instances, the macrostructure and shape and number of mini-modules in the production bioreactor can be adjusted to various factors such as the cell division rate of the cells being grown, the liquid medium, gas exchange, adjusting the speed of cell movement through the bioreactor, and other factors. Each macrostructure can offer different possibilities for interacting with the cells and can be selected taking into account the particular process the production bioreactor is intended to carry out.

[0234] Example bioreactors can include macrostructure shapes. For example, multiple mini-modules can be assembled to create a macrostructure. The macrostructures can have a variety of shapes. The macrostructures can be spheres, pyramids, hollow pyramids, lamellae, or other shapes, structures, or topologies, such as the macrostructure shapes and / or topologies provided elsewhere herein.

[0235] In some instances, the reactor can be equipped with a pyramidal or hollow pyramidal macrostructure shape. Such a structure can allow for a suitable environment for growth while maintaining a consistent rate and cell density throughout the bioreactor. More sensitive strains may require more intervention over time, and hollow pyramids can provide that capability.

[0236] In some instances, the bioreactor can comprise a lamellar pyramid macrostructure shape. Such a macrostructure shape can enable a suitable environment for growth and development, such as by maintaining both velocity and density constant (e.g., substantially constant). In some cases, suitable access to a subset of cells, or in some cases, to each cell, can be provided for a given duration, in some cases, at each moment. The lamellar pyramid macrostructure can also enable direct intervention and treatment.

[0237] In one example, a bioreactor can have a chessboard macrostructure geometry or a log array geometry. The chessboard and log arrays can provide adequate access (e.g., in some cases, complete access) to a subset of cells, and in some cases, to all cells in the bioreactor, for a given duration, and in some cases, at all points in the process. In some examples, the chessboard and / or log array can provide or facilitate control over uniform velocity and / or density of fluids and / or cells within the bioreactor. In some examples, cells can enter the bioreactor at a given point or location (e.g., at the top of the macrostructure), and a cell collection device can be present in the bioreactor at a given location (e.g., at the base of the macrostructure).

[0238] In one example, the bioreactor can have a spherical macrostructure shape. An example of a sphere bioreactor 4700 is shown in FIG. 47. The sphere bioreactor can be a bubble-free bioreactor. For example, a bioreactor can be manufactured using the methods of the present disclosure, and the bioreactor can include minimal to substantially no bubbles. In some cases, some bubbles may be present in the bioreactor. In some examples, the sphere bioreactor 4700 can have multiple planes of symmetry (planes of symmetry). For example, the bioreactor can have one or more units that can be repeated to build the bioreactor's structure. As an example, the illustrated sphere bioreactor 4700 has three planes of symmetry (e.g., planes 4740, 4750, and 4760). The planes of symmetry can divide the sphere bioreactor's structure into multiple repeating units (e.g., eight repeating units in this example). The repeating units can be similar or substantially identical to one another. For example, in sphere bioreactor 4700, the repeating unit can be 1 / 8 of a sphere. An example of such a repeating unit 4698 is shown in FIG. 46A. Repeating unit 4698 can form 1 / 8 of the volume of bioreactor 4700. In other words, eight repeating units, which can be at least somewhat similar to repeating unit 4698, can be repeated (e.g., symmetrically in volume) to form sphere bioreactor 4700. In some instances, the repeating units can be completely similar or identical. In some instances, the repeating units can be similar to a certain extent. In some instances, the repeating units can differ to a certain extent and can include some differences compared to each other. Similar concepts and / or approaches can be used to construct bioreactors with different macrostructural shapes and / or topologies.

[0239] A bioreactor (e.g., a sphere bioreactor) can include one or more channels. The bioreactor channels can include one or more harvesting exhaust channels 4710, which can be used to harvest cells. The bioreactor channels can include one or more gas intake channels 4720. The gas intake channels can be used to inject gas into the bioreactor, such as into a gas chamber (e.g., 4620 or 4840). The channels can include one or more liquid (e.g., culture media) intake channels 4730, which can be used to introduce a liquid feed, such as growth media, into the bioreactor. Providing the liquid feed can be according to the methods and systems provided elsewhere herein for any bioreactor macrostructure. For each structure or configuration, the overall system can be optimized, and adjustments can be made accordingly.

[0240] In some examples, the various gas intake channels 4710 of a bioreactor can be similar to one another to some extent. In some examples, the various gas intake channels of a bioreactor can be different to one another to some extent. For example, gas intake channels, each of which can include an opening for inputting gas, can be provided to supply gas into a given region of the bioreactor, which can be at a given distance from the center of the sphere. In some examples, gas intake channels provided to deliver gas to different regions of the bioreactor (e.g., located at different radial distances from the center of the sphere) can include some similarities and some differences based on their intended application.

[0241] Cross-sectional views of an example sphere bioreactor are provided in Figures 46A and 46B. Figure 46A shows a culture medium intake channel 4600 that can be used to inject a liquid feed into the bioreactor. The liquid feed can include culture medium. The liquid feed can include additional components. The liquid feed or medium can be according to the feeds and media provided elsewhere herein, or a combination thereof.

[0242] As an example, FIG. 46B shows a cross-sectional view of a cross section of an example sphere bioreactor in accordance with the methods and systems provided herein. The bioreactor can include one or more channels, such as multiple channels. The channel can include a harvest channel 4696. In some cases, the harvest channel can be according to channels provided elsewhere herein. The bioreactor can further include a harvest layer 4610, one or more gas chambers, one or more culture layers, and other components and / or modules. The harvest channel and harvest layer can be used to harvest liquid medium and cells from the bioreactor. In some examples, the bioreactor can further include a similar harvest channel for gas (not shown) to harvest spent gas from the bioreactor. 46B, the bioreactor comprises a first gas chamber 4620, a fourth culture layer 4630, a second gas chamber 4640, a third culture layer 4650, a third gas chamber 4660, a second culture layer 4670, a fourth gas chamber 4680, a first culture layer 4690, a fifth gas chamber 4692, and other components. The bioreactors provided herein, such as a sphere bioreactor or any other bioreactor comprising any macrostructural shape, can comprise any number of layers, any number of channels, e.g., any number of culture layers, any number of gas chambers, and / or other components, modules, channels, or chambers in any configuration, and any combination thereof.

[0243] A bioreactor (e.g., a sphere bioreactor such as the bioreactor shown in FIG. 46B) can include one or more culture layers and / or one or more production layers or production volumes. A culture layer (e.g., 4630, 4650, 4670, 4690, and / or other culture layers) can be a layer of a bioreactor where cells can be cultured. In some examples, a production volume can be within a culture layer. For example, a culture layer of a bioreactor can include a production layer. A production layer can include multiple channels therein, an example of which is shown as production channel 4690. Production channel 4690 can be saturated. For example, a large number of channels (e.g., a high density of channels) can fit into a relatively small volume. Alternatively, the channel can be unsaturated. A cross-sectional view 4695 of a production channel is shown in FIG. 46B as an example.

[0244] A bioreactor comprising a macrostructure of a given shape, such as any macrostructure shape provided elsewhere herein, e.g., a pyramid, hollow pyramid, chessboard, log, sphere, cube, cylinder, or any other macrostructure provided herein, can comprise multiple mini-modules that can be assembled to create the macrostructure. Arranging mini-modules (e.g., DG mini-modules or mini-modules of any shape, e.g., any mini-module provided elsewhere herein) into a macrostructure can provide a mechanism for determining and optimizing liquid medium and gas flows within the bioreactor. In some examples, a macrostructure is composed of multiple layers or levels of mini-modules. In some examples, mini-modules can be arranged in multiple levels or layers, and the liquid medium velocity at each level can be substantially the same. Alternatively or additionally, the liquid medium velocity at each level or layer can vary. For example, the liquid medium velocity can increase or decrease between levels or layers. The liquid medium velocity can vary from mini-module to mini-module, or can be substantially the same between or across mini-modules.

[0245] In some examples, the bioreactor (e.g., a production bioreactor or a production volume or layer of a bioreactor) can further comprise a liquid medium input device. The liquid medium device can be constructed to provide liquid medium to each level of mini-modules within the macrostructure. In some examples, the volume of liquid medium provided to each level can maintain a substantially constant cell density in each of the levels.

[0246] The bioreactor can include one or more microchannels. The microchannels can include various sizes. In some examples, the microchannel radius can be linked to the radius of the cells, the cell density, or other parameters (e.g., fiber alignment, chain arrangement, etc.). In some examples, the cell density is greater than 1×10 6 cells / ml~1×10 12 cells / ml. In some examples, the velocity of the liquid medium through each mini-module can be determined by the cell division rate, such that the time for a cell to traverse a single mini-module or level of a mini-module can be substantially the same as the cell division rate, or can be proportional to the cell division rate, such that a cell can divide 1, 2, 3, 4, 5, or more than 5 times during passage. In some examples, a first level can contain an example volume "x" of liquid medium, such that with a given number of cells, density at x, and a second level having twice the volume of liquid medium, and within the duration of passage of the cells from the first level to the second level, the number of cells will double (e.g., a subset of cells (e.g., each cell) will divide once, on average), the density of the second level can remain at x (constant cell density between levels).

[0247] Further optimization can be achieved by determining the expected number of cells at the base of the macrostructure, the terminal end where the cells and / or bio-products arrive before exiting the structure through the output to a collection container. Expected cell numbers can also be determined for different levels of the macrostructure. Based on the expected cell numbers at the base and different levels, the gas and liquid medium flow rates can be adjusted for each level to compensate for increased gas and liquid medium requirements—because as cells progress through the bioreactor toward the base of the structure, the number of cells increases through cell division, cell migration, and cell accumulation.

[0248] Liquid medium supply in bioreactors A bioreactor can include one or more components for supplying a liquid medium to the bioreactor or its modules. The components can include one or more of a culture medium formulator, an electroporator or other sterilization device, a reservoir, a pump, a bubble sensor, and a bubble trap. The culture medium formulator can generate a liquid medium for the bioreactor by appropriately mixing the components of the medium with water for growing cells in the modules. The electroporator can be interconnected to the media generator, for example, to wash the medium and provide a sterile starting medium for supply to one or more modules for growing cells. The bubble sensor and bubble trap can be included to detect and / or remove any gas bubbles in the liquid medium that may have been introduced during media generation, washing, or for any other reason.

[0249] In some examples, a system (e.g., a bioreactor) can include one or more reservoirs for holding reserve medium, for example, before supplying the reserve medium to a module or mini-module. In some examples, a system (e.g., a bioreactor) can include at least 2, 3, 4, 6, 8, 10, or more reservoirs, including increments therein. The reservoirs can be filled asynchronously, so that one reservoir is filled while another reservoir, already fully filled, can be used to supply liquid medium to the bioreactor and / or its modules. Such reservoir separation can be advantageous for isolating a cell growth module of a system (e.g., a bioreactor) from connection to electrical current, for example. A reservoir being filled can have some exposure to electrical current that may flow from upstream components, such as an electroporator. A filled reservoir can be isolated from the electrical current and thereby not transmit electrical current to downstream components and modules of the system (e.g., a bioreactor). In some instances, the volume of a reservoir can be linked to the throughput of the production bioreactor over the split time of the cells selected for the process. In some instances, multiple reservoirs can be installed in parallel and decoupled from one another. In some instances, multiple reservoirs can be installed in series. In some instances, multiple reservoirs can be installed in a combination of series and parallel configurations, in other configurations, and / or any combination thereof.

[0250] In some examples, the liquid medium supply component of the system (e.g., bioreactor) can further include one or more sensors. The sensors can measure parameters including the pH and temperature of the medium. The sensors can be in-line sensors or can be connected to a sampling device that intermittently samples the medium from one or more components of the liquid medium supply. The supply system can provide the liquid medium at a range of rates depending on the use, scale, and operation of the system. In some examples, the liquid medium supply can provide between about 100 microliters / hour and 1000 liters / hour to the bioreactor or its modules, channels, or chambers, such as cell growth chambers. In some examples, the liquid medium supply can provide between about 0.5 liters / hour and 1000 liters / hour to the bioreactor or its modules, channels, or chambers, such as cell growth chambers. In some examples, the liquid medium supply can provide between about 0.5 liters / hour and 5 liters / hour to the bioreactor or its modules, components, channels, or chambers. In some examples, the liquid medium supply can provide between about 10 liters / hour and 80 liters / hour to a bioreactor or its modules, components, channels, or chambers, such as channels or chambers for cell growth. In some examples, the liquid medium supply can provide between about 100 liters / hour and 1000 liters / hour to a bioreactor or its modules, components, channels, or chambers, such as channels or chambers for cell growth.

[0251] The liquid media supply component can include one or more pumps for flowing media from a reservoir or media formulator to components of a bioreactor system, such as a cell chip, sandbox bioreactor, or production bioreactor. In some examples, a system (e.g., a bioreactor system) can include 1, 2, 3, 4, 6, 8, 10, or more pumps, including increments therein. The pumps can be the same type of pump or can be different types of pumps. Example pumps can include syringe pumps, peristaltic pumps, and / or pressure pumps.

[0252] In some cases, the liquid media supply system can be configured to provide unidirectional flow through a given region, module, component, channel, or chamber of the bioreactor. In some examples, the pump can be a syringe pump that can be used to supply media to a cell chip. The cell chip can be a cell chip or cell chip module provided elsewhere herein. In some examples, the pump can be a syringe pump that can be used to supply media to a sandbox bioreactor. In some examples, the pump can be a peristaltic pump used to supply media to a production bioreactor. In some examples, a system (e.g., a bioreactor system) can include three pumps: two syringe pumps that supply the cell chip and sandbox bioreactor, and a peristaltic pump that supplies the production bioreactor. The pumps can operate synchronously or individually. In some examples, all three pumps can operate synchronously. The one or more pumps can deliver media (e.g., with a high degree of volume and rate accuracy) to the bioreactor or to a module or component thereof, such as a module downstream of the pump (e.g., a downstream module). The downstream module can be according to downstream modules provided elsewhere herein. In some examples, the accuracy can be within 1, 2, 3, 4, or 5 nanoliters.

[0253] Gas supply and gas composition in bioreactors In some examples, the systems (e.g., bioreactor systems) provided herein can be adapted for use with cells that may benefit from or require a particular gas component, such as cells that may require oxygen to grow and / or survive. Materials for use in constructing bioreactor modules can include glass, acrylic, collagen, polydimethylsiloxane (PDMS), poly(ethylene glycol) (PEGDA), poly(D,L-lactic acid), silk, cellulose, GelMA, alginate, ceramic, and / or other biocompatible polymers that can enable oxygenation of the medium. In some examples, the system (e.g., bioreactor system) can further comprise a controller that can control the diffusion of oxygen and other gas solutions in the bioreactor or its modules. In some examples, gas solutions can be formulated from pure component gases, such as from gas storage tanks or other supply mechanisms, to establish mixtures or pure gas solutions at various concentrations and flow rates. Alternatively or additionally, the gas mixture can be provided by a purified air mixture. The gas solution can be used to provide an aerated environment and can control pH. The gas solution can provide carbon, nitrogen, phosphorus, sulfur, and / or other media components to the liquid phase. In some instances, the system can have two or more gas controllers or mechanisms so that different gas solutions can be provided to different modules, components, sections, channels, or chambers within the system (e.g., within a given section of a bioreactor).

[0254] In some instances, the flow of gas and / or liquid within the structure of the bioreactor can be along a linear axis, such as a single linear axis. Examples of this can include a lamellar bioreactor, a hollow pyramid reactor, or a bioreactor comprising another macrostructure. In such instances, in some cases, the flow can be described based on the average displacement in a single axis.

[0255] 46A and 46B, in some examples, in a sphere bioreactor, channels for delivering liquid feed (e.g., channel 4600), channels for injecting gas (e.g., gas chambers 4620, 4640, 4660, 4680, and 4692), and one or more inoculation channels (not shown) can pass through the production structure (e.g., production volume 4694, which can be inside culture layers 4630, 4650, 4670, and 4690) to reach their appropriate points. The direction and / or rate of liquid and gas supply in the bioreactor can affect the rate of cell or microorganism growth in the bioreactor. For example, channel 4600 in FIG. 46A can extend in the radial direction of the sphere bioreactor and serve as a liquid supply channel (e.g., a culture medium intake channel). In some examples, channels such as channel 4600 can be used to inject liquid media, such as culture media, into different portions (e.g., different layers) of a bioreactor (e.g., a sphere bioreactor). The direction of liquid flow 4697 can be angular, as shown in FIG. 46A. In some examples, the direction of liquid flow can be angular, radial (the radial direction of liquid flow is not shown in the figures), and / or a combination of both. Liquid media can flow within the bioreactor, e.g., within its layers, delivering the culture media to cells being grown within the bioreactor (e.g., in culture layers 4630, 4650, 4670, 4690, and any other culture layers). The liquid media can reach the cells and provide nutrients for the cells to survive and / or grow. The topology and macrostructure of the bioreactor and the direction and method of liquid and gas injection and inflow can affect the rate of cell growth.

[0256] In some instances, a bioreactor, such as the bioreactors shown in Figures 46A, 46B, and / or 47, can include one or more inoculation channels (not shown). In one example, the bioreactor includes a single inoculation channel. In some cases, one or more inoculation channels can be used to treat and / or inoculate cells as needed.

[0257] Figure 48 shows a schematic view of the internal channels and chambers of a bioreactor provided herein and the flow of gas and liquid supplies (e.g., culture media, water, nutrients, etc.) within the bioreactor. The bioreactor shown in Figure 48 can have any macrostructure shape and any mini-module shape. In one example, the bioreactor shown in Figure 48 can be a sphere bioreactor, such as bioreactor 4700 shown in Figure 47.

[0258] Gas (e.g., gas stream 4830) can be input into the bioreactor through an opening (e.g., the opening of gas intake channel 4720 shown in FIG. 47) and undergo flow in gas flow channel 4820. The input gas can include a fresh gas supply having an appropriate composition (e.g., according to the gas compositions provided elsewhere herein). In some cases, the gas intake channel, or another intake channel that can be substantially similar to gas intake channel 4720, can be used to vent or remove gas from the bioreactor after it passes through a specific area of ​​the bioreactor and reaches the cells inside the bioreactor. In some instances, different methods for venting gas from the bioreactor can be used. An example of such an approach can include using an outer layer or outer shell around the bioreactor (e.g., a membrane around the bioreactor) that can be exposed to the external environment. Such an outer layer or membrane can be porous and can allow gas to vent from the bioreactor. Alternatively or additionally, the bioreactor can include a gas collection layer (not shown) and / or gas collection channel (not shown), which can be similar to and / or different from collection channel 4690 and collection layer 4610 to some extent. For example, the gas collection channel can be located in a different region than collection channel 4696, and the gas collection channel can be configured to have gas flow therein and can be used to exhaust gases from the bioreactor after such gases have passed through a subset of the regions of the bioreactor. Gases can be exhausted from the bioreactor using any of these approaches. In some cases, similar approaches can be applied to bioreactors other than sphere bioreactor 4700.

[0259] Liquid can be introduced into the bioreactor through an opening (e.g., an opening in liquid intake channel 4730) and subjected to flow in the liquid flow channel (liquid flow channel 4810). The liquid can include culture medium or a composition listed elsewhere herein that can be supplied to the bioreactor to aid in growing cells. The liquid can flow through the structure of the bioreactor. The liquid can include culture medium. In some cases, the liquid can include cells suspended within the liquid. The liquid composition can be according to the liquid compositions provided elsewhere herein.

[0260] There can be multiple mini-modules within a bioreactor. A mini-module can be a bioreactor mini-module. The mini-module itself can be constructed from smaller units. In some cases, multiple unit cells can be assembled to create a mini-module, such as a mini-module. In some examples, a mini-module (e.g., a mini-module such as building block 4860) can include at least a liquid flow channel 4810 and a gas flow channel 4820 through which a gas flow (e.g., gas flow 4830) can be input and received. Mini-modules (e.g., building block 4860) can be repeated throughout the structure of a bioreactor. While FIG. 48 shows gas and fluid flow in a sphere bioreactor as an example, similar schemes can be used in other bioreactor topologies and structures.

[0261] The bioreactor can further include a gas chamber 4840 (e.g., similar to gas chambers 4620, 4640, 4660, 4680, and 4692). The gas chamber 4840 can have any topology and / or configuration in example bioreactors of any shape and / or configuration. In sphere bioreactor 4700, the gas chamber can be a hollow sphere chamber. For example, in some cases, as shown in FIG. 48, the gas flow channel 4820 and the liquid flow channel 4810 can not intersect or pass through the sphere hollow gas chamber (e.g., 4810). The hollow gas chamber 4840 can contain multiple culture channels 4850 in which cells or microorganisms can be cultured. In some cases, as shown in FIG. 48, the culture channels 4850 can be internal to the gas chamber 4840.

[0262] Gas and liquid streams can flow through their respective channels (e.g., channels 4810 and 4820) within a mini-module (e.g., building block 4860), and when such channels reach gas chamber 4840, the gas and liquid streams can enter and pass through culture channel 4850 housed in the gas chamber. Culture channel 4850 can thus comprise both gas and liquid supplies that can help cells grow and / or survive. In some examples, the channels can be conduits.

[0263] The macrostructure and topology of the bioreactor can be selected based on the application and target characteristics of the process (e.g., cell growth). In some cases, a sphere bioreactor may be more suitable than other geometric shapes and may offer several advantages over other bioreactor topologies and / or macrostructure shapes, such as lamellae, pyramids, hollow pyramids, or other bioreactor configurations. A feature of an example sphere bioreactor is that the volume of the sphere, or the volume of an example shell within a sphere (the volume between two respective radii of the sphere), follows a cubic relationship with its radius (e.g., V=(4πr3 ) / 3, where V = volume and r = radius. An example graph representing this is shown in FIG. 45. The volume of a bioreactor or its spherical shell corresponds to or can contain the volume in which cells or microorganisms grow. Thus, the volume in which cells grow can increase cubed relative to, for example, a linear increase in the radius of the sphere based on the radial distance from the center of the sphere. This may not be the same as bioreactors with pyramidal or lamellar structures. This feature can be advantageous, and in many cases can be beneficial, in that the increased (e.g., cubed) growth trend or rate can bear more similarity to the trend of the proliferation rate (e.g., natural growth rate) of example microorganisms or cells that may be growing in the bioreactor compared to other bioreactor topologies and structures. For example, maintaining constant and / or homogenous pressure, fluid flow rate, cell growth, and cell concentration can be convenient, efficient, and / or feasible in a sphere bioreactor, and appropriate conditions for growing cells can be provided. In one example, cell apoptosis as a result of cell overcrowding in a given area can be prevented.

[0264] How to use a bioreactor In some examples, a reaction vessel or bioreactor provided herein can be used to produce or grow cells. Figure 44 shows an example method utilizing a reaction vessel or bioreactor provided herein to produce cells. In some cases, the bioreactor can include an output channel. In some cases, cells can be collected through the output channel of the bioreactor or a module of the bioreactor. In some examples, cells can be collected in the bioreactor or a module thereof and further stored in the bioreactor or a module thereof, for example, storing cells in a cell chip module of the bioreactor.

[0265] In some examples, bioreactors can be utilized to produce bioproducts (e.g., from cells), such as small molecules, proteins, antibodies, metabolites, or other products produced by cells grown in the bioreactor. The bioproducts can be collected through an output channel of the bioreactor and separated from the growing cells, such as by diffusion through a porous membrane, by filtration, or using another technique. In some examples, the bioproducts can be internal to the cells. To harvest the bioproducts, the cells can be harvested and / or lysed, and the bioproducts can then be further purified if / when necessary. In some examples, the bioproducts can be secreted from the cells and collected without harvesting or lysing the cells.

[0266] The bioreactors described herein and systems including such bioreactors have the flexibility to be optimized for the growth and scale-up of various cell types. In some examples, the bioreactor of the system is a production bioreactor that scales up cell growth, produces large volumes of cells, or grows cells under predetermined conditions to produce and harvest a bioproduct in a continuous and / or large-scale manner. In some examples, a system including a production bioreactor can include one or more additional modules. An example of an additional module can include a cell chip module. In some examples, the system can include a cell chip module that is utilized for initial cell growth and / or cell storage to provide a particular type of cell(s) to a production bioreactor, which is subsequently utilized for scaling up cell growth or production and / or bioproduct production. Another example of an additional module can include a sandbox module. In some examples, the system can include a sandbox module (such as in series or in any other configuration) with a production bioreactor module (with or without a cell chip module as part of the system), where such a sandbox module is included to test, analyze, and / or optimize cell growth conditions prior to scale-up in the bioreactor production module.

[0267] Systems including bioreactors can be used to produce a variety of cell types and bioproducts. For example, a system can include a bioreactor described elsewhere herein, alone or in combination with one or both of a cell chip module and / or a sandbox module (also referred to elsewhere herein as a sandbox bioreactor). The system can accommodate the production of stem cells and any other type of cell therapy, including autologous and allogeneic products. In some instances, expansion, gene delivery, or T cell activation can be performed for personalized chimeric antigen receptor T cell (CAR-T) treatment. In some instances, stem cells can be undifferentiated, mature, and / or differentiated.

[0268] In some instances, the cells grown in the system can be prokaryotic cells, such as bacterial cells. In some instances, the cells grown can be eukaryotic cells, such as yeast cells, fungal cells, algal cells, plant cells, avian cells, or mammalian cells. The cells can be free-floating in culture or can be adherent cells, attached to one or more surfaces, such as surfaces within the bioreactor and / or other modules of the system. The cells can be transformed or otherwise engineered to produce bioproducts, such as heterologous proteins, antibodies, small molecules, and / or metabolites.

[0269] In some instances, a system including the bioreactors described herein can accommodate the production of viruses, phages, and / or antigens thereof.

[0270] In some instances, systems including the bioreactors described herein can accommodate the production of non-naturally occurring organisms, non-naturally occurring viruses, synthetic organisms, and / or xenobots.

[0271] In some instances, the systems, devices, and methods described herein may be used in zero gravity or under microgravity conditions, whereby cells are grown under zero gravity or microgravity conditions.

[0272] Methods and materials for constructing bioreactor modules The systems, components, and modules herein can be fabricated from a variety of materials, and such materials can be tailored depending on the cells being grown and the cellular environment in which they are used. In some examples, the components and modules, or portions thereof, can be fabricated by 3D printing. In some examples, 3D printing can be performed using methods and / or systems provided elsewhere herein, other methods and / or systems, and / or any combination thereof. Printing can use commercially available resins and infrared (UV) curable biocompatible polymers. In some examples, each mini-module shape can be discretely designed in a virtual environment. In some examples, the components and modules can be provided by commercially available components that can be combined and arranged together as described herein. In some examples, the biomaterial used can include a combination of three subcomponents: a biocompatible polymer, a photoinitiator, and a UV absorber.

[0273] The devices and systems of the present disclosure can be formed by 3D printing, such as stereolithography. In some examples, a computer-aided manufacturing (CAM) or computer-aided design (CAD) model of a device of the present disclosure can be provided to a 3D printing system capable of using stereolithography. Such a method can include providing a container with a resin including a photoinitiator and one or more polymer precursors. For example, a light source (e.g., an ultraviolet (UV) laser or any other suitable light) can be used to draw a preprogrammed design or structure into the surface of the container with the resin. The resin can be a photopolymer that photochemically solidifies to form a single layer upon contact with light (e.g., a UV laser). Additional resin can be added and solidified during the manufacturing process. In some examples, the manufacturing process can include or be a layer-by-layer manufacturing process. Stereolithography can be used to build objects and / or modules in any orientation. In some examples, stereolithography can be used to build modules in a top-down or bottom-up additive manufacturing approach.

[0274] In some examples, constructing a reactor, bioreactor, or module thereof can include self-assembly or subtractive manufacturing methods of polymers, e.g., block copolymers, to form 3D structures (e.g., gyroids, geometric shapes, or structures of any shape, form, geometry, or size).

[0275] Subtractive manufacturing methods can include chemical and mechanical removal of sacrificial materials. For example, the sacrificial material can be formed using adhesive manufacturing with a sintering laser. The sacrificial material can be immersed, dipped, or otherwise coated into a biocompatible polymer. The sacrificial material can then be dissolved or mechanically removed to form a 3D shape or structure (e.g., a gyroid) from the biocompatible polymer.

[0276] Example 3D printed bioreactor Bubble-free bioreactors can be printed using the 3D printing devices and methods described elsewhere herein. Figure 57A shows an example printing process. The tubing and matrix of the bioreactor, along with supporting structures, can be constructed using 3D modeling. The 3D model can be converted into a slide for 3D printing. Prior to printing, a biopolymer resin can be formulated and a printer controller can be prepared. The bioreactor can then be printed using a 3D printing device, and after printing, the bioreactor can be post-processed. Figure 57B shows a digital rendering of a 3D-printed bioreactor and cross-sectional views as a function of location height. The first cross-sectional view shows the inlet and outlet ports of the reactor. The second cross-sectional view shows the internal structure of the gyroid shape. The third cross-sectional view shows the reactor main channel connecting to the gyroid channel.

[0277] An example 3D printer device and 3D printed bioreactor are shown in FIG. 58. The printed bioreactor comprises a double gyroid crystal with a total void volume of approximately 500 milliliters (mL). The gyroid channel diameter is 500 μm and has a membrane-to-membrane thickness of 300 μm. In other examples, the membrane-to-membrane thickness can be less than approximately 300 μm. For example, the membrane-to-membrane thickness can be less than 275, 250, 225, 200, 175, 150, 125, 100, 75, or even less μm. The example 3D printer device includes a printing fluid reservoir 5804 with a drain tube 5801. Material in the printing fluid reservoir 5804 is pumped through a recirculation system to the interior of the printing fluid reservoir 5804. The recirculation system includes a reservoir 5806 containing a photocurable bio-resin, a magnetic agitator 5805 for mixing the bio-resin, and a recirculation peristaltic pump 5807 for pumping the bio-resin into the printing fluid reservoir 5804. The bioreactor may be disposed between the printing fluid reservoir 5804 and the printing platform 5802. The printing platform 5802 may be connected to a recirculation ball screw 5803 configured to elevate the printing platform 5802.

[0278] example In some examples, the executable instructions provided herein can include methods for constructing a space or structure with multiple units, mini-modules, unit cells, and elements according to methods provided elsewhere herein. Such methods can include assembling multiple mini-modules to construct a macrostructure. The macrostructure can have any shape provided elsewhere herein, such as a sphere, pyramid, hollow pyramid, lamella, chessboard, or any other macrostructure. In some examples, the macrostructure can form a bioreactor. The bioreactor can be constructed with multiple mini-modules assembled using the methods provided herein. The method can include providing a mathematical model and one or more operators and / or operations to manipulate the mini-modules (e.g., crystallography units or crystals) using computer-implemented methods such as software (e.g., computer systems provided elsewhere herein).

[0279] Provided herein are structures that can be used as bioreactors. Methods for constructing such structures are also provided. In some examples, the structures can be 3D printed using the methods provided herein. Methods for constructing the structures can include stereolithography and / or crystallography. In some examples, the computer-readable instructions can include methods for constructing a space using multiple mini-modules and methods for constructing a structure such as a bioreactor.

[0280] In one example, a structure (e.g., a conduit or any other structure) can be created using the methods provided herein. In some cases, a unit cell can be defined or simulated by a distribution of lattice points within a body or lattice structure of the unit cell. The points can be elements. The body can be a crystal or the body of the unit cell. The elements can be within the unit cell. For example, within a unit cell or lattice, the placement of points can represent the positions or locations of atoms. For example, points can be represented as atoms of the lattice. The atoms within the lattice can be allowed to vibrate to minimize the total surface of the lattice as a result of equilibrium (e.g., balance of electrostatic forces) that can connect the atoms and / or keep the atoms in place. In some cases, the structure can be defined by a minimized surface created as a result of the placement of the points or elements. Alternatively or additionally, in some cases, it can be appropriate and / or advantageous to create and / or define a structure (e.g., a conduit or another structure) based on loci that can connect a subset of the lattice points.

[0281] Structures that can be constructed and used according to the methods of the present disclosure can include one or more mini-modules. In some examples, the mini-modules can be building blocks of a bioreactor. The mini-modules can include one or more external mini-modules (e.g., building blocks) and / or one or more internal mini-modules (e.g., building blocks). In some examples, the external and / or internal mini-modules (e.g., building blocks) can include one or more conduits. An example can include an external conduit, such as a conduit in an external mini-module of a bioreactor provided herein. The function of the external mini-module can include supplying one or more internal mini-modules by, for example, supplying liquid and / or gas from an external source, such as a reservoir, into one or more internal mini-modules. The reservoir can be a reservoir of a bioreactor system provided elsewhere herein. In some examples, the external mini-module can be a bioreactor supply system provided elsewhere herein, such as a system for supplying gas and liquid into a bioreactor or portion thereof.

[0282] In some examples, the method for making an internal mini-module or a component thereof (e.g., a conduit of an external mini-module) can be similar to and / or different to a certain extent from the method for making an internal mini-module or a component thereof (e.g., a component inside a bioreactor, an internal channel, an internal conduit, or another component of an internal mini-module of a bioreactor). For example, in some cases, an internal mini-module can comprise or be a unit cell. The unit cell can be symmetric. In some examples, an external mini-module (e.g., a building block making up an external supply system such as an external conduit) can be non-unitary and / or non-symmetrical. In some cases, a mathematical or crystallographic representation of the external mini-module can be present in the input and / or output links of the mini-module (e.g., a building block).

[0283] The mini-modules or building blocks can include transition mini-modules or building blocks. In some instances, the transition mini-modules can connect or facilitate communication between the internal and external mini-modules. In some instances, the features of the transition mini-modules can depend on or be associated with the internal and external mini-modules and / or external sources (e.g., external units such as reservoirs or other external components of the bioreactor system). In one example, one or more conduits and / or channels can pass through one or more internal mini-modules of multiple adjacent volumes (e.g., two adjacent volumes). The transition mini-modules can connect one or more conduits or facilitate communication between the conduits. For example, the transition mini-modules can facilitate fluid flow between one conduit and another conduit.

[0284] Fluid flow within a bioreactor mini-module can include characteristics including fluid dynamics (e.g., flow regime), thermal profile, composition profile, and fluid, heat, and mass transfer between various fluids and regions. In some instances, these characteristics and / or properties can be considered, designed, and / or controlled. In some cases, the design and / or construction of the transition mini-module can take into account the noted characteristics.

[0285] The transition building block construction method may be performed by a user who can provide instructions (e.g., any type of executable instructions and / or computer-implemented method). In some examples, a user can perform a manual design using an example drawing tool (e.g., AUTOCAD or any other drawing tool) and provide the manual design to a computer-implemented method provided elsewhere herein to achieve the design and / or construction of mini-modules (e.g., interior mini-modules, exterior mini-modules, and / or transition mini-modules). In some cases, such design and construction by a user may be time-consuming. Alternatively or additionally, the design of building blocks (e.g., transition mini-modules) may be achieved or facilitated by artificial intelligence-driven generative design, which can automate the design and / or construction of mini-modules, at least to some extent. Artificial intelligence-driven generative design may, in some cases, improve features such as fluid dynamics (e.g., flow regimes), thermal profiles, composition profiles, and fluid, heat, and mass transfer between various fluids and regions within the mini-module. In some cases, two mini-modules that need to be connected may be labeled. Alternatively or additionally, multiple external variables of the structure can be labeled. The labeling procedure can be used to provide a set of training data upon which a deep learning algorithm can be trained. In some examples, the algorithm can include a neural network. Examples of algorithms and / or neural networks include generative adversarial networks and variational autoencoders.

[0286] In some examples, a structure may be represented mathematically. The structure may comprise or be an internal and / or external mini-module. In one example, the represented structure may be a conduit. The conduit may be internal or external. An example of a mathematical representation of a conduit driven by grid points (e.g., elements) is shown in FIG. 49. The mathematical representation of the conduit 4900 may include one or more curves (e.g., parametric curves) 4910. The curves 4910 may be mathematically represented or formulated using polynomials. Polynomials may be suitable for such representation, for example, due to their simplicity and performance. Polynomials may include flexibility for representing curves and / or for various applications, such as for constructing mini-modules and structures, if needed. In some examples, various mathematical equations may be used to represent the curves; examples of mathematical equations that may be used include polynomials, sine, cosine, logarithmic, exponential, and / or any other suitable mathematical equations. In some instances, Bezier curves may be used (e.g., in 3D). In some cases, grid points may be used at the control points and / or extreme ends of the curve. Examples of extreme points may include points A, B, C, D, and E in Figure 49. An example of a control point may include point C in Figure 49. A1 , C A2 , C B1 , C B2 , C C1 , C C2 , C D1 , and C D2 may include:

[0287] A method for mathematical representation of chambers is provided herein. In some instances, the chambers can be within a mini-module. In some instances, the chambers can be shapes resulting from the intersection of paths passing through lattice points. The representation can vary based on the type of chamber and structure, among other factors. In some instances, conduits or channels can generate chambers, for example, from colliding paths passing through lattice points. The design, in each case, can depend on the features of the bioreactor in which such conduits and / or channels may be used. An example representation of this is shown in Figure 50. In this figure, C P1 and C P3 is the control point of A. C P1 and C P2 are the control points of C. C P2 and C P3 is the control point of B.

[0288] In some cases, a function, such as a mathematical function or mathematical operator, may be used to generate a chamber. For example, a chamber may be generated by an intersection function used for a curve (e.g., a 3D curve). In some cases, further modeling may not be required to complete and / or construct the representation of the chamber. Alternatively, in some cases, further modeling may be appropriate, helpful, or required to perform at least a subset of the process steps. FIG. 51A shows a representation 5100 of an example structure. Representation 5100 may be an implicit chamber. In some cases, when two or more paths (e.g., curves, such as 2D, or 3D curves, such as curve 5110) reach the same point (e.g., intersect at the same point, such as at intersection point 5120), an intersection mathematical function or operator may join, connect, and / or merge the two curves or paths to create a shape, such as a structure. Depending on the intersection function used to create the connection between the curves, the intersection point can be smooth (such as intersection point 5120) or can be sharp, such as the edge of a pyramid or another structure (example not shown). The generated structure (e.g., representation 5100) can be any structure. For example, the curves can be conduits and / or channels; the curves can intersect at certain points; the intersection function can connect and / or join the curves, and perform some further modification on them to generate structures such as chambers. As an example, the intersection function used to generate representation 5100 is a strict intersection function. Another example of generating a structure using this method is shown in FIG. 51B. A similar approach can be taken to generate representation 5130 shown in FIG. 51B. As an example, the intersection function used to create representation 5130 is an exponentially smooth intersection function. Representation 5130 can be an implicit chamber.

[0289] In some instances, a structure such as a chamber and / or its representation can be explicit (e.g., an explicit chamber). The choice of an implicit or explicit structure or its representation can depend on the target characteristics of the resulting mini-module or structure such as a bioreactor. In some cases, a structure such as a chamber or its representation can be parametric. The results may vary depending on the method used to generate the structure (e.g., chamber).

[0290] In some examples, multiple unit cells can be assembled to generate a mini-module. For example, unit cells can be used as voxels to voxelize a structure, such as a bioreactor mini-module or an entire bioreactor. A mini-module can be a building block of the entire structure. In some cases, a mini-module or building block can inherit some properties from the unit cell that can be used to generate the mini-module. For example, in some cases, opposing faces of a unit cell can be parallel to each other. In some cases, adjacent faces of two mini-modules or building blocks can be connected by an equivalent link. In some cases, it can be possible to build a voxelized structure (e.g., an upper voxelized structure) using example unit cells as voxels. A unit cell can have any shape listed herein, such as a cube or other shapes (e.g., those provided in Table 1.1).

[0291] An example of creating a structure by assembling unit cells is shown in FIG. 52. This figure shows its voxelized representation using 3D sphere and cubic unit cells. In some examples, the first step of the method can be to define the shape of the structure to be built. For example, the shape of the structure can be defined by a mixture of mathematical equations (e.g., parametric equations) and constructive solid geometry. The shape of the structure (e.g., a macrostructure) can, in some cases, be defined as a 3D object (e.g., a complete 3D shape), regardless of the shape of the unit cells or voxels that will be used to build the structure. In some examples, the structure to be built can be a macrostructure such as a bioreactor. In some cases, the structure to be built can be a mini-module. As an example, once the geometry of the macrostructure (e.g., sphere 5200) is defined, voxelization can be performed to represent the macrostructure as an assembly of multiple unit cells or voxels (e.g., unit cells or voxels 5210). In some cases, voxelization may be performed based on the type of unit cell (see, e.g., Table 1.1). In some instances, the placement of lattice points within the interior of a unit cell may be ignored for voxelization purposes. During this process, mini-modules and / or building blocks may be created. The overall macrostructure may comprise multiple such mini-modules or building blocks. Such mini-modules and / or building blocks may comprise interior, exterior, transition, and / or any type of mini-module or building block provided elsewhere herein.

[0292] A next step may include incorporating the conduits into the structure, such as into the mini-modules and / or building blocks. The characteristics of the conduits may be precise and may be integrated (e.g., according to methods described elsewhere herein). The conduits may comprise elongated conduits capable of carrying gases and liquids throughout the structure of the bioreactor.

[0293] External Connector In some examples, a structure can include multiple external connectors. For example, a structure can include multiple intake channels (e.g., channel 4720 or 4730) as shown in FIG. 47 . For example, a structure such as a bioreactor (e.g., bioreactor 4700) can include at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 20, or more intake channels, including increments therein. In some cases, it may be appropriate to have a relatively small number of intake channels, or in some cases, to minimize the number of intake channels. A structure can further include multiple channels, such as internal channels (e.g., channels 4810 and 4820 as shown in FIG. 48 ). A channel can be a conduit. An external connector (e.g., an intake channel, e.g., channel 4720 or 4730) can feed into the internal channels (e.g., channels 4810 and 4820). A channel can be a conduit (e.g., conduit 1905 as shown in FIG. 19 ). A structure can have any number of conduits. In some instances, a structure can comprise millions to millions of conduits (including any number therebetween). It may be appropriate to create an appropriate (e.g., uniform) distribution of gas and / or liquid among the channels and / or conduits, in some cases among all channels of a bioreactor. In some cases, it may be appropriate to have a small number of intake channels so that controlling the intake channels is more convenient and efficient. In some cases, the method of constructing the structure (e.g., procedural design) can include tracing intake channels from external building blocks or mini-modules and / or connecting conduits to different types of external connectors. In some cases, connectors may be pre-tested to ensure that intake and output channels distribute incoming flow evenly through the channels (e.g., conduits) of the structure.

[0294] Tree-like connector The structures provided herein can include one or more connectors. The structure can be a bioreactor provided herein that can be 3D printed using the methods of the present disclosure. A structure, such as a bioreactor or another structure that can be 3D printed according to the methods provided herein, can include one or more connectors. The connectors can include various shapes and forms. An example connector can include a tree-like connector. An example tree-like connector is shown in FIG. 53. The shape of these connectors can correspond to the shape of a tree. For example, the base of the example tree can represent an external connector (e.g., a connector on the external surface of the bioreactor). The leaves of the tree can represent intake channels from external mini-modules of the bioreactor. In some examples, for each level, the number of input intake channels can be subdivided by a positive integer (e.g., an integer > 1) until one channel is reached. The resulting one channel can be the root of the tree representing the external connector.

[0295] Examples of connectors of different shapes can include tree-like connectors, single-sided connectors, and other shaped connectors. In some examples, the shape of the single-sided connector can vary in different designs. In a single-sided connector, the external connector can fill a chamber that can include one or more channels or conduits (e.g., multiple conduits) that can be connected to intake channels of an external mini-module (e.g., external building block). In some examples, to promote homogeneous and / or uniform distribution of fluid among the conduits, the width of the connector, chamber, and / or conduit can be adjusted, for example, to allow a target amount of fluid to be filled into the conduit when the chamber is filled.

[0296] Architectural designs and methods for architectural designs of structures such as bioreactors are provided herein. In some examples, the methods can include functionalizing mini-modules (e.g., building blocks). In some examples, building blocks and / or mini-modules can be connected to each other by links (e.g., link 1915 shown in FIG. 19 ). The crystalline unit cell shown in FIG. 19 can be an example of a mini-module with multiple faces (e.g., faces 1910 and 1920) and multiple conduits (e.g., conduit 1905). Such a crystalline unit cell or mini-module can be connected to other unit cells, mini-modules, or building blocks through links (e.g., link 1915). In some examples, the links (e.g., link 1915) can be external links and can be positioned within one or more faces (e.g., face 1910) of the mini-module. A mini-module can be represented as a crystalline unit cell. In some cases, an example of a mini-module can be a repeating unit, such as building block 4860 shown in FIG. 48 . In some cases, links can be positioned over the edges of two or more faces, such as on the sides of a unit cell geometry (e.g., a cube or another shape) as shown in Figure 19. In some examples, links can be shared by more than two faces, such as three or more faces, and links can be positioned at the vertices of building blocks, such as the vertices of a cubic unit cell crystal as shown in Figure 19 or a unit cell crystal of any other shape or type. In some examples, two or more neighboring blocks (e.g., neighboring mini-modules or neighboring crystal unit cells) can be compatible (e.g., connectable) if they share the same location within the faces to be connected and if the links attached to the neighboring blocks share the same cross-sectional shape. The links can then connect the two neighboring mini-modules.

[0297] In some instances, a bioreactor design can include a variable number of topological volumes that can be connected to one another. Topological volumes can, in some instances, be important for macrostructures built with multiple internal mini-modules (e.g., building blocks). For example, in some instances, methods for connecting mini-modules and / or building blocks can include considering media internal to such mini-modules. For example, mini-modules can be configured to allow fluids, such as liquids, to flow within the mini-modules. Examples of such mini-modules can be conduits or channels (e.g., in a bioreactor) or other structures. For example, a consistently integrated conduit can be constructed as a result of connecting two neighboring conduits, and the media transported within such conduits can be matched. This matching can be achieved by labeling the conduits used within the building blocks or mini-modules (e.g., in the volume topology). In some instances, such labels can be associated with properties such as pressure, heat, fluid composition, etc. In some instances, such properties may need to be preserved. For example, such properties can be unperturbed as a result of connecting building blocks or mini-modules. In one example, two conduits may be connected to one another, each of which may have a fluid flowing therethrough, each of which may include a set of properties, such as flow rate, temperature, pressure, composition, etc. The conduits may be connected while taking these properties into consideration, such that connecting the conduits results in such properties being preserved or maintained in an appropriate condition. This may be achieved by the labeling schemes described herein. In some examples, multiple such considerations are tested, investigated, and / or verified, for example, before finalizing the structural design.

[0298] The mini-modules or building blocks may comprise transitional mini-modules and / or building blocks. The transitional mini-modules may comprise transitional topological volumes. The transitional topological volumes of the mini-modules may take into account both the topological volumes formed by the connected transitional mini-modules and the relevant characteristics of the neighboring topological volumes of these transitional mini-modules.

[0299] In some examples, the connector can be configured to carry a medium (e.g., a fluid such as a gas or liquid) from outside the bioreactor to an input conduit or intake channel (e.g., an intake channel such as intake channel 4720 or 4730) in an external building block or mini-module of the bioreactor, in some cases to all of the intake channels. The connector can include multiple levels. The connector can comprise a lower-level connector. In some examples, the lower-level connector (e.g., a first-level connector) can comprise a configuration that can convert the conduit into a larger intake channel that can gradually provide multiple intake channels (e.g., intake channel 4720 or 4730) outside the bioreactor (e.g., bioreactor 4700).

[0300] The connectors may further comprise higher-level or higher-level connectors, which may build larger intake channels incrementally (e.g., layer by layer) from lower-level connectors. Such connectors may be external connectors, tree-like connectors, and / or single-sided connectors, and their functionality may be according to information provided elsewhere herein.

[0301] Simulations and Models Provided herein are methods for modeling and / or simulating unit cells (e.g., crystallographic unit cells) and their behavior and / or function. Such simulations can facilitate the determination of design features based on the intended application and / or intended outcome for the resulting bioreactor. Simulations can include computational and / or numerical simulations. Examples of simulations or models include integral simulations, lattice Boltzmann simulations, finite element simulations, functional microfluidic feedback and correction (e.g., at the second and / or third level), phase continuity, and other methods.

[0302] As an example, finite element analysis (FEA) may be used to solve problems related to designing and / or building structures of the present disclosure. In some instances, FEA may be used to predict, model, and / or simulate the behavior of a 3D or 3D model with respect to various factors, including external forces, heat, fluid flow, and other factors such as physical phenomena. In some cases, simulation may be used in the product development process as feedback to improve the quality of the design. In some cases, FEA may begin by subdividing an object into multiple finite elements (e.g., millions of finite elements). This may be a critical procedure for the efficiency and accuracy of the prediction. In some cases, performing FEA may be time-consuming due to, for example, the topology of a crystalline structure. The way in which a structure is divided into finite elements may be important for the efficiency and / or accuracy of the model.

[0303] In some examples, the modeling or simulation may include a lattice Boltzmann method. In some examples, the lattice Boltzmann simulation may be adapted to an implicit representation of the model or structure. The method may further include using a function to improve the performance and / or accuracy of the lattice Boltzmann simulation. In some examples, such a function may be a mathematical function or operator, such as a signed distance function.

[0304] The crystal structure simulation method can include pre-calculation of building blocks. In some instances, the building blocks or mini-modules can be substantially similar, and in some cases, identical. Categorization of mini-modules using a limited number of samples (e.g., a small number of samples) can be performed. For example, it can be possible to pre-calculate experiments using a variable number of input variables for a subset or all of the samples. Pre-calculation can be used to accelerate the simulation of the bioreactor. Pre-calculation can be performed for a subset of the structure (e.g., samples). In some instances, the design of the internal and external mini-modules or building blocks can be improved. Such improvements can be independent of the macro-structure of the bioreactor as a whole. Alternatively, in some cases, the macro-structure of the bioreactor can also be taken into account.

[0305] In some examples, methods and systems can include a database of simulations and methods for creating and using the same. For example, calculated and performed simulations can be saved and stored in a database. The database of simulations can be used to provide insight into subsequent simulations. Simulations can be performed at a given speed. The speed of a simulation can be increased by using pre-computations. In some cases, faster approximations can be provided. For example, such approximations can be based on information stored in the database of simulations or other calculations stored elsewhere. This can make simulations computationally inexpensive.

[0306] The methods of the present disclosure can include artificial intelligence and / or machine learning. In some examples, a subset of information can provide training data for an algorithm, such as an AI-driven platform, based on, for example, deep learning. The purpose of this can include generating faster and / or better predictions and simulations. In some examples, labeling mini-modules and / or building blocks can facilitate storing meta-information derived from prior simulations and / or experiments or prior calculations. In some examples, a database of simulations can be used to store such data. The training data can be used to train a model. A platform (e.g., an AI-driven platform) can provide information by performing faster, more efficient, and / or more accurate simulations. This can be part of a product development cycle according to the methods provided herein. The methods can include user-driven simulations, AI-driven simulations, and / or a combination thereof. The methods can include an iterative process. Using AI can increase the speed, efficiency, and / or accuracy of iterations. The resulting design and / or production configuration can include, among other factors, constructional and functional considerations. Example design features may include mechanical strength, industrial compatibility, and the like.

[0307] While preferred embodiments of the present subject matter have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the present subject matter. It should be understood that various alternatives to the embodiments of the present subject matter described herein may be employed in practicing the present subject matter.

Claims

1. 1. A computer-implemented system including at least one processor, a memory, and instructions stored in the memory executable by the at least one processor to create a procedural modeling application, the procedural modeling application comprising: a) an interface comprising at least: i) defining at least one volume within the scene; ii) identifying a crystallographic unit for said at least one volume; iii) identifying symmetries for said crystallographic units; and iv) Editing the properties of said crystallography units. an interface that allows a user to perform the b) a presentation module, i) replicating the identified crystallographic units according to the identified symmetries to generate a three-dimensional crystal lattice, the three-dimensional crystal lattice being functionalized and fluidly interconnected to provide at least one microchannel or chamber; ii) representing the scene using one or more features, configurations, or both selected by the user; and iii) rendering said scene; a presentation module configured to: c) a simulation editor that enables the user to configure one or more simulations of the scene; d) a simulation module configured to perform said one or more simulations within said scene; e) a print editor that enables the user to configure the scene for printing; f) a printing module configured to send the scene to a three-dimensional printer; 1. A computer-implemented system comprising:

2. The computer-implemented system of claim 1 , wherein the interface further enables the user to configure one or more microchannels within the at least one volume.

3. The computer-implemented system of claim 1 , wherein the at least one microchannel or chamber comprises a fluidly continuous liquid or gas transport system.

4. 10. The computer-implemented system of claim 1, wherein the characteristics of the crystallography unit include links for connecting to one or more adjacent crystallography units and conduits connecting the links.

5. The computer-implemented system of claim 1 , wherein the crystallography unit comprises a single gyroid.

6. The procedural modeling application comprises: a) the transition volumes between volumes of different functionalization, and b) a transition crystallography unit for said transition volume; 10. The computer-implemented system of claim 1, further comprising a deep learning algorithm trained to predict

7. The computer-implemented system of claim 6 , wherein the algorithm comprises one or more neural networks (NN).

8. The computer-implemented system of claim 1 , wherein the one or more simulations evaluate microfluidic continuity of the at least one microchannel or chamber.

9. The computer-implemented system of claim 1 , wherein performance of the procedural modeling application does not degrade with increasing size of the scene or increasing detail of the scene.

10. 1. A computer-implemented method for procedural modeling, the computer-implemented method comprising: a) by one or more computers at least: i) defining at least one volume within the scene from received user input; ii) identifying a crystallography unit for the at least one volume from the received user input; iii) identifying symmetries for the crystallography unit from the received user input; and iv) editing characteristics of said crystallography unit from said received user input. and b) by said one or more computers at least: i) replicating the identified crystallographic units according to the identified symmetries to generate a three-dimensional crystal lattice, the three-dimensional crystal lattice being functionalized and fluidly interconnected to provide at least one microchannel or chamber; ii) representing the scene using one or more features, configurations, or both from the received user input; and iii) rendering said scene; and c) constructing, by said one or more computers, one or more simulations of said scene based on received user input; d) running, by said one or more computers, said one or more simulations within said scene; e) configuring, by the one or more computers, the scene for printing based on the received user input; f) transmitting, by said one or more computers, said scene to a three-dimensional printer; A computer-implemented method comprising:

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