Platform, system and apparatus for 3D printing

Abstract

A 3D printing platform is described, comprising a stereolithography 3D printing device using static optical components and a process modeling application representing 3D scenes as signed distance functions. Structures that can be printed using the platform, such as bioreactors, are also described, as well as their properties and uses.

Description

[0001] Cross Reference To

[0002] 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 by reference herein in its entirety. BACKGROUND

[0003] A lattice can be a unit (e.g., a symmetry unit), which can include a one- or multi-dimensional pattern that, when repeated at a given interval (e.g., regular interval), can produce a structure, such as a crystal structure. Such structures have been extensively studied in different fields of science and technology.

[0004] In the field of 3D printing, stereolithography (SLA) works by projecting light on a photosensitive resin contained in a print tray. The projected light can initiate a polymerization reaction that can generate a cross-linked polymer structure that can adhere to the print bed. SUMMARY

[0005] Modeling and / or manufacturing objects using crystal structures can be time consuming. Moreover, depending on the number of crystals involved in a scene, it can be difficult to visualize such a scene using techniques such as grid-based renderers and / or manual operations. In many cases, such techniques can require modeling tools to provide suitable functionality to users. In some cases, testing such complex scenes using traditional geometry-based modeling tools can be computationally very expensive and time consuming, and in some cases even infeasible.

[0006] Process geometry can be an alternative to traditional geometry-based modeling, which can include using one or more algorithms to describe one or more scenes as a list of geometric primitives instead of or in conjunction with a list of geometric primitives. In several fields of computer graphics, process modeling can be applied as an alternative or complementary method to geometry-based methods. In some examples, modeling tools such as AutoCAD, SolidWorks, or Inventors can use process modeling to generate certain types of geometry. However, for practical reasons, existing tools can not be able to effectively visualize or manipulate geometry as a function; instead, in most cases, they can convert implicit representations of geometry to a list of vertices. In many cases, this approach can at least partially contain or nullify the potential advantages of process modeling methods. These advantages of process modeling methods can include the ability to effectively visualize scenes, including large and detailed scenes, and / or to store such visualizations by occupying less disk space, in some cases, using only a few bytes of disk space.

[0007] In one aspect, described herein is a process modeling suite that provides many advantages (e.g., the ability to visualize and manipulate crystal structures composed of an unlimited number of lattices with an unlimited level of detail). It also provides a novel and compact approach to save those complex scenes in a few kilobytes of file, instead of wasting terabytes of space to store the geometry of only one scene, in terms of the utilization of storage space. In some cases, the process modeling suite described herein transmits instructions to one or more 3D printing devices so that the modeled structures can be physically realized to benefit many scientific and technological fields.

[0008] In another aspect, described herein is a 3D printing technology that includes improvements to SLA, specifically Digital Light Processing (DLP) based SLA. In the case of DLP based SLA, the projected pattern is delivered by a digital mask. Once the first layer is projected for a predetermined time and the polymerized layer is adhered to the print bed, the print bed is moved upwards along the Z-axis and the second layer is projected. This layer is then adhered to the previous layer. As the subsequent layers are projected, a 3D geometry is generated.

[0009] In some embodiments, the DLP based SLA described herein is capable of pixel-based light modulation and management and is suitable for fabricating micron-sized structures. Important micron-sized structures include, but are not limited to, structures comprising crystal geometries spatially distributed in a periodic manner to form a lattice. In some cases, such structures are porous structures, and in further examples, such structures are microfluidic structures. In particular cases, the 3D printing technology described herein is suitable for printing continuous flow microbial reactors at commercial scale and size, such as those disclosed in U.S. Patent Application Serial No. 62 / 743,974 and International Application No. PCT / US19 / 55231, which are incorporated by reference in their entirety herein.

[0010] The main limitations faced in these efforts include the fact that the SLA technologies available in the market (e.g., LCD, laser, and DLP based) are unable to achieve the resolution required for many microstructures. LCD and laser technologies are unable to reach the required resolution due to the size of the pixels or laser spots, respectively. In addition, commercially available technologies based on SLA-DLP can reach the required resolution, but are only suitable for the printing of low “pore volume” parts.

[0011] Maintaining high resolution in 3D printing of large scale parts is particularly challenging. One method to print large parts while maintaining high resolution is called scanning projection stereolithography. It is based on the use of a gantry that enables the projector to roll underneath the print bed. For scanning-projection stereolithography, the main limitations include the fact that mechanical noise can translate into the printing process, causing printing errors in the range of the printing resolution, and the fact that the printing speed is slowed down by the large displacement distance of the projector over the printing area.

[0012] A continuous 3D printing technique is called continuous liquid interface production (CLIP), but for CLIP, the printed volume is small and large structures cannot be printed. To overcome these limitations of existing methods, we propose a 3D printing technique based on a static optical setup for printing high resolution large scale structures.

[0013] Accordingly, in one aspect, disclosed herein is a stereolithography 3D printing apparatus, comprising: a static optical assembly comprising: a light engine configured to project a lux beam comprising a plurality of pixels along a Z-axis; at least one collimating lens configured to collimate the lux beam; a microlens array (MLA) configured to focus the collimated lux beam to a final beam of smaller diameter, wherein each pixel of the lux beam is subdivided into a plurality of sub-pixels to multiply the resolution of the final beam; a microdiaphragm array (MDA) configured to reduce noise and cross-talk 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 an X-Y plane; wherein a distance between the light engine, the collimating lens, the MLA, the at least one projection lens, and the movable stage of the static optical assembly along the Z-axis is fixed; a print bed comprising a print stage movable on a Z-axis; and a control circuit configured to control at least the light engine, the movable stage, and the print stage to enable stereolithography 3D printing. In some embodiments, the light engine comprises a UV projector and / or a deep UV projector. In various embodiments, the light engine has an operating wavelength between 370 nm and 415 nm. In particular embodiments, the light engine has an operating wavelength of about 405 nm. In other particular 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 apparatus further comprises a second light engine configured to project a second operating wavelength. In further embodiments, the second light engine operates in parallel with the first light engine, and the second operating wavelength is selected to inhibit polymerization of a photocurable resin in the print bed. 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 particular embodiments, the light engine has a light generation area of about 90 mm by about 50 mm. In other particular embodiments, the light engine has a light generation area of about 140 mm by about 90 mm. In some embodiments, the 3D printing apparatus comprises a collimating lens system. In further embodiments, the collimating lens system comprises 2 to 6 collimating 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 X-Y plane.In further implementations, the piezoelectric mechanism translates one or more of the at least one projection lens in the X-Y plane with nanometer resolution. In further implementations, the stage has a translation range of at least 50 pm in the X-axis and at least 50 pm in the Y-axis. In still further implementations, the stage has a translation range of about 100 pm in the X-axis and about 100 pm in the Y-axis. In some implementations, the stage has a translation resolution that is less than or equal to the sub-pixel length. In various implementations, the MLA includes a bi-convex array, a bi-concave array, a mono-convex array, a mono-concave array, or a combination thereof. In particular further implementations, the MLA includes a single piece bi-convex array. In some implementations, the MLA includes a planar substrate and a plurality of microlenses located on each of two largest opposite sides of the substrate plane. In various further implementations, the planar substrate is borosilicate or etched glass, and the plurality of microlenses is polymer or glass. In particular implementations, the MDA is located between the planar substrate and one of the plurality of microlenses of the MLA. In some implementations, the 3D printing apparatus includes a plurality of MDAs, e.g., 2, 3, or 4 MDAs. In various implementations, the MDA has an aperture size of 10 pm to 15 pm. In various implementations, the MLA subdivides each pixel of the lux light beam into 4 to 7498 sub-pixels. In further various implementations, the MLA subdivides each pixel of the lux light beam into 4 to 100 sub-pixels. In particular implementations, the MLA subdivides each pixel of the lux light beam into 9 sub-pixels. In other particular implementations, the MLA subdivides each pixel of the lux light beam into 25 sub-pixels. In other particular implementations, the MLA subdivides each pixel of the lux light beam into 49 sub-pixels. In some implementations, the at least one projection lens expands the final print area. In alternative implementations, the at least one projection lens reduces the final print area. In some implementations, the final print area is at least 2 times the light generation area of the light engine. In further implementations, the final print area is at least 4 times the light generation area of the light engine. In some implementations, the control circuitry is configured to control at least the light engine, the movable stage, and the print stage to enable a semi-continuous, substantially continuous, or continuous mode of stereolithography 3D printing. In some implementations, the control circuitry is configured to control the print stage to move in the Z-axis at a predetermined constant speed. In some implementations, the control circuitry is configured to control the movable stage to translate one or more of the at least one projection lens in the X-Y plane to scan the lux light beam in a predetermined pattern. In further implementations, the predetermined pattern includes a spiral pattern.In some embodiments, the predetermined pattern comprises a continuous space-filling curve. In further embodiments, the predetermined pattern comprises a Sierpinski curve. In a particular non-limiting embodiment, the control circuit is configured to control at least the light engine, the movable stage, and the printing stage to implement stereolithographic 3D printing of a porous structure comprising a helical geometry spatially distributed in a periodic manner. In some embodiments, the 3D printing device further comprises a robotic gantry configured to roll the static optical assembly in the X-Y plane relative to the printing tray. In further embodiments, the control circuit is further configured to control the robotic gantry. In some embodiments, the control circuit is configured to control the printing stage to implement bottom-up stereolithographic 3D printing. In alternative embodiments, the control circuit is configured to control the printing stage to implement top-down stereolithographic 3D printing. In some embodiments, the printing tray comprises a multi-phase light-cured resin. In some embodiments, the 3D printing device is configured for aseptic 3D printing, and the printing tray comprises aseptic light-cured resin.

[0014] In another aspect, disclosed herein is a computer-implemented system, comprising: at least one processor, a memory, and instructions executable by the at least one processor to create a process modeling application, the process modeling application comprising: a graphical user interface (GUI) comprising a viewport; a rendering module configured to represent a scene as a signed distance function and render the scene by utilizing ray marching, the rendering module comprising: a scene library comprising one or more process 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 process object (PO) editor that allows the user to edit properties of each PO added to the scene; a simulation editor that allows the user to configure one or more simulations of the scene; and a print editor that allows the user to configure a printed scene; a simulation module configured to conduct the one or more simulations in the scene; and a print module configured to generate a queue of slice files and transmit the slice files to a 3D printer. In some embodiments, the rendering module allows a user to drag a PO from the scene library into the viewport to add it to the scene. In some embodiments, the rendering module allows a user to save an edited PO in the scene library. In some embodiments, the one or more POs comprise a crystalline unit. In further embodiments, the rendering module allows a user to duplicate the crystalline unit to form a lattice in the scene. In some embodiments, properties of a PO comprise links for connecting to one or more adjacent POs and a duct connecting the links. In some embodiments, the signed distance function comprises a mathematical equation representing an entire lattice. In a particular non-limiting embodiment, the crystalline unit comprises a helix. In a further particular non-limiting embodiment, the lattice comprises helix geometries spatially distributed in a periodic manner. In some embodiments, the signed distance function does not comprise a list of geometric primitives. In various embodiments, the one or more simulations comprise one or more of: a microfluidics simulation, a computational fluid dynamics (CFD) simulation, a CFD simulation using a Lattice Boltzmann Method (LBM) in conjunction with a signed distance function, or a combination thereof. In some embodiments, the one or more simulations comprise a visualization of one or more features of the simulation. In various embodiments, the print editor allows the user to configure one or more of: a surface contour, a printer execution order, a layer thickness, a lux beam exposure time, and a pixel resolution. In some embodiments, performance of the process modeling application does not decrease as a size of the scene or a level of detail of the scene increases.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.

[0015] In another aspect, disclosed herein are non-transitory computer-readable storage media encoded with instructions executable by at least one processor to create a process modeling application, the process modeling application comprising: a graphical user interface (GUI) comprising a viewport; a rendering module configured to represent a scene as a signed distance function and render the scene by utilizing ray marching, the rendering module comprising: a scene library comprising one or more process 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 process object (PO) editor that allows the user to edit properties of each PO added to the scene; a simulation editor that allows the user to configure one or more simulations of the scene; and a print editor that allows the user to configure a printed scene; a simulation module configured to conduct the one or more simulations in the scene; and a print module configured to generate a queue of slice files and transmit the slice files to a 3D printer. In some embodiments, the rendering module allows a user to drag a PO from the scene library into the viewport to add it to the scene. In some embodiments, the rendering module allows a user to save an edited PO in the scene library. In some embodiments, the one or more POs comprise a crystalline unit. In further embodiments, the rendering module allows a user to duplicate the crystalline unit to form a lattice in the scene. In some embodiments, properties of a PO comprise links for connecting to one or more neighboring POs and a tube connecting the links. In some embodiments, the signed distance function comprises a mathematical equation representing an entire lattice. In a particular non-limiting embodiment, the crystalline unit comprises a helix. In a further particular non-limiting embodiment, the lattice comprises helix geometries spatially distributed in a periodic manner. In some embodiments, the signed distance function does not comprise a list of geometric primitives. In various embodiments, the one or more simulations comprise one or more of: a microfluidics simulation, a computational fluid dynamics (CFD) simulation, a CFD simulation using a lattice Boltzmann method (LBM) in conjunction with a signed distance function to solve the CFD simulation, or a combination thereof. In some embodiments, the one or more simulations comprise a visualization of one or more features of the simulation. In various embodiments, the print editor allows the user to configure one or more of: a surface contour, a printer execution order, a layer thickness, a lux beam exposure time, and a pixel resolution. In some embodiments, performance of the process modeling application does not decrease as a size of the scene or a level of detail of the scene increases. 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.

[0016] In another aspect, disclosed herein are computer-implemented methods for process modeling, comprising: providing a process modeling application comprising: a library of scenes comprising one or more process 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 process object (PO) editor that allows the user to edit properties of each PO added to the scene; a simulation editor that allows the user to configure one or more simulations of the scene; and a print editor that allows the user to configure a printed scene; representing the scene as a signed distance function; rendering the scene by utilizing ray marching; conducting one or more simulations in the scene; generating a queue of slice files; and transmitting the slice files to a 3D printer. In some embodiments, the presentation module allows a user to drag a PO from the library of scenes into the viewport to add it to the scene. In some embodiments, the presentation module allows a user to save an edited PO in the library of scenes. In some embodiments, the one or more POs comprise a crystalline unit. In further embodiments, the presentation module allows a user to duplicate the crystalline unit to form a lattice in the scene. In some embodiments, properties of a PO comprise links for connecting to one or more neighboring POs and pipes connecting the links. In some embodiments, the signed distance function comprises a mathematical equation representing the entire lattice. In particular non-limiting embodiments, the crystalline unit comprises a helix. In further particular non-limiting embodiments, the lattice comprises helix geometries spatially distributed in a periodic manner. In some embodiments, the signed distance function does not comprise a list of geometric primitives. In various embodiments, the one or more simulations comprise one or more of: a microfluidics simulation, a computational fluid dynamics (CFD) simulation, a CFD simulation using a Lattice Boltzmann Method (LBM) in conjunction with a signed distance function, or a combination thereof. In some embodiments, the one or more simulations comprise visualization of one or more features of the simulation. In various embodiments, the print editor allows the user to configure one or more of: a surface contour, a printer execution order, a layer thickness, a lux beam exposure time, and a pixel resolution.

[0017] In another aspect, disclosed herein are methods of manufacturing a 3D object comprising a plurality of repeating units, the method comprising: providing a process modeling application that allows a user to at least perform: adding one or more crystalline units to a 3D scene; replicating the one or more crystalline units to form a lattice in the scene; and configuring links for connecting the replicated crystalline units and conduits connecting the links; 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 transferring the slice files to a 3D printing device, such as a stereolithography 3D printing device. In some embodiments, the crystalline units are spatially distributed in a periodic manner to form the lattice. In various embodiments, the process modeling application further allows the user to at least perform one or more of: selecting one or more crystalline units from a library of scenes; editing properties of each crystalline 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 comprises performing the one or more simulations in the scene. In further embodiments, the one or more simulations comprise microfluidic simulations. In other embodiments, the one or more simulations comprise computational fluid dynamics (CFD) simulations. In yet another embodiment, the one or more simulations comprise CFD simulations solved using the lattice Boltzmann method (LBM) in conjunction with the signed distance function. In some embodiments, the one or more simulations comprise visualization of one or more features of the simulation. In some embodiments, the signed distance function comprises a mathematical equation representing the entire lattice. In some embodiments, the signed distance function does not comprise a list of geometric primitives. In some embodiments, the crystalline units are replicated at a high density in the lattice. In a particular non-limiting embodiment, the 3D object comprises a bioreactor.

[0018] In another aspect, disclosed herein are methods of manufacturing a bioreactor, the method comprising: providing a process modeling application that allows a user to at least perform: adding a plurality of micro-modules to a 3D scene; and assembling the plurality of micro-modules into a macro-structure to create a 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 transferring the slice files to a stereolithography 3D printing device. In some embodiments, one or more of the micro-modules are double gyroids (DGs) or modified DGs. In some embodiments, the micro-modules are arranged in multiple layers within the macro-structure. In further embodiments, the multiple layers are assembled into a first matrix and a second matrix, wherein the second matrix occupies free space in the first matrix, and wherein 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 the slice files are configured for a print surface of up to about 320 mm x 320 mm. In some embodiments, a cubic millimeter volume of the 3D scene comprises up to about 14 micro-modules. In some embodiments, a print volume of the bioreactor is up to about 102,400,000 cubic millimeters. In some embodiments, a print volume of the bioreactor comprises up to about 1,496,704,035 micro-modules. In some embodiments, one or more of the micro-modules comprise a channel, and wherein the channel has a diameter of about 8 pm to about 2000 pm. In various embodiments, each micro-module has an edge length of about 40 pm to about 9797 pm. In various embodiments, each micro-module has a volume of about 68417 to about 9.4 x 1010 11 cubic micrometers.

[0019] In another aspect, disclosed herein are bioreactors, comprising: a plurality of volumes, each volume comprising crystalline units symmetrically repeating into a three-dimensional lattice, each three-dimensional lattice functionalized and fluidically interconnected to provide at least one microchannel or cavity; 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 the at least one microchannel or cavity of one or more of the plurality of volumes; and a second channel system comprising at least one microchannel formed by the at least one microchannel or cavity of one or more of the plurality of volumes; wherein the first channel system and the second channel system provide 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 medium. In some embodiments, the bioreactor produces a continuous laminar flow gas. In some embodiments, the bioreactor has a spherical topology. In further embodiments, the plurality of volumes are arranged in concentric layers at different 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 particular embodiments, the bioreactor comprises 8 volumes. In some embodiments, the crystalline units comprise a double helix structure or a modified double helix structure. In some embodiments, the inoculation channel delivers the plurality of cells to a central volume of the bioreactor. In some embodiments, the first channel system is a liquid medium system fluidically connecting 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 flow a liquid medium into each medium intake microchannel. In further embodiments, the medium system is configured to provide uniform distribution of the medium. In some embodiments, the plurality of volumes comprises one or more volumes functionalized for cell culture. In particular embodiments, the plurality of volumes comprises 4 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 fluidically connects the at least one gas intake microchannel with an 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 the gas. In some embodiments, the plurality of volumes comprises one or more volumes functionalized for gas distribution and comprising a gas distribution chamber.In particular embodiments, the plurality of volumes includes 5 volumes functionalized for gas distribution and including 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 includes a harvest layer in fluid communication with the harvest microchannel and including a harvest chamber. In some embodiments, the bioreactor further includes an outer layer. In some embodiments, the plurality of volumes includes one or more transition layers between different functionalized volumes, and the crystallization unit includes a transition crystal.

[0020] In another aspect, disclosed herein are methods for culturing a plurality of cells or derivatives thereof, comprising: providing a bioreactor comprising: a plurality of volumes, each volume comprising crystalline units symmetrically repeating into a three-dimensional lattice, each three-dimensional lattice functionalized and fluidically interconnected to provide at least one microchannel or cavity; 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 biological product from the bioreactor; a first channel system comprising at least one microchannel formed from the at least one microchannel or cavity of one or more of the plurality of volumes; and a second channel system comprising at least one microchannel formed from the at least one microchannel or cavity of one or more of the plurality of volumes; wherein the first channel system and the second channel system provide separate inputs to the bioreactor; and directing the first plurality of cells to the inoculation microchannel, the plurality of cells flowing from the inoculation microchannel through the at least one microchannel or cavity of the plurality of volumes, and wherein the first plurality of cells undergo cell growth to produce the second plurality of cells. In some embodiments, the methods further comprise 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 the biological product. In some embodiments, the methods further comprise harvesting the biological product from the harvest channel. In some embodiments, the biological product 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 medium. In some embodiments, the bioreactor produces a continuous laminar flow gas. In some embodiments, the bioreactor has a spherical topology. In further embodiments, the plurality of volumes are arranged in concentric layers at different 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 particular embodiments, the bioreactor comprises 8 volumes. In some embodiments, the crystalline units comprise a double helix structure or a modified double helix structure. In some embodiments, the inoculation channel delivers the first plurality of cells to a central volume of the bioreactor. In some embodiments, the first channel system is a liquid medium system fluidically connecting 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 media input device configured to flow liquid media into each media intake microchannel. In further embodiments, the media system is configured to provide uniform distribution of media. In some embodiments, the plurality of volumes comprises one or more volumes functionalized for cell culture. The plurality of volumes comprises 4 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 fluidically 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 flow a gas component 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 particular embodiments, the plurality of volumes comprises 5 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 harvest layer in fluid communication with the harvest microchannel and comprising a harvest 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 different functionalized volumes, and the crystalline unit comprises a transition crystal.

[0021] In another aspect, disclosed herein is a computer-implemented system comprising: at least one processor, a memory, and instructions executable by the at least one processor to create a process modeling application comprising: an interface that allows a user to at least: define at least one volume in a scene, identify a crystalline unit for the at least one volume, identify a symmetry of the crystalline unit, and edit properties of the crystalline unit; a rendering module configured to: replicate the identified crystalline unit according to the identified symmetry to generate a three-dimensional lattice, the three-dimensional lattice being functionalized and fluidically 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 allows the user to configure one or more simulations of the scene; a simulation module configured to conduct the one or more simulations in the scene; a printing editor that allows the user to configure a printed scene; and a printing module configured to generate a queue of slice files and transmit the slice files to a 3D printer. In some embodiments, the interface further allows the user to configure one or more microchannels in the at least one volume. In some embodiments, the at least one microchannel or chamber comprises a fluidic continuous liquid or gas transport system. In some embodiments, the properties of the crystalline unit comprise links for connecting to one or more adjacent crystalline units and conduits connecting the links. In some embodiments, the signed distance function comprises a mathematical equation representing the entire lattice. In some embodiments, the crystalline unit comprises a helix. In further embodiments, the lattice comprises helix geometries spatially distributed in a periodic manner. In some embodiments, the process modeling application further comprises a deep learning algorithm trained to predict: a transition volume between different functionalized volumes, and a transition crystalline unit of the transition volume. In some embodiments, the algorithm comprises one or more neural networks (NNs). In various further embodiments, the one or more NNs comprise one or more generative adversarial networks (GANs) or one or more variational autoencoders (VAEs). In some embodiments, the one or more simulations comprise finite element analysis (FEA). In some embodiments, the one or more simulations assess microfluidic continuity of the at least one microchannel or chamber. In some embodiments, the signed distance function does not comprise a list of geometric primitives. In some embodiments, performance of the process modeling application does not decrease with an increase in size of the scene or in detail of the scene. 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. BRIEF DESCRIPTION OF DRAWINGS

[0022] A better understanding of the features and advantages of the present subject matter can be obtained by reference to the following detailed description of the illustrative embodiments and the appended drawings in which:

[0023] Figure 1 An example of a 3D geometry is shown; in this case, the crystal structure comprises a three-dimensional pattern formed by monomers repeated at regular intervals;

[0024] Figure 2 A non-limiting schematic of a rasterization pipeline is shown; in this case, the rasterization pipeline starts from a 3D mesh, comprising performing vertex processing, rasterization, raster operations and fragment processing to generate an image output;

[0025] Figure 3 A non-limiting schematic of a ray tracing method is shown; in this case, the ray tracing method comprises projecting a ray from a camera origin to find out which part of the scene is covered by each ray;

[0026] Figure 4 A non-limiting example of a flowchart is shown; in this case, the flowchart illustrates a ray marching pipeline for representing a complete procedural environment from a single mathematical equation, such as a signed distance function;

[0027] Figures 5 to 7 A non-limiting example of a ray marching method for rendering a 3D scene is shown; in this case, a ray marching method in which a ray is projected from a virtual camera viewing a 3D scene, wherein for each ray, the technique involves marching along the ray direction and at each step, evaluating a mathematical equation representing the scene to compute the distance to the nearest point on the surface;

[0028] Figure 8 A non-limiting platform architecture diagram is shown; in this case, the platform architecture diagram comprises a software suite with a presentation module, a save module, a simulation module and a print module used by the model and simulation designer, a 3D printer device and a cloud computing system;

[0029] Figure 9 A non-limiting example of an overview of a graphical user interface (GUI) for a procedural modeling application is shown; in this case, the overview of the GUI comprises a central viewport, a window displaying a CSG tree representation of the current scene, a scene library comprising procedural objects and a window displaying the properties of the currently selected procedural object;

[0030] Figure 10 A non-limiting example of a GUI for a procedural modeling application is shown; in this case, the GUI allows the user to select a procedural object, wherein interface elements for the user to edit the properties of the procedural object are provided;

[0031] Figure 11 A non-limiting example of a GUI for a procedural modeling application is shown; in this case, the GUI allows the user to select a texture, wherein a format and a preview are provided;

[0032] Figure 12 A non-limiting example of a GUI for a process modeling application is shown; in this case, the GUI allows a user to drag a process object from a library of scenarios and drop it into a process object editor to start editing the properties of the process object;

[0033] Figure 13 A non-limiting example of a GUI for a process modeling application is shown; in this case, the GUI allows a user to view editable properties of a selected process object (cubic crystal) depicted in a viewport and create multiple unit cells from the cubic crystal;

[0034] Figure 14 A non-limiting example of a GUI for a process modeling application is shown; in this case, the GUI allows a user to set links for each face of a cubic crystal process object and set the location of the links on the faces to form, for example, a helix;

[0035] Figure 15 A non-limiting example of a GUI for a process modeling application is shown; in this case, the GUI allows a user to save an edited process object (helix monomer) in a library of scenarios;

[0036] Figure 16 A non-limiting example of a GUI for a process modeling application is shown; in this case, the GUI allows a user to identify a process object saved in a library of scenarios, where the edited object (helix monomer) inherits properties from the process object that created it, and where the GUI also allows a user to duplicate the process object to form a lattice, for example, a helix lattice;

[0037] Figure 17 A non-limiting example of a flowchart is shown; in this case, the flowchart illustrates the process by which a user interacts with the application to create, edit, and save a process object from a previously created object;

[0038] Figure 18 A non-limiting example of a flowchart is shown; in this case, the flowchart illustrates the process by which a user interacts with the application to create and edit a new process object;

[0039] Figure 19 A non-limiting example of a diagram of a unit cell is shown; in this case, the diagram illustrates the nomenclature of features of a unit cell, for example, faces, links, and channels;

[0040] Figure 20 A non-limiting example of a GUI for a process modeling application is shown; in this case, the GUI shows the setup of a simulation to be performed in a 3D scene model;

[0041] Figure 21A non-limiting example of a GUI for a process modeling application is shown; in this case, the GUI shows the results of a simulation performed in a 3D scene model;

[0042] Figure 22 A non-limiting example of an architectural diagram is shown; in this case, an architectural diagram of a slicer and printer synchronization module;

[0043] Figure 23 A non-limiting example of a schematic structural diagram of a 3D printer device is shown; in this case, the schematic structural diagram of the 3D printer device includes a lux beam generating element, a collimator lens, a single piece MLA, and a series of projection lenses, one of which is articulated by a piezoelectric stage;

[0044] Figure 24 A non-limiting example of a graph showing the movement of a piezoelectric stage of a projection lens and its effect on the scan path of a lux beam is shown; in this case, the scan path illustrates a semi-continuous brick printing process with a spiral pattern;

[0045] Figures 25A to 25C A non-limiting example of a graph showing the movement of a piezoelectric stage of a projection lens and its effect on a lux beam is shown; in this case, the X-Y plane pixel displacement of a lux beam within a pixel field;

[0046] Figure 26 A non-limiting example of a graph showing a brick printing process is shown; in this case, an object is printed by a semi-continuous brick printing process;

[0047] Figure 27 A non-limiting example of a schematic structural diagram of a 3D printer device is shown; in this case, the schematic structural diagram of the 3D printer device capable of producing a printed result includes a light engine, a collimator, a single piece MLA, a piezoelectric element, a series of projection lenses, a tray window, a volume of light-curing (e.g., photocurable) resin, a print bed, and a rail and screw;

[0048] Figure 28 A non-limiting example of a light engine for a 3D printing device is shown;

[0049] Figure 29 A non-limiting example of an amplitude modulation element for a 3D printing device is shown;

[0050] Figure 30A A non-limiting example of a microlens is shown; in this case, a single biconvex microlens;

[0051] Figure 30B A non-limiting example of a structural diagram of an MLA is shown; in this case, the MLA includes a planar substrate and an array of microlenses applied to each major face of the substrate;

[0052] Figure 30C A non-limiting example of an optical diagram of an MLA is shown; in this case, the optical diagram comprises an optical path through a first microlens array, a substrate, and a second microlens array;

[0053] Figure 31 A non-limiting example of a piezoelectric stage for a 3D printing device is shown;

[0054] Figure 32 A non-limiting example of a processing (e.g., computing) device is shown; in this case, the device has one or more processors, memory, storage, and a network interface;

[0055] Figures 33A to 33F An example schematic of assembling micro modules into a macro structure is shown; Figure 33A An example of a micro module is shown, with pairs of parallel planes: A / a-B / b-C / c-D / d-E / e, for a total of 10 connecting planes; Figure 33B An example of assembling micro modules into an example three-dimensional matrix is shown; Figure 33C An example of a three-dimensional matrix is shown; Figure 33D An example layer of a three-dimensional matrix is shown; Figures 33E to 33F An example assembly comprising multiple three-dimensional layers is shown;

[0056] Figures 34A to 34F Examples of layer assemblies of various shapes are shown, such as square and square-like assembly shapes;

[0057] Figures 35A to 35F An example of a module layer connected to an example feed circuit is shown;

[0058] Figure 36 An example layer of a hollow pyramid shape is shown;

[0059] Figure 37A And Figure 37B A growth example of a hollow pyramid shape is provided;

[0060] Figure 38 An example of an external feed circuit for a hollow pyramid shape is shown;

[0061] Figure 39 An example of a layered macro structure is shown;

[0062] Figure 40 An example of a layered macro structure with a feed circuit is shown;

[0063] Figure 41 An example macro structure is shown;

[0064] Figure 42An example feed and collection arrangement is shown;

[0065] Figures 43A to 43E An example connection system is shown; Figure 43A An overview of an example connection system including connectors between a cell chip module and a fluid source is shown (where: 1 - connector support; 2 - input 1; 3 - output 1; 4 - waste 1; 5 - waste 2; 6 - input 2; 7 - output 2; 8 - SoC housing 1; 9 - clean room; 10 - safety membrane; 11 - CM input channel; 12 - harvest channel; 13 - filtered CM output; 14 - filtered flow; 15 - porous membrane; 16 - microorganisms; 17 - gas flow; 18 - SoC housing 2; 19 - septum); Figure 43B An example connection system is shown with an input needle and an output needle; Figure 43C An example connection by an example connector system is shown; Figure 43D An example implementation of a connection system is shown where a needle penetrates a chamber in an example cell chip module; Figure 43E An example connection system is shown where a needle penetrates a second chamber;

[0066] Figure 44 A schematic of an example method of cell growth, storage, environmental optimization, and scaled production is shown;

[0067] Figure 45 A cubic growth rate of a spherical structure relative to its radius is shown;

[0068] Figure 46A And Figure 46B A cross-sectional view of an example spherical bioreactor and its components is shown;

[0069] Figure 47 An example of a spherical bioreactor is shown;

[0070] Figure 48 An example of an internal micro-module or building block of an example bioreactor and internal components configured for fluid flow in a bioreactor, such as channels, tubes, and chambers, is shown;

[0071] Figure 49 Mathematical representations of structures according to the methods and systems of the present disclosure are shown;

[0072] Figure 50 Mathematical and geometric representations of structures according to the methods and systems of the present disclosure are shown;

[0073] Figure 51A And Figure 51B Example structures, such as shapes or micro-modules, that can be constructed according to the methods of the present disclosure are shown;

[0074] Figure 52An example 3D spherical macrostructure and its voxelated representation are shown;

[0075] Figure 53 Example structures of the plurality of connectors provided herein are shown;

[0076] Figure 54 An example 3D printer optical configuration with a micro-aperture array and a micro-lens array is shown;

[0077] Figure 55A and Figure 55B An example schematic of a 3D printer apparatus including a secondary wavelength generator is shown;

[0078] Figure 56A and Figure 56B An example schematic of a 3D printer apparatus including a coating on a tray window is shown;

[0079] Figure 57A and Figure 57B An example printing process and digital rendering of a 3D printed bioreactor is shown; Figure 57A An example printing process is shown; Figure 57B A digital rendering and cross-sectional view as a function of position height of a 3D printed bioreactor is shown; and

[0080] Figure 58 An example 3D printer apparatus and printed bioreactor is shown. DETAILED DESCRIPTION

[0081] Provided herein are systems, methods, and apparatuses for printing objects. The systems, apparatuses, and methods can include apparatuses and methods for 3D printing objects.

[0082] 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 to“or” herein is intended to encompass“and / or” unless otherwise stated.

[0083] Whenever the term“at least,”“greater than,” or“greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term“at least,”“greater than,” or“greater than or equal to” applies to each of the numerical values in that series of numerical values. 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.

[0084] Whenever the term“not greater than,”“less than,” or“less than or equal to” precedes the first numerical value in a series of two or more numerical values, the term“not greater than,”“less than,” or“less than or equal to” applies to each of the numerical values in that series of numbers. 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.

[0085] As used herein, the term“monomer” generally refers to the smallest repeating unit having full symmetry of the crystal structure (see, e.g., Figure 1 of 105).

[0086] As used herein, the term“lattice” generally refers to a unit having a three-dimensional pattern that, when repeated, produces a crystal structure (see, e.g., Figure 1 of 110).

[0087] As used herein, the term“helicoid” generally refers to a connected periodic minimal surface that does not contain straight lines. Such surfaces can have a mathematically infinite number of connections. In some examples, the helicoid is the only non-trivial embedded member of the associated family of Schwarz P and D surfaces with an associated angle of approximately 38.01°. The helicoid can be configured as a single helicoid or a double helicoid. The double helicoid can be oriented and configured for specific applications in a microfluidic device. The double helicoid can be configured by balancing geometric aspects related to fluid dynamic performance observed in micro-modules and macro-structures (e.g., macro-shapes), such as double helicoid crystal structures and space groups. The helicoid or double helicoid can be implemented in a variety of crystal structures.

[0088] As used herein, the term“production bioreactor” or“bioreactor” generally refers to a bioreactor apparatus suitable for large-scale production of cells and / or products produced by the cells. The production bioreactor can include one or more passages or other openings for inputting cells, for providing liquid media, gaseous components, and other cell environmental factors, and one or more passages for harvesting cells and / or products produced by the cells.

[0089] As used herein, the term“culture media formulator” generally refers to an assembly or apparatus for mixing ingredients for use as a culture medium for growing cells.

[0090] As used herein, the term“micro-module” generally refers to a portion of a bioreactor that can be interconnected and assembled into a larger structure (e.g., a macro-structure or macro-shape) to constitute at least a portion or all of a bioreactor.

[0091] As used herein, the term "spiral" generally refers to a periodic minimal surface that does not contain straight line connections. Such surfaces can have a mathematically infinite number of connections. In some examples, the spiral is the only non-trivial embedded member of the family of associated Schwarz P and D surfaces with an associated angle of approximately 38.01°. The spiral can be configured as a single spiral or a double spiral. The double spiral can be oriented and configured for specific applications in a microfluidic device. The double spiral can be configured by balancing geometric aspects related to fluidic dynamic performance observed in micro-modules and macro-structures (e.g., macro-shapes), such as double spiral crystal structures and space groups. The spiral or double spiral can be implemented in a variety of crystal structures.

[0092] As used herein, the term "bubble-free" generally refers to a bioreactor or other device that has substantially laminar or laminar fluid flow, thereby having no or substantially no bubbles. A bubble-free bioreactor generally does not have mixing elements that can generate bubbles in the fluid, such as moving blades, fins, propellers, and the like.

[0093] Provided herein are devices and systems for 3D printing. The devices can include stereolithography 3D printing devices. Methods of using such devices for applications such as 3D printing are also provided. The stereolithography devices can include 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 devices can also include a light engine, which can be configured to project one or more light beams. The light beams can include or be lux light beams. The light beams (e.g., lux light beams) can include one or more pixels. The one or more pixels can include a plurality of pixels. The one or more pixels can be positioned along an axis (e.g., a Z-axis).

[0094] The devices and / or optical assemblies can also include one or more lenses. The one or more lenses can include a collimating lens. The lenses (e.g., collimating lenses) can be configured to collimate the lux light beams. In some examples, the optical assembly can include a microlens array (MLA). The MLA can be configured to focus the collimated lux light beams onto a modified light beam, which can have a smaller diameter compared to the lux light beam. In some cases, the modified light beam can be the final light beam. Alternatively, the modified light beam can not be the final light beam, e.g., it can be an intermediate light beam, and can further generate more light beams. In some examples, one or more pixels (e.g., each pixel) of the lux light beam can be divided into a plurality of sub-pixels, which can multiply the resolution of the modified light beam and / or the final light beam.

[0095] The devices can also include a micro-aperture array (MDA), which can be configured to reduce noise and / or cross-talk between the lenses of the MLA.

[0096] The apparatus can also include at least one projection lens and a movable stage that can be configured to translate one or more of the at least one projection lens in a plane. The plane can be a two-dimensional (2D) plane, such as a plane in a space. The 2D plane can be a plane between two axes in the space. The space can be a multi-dimensional space, such as a three-dimensional (3D) space. For example, the plane can be a plane between an X-axis and a Y-axis (e.g., an X-Y plane). Or, the plane can be an X-Z plane or a Y-Z plane. The plane can be defined by two vectors, where each vector can be parallel to two axes in the space. For example, the plane can be an X-Y plane, and a distance between the light engine, the collimating lens, the MLA, the at least one projection lens, and the movable stage of the optical assembly along a Z-axis (or any other axis perpendicular to the plane) can be fixed. Or, in some cases, the distance can not be fixed and can change over time.

[0097] The apparatus can also include a print stage. The print stage can include a print table. In some examples, the print table can be fixed. In some examples, the print table can be movable. The print table can be configured to move in any direction or along any axis in a space. The movement of the table can be defined in a Cartesian coordinate, a polar coordinate, a spherical coordinate, or any other coordinate system. In some examples, the print table can be configured to move (e.g., can be movable) in a 3D space in a Cartesian coordinate system along an X-axis, a Y-axis, and / or a Z-axis. In some examples, the table can move along more than one axis. In some examples, the table can be configured to rotate and / or move in a direction of an angle or a radius of an example circle in a polar coordinate system or a spherical coordinate system.

[0098] The apparatus, such as the print stage of the apparatus, can also include a control circuit. The control circuit can be configured to control one or more apparatus components, such as the light engine, the movable stage, and / or the print table, to achieve a given target, such as to print an object, for example, by stereolithography 3D printing.

[0099] In some examples, computer systems and computer-implemented systems and methods are also described herein, which can include one or more processors and one or more memories. The computer systems can include instructions that are executable by the at least one processor and that can create an application. The application can include modeling, such as process modeling.

[0100] The process modeling application can include a graphical user interface (GUI). The graphical user interface can include a viewport. Methods and systems, such as the process modeling application, can also include a rendering module. The rendering module can be configured to render a scene. In some examples, the scene can be represented as a signed distance function, and the scene can be rendered by utilizing ray marching.

[0101] The presentation module can include a scene library. The scene library can include one or more process objects (POs). The presentation module can also include a scene editor. The scene editor can allow 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 a scene. The presentation module can also include a process object (PO) editor that can allow a user to edit properties of a PO that can have been added to a scene. The presentation module can also include a simulation editor that can allow a user to configure one or more simulations for a scene. The presentation module can also include a print editor that can allow a user to configure a scene for printing.

[0102] The method and system, e.g., the presentation module, can also include a simulation module. The simulation module can be configured to conduct one or more simulations. The simulation can be conducted in a scene. The method and system, e.g., the presentation module, can also include a print module. The print module can be configured to generate a queue of slice files and transmit the slice files to a 3D printer. The 3D printer can include or be the device or system provided elsewhere herein or another device or system.

[0103] Provided herein are non-transitory computer-readable storage media that can be encoded with instructions. The instructions can be executed by at least one processor, e.g., to create a process modeling application.

[0104] The process modeling application can include a graphical user interface (GUI). The GUI can include a viewport and a presentation module. The presentation module can be configured to represent a scene as, e.g., a signed distance function, and can render the scene by utilizing ray marching. The presentation module can include a scene library.

[0105] The scene library can include one or more process objects (POs). The presentation module can also include a scene editor that can allow 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 a scene. The presentation module can include a process object (PO) editor that can allow a user to edit properties of each PO added to a scene, a simulation editor that can allow a user to configure one or more simulations for a scene, and a print editor that can allow a user to configure a scene for printing, a simulation module that can be configured to conduct one or more simulations of a scene, and a print module that can be configured to generate a queue of slice files and transmit the slice files to a 3D printer, etc. The 3D printer can be the device or system provided elsewhere herein or another device or system.

[0106] Provided herein are computer-implemented methods for process modeling. A computer-implemented method for process modeling can include providing a process modeling application. The process modeling application can include a scene library. The scene library can include one or more process objects (POs). The process modeling application can also include a scene editor that can allow a user to add one or more POs to a scene and / or create geometry, such as a Constructive Solid Geometry (CSG) tree for a scene. The process modeling application can also include a process object (PO) editor that can allow a user to edit properties of a PO (e.g., each PO added to a scene). The process modeling application can also include a simulation editor. The simulation editor can allow a user to configure one or more simulations of a scene. The process modeling application can include a print editor that can allow a user to configure a scene for printing, represent a scene as a symbolic distance function, render a scene by utilizing ray marching, perform one or more simulations in a scene, generate a queue of slice files, and / or transfer slice files to a 3D printer. The 3D printer can be a device or system provided elsewhere herein, or another device or system.

[0107] Provided herein are methods of manufacturing multi-dimensional objects, such as 2D or 3D objects. In some cases, a multi-dimensional object (e.g., a 3D object) can include one or more cells. In some examples, the one or more cells can include a plurality of cells or a plurality of cells. In some examples, the cells can include or be repetitive or repeating cells. The method can include providing a process modeling application. The process modeling application can be according to a process modeling application provided elsewhere herein or another process modeling application. The process modeling application can be configured to perform one or more functions. In some examples, the functions can be performed according to a request of a user that can provide input or instructions to the application. Alternatively, one or more functions can be performed using artificial intelligence, machine learning, or other techniques.

[0108] In some examples, a process modeling application can be configured to add one or more cells to a scene. The scene can be a multi-dimensional scene. The scene (e.g., multi-dimensional scene) can include any number of dimensions, such as 1, 2, 3, 4, 5, 6, 7, or more. In some examples, the cells can be crystalline cells. For example, crystalline cells can be added to a scene (e.g., 3D scene). The method can also include duplicating one or more cells (e.g., crystalline cells) to form a structure. The structure can include or be a lattice. For example, the structure can include a lattice in the scene. The method can also include and configuring links and / or connections that can connect the cells (e.g., duplicated crystalline cells). The structure can also include one or more conduits. The conduits can connect the links. The method can include creating a Constructive Solid Geometry (CSG) tree for the scene. The method can also include representing the 3D scene as a signed distance function, rendering the scene by utilizing ray marching, generating a slice file queue, and / or transferring the slice files to a device such as a stereolithography 3D printing device, etc. The device can include any of the devices, other devices, or any combination thereof provided elsewhere herein.

[0109] When visualizing and manipulating any virtual scene, something to focus on can be a representation of a geometry or a plurality of geometries included in the scene or any structure therein. An example of a method that can be used to address this issue can include using an explicit representation and / or an implicit representation.

[0110] In some examples, in an explicit representation, a geometry can be stored as a list of geometric primitives. A geometric primitive can include a geometric primitive of any size with any shape. For example, a geometric primitive can include a point, a triangle, a polygon, or other geometric primitive. A geometric primitive can include one or more dimensions, such as 1, 2, 3, 4, 5, 6, 7, or more dimensions. In some examples, a geometric primitive can include n dimensions, where n is an integer from 0 to infinity in n-dimensional space.

[0111] In some cases, an explicit representation can not require conversion to extract a 3D representable model for printing, and it can allow local operations on the model, such as vertex-by-vertex. In some cases, an explicit representation can contain drawbacks. Examples of drawbacks of explicit representation can include fixing a maximum level of detail established by a vertex distribution, losing intrinsic information of a geometry (which can be represented in some cases by only a few lists of geometric primitives), difficulties related to performing global operations, and lack of definition of a compact data representation of a complete scene. For example, in some cases, a data representation of a complete scene can not be compact and can take up a lot of space, for example, on memory. Examples of widely used explicit representations can include geometric primitives, such as polygons and / or triangles. In some examples, surfaces can be divided or tessellated, for example, using rasterization, and rendered.

[0112] In an implicit representation, a geometry can be stored as a mathematical function or equation that can be defined on a manifold. Implicit representations can benefit from mechanisms that extract the information needed for printing and can facilitate local or global operations on the model. Implicit representations can include several advantages. For example, implicit representations can not fix a given level of detail and can provide the possibility of obtaining an infinite level of detail. Implicit representations can not result in the loss of intrinsic information of the geometry. Global operations in implicit representations can be convenient. In some examples, data can be compact and can occupy less disk space, for example, compared to explicit representation methods.

[0113] Marching cubes / tetrahedra: This technique involves converting an implicit representation of the entire scene to its explicit representation. This is less suitable for large scenes because it loses the data compactness of the implicit representation after conversion.

[0114] Rasterization: This technique has been widely used in real-time computer graphics for the past few decades because of its good performance and versatility to achieve good enough visual effects. The running time complexity of rendering is usually linear with the number of triangles that need to be drawn. On the other hand, the space-time complexity of the problem is linear with the number of vertices needed to represent the entire scene.

[0115] Reference Figure 2 An example rasterization pipeline is provided. In this example, the rasterization pipeline starts with a 3D mesh 205. In a first example vertex processing step 210, the host program fills the vertex buffer memory of the API with an array of vertices. These vertices are usually defined in global coordinates; therefore, they are converted to camera-space coordinates. The vertices can now be projected to screen coordinates. This conversion is 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 to pixel fragments 225. In a third example rasterization operation step 230, the fragments are shaded according to the desired lighting technique and optionally texture filtering to produce colored fragments 235. Finally, in this example, a fragment processing step 240 produces a final image output 245.

[0116] This process, sometimes called the "graphics pipeline," is usually implemented in hardware, but can be operated through intermediate steps called "shaders." Over the past two decades, this graphics pipeline has been improved to maximize the number of triangles that can be drawn. Rasterization has important performance considerations; specifically, the execution time complexity of the algorithm is linear with the number of vertices, as all vertices need to be tested to produce the final image. It is important to note that this can be reduced to logarithmic order of complexity by sorting the elements in the scene using an AABB; nonetheless, the time complexity is still closely related to the number of elements in the scene. Therefore, this algorithm does not scale well. That is, this approach is popular because of its ease of parallelization using a GPU.

[0117] Raytracing (Raycasting): In the instant methods described herein, in some examples, raytracing is used as the rendering method, which has key advantages over rasterization. Modern GPUs have evolved into highly programmable parallel floating point processors today. This new paradigm of multithreading executing simultaneously on multiple data sources (MTMD processors) opens the door to new opportunities for the traditionally well-known raycasting rendering technique.

[0118] Referring to Figure 3 An example raytracing diagram is provided. Unlike the rasterization pipeline, this approach starts with the pixels of the raster image 310 to produce a ray along the camera frustum 305 to shoot a ray to find the part of the scene that each ray / pixel covers. Some rays can hit 320 objects in the scene 315, and some can miss 325.

[0119] Referring to Figure 4 An example ray marching method is provided. In this example, for each pixel in the screen, a ray is traced 405 through the scene, usually it is done by using a BVH. Also, in this example, if the ray intersects 415 with any object, the hit is computed and saved 420. After traversing the whole structure 410, the algorithm evaluates 425 if the ray hit a surface 435 or 430, if so, the color is computed, or an additional ray is cast from the desired position.

[0120] Light ray tracing and lattice

[0121] 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 provides useful properties that are beneficial to improve the execution time of rendering techniques.

[0122] Light ray travel

[0123] This technique involves determining the intersection of the orthographic projection of the entire scene with a single plane. Typically, a 3D printer requires only a limited set of layers, often just one. Once the printing process begins, it can be updated one layer 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 for these tasks because extracting the intersection of the 3D scene with a plane is straightforward.

[0124] This technique may be similar to ray casting, but it can be used to generate completely procedural environments from a single mathematical equation. The idea is to change the scene's abstract representation and rendering techniques to combine them in a method that can handle better spatial and execution time complexity. The scene is now represented as a mathematical function, such as an SDF. Since a lattice is composed of an orderly arrangement of particles, finding such a function is not impossible. The SDF takes a point in space and calculates its distance from the surface.

[0125] Example: The following function describes a circle in two dimensions:

[0126] / / params:

[0127] / / p:arbitrary point in 3D space

[0128] / / c:the center of our sphere

[0129] / / r:the radius of our sphere

[0130] float sphere_distance(in vec3 p,in vec3 c,float r)

[0131] {

[0132] return length(pc)-r;

[0133] }

[0134] To render a scene, the technique shoots rays from a virtual camera that is viewing the scene (see, e.g. Figure 5 ). For each pixel of the raster image, the technique proceeds along this ray direction (see, e.g. Figure 6 ), and at each step, evaluate the SDF to compute its distance to the nearest point on the surface (see, e.g. Figure 7 ).

[0135] Light ray marching brings significant performance improvements. Since, when using light ray marching, the entire scene is represented as a single mathematical equation, the execution time complexity does not depend on the number of objects in the scene, but rather on the complexity of the SDF. When analyzing the space complexity, it is clear that a scene can be described with a single mathematical function, without the need to discretize the scene with vertices. This can greatly reduce the space needed to store the scene, while preserving the details of the original geometry inherited by the mathematical function.

[0136] These performance improvements are amplified when modeling lattices, which are composed of an ordered repetition of the same unit structure. To achieve the necessary amount of repetition, in some examples, the rendering suite described herein does not specify each unit position individually, but rather, in such examples, to represent the entire crystal structure, a mathematical equation is established.

[0137] Process modeling application

[0138] Reference Figure 8 In particular embodiments, the process modeling application has an architecture that includes a presentation module, a save module, a print module, and a simulation module. In this embodiment, the application architecture is also operatively in communication with a cloud computing system and at least one 3D printing device, such as the 3D printing apparatus described herein.

[0139] With continued reference to Figure 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 process object (PO) editor, and a scene editor. In this embodiment, the scene editor allows the user to access features of the print editor and the simulation editor.

[0140] In some examples, the presentation module of the process modeling application includes a scene library. In further examples, the scene library includes one or more POs that are available for addition to a scene. In various examples, the POs in the scene library include POs that are pre-made and provided with the application, created from scratch by a user, created by a user by editing properties of other POs, loaded from an external source, etc. In particular embodiments, a user optionally adds a PO to a scene by dragging an icon representing the PO from the scene library and dropping it into a viewport or other feature of the presentation module that represents a scene.

[0141] In some examples, the presentation module of the process 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 for connection to one or more adjacent POs (including the type, scale, shape, and position of each link), pipes connecting links (including the type, scale, shape, path, and position of each pipe), and replication properties such as replication quantity, replication pattern, replication density, and the like.

[0142] In some examples, the presentation module of the process modeling application includes a scene editor. In further examples, the scene editor allows for the creation and editing of project files for a scene. In still further examples, the scene editor provides features that allow a user to add one or more POs to a scene. In still further examples, the scene editor creates a Constructive Solid Geometry (CSG) tree for a scene and updates the CSG tree as the scene is built and modified. In particular implementations, the scene editor provides features that allow a user to replicate a unit cell with precisely specified scale, pattern, density, and the like to form a lattice in a scene.

[0143] In some examples, the process modeling application includes a save module. In further examples, the PO files are referenced by project files and the project files are referenced by print files. In still further examples, the PO files, project files, and / or print files are stored in a project database by the save module, the project database being in communication with a local file system that allows for searching, retrieving files, and the like.

[0144] Still referring to Figure 8 In this implementation, the presentation module further includes tools configured for use by a simulation designer user, which can be the same user as the model designer user or a different user, and the process modeling application includes a simulation module. Non-limiting examples of tools configured for use by a simulation designer user include a simulation editor. In further examples, the simulation editor provides features that allow a user to configure one or more simulations of a scene. In still further examples, the simulation editor generates and maintains a simulation input file that is ingested by the simulation module in conjunction with scene and project information to perform simulations utilizing cloud computing resources.

[0145] Many types of simulations are suitable for the process modeling applications described herein. As non-limiting examples, suitable simulations include microfluidic simulations, computational fluid dynamics (CFD) simulations, and lattice Boltzmann methods (LBM) combined with a symbolic distance function to solve CFD simulations. In particular examples, the simulation module provides visualization of one or more features of the simulation, such as performance characteristics.

[0146] Still referring to Figure 8 In this implementation, the presentation module includes a print editor and the process modeling application includes a print module. In some examples, the print editor allows for creation and editing of print files for a scene. In further examples, the print editor provides features that allow a user to configure a scene for printing. In still further examples, the print editor provides features that allow a user to configure surface contours, printer execution order, layer thickness, lux beam exposure time, and pixel resolution, as non-limiting examples. In some examples, the print module ingests print files and other information from the print editor through a slicer as well as simulation information to produce slice files. In further examples, a file server provides slice files to a cache internal or external to one or more 3D printing devices. Figure 22 An example slicer / printer synchronization architecture is provided.

[0147] Graphical user interface

[0148] In some examples, the process modeling application includes a GUI to present elements and features that allow one or more users to access application functionality.

[0149] Referring to Figure 9 In particular implementations, the process modeling applications described herein include a GUI that includes a central viewport, a window that displays a CSG tree representation of a current scene, a scene library that includes process objects, and a window that displays properties of a currently selected process object.

[0150] In some examples, the process modeling applications described herein include a GUI that allows a user to access a number of functionalities, including, as non-limiting examples, allowing a user to select a process object, where interface elements for the user edit properties of the process object (see, e.g., Figure 10 ) allowing a user to select a texture, where formatting and a preview are provided (see, e.g., Figure 11 ) allowing a user to drag a process object from a scene library and drop it into a process object editor to begin editing properties of the process object (see, e.g., Figure 12 ) allowing a user to view editable properties of a selected process object (cubic crystal) depicted in a viewport and create multiple unit cells from the cubic crystal (see, e.g., Figure 13), allowing the user to set links for each face of a cubic crystal process object and set the location of the links on the face to form, for example, a gyroid (see, e.g. Figure 14 ), allowing the user to save the edited process object (gyroid monomer) in the scene library (see, e.g. Figure 15 ), and allowing the user to identify saved process objects in the scene library, where the edited object (gyroid monomer) inherits properties from the process object that created it, and where the GUI also allows the user to duplicate the process object to form a lattice, e.g., a gyroid lattice (see, e.g. Figure 16 ).

[0151] Referring to Figure 19 , a schematic of a unit cell is provided, including nomenclature. The illustrated nomenclature includes the terms “face” 1910, “symmetry face” 1920, “link” 1915, and “pipe” 1905.

[0152] In various further examples, the process modeling application described herein includes a GUI that allows the user to access a plurality of simulation functions, including, by way of non-limiting example, allowing the user to set up a simulation to be performed in a 3D scene model (see, e.g. Figure 20 ), and allowing the user to view simulation results performed in the 3D scene model (see, e.g. Figure 21 ).

[0153] An example process

[0154] Referring to Figure 17 , in a particular implementation, the user is provided with a process to interact with the application to create, edit, and save a process object from a previously created object. In this implementation, the user selects a PO from the scene library 1705, in this case, a cubic crystal PO. Next, the user selects the PO by right clicking on the PO and selecting “duplicate” from the options menu 1710. As a result, a new cubic crystal PO is added to the scene library 1715. The user can then select the new PO 1720 and rename the new PO to “gyroid lattice” 1725. Next, the user can set a plurality of links for each pair of symmetry faces on the PO 1730, and can also set a plurality of pipes 1735. Finally, in this example process, the user connects a set of links from different faces using pipes 1740 to complete the fluidic connections within the lattice.

[0155] Further, referring to Figure 18 , in a particular implementation, the user is provided with a process to interact with the application to create and edit a new process object. In this implementation, the user begins the process by dragging a PO from the scene library 1805. The user then drops the PO into a location 1810. If the location is invalid, the user must start over.

[0156] Continuing to refer toFigure 18 If the position is valid and the user has dragged the PO into the editor viewport, the new PO is added to the scene library 1815. Subsequently, the user can select the new PO 1820 and the default property browser 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.

[0157] With continuing reference to Figure 18 If the position is valid and the user has not dragged the PO into the editor viewport, the new node is added to the CSG tree of the scene 1845 and the new PO is added to the scene library 1850. The user can then select the new node 1855 and the property browser 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 visualized in the viewport 1880.

[0158] 3D printing device

[0159] In some examples, the 3D printing device described herein includes 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 a Z-axis; at least one collimating lens configured to collimate the lux beam; a microlens array (MLA) configured to focus the collimated lux beam to a final beam of smaller diameter, wherein each pixel of the lux beam is subdivided into a plurality of sub-pixels to multiply the resolution of the final beam; a microdiaphragm array (MDA) configured to reduce noise and cross-talk between the MLA lenses; at least one projection lens; and a movable stage configured to translate one or more of the at least one projection lens in an X-Y plane. In further examples, with respect to the static optical assembly, the distance along the Z-axis between the light engine, the collimating lens, the MLA, the at least one projection lens, and the movable stage of the static optical assembly is substantially fixed or fixed.

[0160] With reference to Figure 23 In a particular implementation, a stereolithography 3D printing device includes a frame structure that supports other components of the device and defines a Z-axis. In this implementation, the 3D printing device also includes a static optical assembly. Proceeding along the Z-axis from the bottom to the top of the device, 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 implementation, a stepper motor drives a screw that adjusts the position of a print platen including a print stage in the Z-axis. Other components include linear guides, ball screws, control electronics, etc. Finally, in this implementation, the static optical assembly is configured to project a field of pixels onto the print stage.

[0161] Slicer / printer synchronization architecture

[0162] In some examples, the process modeling application communicates print instructions to one or more 3D printing devices through a slicer / printer synchronization device, device, or pipeline. Many hardware and / or software architectures are suitable for generating and managing a queue of slice files that instruct, for example, a stereolithography 3D printing apparatus. In some examples, the process modeling application described herein communicates print instructions to one 3D printing device. In other examples, the process modeling application described herein communicates print instructions to multiple 3D printing devices in a serial or parallel manner. 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.

[0163] Reference Figure 22 In a particular implementation, the slicer / printer synchronization architecture includes a print editor 2205 of a presentation module of a process modeling application. In this implementation, 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 that is sent to a file server 2225 for coordination with a 3D printer 2230 through a “latest slice signal.” Further, in this implementation, the printer 2230 generates a sent “slice continue signal” through a synchronization gate 2230 that generates an “iteration signal” to form a feedback loop to the slicer 2215. In various examples, the slicer 2215 and / or the file server 2225 can be separate devices, can be combined with one another, and / or can be integrated with the 3D printer 2230.

[0164] Semi-continuous printing: brick printing process

[0165] In some examples, the 3D printing device described herein includes control circuitry configured to control at least a light engine, a movable stage, and a print stage to enable stereolithography 3D printing. In further examples, the control circuitry is configured to control the print stage to move at a predetermined constant speed in 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 X-Y plane.

[0166] In various examples, the 3D printing apparatus described herein includes control circuitry configured to control at least the light engine, the movable stage, and the printing stage to implement a stereolithography 3D printing in a semi-continuous, substantially continuous, or continuous mode. In particular examples, the 3D printing apparatus described herein is configured to perform a semi-continuous printing process. In further examples, the semi-continuous printing process includes a brick printing process.

[0167] 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 X-Y plane to scan the lux light beam in a predefined pattern. Numerous patterns are suitable for scanning the lux light beam, including, by way of non-limiting examples, a row-by-row pattern, a column-by-column pattern, a cross-hatch pattern, and a pattern dictated by the geometry of the 3D object / scene to be printed. In some examples, the predefined pattern includes a continuous space-filling curve. In further examples, the predefined pattern includes a Sierpinski curve. In some examples, the predefined pattern is substantially a spiral pattern or is a spiral pattern.

[0168] In some examples, the printing process is based on a plurality of technical points. In these examples, one point is the movement of the piezoelectric stage in the X-Y plane for scanning the light beam underneath the printing bed. In such examples, another point is the number of frames per second (fps) of the projected image. In such examples, there is also a point of the movement of the printing stage along the Z axis at a predetermined constant speed.

[0169] In particular examples, the process includes scanning the light beam in a spiral manner, as shown in Figure 24 In further particular examples, the exposure time of each frame is defined by the number of sub-pixels involved in the printing area. By way of non-limiting example, if the number of sub-pixels is 9, the first frame will expose the resin at 1 / 9 of the time per frame, the second frame at 2 / 9, and so on until it completes the last frame. In such examples, the process is repeated for each pixel that is illuminated. In some examples, the scanning of the illumination pattern is delivered by the piezoelectric stage moving in the X-Y plane by 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 pm per side, by way of non-limiting example. In this example, by virtue of the scanning, the advantages of the continuous printing method and the static setup can be leveraged to “write” on the resin at very high resolution. In some examples, the printing bed has a bottom material that is semi-permeable and / or substantially permeable to oxygen. In such examples, the permeability of the printing bed to oxygen allows for the inhibition of the polymerization reaction. Figure 24 A piezoelectric movement in a spiral path is shown.

[0170] Figure 25A A neutral positioning of the piezo stage in the X-Y plane is shown, where there is no pixel displacement due to light scanning. Figure 25B A right positioning of the piezo stage in the X-Y plane is shown, which generates a left pixel displacement due to light scanning. Figure 25C A left positioning of the piezo stage in the X-Y plane is shown, which generates a right pixel displacement due to light scanning. Figure 26 A series of steps during an example tile printing process is shown.

[0171] Example 3D printing device implementation

[0172] Reference Figure 27 In a particular implementation, light from the light engine 2701 is projected to the collimator 2702. After passing through the invasive collimator, the light reaches the single piece MLA 2703. The single piece MLA 2703 focuses the collimated light beam, resulting in a final light beam of smaller diameter. In this implementation, this is the key pillar of the resolution enhancement of the static optical setup described herein. Depending on the required printing resolution, the area of one pixel can now be subdivided into, for example, 9, 25, or 49 sub-pixels, or even up to 7498 sub-pixels, and any increment between 4 and 7498. Once the light beam is focused by the MLA 2703, the light scanning is performed by the movement of the piezo stage 2704 in the X-Y plane of the lens. The piezo stage 2704 enables the light beam to scan a larger area. The diameter of all the sub-pixels is magnified and projected on the build plate window 2706 within the scanned area by a series of three projection lenses 2705. This conformation and magnification is produced by the projection lenses 2705 located after the MLA 2703 in the light path. In this example implementation, the final printed area is estimated to be about 4 times the initial area of 90 mm x 85 mm. The printing build plate contains the light-cured resin 2707. When the light-cured resin 2707 is activated by the UV light of the light engine, the printed result 2708, for example a 3D object, is generated layer by layer on the print bed 2709, and the print bed 2709 is advanced upwards on the guide rails 2710 by a screw 2711 driven by a stepper motor 2710.

[0173] Light engine

[0174] In some examples, the 3D printing apparatus described herein includes 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 light-cured resin in a print tray.

[0175] The first example light engine method described herein is based on DMD technology. In some examples, the method uses an industrial UV projector (lux beam) operating at 405 nm or 380 nm. The light engine illuminates the optical path to a tray containing a photosensitive resin. In further examples of the method, spatial modulation of the light is performed by a DMD, which consists of an electromechanical device based on an array of micron-sized mirrors on an aluminum base. The light is projected onto the micro-mirrors by a UV LED and is reflected by the activated mirrors. Each mirror has two states: “on” and “off”. When they are on, they can reflect the incident light. Each micro-mirror represents a pixel. In some examples of this method, the pixel pitch of the DMD is 5.4 pm. In some examples, the working distance of the light engine is 177.8 mm, corresponding to a pixel pitch of, for example, 35 pm, with an area of 90 x 50 mm 2 . In one implementation, the lux beam has a resolution of 2560 x 1600 pixels and an output of 7 W. In some examples, the irradiance of the lux beam at the working distance is 150 mW / cm 2 . Figure 28 A non-limiting example of a suitable lux beam is shown.

[0176] The second example light engine method described herein is based on LCoS technology. In some examples, the LCoS is responsible for spatial light modulation (based on amplitude). In further examples, the LCoS includes an LCD panel on top and a mirror on the backplane. The LCD enables pixels, where incident light can hit the back mirror and be reflected into the optical path up to the tray. In examples, the pixel pitch of the LCoS can be 3.5 pm and can have a resolution of 4K x 2K (4096 x 2400) pixels. Figure 29 An example of a suitable LCoS is shown.

[0177] In some examples, the 3D printing apparatus described herein includes 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 a photocurable resin in a print tray. 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 improve the fidelity and accuracy of the printed object.

[0178] collimator

[0179] In some examples, the 3D printing apparatus described herein includes a collimator. In some examples, the collimator includes one or more collimating lenses. A collimator is an optical lens or multiple lenses that converts an incident divergent light beam into a parallel light beam. A lux beam has a non-collimated beam. Beam collimation is necessary to ensure a uniform distribution of light intensity. Many optical arrangements of collimating lenses are suitable. In some examples, the collimator includes a single collimating lens. In other examples, the collimator includes multiple collimating lenses. In some examples, the multiple collimating lenses include, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more collimating lenses arranged in a collimating lens assembly or system.

[0180] Microlens Array (MLA)

[0181] In some examples, the 3D printing devices described herein include an MLA. In some examples, the MLA is an optical device that includes a square-packed array of micron-sized lenses (see, e.g., Figure 30A The MLA can be located within, before, or after the light engine. Many types of microlenses are suitable for use with the MLA and determine the array's properties. As non-limiting examples, the MLA includes a biconvex array, a biconcave array, a single convex array, a single concave array, or a combination thereof. In a particular embodiment, the MLA includes a monolithic biconvex array.

[0182] refer to Figure 30B In a particular embodiment, the MLA comprises a planar substrate with a first microlens array MLA1 affixed to one side and a second microlens array MLA2 affixed to the opposite side. In this embodiment, a polymer layer is also positioned between the substrate and each microlens array on either side of the substrate. Furthermore, in this particular embodiment, the MDA is positioned between the substrate and one of the microlens arrays (e.g., MLA2).

[0183] Many materials are suitable for the substrate, including, as non-limiting examples, borosilicate, etched glass, or combinations thereof. Similarly, many materials are suitable for the microlens, including, as non-limiting examples, polymers, glass (e.g., float borosilicate glass or other highly transparent glass capable of withstanding thermal stress) or combinations thereof. In particular embodiments, the main substrate is made of borosilicate, while the microlenses are made of a polymeric material.

[0184] With reference to Figure 30C In particular embodiments, each light beam focuses each pixel of the lux light beam through the path of the MLA facing the lens.

[0185] In various examples, the MLA subdivides each pixel of the lux light beam into 4 to 7498 subpixels. For example, in various examples, the MLA subdivides each pixel of the lux light beam into about 4, 8, 32, 64, 128, 256, 512, 1024, 2048, 4098 or more subpixels, including increments therein.

[0186] In a particular example embodiment, the MLA comprises a monolithic lenticular microlens array, each microlens having a pitch of 30 pm. In this particular embodiment, the dimensions of the MLA are: L: 139.12 mm, W: 88.24 mm, and H: 1.1 mm. Further, in this embodiment, the radius of curvature (ROC) is estimated to be 130 pm, and the sagittal height is 1.5 pm. Finally, in this example, the MLA subdivides each pixel of the lux light beam into 9, 25, or 49 subpixels.

[0187] Microdiaphragm array (MDA)

[0188] In some examples, 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 cross-talk between the light beams passing through the lenses of the MLA. In such examples, the micro-diaphragms of the one or more MDAs are numbered and aligned to correspond to the micro-lenses of the MLA. In some examples, each micro-diaphragm of the one or more MDAs has an aperture size of about 5, 10, 15, 20, 25, 30, or more pm, including increments therein. In other examples, each micro-diaphragm of one of the plurality of MDAs has an aperture size of less than or equal to about 30, 35, 30, 15, 10, 5, or less pm, including increments therein. Reducing the aperture size of the micro-diaphragms of the one or more MDAs can increase contrast and provide higher resolution printing. However, reducing the aperture size of the micro-diaphragms of the one or more MDAs can also reduce the amount of energy provided to the resin for polymerization. Accordingly, in some examples, each micro-diaphragm of the one or more MDAs has an aperture size of about 5 to 10, 5 to 15, 5 to 20, 5 to 25, 5 to 30, 10 to 15, 10 to 20, 10 to 25, 10 to 30, 15 to 20, 15 to 25, 15 to 30, 20 to 25, 20 to 30, or 25 to 30 pm. In examples, each micro-diaphragm of the one or more MDAs has an aperture size of from about 10 to 15 pm.

[0189] In some examples, the 3D printing devices described herein include one MDA. In some examples, the 3D printing devices described herein include a plurality of MDAs. The 3D printing devices described herein suitably include 2, 3, 4, or more MDAs. Many locations within the static optical assembly are suitable for MDAs. As non-limiting examples, the MDAs can be located within the MLA and / or elsewhere within the assembly. In some examples, the MDAs can be located between the planar substrate of the MLA and one or both of the plurality of micro-lenses of the MLA. In some examples, the MDAs and the MLA can be arranged adjacent to one another. In some examples, the MDAs and the MLA can be arranged adjacent to one another and arranged adjacent to the LCoS. In another example, the MDAs and the MLA can be arranged at a location in the lux beam path away 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 with a large operating temperature range and high transmission at the wavelengths used, such as 33borosilicate glass.

[0190] Figure 54An example 3D printer optical configuration with MDA and MLA is shown. 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 can be directed to a polarizing beam splitter (PBS) 5402. The PBS 5402 can direct the light to a waveplate (e.g., quarter waveplate) 5403. The optics can also include an MDA 5404 and an MLA 5406 disposed between the waveplate 5403 and the LCoS 5406. In examples, the MLA 5405 can be disposed between the MDA 5404 and the LCoS 5406. The light beams can pass through the waveplate 5403, the MDA 5404, and the MLA 5405 to reflect from the back of the LCoS 5406 and return through the MLA 5405, the MDA 5404, and the waveplate 5403 as a plurality of discrete light beams. Upon contacting the PBS 5402, the light beams can be reflected at an angle of incidence of at least about 45, 60, 90, 135 degrees. In examples, the light is reflected by the PBS 5402 at an angle of about 90 degrees. The reflected light can pass through one or more projection lenses 5407 to generate microdots 5409 on one side of a print bed window 5408. The microdots 5409 can allow resin to polymerize in contact with or in the vicinity of the print bed window 5408.

[0191] movable stage

[0192] In some examples, the 3D printing apparatus described herein includes a movable stage. In further examples, the movable stage has an operating principle based on the piezoelectric effect, e.g., a piezoelectric movable stage. In some examples, the movable stage is configured to translate one or more projection lenses in the X-Y plane with nanometer resolution in order to scan the lux light beam over the printing area.

[0193] Many travel ranges are suitable for the movable stages described herein. As non-limiting examples, suitable travel ranges include about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 pm or more in the X direction, including increments therein. As non-limiting examples, suitable travel ranges include about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 pm or more in the Y direction, including increments therein. In some examples, the movable stage is a piezoelectric stage and has a travel range of 100 pm in the X direction and 100 pm in the Y direction. In further specific examples, the operating frequency is in the kHz range.

[0194] Many travel increments are suitable for the movable stage described herein. As non-limiting examples, suitable travel increments include about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 nm or more in the X direction, including increments therein. As further non-limiting examples, suitable travel increments include 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 pm or more in the X direction, including increments therein. As non-limiting examples, suitable travel increments include about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 nm or more in the Y direction, including increments therein. As further non-limiting examples, suitable travel increments include 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 pm or more in the Y direction, including increments therein.

[0195] In some examples, the travel (translation) resolution of the movable stage in the X, Y, or both X and Y directions is less than or equal to the length of the sub-pixels into which each pixel of the light engine is divided.

[0196] Figure 31 Non-limiting examples of suitable piezoelectric stages are shown.

[0197] Projection lens

[0198] In some examples, the 3D printing apparatus described herein includes one or more projection lenses. In further examples, the 3D printing apparatus described herein includes one projection lens. In some examples, the 3D printing apparatus described herein includes a plurality of projection lenses, as non-limiting examples, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more projection lenses. In such examples, the projection lenses can be arranged into a projection lens assembly or system.

[0199] In some examples, the one or more projection lenses are a concentric set of lenses whose primary purpose is to configure the final conformation of the light beam to ensure good distribution of energy and light beam spatial quality at the printing vat. The projection lenses are composed of aspherical lenses designed to meet the quality requirements of a specific printing resolution. In some examples, the one or more projection lenses expand the final printing area. In some examples, the one or more projection lenses expand the final printing area to about 2X, 3X, 4X, 5X, 6X, 7X, 8X, 9X, 10X, 20X, 30X, 40X, 50X, 60X, 70X, 80X, 90X, 100X, or more of the light generating area of the light engine, including increments therein. In some examples, the one or more projection lenses reduce the final printing area.

[0200] Printing vat

[0201] In some examples, the 3D printing apparatus described herein includes a printing vat. In some examples, a vat is a container of photosensitive resin used in a stereolithography 3D printing process. In some examples, the material at the bottom of the vat is permeable or semi-permeable to oxygen to enable termination of photopolymerization. In some examples, the printing vat is configured for aseptic 3D printing and the photocured resin is maintained in an aseptic state. The printing vat can include one or more optically transparent surfaces (e.g., a vat window). The one or more optically transparent surfaces can allow a lux light beam to be transmitted from a light engine through a portion of the printing vat to polymerize photocured resin. Non-limiting examples of optically transparent surfaces (e.g., a vat window) include glass or optically transparent polymers, such as cyclic olefin copolymers.

[0202] Second wave generator

[0203] In some examples, the 3D printing device can include a second wave generator. The second wave generator can be disposed adjacent to an end of the optically transparent surface of the print bed (e.g., disposed adjacent to an end of the bed glass). The second wave generator can project a light beam to an end of the optically transparent surface of the bed (e.g., the bed window) such that the light beam undergoes total internal reflection within and along the long dimension of the optically transparent surface. The total internal reflection can generate an evanescent field that is transmitted outside of the optically transparent surface and through the resin disposed adjacent to the optically transparent surface. The evanescent field can reduce, substantially prevent, or prevent polymerization of the photocured resin disposed adjacent to or in contact with the surface of the print bed to reduce or prevent the polymerized resin from adhering to the surface of the print bed window. The evanescent field can reduce or prevent polymerization within a range of about 10, 20, 30, 50, 75, 100, 125, 150, 200, or more nanometers from the surface of the print bed window. In examples, the evanescent field reduces or prevents polymerization within about 100 nm of the optically transparent surface of the print bed. The air incident angle and critical refraction angle of the wavelength of light projected to the optically transparent surface (e.g., the bed window) and internally reflected to allow total internal reflection can be determined by Equations 1 and 2.

[0204]

[0205] where n R is the refractive index of the resin, n G is the refractive index of the optically transparent surface (e.g., the bed window), and n A is the refractive index of air. The wavelength of the light beam can be any wavelength of light that reduces or inhibits polymerization. For example, the wavelength of the light beam can be a UV wavelength (e.g., from about 350 to about 450 nm) or can be a red wavelength (e.g., from 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 more nm, including increments therein. In examples, the wavelength of the light beam can be from about 375 nm to 400 nm. In another example, the wavelength of the second light beam can be from about 600 nm to 650 nm. The wavelength of the light beam can be greater than or less than but not equal to the wavelength used to polymerize the resin.

[0206] Figure 55A and Figure 55B An example schematic of a 3D printer device including a secondary wavelength generator is shown. Reference is made toFigure 55A Light from the light engine 5501 is projected to the collimator 5502. After passing through the invasive collimator, the light reaches the MLA 5503. The MLA 5503 focuses the collimated beam, resulting in one or more beams of smaller diameter. Once the beam is focused by the MLA 5503, the light scanning is performed by the movement of the piezoelectric stage 5504 in the X-Y plane of the lens. The piezoelectric stage 5504 enables the light beam to scan a larger area. The diameter of all sub-pixels is magnified and projected onto the vat window 5506 within the scanned area by a series of three projection lenses 5505. This conformation and magnification is created by the projection lenses 5505 located in the optical path after the MLA 5503. The printing vat contains a photocurable resin 5507. As the photocurable resin 5507 is activated by the UV light of the light engine, a printed result 5508, such as a 3D object, is generated layer by layer on the print bed 5509, and the print bed 5509 is advanced upwards on the guide rails 5510 by a screw 5511 driven by a stepper motor 5512. The 3D printing device includes a second wave generator 5513 configured to project a light beam 5514 through the long dimension of the vat window 5506. Figure 55B An enlarged schematic of the interface of the second wave generator 5512 and the vat window 5506 is shown. The light beam 5513 projected through the long dimension of the vat window 5506 experiences total internal reflection to generate an evanescent field that reduces or inhibits polymerization of resin in contact or adjacent to the surface of the vat window 5506. The light source of the light beam 5513 can be an LED or a laser. The second wave generator can include one or more lenses configured to shape or direct the light to allow for total internal reflection of the light beam 5513.

[0207] Printed vat coating

[0208] In some examples, the 3D printing device can include one or more coatings disposed on the vat window or other surface of the printing vat to reduce, substantially prevent, or prevent the polymerized resin from adhering to the vat window. The coating can be any coating type that inhibits polymerization at the interface or otherwise includes anti-adhesion properties. In examples, the coating is a mesoporous coating. The mesoporous coating can include one or more base compounds such as, but not limited to, a metal oxide, silica, organosilica, carbon, metal-organic framework, zeolite, 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.

[0209] The coating can have any thickness that can be used to reduce or prevent adhesion of the polymeric 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 to 10, 5 to 25, 5 to 50, 5 to 75, 5 to 100, 5 to 125, 5 to 150, 5 to 175, 5 to 200, 10 to 25, 10 to 50, 10 to 75, 10 to 100, 10 to 125, 10 to 150, 10 to 175, 10 to 200, 25 to 50, 25 to 75, 25 to 100, 25 to 125, 25 to 150, 25 to 175, 25 to 200, 50 to 75, 50 to 100, 50 to 125, 50 to 150, 50 to 175, 50 to 200, 75 to 100, 75 to 125, 75 to 150, 75 to 175, 75 to 200, 100 to 125, 100 to 150, 100 to 175, 100 to 200, 125 to 150, 125 to 175, 125 to 200, 150 to 175, 150 to 200, 175 to 200 nm. In an example, the coating has a thickness of about 25 to 100 nm. The coating can have pores with a diameter of about 2 to 50 nm. The inter-pore distance can vary from about 5 to 10, 5 to 15, or 5 to 20 nm. In an example, the inter-pore distance ranges from 5 to 20 nm. The coating can have a contact angle of at least about 10, 15, 20, 25, 30, 40, 50, or 60 degrees. In an example, the coating has a contact angle of at least about 25 degrees.

[0210] Figure 56A and Figure 56B An example schematic of a 3D printer device including a coating on a vat window is shown. Referring to Figure 56A Light from the light engine 5601 is projected to the collimator 5602. After impinging on the collimator, the light reaches the MLA 5603. The MLA 5603 focuses the collimated light beam, resulting in one or more beams of smaller diameter. Once the light beam is focused by the MLA 5603, the light scanning is performed by the movement of the piezoelectric stage 5604 in the X-Y plane of the lens. The piezoelectric stage 5604 enables the light beam to scan a larger area. The diameter of all sub-pixels is magnified and projected on the vat window 5606 within the scanned area by a series of three projection lenses 5605. This configuration and magnification are produced by the projection lenses 5605 located in the light path after the MLA 5603. The printing vat contains the photocurable resin 5607. As the photocurable resin 5607 is activated by the UV light of the light engine, a printed result 5608, such as a 3D object, is generated layer by layer on the print bed 5609, and the print bed 5609 is advanced upwards on the guide rails 5610 by a screw 5611 driven by a stepper motor. The 3D printing device includes a coating 5612 disposed on the surface of the vat window 5606.Figure 56B An enlarged schematic of the interface of the coating 5612 and the tray window 5506 is shown. The coating 5512 is disposed on the surface of the tray window 5506 that contacts the resin. The coating can reduce or prevent the polymeric resin from adhering to the surface of the tray window 5606.

[0211] Print bed (table)

[0212] In some examples, the 3D printing apparatus described herein includes a print bed. In some examples, the photocurable resin is photopolymerized on the surface of the print table. The print table is articulated to move along the Z-axis under the control of an electrical circuit to effect the printing process. For example, the print table can be assembled on a guide rod and mounted to a screw rod driven by a stepper motor. In some examples, the 3D printing apparatus described herein uses a bottom-up printing method, and the print table is correspondingly moved in the Z-axis. In some examples, the 3D printing apparatus described herein uses a top-down printing method, and the print table is correspondingly moved in the Z-axis.

[0213] Example 3D objects / scenes

[0214] The platforms, systems, and apparatuses provided herein (collectively, “printer systems”) are suitable for printing of porous structures based on crystal geometries that are spatially distributed in a periodic manner. In examples, the printer systems are used to generate such structures. In some examples, the crystal geometries can include or be based on a unit cell. The unit cell can include a shape. The shape of the unit cell can be any shape, such as those described elsewhere herein. In examples, the shape of the unit cell can include a helix, a double helix, or a modified helix or a modified double helix. For 3D printing purposes, in some cases, a helix can be a suitable geometry because it is self-supporting, avoiding the addition of external support for the fabrication of a 3D object that includes the structure. In some examples, the porous structure includes channels ranging from 150 pm to 600 pm in diameter and intermembrane spaces (e.g., separating two independent electrical circuits of material) ranging from 200 pm to 400 pm at their thinnest points. In these examples, to obtain a sufficient level of detail, 15 pm of voxels are needed per edge to ensure a smooth termination on the 300 pm size scale of the structure. The smaller the voxels, the smoother the surface on a macroscopic scale.

[0215] The printer systems provided herein can also be suitable for printing of bioreactors. In some examples, the printer systems are used to generate bioreactors, such as miniaturized bioreactors. In some examples, the bioreactor is composed of a plurality of microscale modules. Each microscale module can have a shape, and the microscale modules can be arranged, i.e., printed, into a macrostructure. Examples of such bioreactors having various macrostructures and microscale modules are also provided herein. The bioreactors provided herein include various macrostructures, various microscale modules of different shapes, and various features detailed elsewhere herein. Methods of making and using such bioreactors are also provided herein.

[0216] In some examples, the printer systems herein can generate microscale modules of defined dimensions, e.g., such that one or both channels of a structure (e.g., a microscale module and / or a plurality of microscale modules incorporated into a macrostructure, such as a bioreactor or a layer of a bioreactor) accommodate flow of a set size of objects (e.g., flow of biological organisms and cells). In one embodiment, at least one channel of the structure is configured to limit the number of cells flowing through the channel at any point, e.g., flow of a single cell, rather than 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 pm and about 100 pm. In some examples, the cells are prokaryotic cells and the single cells are between about 0.5 pm and about 5 pm. In some examples, the cells are microorganisms, e.g., bacteria, yeast, fungi, and the cells are between about 0.5 pm and about 30 pm, or between about 3 pm and about 30 pm. In some examples, the cells are eukaryotic cells and the single cells are between about 10 pm and about 100 pm, or between about 10 pm and about 30 pm.

[0217] In some examples, the microscale modules can be printed to have a channel diameter of about 8 pm to 2000 pm. In some examples, the microscale modules are printed to have an edge of 40 pm to 9797 pm. In examples herein, the microscale modules are printed to have a volume of about 68417 to 9.4 x 1010 11 cubic microns.

[0218] In some examples, the micro-modules can have a regular cubic wrapping structure with edges of length "L". L can be related to the scan diameter. In some examples, L is equal to two-thirds of the scan diameter of the microchannel, multiplied by the square root of two, multiplied by the square root of three. If the radii of two components within a micro-module are the same, the total surface area and total volume of the microchannel corresponding to the liquid component can be equal to the respective dimensions of the gas component. In some examples, the radii of the components can be different. In some examples, when the two radii are equal, the microchannel radius cannot be greater than 0.7 times the scan radius. The shortest distance between two micro-modules of two different faces is equal to the scan radius multiplied by the square root of two, minus the sum of the radii of each component channel.

[0219] In some examples, the area of the first channel with the DG can be equal to the area of the second channel within the DG, and wherein the area of the matrix phase is the sum of the area of the first channel and the area of the second channel. The distance between the matrix phase separating the channels and the center of each channel is constant.

[0220] In some examples, the printer system can print a series of micro-modules in a macrostructure. In some examples, the micro-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 micro-modules can be arranged in layers within the macrostructure. The combination of interconnected micro-modules of the same orientation is referred to as a "layer". For example, the layer can be arranged in a diamond shape such that, in some examples, if the same number of modules are connected in a selected orientation, the resulting growth is disproportionate, so the growth of the layers is irregular with respect to each other. In some examples, the layer is arranged in a square or such that the resulting growth is proportional.

[0221] In some examples, the components of a micro-module layer ("first matrix") can be co-located with a second set of components of a micro-module layer ("second matrix"), whereby the second matrix occupies the free space left by the first matrix, so that the matrices of the same volume have no contact points and maintain a constant minimum distance.

[0222] In some examples, the micro-modules can be assembled into a hollow-pyramid macrostructure. In some examples, the hollow-pyramid macrostructure can fabricate a hollow-pyramid bioreactor provided elsewhere herein. The hollow-pyramid can have a hollow volume and an increasing cross-section. In some examples, the inter-layer volume of the hollow-pyramid can increase (this is the number of micro-modules added between a layer and the next layer in the direction of flow) and is ordered by (i) the alternating growth sense between the edges of its outer perimeter; and (ii) its inner perimeter (i.e. the perimeter of the internal hollow). For example, if N is the number of modules of one of the edges of the outer perimeter of the hollow-pyramid, and n is the number of micro-modules that make up one of the edges of the inner perimeter of the hollow-pyramid, then if at a layer, N = (8; 8), then n = (4; 4). This logic repeats alternately between the outer edges of the pyramid at each layer and in the clockwise direction (considering the direction of flow). The result is a stepped pyramid, whose steps form a multi-faceted spiral. The inner perimeter also spirals, but at a lower frequency than the outer perimeter, and in the opposite direction to the outer perimeter.

[0223] In some examples, provided herein are methods and systems (e.g., 3D printing devices, other systems, such as hardware, software, and any methods, systems, or materials provided elsewhere herein) for generating a layered macrostructure. In some examples, the layered macrostructure can be used as a layered bioreactor. In some examples, the bioreactor employs a layered macrostructure composed of a plurality of micro-modules. The micro-modules can be DGS or can include other shapes. The layered macrostructure has a sheet of constant thickness and increasing cross-section composed of micro-modules. The constant thickness of the layering allows for uniform access of materials into the bioreactor, such as from a feed circuit. The increase in inter-layer volume (this is the number of modules added between a layer and the next layer in the direction of flow) can be determined by the bioreactor and can be ordered by the alternating growth sense between the shortest edges of the sheet. In the layered macrostructure, there can be one or more than one sheet, such as 2, 3, 4, 5, 6, 7, 8, or more than 8 sheets arranged in parallel. The space between each sheet can be used to place a feed circuit or portions of the modules in its feed sheet.

[0224] In some examples, the methods and systems provided herein can be used to make a tree, such as a checkerboard macrostructure. The checkerboard macrostructure can be fabricated into a checkerboard bioreactor. In some examples, micro-modules of any shape (e.g., DGS or any other micro-module shape provided elsewhere herein) can be assembled into a tree-shaped checkerboard macrostructure that has at least one hollow column of constant cross-section that runs longitudinally through the layers of micro-modules. In some examples, the tree-shaped checkerboard macrostructure has 1, 2, 3, 4, or more than 4 such columns. The columns can be used to provide a region to transport liquid media and other materials through a channel along the longitudinal column.

[0225] In some examples, the 3D printing systems and methods provided herein, e.g., printer systems, can provide the ability to print a continuous printable surface with high resolution, e.g., to build a bioreactor with a macrostructure comprising repeating micro-modules. In some examples, the printed surface can be up to about 320 mm x 320 mm. In some examples, the printed surface is up to about 320 mm x 320 mm, with each 1 x 1 x 1 mm printed area containing up to about 14.616 micro-modules (e.g., such as a DG or modified DG). In some examples, the printed volume is up to about 320 mm x 320 mm x 1000 mm (X, Y, Z coordinates of the printed volume), and the printed volume contains up to about 1,496,704,035 or fewer micro-modules. Although in many examples, the methods, apparatuses, and systems of 3D printing are used to manufacture bioreactors, such 3D printing methods, apparatuses, and systems can be used to manufacture any object, e.g., any 3D object. Likewise, even though in many examples, reaction vessels such as bioreactors are manufactured using the 3D printing systems and methods described herein, such bioreactors can be manufactured using other methods in other examples.

[0226] Methods for building 3D objects using techniques such as 3D printing, which can include using the methods and systems provided elsewhere herein, are provided herein. In some examples, the methods and / or systems provided herein can be used to build 3D structures that can have various applications. In some cases, the 3D structures to be built or manufactured can include components, assemblies, parts, or units, e.g., sub-units or modules, which in some cases can be assembled to manufacture a structure or object. For example, the 3D object can be a reaction vessel or bioreactor. The bioreactor can be any bioreactor provided elsewhere herein. The bioreactor can include one or more micro-modules. The micro-modules of the bioreactor can be assembled into a macrostructure. The macrostructure can be a macrostructure of a bioreactor provided herein.

[0227] 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, e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more. In examples, the matrix can be a 3D matrix. The space can be a 3D space. In some cases, the matrix can be continuous and ordered, e.g., a continuous and ordered three-dimensional (3D) matrix. The matrix can demarcate the available space in which elements can be placed to functionalize the space according to the requirements of the space they occupy. The methods can be implemented using a computer. A computer system that can be used to perform the methods of the present disclosure is provided herein. In some examples, the methods can include computer- implemented methods, e.g., software, code, or a set of instructions to perform the methods described herein. Such methods can be explained in greater detail elsewhere herein.

[0228] In some cases, the micro-modules can be assembled into structures (e.g., macro-structures) to provide targeted control of media and gas flow and distribution in the structure (e.g., a bioreactor). In other examples, the same approach can be implemented to fabricate multiple components, units, assemblies, modules, or micro-modules to build structures other than reactors or bioreactors. The 3D objects, structures, or modules fabricated using the methods or systems provided herein can include various applications.

[0229] In some examples, the micro-modules can include a shape or structure. The shape or structure can include any of the shapes or structures provided elsewhere herein. In examples, the shape or structure of the micro-module can include a modified double gyroid (DG), which can be assembled into a macro-structure to produce a production bioreactor provided herein. Figures 33A to 33F An example is shown of assembling from a first micro-module (e.g., a DG) and assembling additional micro-modules such that the geometry is repeated to form a three-dimensional (3-D) matrix, the growth of which can be limited to two of the three possible dimensions. The connection point from one micro-module to another micro-module can be referred to as a “mouth.” A first assembly of interconnected micro-modules that can be identically oriented is referred to as a “layer.” For example, the layer can be arranged in a diamond shape such that in some examples, 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 with respect to one another. In some examples, the layer can be arranged in a square or such that the resulting growth is proportional. Figure 37A and 37B An example of layer assembly and growth is shown. Layer assembly and growth can occur in any direction.

[0230] Micro modules can be building blocks of larger structures of bioreactors. Micro modules can be constructed by assembling multiple smaller units, e.g., voxels or monomers, which can be voxels that can be used to define a space or a structure in a space. Monomers can comprise shapes. Shapes of micro modules can comprise any shape, e.g., any geometric shape and any size. Micro modules can be crystalline units that can be used to arrange or define a space. For example, its space or properties can be defined, structured, or shaped due to the presence or absence of monomers or its location in a space. For example, in a given region of a space, a high density of example monomers or voxels can be provided to define or manufacture a solid object. For example, a large number of monomers or voxels can be located within a small region, thus, the region can be a monomer or voxel dense region and can be defined as or perceived by a user, entity, software, machine, or artificial intelligence (AI) as a solid structure, e.g., a wall with a given thickness. In another example, monomers can be sparse in a given region. In this case, monomers or voxels can be assembled to form a hollow space, a substantially void space, a channel, a hole, etc. For example, multiple monomers of suitable shapes can be assembled to manufacture a micro module or building block, e.g., a pipe, or a hollow chamber, e.g., a hollow chamber of a bioreactor (e.g., chamber 4840). Methods of constructing such constructs are provided herein. Methods of constructing such constructs can be implemented by a computer system, e.g., software components, AI, machine learning, other computer-implemented methods provided herein, and any combination thereof. In some examples, computer-implemented methods can provide a set of instructions (e.g., executable instructions) that can be used by a device provided herein to 3D print a given structure, e.g., a bioreactor provided herein.

[0231] Micro modules can be constructed from assemblies of multiple smaller units, e.g., voxels or monomers. In some examples, micro modules can be composed of unit cells that can be used to define and / or order a space, e.g., a 3D space, according to methods of the present disclosure. Shapes of monomers can belong to a given category. Examples of a category of monomers or unit cells can include primitive, body-centered, face-centered, side-centered, other categories, and combinations thereof. Examples of shapes of monomers can include a cube, a sphere, a rectangle, a pyramid, a helix, a double helix, a triclinic, a monoclinic, an orthorhombic, a trigonal, a hexagonal, or any other geometric shape. Shapes of monomers can comprise a Bravais lattice. Bravais lattices can comprise shapes provided herein. Examples of Bravais lattices and shapes of monomers or unit cells are provided in Table 1.1. Monomers can be used as voxels to order or generate a space and make micro modules.

[0232]

[0233] Table 1.1: Bravais lattices in three dimensions

[0234] A cell or monomer can include one or more elements, in some examples, a finite number of elements. An element can be a set of coordinates that can be imbued with meaning. Examples of elements can include a point, an axis, a proper axis, an improper axis, a center, a plane, or other elements. In some examples, an assembly of monomers and elements can form a structure, such as a macrostructure or a micro module. In examples, such an assembly can form a hollow cylinder that can be configured to allow fluid, such as a gas or a liquid, to flow. For example, an assembly of monomers, elements, and / or their combinations can fabricate a channel, a duct, a chamber, or another micro 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 monomers and elements can form a solid structure, such as a solid wall, a solid block, or other structure.

[0235] In some cases, the arrangement of elements within a monomer (e.g., within a cell or within a crystal) can be important to minimize or avoid as much as possible potential disruptions of functional continuity within a volume or structure (made from an assembly of these monomers and / or elements) under consideration. In some examples, the arrangement of monomers and / or elements can be performed by example mathematical instructions, equations, or formulas, which can include mathematical functions, mathematical operations, and / or mathematical operators. One example of such a mathematical operator can be a symmetry operator.

[0236] Mathematical operators can generally be referred to as mappings or functions that can act on elements of a first space (e.g., a 3D space) to produce elements of another space. In some cases, the second space can be the same as the first space. Operators can include linear mappings that can act on vector spaces. In some cases, operators can preserve properties of spaces and / or elements, such as their continuity. Operators can be linear operators, bounded operators, or other types of operators. Examples of operations that can be performed on elements can include a translation operator, a rotation operator, an inversion operator, a reflection operator, and an identity operator. An example operator that can be used to perform the methods of the present disclosure can be a symmetry operator.

[0237] In some examples, a micro-module of a bioreactor can comprise a double gyroid or a modified double gyroid shape. A double gyroid (DG) comprises two gyroids and can comprise two interpenetrating non-overlapping domains. A modified double gyroid (DG) can comprise two interpenetrating non-overlapping domains that can be bounded by two constant mean curvature (CMC) surfaces separated by a matrix. A modified double gyroid structure can comprise a slight modification to the connections of an unmodified double gyroid in order to adapt the structure to a given macrostructure or function. The modification can comprise blocking a portion of the connection or intersection point (e.g., a "mouth"), modifying the diameter of one or both of the channels of the structure, or completely or partially eliminating any of the channels present in the DG structure. A DG or modified DG can comprise a first gyroid structure interwoven with a second gyroid structure. The two channels can be separated, for example, by a porous membrane.

[0238] In examples, in the bioreactors provided herein, at the edges of each layer, the unconnected mouths of the units (e.g., micro-modules) can be used to connect the layer to other functions, such as for media flow or for input of gas and output of used media (e.g., collection layer 4610 and / or collection channel 4696), used gas (e.g., gas intake channel, gas collection channel, not shown), and output of cells or biological products produced by the cells. In some cases, the output of cells or biological products produced by the cells can be the same as or different from the output of used media.

[0239] In some examples, an assembly of micro-module layers (a "first matrix") can be co-located with a second assembly of micro-module layers (a "second matrix"), whereby the second matrix can occupy the free space left by the first matrix, thus matrices of the same volume can have no contact points and can maintain a constant minimum distance. In further examples, higher order assembly of micro-module layers 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, whereby the one or more subsequent matrices occupy the free space left by the initial matrix, thus matrices of the same volume can have no contact points and can maintain a constant minimum distance. An example assembly of two matrices is shown in Figures 34A to 34F . An example of a portion of a double gyroid inscribed in a cube is shown. Figure 34A An orthogonal cross-sectional view of the structure of Figure 34B is shown. Figure 34A An orthogonal cross-sectional view of the structure of Figure 34C and Figure 34D An example of a second layer relative to the growth direction of a first layer is shown. Figure 34E An example of a volume subtracted from a pyramid and grown counterclockwise is shown. Figure 34F An example of a macrostructure grown in a clockwise direction along the vertical axis of a hollow pyramid is shown.

[0240] Examples of macrostructures

[0241] Hollow pyramid macrostructure

[0242] In some examples, the micromodules can be assembled into a hollow pyramid macrostructure. The hollow pyramid macrostructure can have a hollow volume and an increased cross-section. Using the hollow pyramid macrostructure, the feed circuit can serve both the external and internal perimeters. For the hollow pyramid construction, the matrix can have an initial layer that can be connected to a distributor and layers that can in turn be connected to collectors. The number of upper ports of the initial layer, and the number of lower ports of the layer connected to the collector may belong to the set M = 2 n In this way, the connecting channels or trees can branch in pairs in a balanced manner. The tree can be a distributed structure (input) and a collection (output) of the bioreactor. In some cases, the bioreactor may not have bubbles. In the input and output of the bioreactor and / or its modules, the channels can be transformed or branched from a single channel to multiple channels, for example to 2 n channels. The increase in volume between the layers (this is the number of micromodules added between one layer and the next in the direction of flow) can be determined by the bioreactor and can be ordered by alternating growth between (i) the edges of its outer periphery; and (ii) the increase of its inner periphery (i.e. the periphery of the hollow interior). For example, if N is the number of modules forming one of the edges of the outer periphery of the hollow pyramid and n is the number of micromodules forming one of the edges of the inner periphery of the hollow pyramid, then if in one layer N = (8; 8), then n = (4; 4) (see e.g. Figure 36 ). This logic is repeated alternately between the outer edges of the pyramid in each layer and in a clockwise direction (considering the flow direction). The result can be a stepped pyramid whose steps form a multifaceted spiral. In some examples, the inner periphery can have a spiral growth, in some cases with a lower frequency than the outer periphery, and the growth direction of the inner periphery can be opposite to the growth direction of the outer periphery (see Figure 37A and Figure 37B In some examples, the interaction between the inner and outer spirals and the flow direction can result in vortex-like motion of the flowing medium within the hollow pyramid structure.

[0243] In some examples, the feed system of the bioreactor can be connected to the bioreactor via one or more channels (e.g., subchannels). The subchannels of the feed circuit can surround the perimeter of one or more layers in the bioreactor at an example distance (e.g., equivalent distance) on each side of a given layer. The subchannels can connect to one or more ports of the micromodules that are at the edge of the layer. A set of example connections Figure 38 Shown in.

[0244] In some examples, a feed circuit can be connected to a bioreactor at 1, 2, 3, 4, 5, 6, 7, 8, or more than 8 points. In one example, a feed circuit can serve a hollow pyramid macrostructure bioreactor, and the feed circuit can have a division of 5 subchannels. One or more of these subchannels can extend to the interior of the pyramid interior channel, with the remaining feed subchannels parallel to the edge of each layer (exterior channels). Pressure and flow balance of the feed circuit can be maintained by the ratio of the exterior and / or interior channels of the feed system. An example feed circuit for a hollow pyramid shape is shown in Figure 38 .

[0245] Layered macrostructure

[0246] In some examples, a macrostructure of a bioreactor can be layered. In some examples, a feed system can connect a bioreactor through one or more subchannels. The subchannels of a feed circuit can surround the perimeter of one or more layers in a bioreactor at an equivalent distance on each face of a given layer. The subchannels can connect to one or more ports of a micro module that is an edge of a layer. A set of example connections is shown in Figures 35A to 35F . A subset of matrix gas circuit and matrix feed circuit components are shown in Figure 35E .

[0247] In some examples, a bioreactor can employ a layered macrostructure composed of micro modules. Such micro modules can include any shape or structure. The shape or structure can be according to any shape or structure provided anywhere herein, such as a DG or other shape. A layered macrostructure has a constant thickness and increasing cross section sheet composed of micro modules. The constant thickness of the sheet can allow for uniform or even entry of material from a feed circuit. The increasing interlayer volume (which is the number of modules added between one layer and the next in the direction of flow) can be determined by the bioreactor and can be ordered by alternating growth sense between the shortest edges of the sheet (see, e.g., Figure 39 ). In a layered macrostructure, there can be one or more than one sheet, such as 2, 3, 4, 5, 6, 7, 8, or more than 8 sheets, which can be arranged in parallel or in different configurations. The space between each sheet can be used to place a feed circuit or place one of its parts that can feed the modules in the sheet (see, e.g., Figure 40 ).

[0248] Checkerboard macrostructure

[0249] In some examples, the micro-modules can be assembled into a tree-chessboard macrostructure, which can have at least one constant cross-section hollow column that can span (e.g., longitudinally or along another direction) layers of the micro-modules. In some examples, the tree-chessboard macrostructure can have 1, 2, 3, 4, or more than 4 such columns. The columns can be used to provide regions to transport liquid media and other substances through the channels and / or along other features of the longitudinal columns. Used media, gases, cells, and biological products can be collected on one or more or all of the outer surfaces of the structure, which can be driven by a pressure difference between the column center and the faces or using another technique or force. An example tree-chessboard macrostructure is shown in Figure 41 and example feed and collection arrangements are shown in Figure 42 .

[0250] Spherical macrostructure

[0251] In some examples, the micro-modules can be assembled into a spherical macrostructure. The spherical structure can be used to manufacture a spherical bioreactor. An example of using multiple micro-modules to build a spherical macrostructure is shown in Figure 52 . Multiple micro-modules 5210 are assembled into a 3D spherical macrostructure shape.

[0252] Examples of spherical bioreactors are shown in Figure 46A , Figure 46B and Figure 47 and are described in further detail elsewhere herein.

[0253] Connection system

[0254] The modules can be connected, coupled, or in fluid communication through one or more connection systems. Figure 43A and Figure 43B show that an example connection system 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, which can allow fluid and / or cell-containing fluid to pass in and out. In some examples, the connector is connected 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 multiple sets, such that each set of needles can include a needle for inputting fluid and another for outputting fluid 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, collection device, or another module.

[0255] In some examples, the 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, into which fluid can be directed for input or removed for output.

[0256] 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 apparatus can also include one or more connectors that can connect the modules to each other or to external components, devices, sources, modules, etc. For example, the connectors can connect the cell chip module to one or more fluid sources, such as media, nutritional supplements, chemical inputs, trypsin, wash solutions / buffer solutions, which can be used to provide fluid to the cell chip module and optionally remove used fluid. In some examples, the connectors can connect the cell chip module to a second module, such as a sandbox bioreactor or a production bioreactor, for example, for transferring cells from one module to another.

[0257] In examples, the connection system can also include a cleaning chamber such that the needle can be cleaned and / or sterilized before entering a module, such as a cell chip module. In one example, the cleaning chamber can include one or more chambers (e.g., separate chambers) located at one end of the cell chip module. In some examples, the cleaning chamber can be bounded at a first end by a septum that can contain the cleaning chamber from the environment and the needle can pass through the septum at one end into the cleaning chamber. In some examples, the cleaning chamber can be bounded at a second end by a safety membrane or other boundary that can contain a cleaning or sterilizing fluid (or gas) within the cleaning chamber. In such examples, the connector can be connected to a fluid source at the other end of the needle, such as a fluid source with a cleaning agent or sterilizing agent and a wash solution.

[0258] On the other side of the safety membrane or boundary can be a passageway. Once cleaned and sterilized, the needle can pass through the safety membrane or boundary into the passageway. The passageway can be a media passageway that flows media from the needle to other locations in the cell chip. The passageway can be a cell harvest passageway through which cells present in the chip (e.g., cells grown and propagated in the chip) can be directed to the passageway and then through the needle to a separate module or harvesting assembly. The passageway can be a waste passageway through which used media can be directed and removed from the chip.

[0259] Figure 43C Examples of the connection of the connector system to components containing media, sterilizing agents, and waste collection and sandbox modules are shown. Connection tubes or passageways are connected from the connector system and, in some cases, valves can be utilized to direct fluid from the connector to the appropriate source, collector, or module.

[0260] Figure 43DAn example of a connection system is shown where the needles penetrate a first chamber in the cell chip module, for example for cleaning and disinfecting or other purposes, an example of a connection system during a cleaning process is illustrated, with fluid flow from a component containing disinfectant into a disinfection chamber in the cell chip, and with one of each set of needles to remove used disinfectant.

[0261] Figure 43E An example of a connection system is shown where the needles penetrate a second chamber after cleaning / disinfecting. The first set of needles (left) can be positioned so that the input needles enter the media channel / chamber and can allow new media to flow into the cell chip module. The middle set of needles can be positioned so that one needle is positioned for output of used media and culture waste from the channels in the cell chip module. The third set of needles (right) can be positioned so that only output needles enter the chamber / channel and are positioned to output media and cells from the cell chip module.

[0262] Materials for building bioreactor modules and other printed objects

[0263] The systems, components, and modules described herein can be made of a variety of materials, and these materials can be tailored to the cells being grown and the cell environment being employed. In some examples, the components and modules, or portions thereof, are manufactured by 3D printing using the printing systems herein. The printing can use commercially available resins and ultraviolet (UV) curable biocompatible polymers. In some examples, the biological materials used can include a combination of three sub-components, a biocompatible polymer, a photoinitiator, and a UV absorber.

[0264] Example resins include, but are not limited to, polycaprolactone (PCL), polyethylene glycol (PEG), PEG-diacrylate (PEGDA), polyglycolic acid (PGA), polylactic acid (PLA), polylactic-glycolic acid, polypropylene fumarate (PPF), polyurethane (PU), polyvinyl alcohol (PVA), silk, poly(glyceryl sebacate) acrylate (PGSA), epoxy-based resins, natural polymer-based resins, bioceramic-based resins, alginate-based resins, GelMA-based resins, nanocomposite-based resins, bioink, and cellulose-based resins.

[0265] Computer system

[0266] Reference Figure 32 A block diagram illustrating an example machine describing an example machine is shown that includes at least one processor 3200 (e.g., processing or computing system), where the set of instructions to cause the device to perform or execute any one or more aspects and / or methods for static code scheduling of the present disclosure can be executed.

[0267] The processing device 3200 can include one or more processors 3201, a memory 3203, and storage 3208, which communicate with one another through a bus 3240 and with other components. The bus 3240 can also link a display 3232, one or more input devices 3233 (which can include a keypad, keyboard, mouse, stylus, etc., for example), one or more output devices 3234, one or more storage devices 3235, and various tangible storage media 3236. All of these elements can interface directly or through one or more interfaces or adapters with the bus 3240. For example, the various tangible storage media 3236 can interface with the bus 3240 through a storage media interface 3226. The processing device 3200 can have any suitable physical form, including but not limited to one or more integrated circuits (ICs), printed circuit boards (PCBs), mobile handheld devices (e.g., mobile telephones or PDAs), laptop or notebook computers, distributed computer systems, computing grids, or servers.

[0268] The processing device 3200 includes one or more processors 3201 (e.g., central processing units (CPUs), general purpose graphics processing units (GPGPUs), or quantum processing units (QPU)) that execute functions. The processor 3201 optionally contains a cache memory unit 3202 for temporary local storage of instructions, data, or computer addresses. The processor 3201 is configured to assist in the execution of computer-readable instructions. As the processor 3201 executes non-transitory processor-executable instructions contained in one or more tangible computer-readable storage media, such as the memory 3203, the storage 3208, the storage devices 3235, and / or the storage media 3236, the processing device 3200 can provide the functionality depicted in the components. Figure 32 The computer-readable media can store software that can implement the methods of the present disclosure, and the processor 3201 can execute the software. The memory 3203 can read the software from one or more other computer-readable media (e.g., the mass storage devices 3235, 3236) or from one or more other sources through a suitable interface, such as the network interface 3220. The software can cause the processor 3201 to execute one or more processes or one or more steps of one or more processes described or illustrated herein. Executing such processes or steps can include defining data structures stored in the memory 3203 and modifying the data structures as directed by the software.

[0269] Memory 3203 can include various components (e.g., machine-readable media), including but not limited to a random-access memory component (e.g., RAM 3204) (e.g., static RAM (SRAM), dynamic RAM (DRAM), ferroelectric random access memory (FRAM), phase- change random access memory (PRAM), etc.), a read-only memory component (e.g., ROM 3205), and any combination thereof. ROM 3205 can be used to uni-directionally communicate data and instructions to processor 3201, and RAM 3204 can be used to bi-directionally communicate data and instructions with processor 3201. ROM 3205 and RAM 3204 can include any suitable tangible computer-readable medium described below. In one example, a basic input / output system 3206 (BIOS), including basic routines that help to transfer information between elements within processing device 3200, such as during start-up, can be stored in memory 3203.

[0270] Fixed storage 3208 is optionally bi-directionally connected to processor 3201 through storage control unit 3207. Fixed storage 3208 provides additional data storage capacity and can also include any suitable tangible computer-readable medium described herein. Storage 3208 can be used to store operating system 3209, executable files 3210, data 3211, applications 3212 (application programs), etc. Storage 3208 can also include an optical disk drive, a solid-state storage device (e.g., a flash-based system), or a combination of any of the above. Information in storage 3208 can be incorporated into memory 3203 as virtual memory, where appropriate.

[0271] In one example, storage device 3235 can be removably interfaced with processing device 3200 through storage device interface 3225 (e.g., through an external port connector (not shown)). In particular, storage device 3235 and associated machine- readable medium can 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 can reside completely, or partial, in machine-readable media on storage device 3235. In another example, software can reside completely, or partial, in processor 3201.

[0272] Bus 3240 connects the various subsystems. Herein, reference to a bus can include one or more digital signal lines as appropriate depending on the context in which the bus is used. Bus 3240 can be any of various types of bus structures including, but not limited to, a memory bus, memory controller, a peripheral bus, a local bus, and any combinations thereof, using any of a variety of bus architectures including, but not limited to, Industrial Standard Architecture (ISA) bus, Enhanced ISA (EISA) bus, Micro Channel Architecture (MCA) bus, Video Electronics Standards Association local (VLB) bus, Peripheral Component Interconnect (PCI) bus, PCI-Express (PCI-X) bus, Accelerated Graphics Port (AGP) bus, HyperTransport (HTX) bus, Serial Advanced Technology Attachment (SATA) bus, and any combinations thereof.

[0273] Processing device 3200 can also include input device 3233. In one example, a user of processing device 3200 can enter commands and / or other information into processing device 3200 through input device 3233. Examples of input device 3233 include, but are not limited to, an alpha-numeric input device (e.g., a keyboard), a pointing device (e.g., a mouse or

[0274] In some examples, when the processing device 3200 is connected to the network 3230, the processing device 3200 can communicate with other devices connected to the network 3230, particularly mobile devices and enterprise systems, distributed computing systems, cloud storage systems, cloud computing systems, and the like. Communications to and from the processing device 3200 can be sent through the network interface 3220. For example, the network interface 3220 can receive incoming communications (e.g., requests or responses from other devices) from the network 3230 in one or more packets (e.g., Internet Protocol (IP) packets) and the processing device 3200 can store the incoming communications in the memory 3203 for processing. The processing device 3200 can similarly store outgoing communications (e.g., requests or responses to other devices) in one or more packets in the memory 3203 and transmit the outgoing communications from the network interface 3220 to the network 3230. The processor 3201 can access these stored communication packets in the memory 3203 for processing.

[0275] Examples of the network interface 3220 include, without limitation, a network interface card, a modem, and any combination thereof. Examples of the network 3230 or network segment 3230 include, without limitation, 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, a building, a 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. A network such as the network 3230 can employ wired and / or wireless communication modes. In general, any network topology can be used.

[0276] Information and data can be displayed through the 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 (OLED) (e.g., a passive-matrix OLED (PMOLED) or an active-matrix OLED (AMOLED) display), a plasma display, and any combinations thereof. The display 3232 can interface to the bus 3240 with the processor 3201, the memory 3203, and the fixed storage 3208, as well as other devices such as the input device 3233. The display 3232 is linked to the bus 3240 via the video interface 3222, and data transfer between the display 3232 and the bus 3240 can be controlled via the 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 examples, the HTC Vive, the Oculus Rift, the Samsung GearVR, the Microsoft HoloLens, the Razer OSVR, the FOVE VR, the Zeiss VR One, the Avegant Glyph, the Freefly VR headset, and the like. In some examples, the display is a combination of devices such as those disclosed herein.

[0277] In addition to the display 3232, the processing device 3200 can include one or more other peripheral output devices 3234, including but not limited to audio speakers, printers, storage devices, and any combinations thereof. Such peripheral output devices can be connected to the bus 3240 via the 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 combinations thereof.

[0278] Additionally, or in the alternative, the processing device 3200 can provide functionality as a result of logic hardwired into a circuit, which can operate alone 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. Reference to software in the disclosure can encompass logic and reference to logic can encompass software. Moreover, where appropriate, reference to a computer-readable medium can encompass a circuit (e.g., an IC) storing software for execution, a circuit that comprises logic for execution, or both.

[0279] 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 can be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps have been described above generally in terms of their functionality, without referring to the particular

[0280] The various illustrative logical blocks, modules, and circuits described in connection with the embodiments disclosed herein can be implemented or performed with 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 can be a microprocessor, but in the alternative, the processor can be any conventional processor, controller, microcontroller, or state machine. A processor can also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0281] The steps of a method or algorithm described in connection with the embodiments disclosed herein can be embodied directly in hardware, in a software module executed by one or more processors, or in a combination of the two. A software module can reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, 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 can be integral to the processor. The processor and the storage medium can reside in an ASIC. The ASIC can reside in a user terminal. In the alternative, the processor and the storage medium can reside as discrete components in a user terminal.

[0282] In light of the description herein, suitable processing devices include, by way of non-limiting examples, server computers, desktop computers, laptop computers, notebook computers, subnotebook computers, netbook computers, netpad computers, handheld computers, Internet appliances, mobile smart phones, and tablet computers.

[0283] In some embodiments, a processing device includes an operating system configured to perform operations of executable instructions. For example, an operating system is software, including programs and data, which 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, Linux, Mac OS X Windows and Those skilled in the art will recognize, as non-limiting examples, suitable personal computer operating systems include Mac OS and UNIX-like operating systems (e.g., GNU / Linux ). In some examples, operating systems are provided by cloud computing. Those skilled in the art will also recognize, as non-limiting examples, suitable mobile smartphone operating systems include OS, Research In BlackBerry Windows OS, Windows OS, and non-transitory computer-readable storage medium

[0284] 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, the program including instructions executable by an operating system of an optionally networked computing device. In some examples, the computer-readable storage media is a tangible component of the computing device. In some examples, the computer-readable storage media is optionally removable from the computing device. In some examples, the computer-readable storage media includes, as non-limiting examples, CD-ROMs, DVDs, flash devices, solid-state memory, disk drives, tape drives, optical drives, distributed computing systems (including cloud computing systems and services, etc.). In some cases, the program and instructions are encoded on the media permanently, substantially permanently, semi-permanently, or non-transitorily.

[0285] executable instructions

[0286] In some examples, the platforms, systems, media, and methods disclosed herein include at least one set of executable instructions (e.g., computer programs, computer applications) or use thereof. A computer program includes a series of instructions, executable by one or more processors of a CPU of a computing device, written to perform a specified task. Computer readable instructions can be implemented as program modules, such as functions, objects, Application Programming Interfaces (APIs), data structures, etc. that perform particular tasks or implement particular abstract data types. Those skilled in the art, in light of the disclosure provided herein, will recognize that a computer program can be written in various versions of various languages.

[0287] The functionality of the computer readable instructions can be combined or distributed as desired in various environments. In some examples, a computer program can include one sequence of instructions. In some examples, a computer program includes multiple sequences of instructions. In some examples, a computer program can be provided from one location. In some examples, a computer program can be provided from multiple locations. In some examples, a computer program includes one or more software modules. In some examples, a computer program can include, in whole or in part, 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 can include methods of using multiple micro-modules to build spaces and methods of building structures such as bioreactors, as described in further detail elsewhere herein.

[0288] Web Application

[0289] In some examples, a computer program includes a web application. In light of the disclosure provided herein, those of skill in the art will recognize that, in some examples, a web application uses one or more software frameworks and one or more database systems. In some examples, a web application is created on a software framework such as NET or Ruby on Rails (RoR). In some examples, a web application uses 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, SQL Server, mySQL TM and Those of skill in the art will also recognize that, in some examples, a web application 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 definition languages, client-side scripting languages, server-side coding languages, database query languages, or a combination thereof. In some examples, a web application is 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 examples, a web application is written, to some extent, in a presentation definition language such as Cascading Style Sheets (CSS). In some examples, a web application is written, to some extent, in a client-side scripting language such as Asynchronous JavaScript and XML (AJAX), ActionScript, JavaScript, or In some examples, web applications are written in client-side scripting languages ​​such as Active Server Pages (ASP), Perl, Java TM , JavaServer Pages (JSP), Hypertext Preprocessor (PHP), Python TM 、Ruby、Tcl、Smalltalk、 In some examples, web applications are written in a database query language such as Structured Query Language (SQL). In some examples, web applications are integrated with enterprise server products, such as Lotus In some examples, the web application includes a media player element. In various further examples, the media player element utilizes one or more of a variety of suitable multimedia technologies, including, by way of non-limiting example, HTML 5, Java TM and

[0290] Mobile App

[0291] In some examples, the computer program includes a mobile application provided to the mobile computing device. In some examples, the mobile application is provided to the mobile computing device during manufacture. In some examples, the mobile application is provided to the mobile computing device via a computer network as described herein.

[0292] In view of 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 are written in a variety of languages. Suitable programming languages ​​include, by way of non-limiting example, C, C++, C#, Objective-C, Java, and C++. TM , JavaScript, Pascal, Object Pascal, Python TM , Ruby, VB.NET, WML and XHTML / HTML with or without CSS or a combination of these.

[0293] Suitable mobile application development environments are available from a variety of sources. As non-limiting examples, commercially available development environments include AirplaySDK, alcheMo, Celsius, Bedrock, Flash Lite, .NET Compact Framework, Rhomobile, and WorkLight Mobile Platform. Other development environments are freely available and include, as non-limiting examples, Lazarus, MobiFlex, MoSync, and Phonegap. In addition, mobile device manufacturers distribute software development kits and include, as non-limiting examples, the iPhone and iPad (iOS) SDK, the Android TM SDK, SDK, BREW SDK, OSSDK, Symbian SDK, webOSSDK and Mobile SDK.

[0294] Those skilled in the art will recognize that several commercial forums may be used to distribute mobile applications, including, by way of non-limiting example, App Store, Play, Chrome Web Store, AppWorld, App Store for Palm devices, App Catalog for webOS, Marketplace, for Ovi Store on your device and Apps.

[0295] Standalone application

[0296] In some examples, a computer program includes a stand-alone application, which is a program that runs as an independent computer process, rather than as an add-on to an existing process, e.g., not a plug-in. Those skilled in the art will recognize that stand-alone applications are often compiled. A compiler is a computer program that converts source code written in a programming language into binary object code, such as assembly language or machine code. By way of non-limiting example, suitable compiled programming languages ​​include C, C++, Objective-C, COBOL, Delphi, Eiffel, Java, and many more. TM , Lisp, Python TM , Visual Basic and VB.NET, or a combination thereof. Compilation is typically performed at least in part to create an executable program. In some examples, a computer program includes one or more executable compiled applications.

[0297] Software Module

[0298] In some examples, the platforms, systems, media, and methods disclosed herein include software, server, and / or database modules, or use of the same. In view of the disclosure provided herein, software modules are created using techniques known to those of skill in the art using machines, software, and languages known to the art. The software modules disclosed herein are implemented in a variety of ways. In some examples, a software module comprises a file, a section of code, a programming object, a programming structure, or combinations thereof. In further various examples, a software module comprises a plurality of files, a plurality of sections of code, a plurality of programming objects, a plurality of programming structures, or combinations thereof. In some examples, one or more software modules comprise, by way of non-limiting example, a web application, a mobile application, and a standalone application. In some examples, a software module is in one computer program or application. In some examples, a software module is in more than one computer program or application. In some examples, a software module is hosted on one machine. In some examples, a software module is hosted on more than one machine. In some examples, a software module is hosted on a distributed computing platform, such as a cloud computing platform. In some examples, a software module is hosted on one or more machines in one location. In other examples, a software module is hosted on one or more machines in more than one location.

[0299] Database

[0300] In some examples, the platforms, systems, media, and methods disclosed herein include one or more databases, or use of the same. In view of the disclosure provided herein, those of skill in the art will recognize that many databases are suitable for storage and retrieval of process objects, 3D scenes, signed distance functions, renderings, print, and 3D object information. In some examples, suitable databases include, by way of non-limiting example, relational databases, non-relational databases, object-oriented databases, object databases, entity-relationship model databases, associative databases, XML databases, and document-oriented databases. Other non-limiting examples include SQL, PostgreSQL, MySQL, Oracle, DB2, Sybase, and MongoDB. In some examples, a database is internet-based. In some examples, a database is web-based. In some examples, a database is cloud-computing based. In particular implementations, a database is a distributed database. In some examples, a database is based on one or more local computer storage devices.

[0301] Bioreactor and method of manufacturing a bioreactor

[0302] The apparatuses and systems provided herein, such as apparatuses and systems for 3D printing, can be used to construct multi-dimensional (e.g., 3D) structures of any shape or of any kind that can perform any function. In some examples, the methods and systems provided herein can be used to manufacture bioreactors. Also provided herein are such bioreactors, their structures, designs, morphologies, applications, and methods of manufacturing and using them.

[0303] In some examples, provided herein are reaction vessels, such as bioreactors, and methods of manufacturing such reaction vessels. In some examples, provided herein are systems comprising reaction vessels. The reaction vessels can comprise 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 generate chemicals. In some examples, the reactors can synthesize biological materials. The biological materials can comprise or be cells, components of cells, such as organelles, nuclei, DNA, any intracellular component or material, and / or any combination thereof. In some examples, the reaction vessels or reactors can comprise or be bioreactors. The systems comprising bioreactors can be similar to the systems provided in Application No. PCT / US19 / 55231, which is incorporated by reference herein in its entirety for all purposes.

[0304] The methods of generating reaction vessels, such as bioreactors, can comprise providing a process modeling application. The process modeling application can be according to the process modeling applications provided elsewhere herein, other applications, or any combination thereof. In some examples, the methods of generating reaction vessels, such as bioreactors, can comprise performing a function. The application can be configured to perform the function according to a request or input from a user or independently of a user. For example, performing the function using the process modeling application can comprise artificial intelligence (AI) and / or machine learning implications. In some examples, performing the function can comprise adding a plurality of units to a scene. The units can be according to any of the units provided elsewhere herein. In some examples, the units can comprise modules or micro-modules. For example, micro-modules can be added to a scene. The scene can be any of the scenes described elsewhere herein. In some examples, the scene can be a 3D scene. For example, micro-modules can be added to a 3D scene.

[0305] In some examples, the method of generating a reaction vessel (e.g., bioreactor), for example using a process modeling application, can also include assembling a plurality of units (e.g., micro modules) into a structure to create a reaction vessel or reactor (e.g., bioreactor). The method can also include creating a Constructive Solid Geometry (CSG) tree for the scene, representing the scene (e.g., 3D scene) as a symbolic distance function, rendering the scene by utilizing ray marching, generating a queue of slice files, and transferring the slice files to a stereolithography 3D printing device or other device. The device (e.g., 3D printing device or system) can include or be any of the devices or systems, another device, and / or any combination thereof provided elsewhere herein.

[0306] Provided herein are reaction vessels, e.g., bioreactors, that can be manufactured and used according to the methods of the present disclosure. In some examples, the reaction vessels (e.g., bioreactors) provided herein can include or be systems, assemblies for producing and maintaining cells and for producing and isolating cells and products made from cells. Methods of manufacturing and using such systems are also provided herein. The systems and assemblies and methods can provide flexibility to tailor production for different types of cells, cell environment types, and types of molecules produced. The systems, assemblies, and methods of manufacturing and using them can also provide flexibility in scale. For example, the systems, assemblies, and methods described herein can provide for scaling up production without changing or significantly changing laboratory scale growth conditions.

[0307] In some examples, the bioreactors provided herein can be used to grow cells. The bioreactors can include any size or scale. In some examples, the bioreactors can be micro bioreactor scale such that the system can be constructed as a benchtop bioreactor capable of growing and producing cells and / or cell products in small and large quantities. The system and methods of use have advantages in their scalability, flexibility, and resource conservation.

[0308] In some examples, the bioreactor provided herein can be a bubble-free bioreactor. In some cases, the process carried out in the reactor or bioreactor may benefit from or may need a process for homogenizing the medium in the reactor. In some cases, it may be necessary or beneficial to mix or be equal to mixing to homogenize the reactor contents in a given region. Traditionally, in some cases, in conventional reactors, a mixing method (such as a propeller or bubble) is used to provide homogenization in the reactor. This mixing can produce turbulence in the bioreactor, which can be homogenized and can increase the rate of mass transfer, heat transfer and fluid transmission in the reactor internal area. However, in many cases, turbulence may not be suitable or optimal. Turbulence in the reactor may make it more difficult to precisely control conditions. Therefore, in some cases, it may be beneficial to avoid mixing, bubbles and / or propellers. Provided herein is a bioreactor that can be able to and / or configured to perform their functions in some cases without the need for a propeller or gas or a mixing method that can produce turbulence inside the bioreactor. For example, bubbles and turbulence in the bioreactor can be avoided. In some examples, the bioreactors provided herein include laminar flow throughout the entire process (e.g., a process or reaction performed by the bioreactor, such as cell growth). The internal and external structures, topologies, and properties provided elsewhere herein can make and use bioreactors that can perform their intended functions in laminar flow and may not require bubbles or turbulence for homogenization. In some examples, homogenous laminar flow of gas and / or liquid can be provided in the reactor.

[0309] 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, such as producing or growing cells or performing other functions, individually or in combination. The cells can be any type of cell. Examples of cells can include bacterial cells, fungal cells, yeast cells, eukaryotic cells, plant cells, or algae cells. The cells can be recombinant cells.

[0310] In some examples, the reaction vessel or bioreactor may include or be a production bioreactor module or production layer (e.g., Figure 47 ). A production bioreactor or production level 4696 of a bioreactor can provide an environment for scaling up the growth and production of cells and / or bioproducts from cells or other biological species.

[0311] The reaction vessels provided herein, e.g., bioreactors (e.g., bioreactor 4700 or any other bioreactor provided elsewhere herein) can include a multi-dimensional structure, e.g., a 3D structure that can include one or more (e.g., a plurality) of micro-modules. The bioreactor can include greater than or equal to 1, 2, 4, 6, 8, 10, or more micro-modules, including increments therein. The micro-modules can create one or more (e.g., a series of) channels and chambers for growth and movement of cells and flow of liquid media, gases, and biological products.

[0312] The micro-modules that produce the bioreactor can include a shape, e.g., a geometric shape. Such a geometric shape can include a helix. The helix can include a variety of shapes and / or structures or be implemented in a variety of shapes and / or structures. In some examples, the shape and / or structure can include a crystal structure.

[0313] In some examples, the micro-modules can include a shape such as a double helix, a modified double helix, or any shape that can be described as a three-periodic minimal surface (TPMS). Such a type of surface can form a lattice system that can grow in any direction or any dimension across any coordinate system. For example, the lattice can grow in one or more axes of a Cartesian coordinate system, e.g., X, Y, and / or Z. In some examples, the growth can occur periodically.

[0314] In some cases, a TPMS can have no self-intersection and can divide a given volume into two (or more) independent sub-volumes. A self-intersection can include a surface with a single normal vector at each point, which can define the surface. A surface is called an equational surface if it divides the volume it encloses into two independent and congruent sub-volumes. In some examples, a TPMS can be described in terms of a fundamental patch or asymmetric unit, from which the entire surface can be built by its symmetrical elements.

[0315] In some examples, the micro-modules can be fluidly connected (e.g., interconnected) to one another such that gases, media, and / or byproducts can flow from one micro-module to another micro-module.

[0316] In some examples, the microscale modules of the production bioreactor can include a shape. The shape can be any shape, such as any geometric representation. The shape of the microscale modules can be provided elsewhere herein, such as in Table 1.1. In some cases, the shape can also include a modification or transition. For example, a modification can be made to the shape of the microscale module, its connections, and / or both. The modification or transition of the shape can be small or large. The modification or transition can adapt the structure or shape (e.g., of the microscale module) to a given macrostructure or function. In some examples, the modification 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 a complete or other change in shape.

[0317] In one example, the shape of the microscale modules of the production bioreactor can include or be a double gyroid shape or a modified double gyroid shape. The double gyroid (DG) shape can include two gyroids and / or two interdigitated non-overlapping domains. The modified double gyroid (DG) shape can include two interdigitated non-overlapping domains that can be bounded by two constant mean curvature (CMC) surfaces separated by a matrix. For example, the modified double gyroid structure can include a modification to the connections of the unmodified double gyroid to adapt the structure to a given macrostructure or function. The modification can be small or large. In some examples, the modification can include blocking a portion of a connection or intersection (e.g., a “mouth”), modifying the diameter of one or two channels of the structure, or completely or partially eliminating any channels present in the DG structure shape. The DG or modified DG can include a first gyroid structure interwoven with a second gyroid structure. The two channels can be separated by a porous membrane (matrix phase). The matrix phase can diffuse gas molecules in a manner that is at least partially based on a particular pressure and gas composition. When the liquid and gas composition microchannel radii are equal, the matrix phase surface can equal their sum. When multiple DGs are interconnected (e.g., assembled together), the two CMC surfaces can create two continuous channels. The two channels can create two non-overlapping channels for the flow of liquid media and / or gas. The porous membrane can provide a surface on which some cell types can adhere and grow. In some examples, one channel can provide liquid media throughout the production bioreactor. In some examples, both channels can provide liquid. In some examples, one channel can provide liquid media while the other channel can provide gas to the production bioreactor. In some examples, the diameter of the microscale channels of the microscale modules can vary depending on the particular cell type, production needs, and characteristics, among others.

[0318] In some examples, the micro-modules can have a regular cubic wrapping structure with a length of the edge "L". L can be related to the scan diameter. In some examples, L can equal two-thirds of the scan diameter of the micro-channels, multiplied by the square root of two, multiplied by the square root of three. If the radii of the two components are the same within the micro-module, the total surface area and total volume of the micro-channels corresponding to the liquid component can equal the respective dimensions of the gas component. In some examples, the radii of the components can be different. In some examples where the two radii are equal, the micro-channel radius can be no greater than 0.7 times the scan radius. In some cases, the shortest distance between two micro-modules of two different faces can substantially equal the scan radius multiplied by the square root of two, minus the sum of the radii of each component channel.

[0319] In some examples, the area of the first channel having a DG shape can equal the area of the 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.

[0320] In some examples, for example in a DG shape, the distance between the matrix phase separating the channels and the center of each channel can be a constant.

[0321] The rate at which media and gas flow through a production layer (e.g., production layer 4696 or any other production layer, production layer, or production bioreactor provided elsewhere herein) in a bioreactor of any shape (e.g., a bioreactor having a DG shape or other shape provided elsewhere herein) can be determined by a variety of factors, such as the cell type selected and the cell density, and the stress conditions to be produced on the cells. The rate at which gas diffuses through the matrix into the liquid media can be determined by a variety of factors, such as the gas component and the gas pressure in the gas channels formed by the structure, as well as the membrane thickness and the material selected for fabricating the channels and the perimeter region. The gas flow rate and the working pressure can be related to the density of the cells being cultured. In some examples, the gas flow can equal the volume of the gas component per minute. In some examples, the gas flow can be greater than or equal to about 2, 3, 5, or 10 times the volume of the gas component per minute. In some examples, the working pressure can vary from about 1 atmosphere (atm) to 5 atm. In some examples, the working pressure can be greater than or equal to about 1 atm, 2 atm, 3 atm, 4 atm, 5 atm, or more.

[0322] The shape of the micro modules of the bioreactor can be configured to provide given characteristics. Each shape can include example advantages. For example, an example advantage of a DG shape can be to mitigate gravity, which can provide uneven media exposure and gas exchange in other structures. The DG shape can create three-dimensional (3D) laminar flow such that any variation in cell-to-structure wall distance can be averaged to provide more constant and uniform exposure in the cell population. Further, the DG shape can help avoid stagnant areas of liquid or gas where flow can not occur or can be interrupted. This can allow for higher throughput at lower velocities through the bioreactor and can result in lower shear stress on the cells. This can avoid turbulent flow in the bioreactor. This can enable homogenization while using laminar flow in the bioreactor.

[0323] In some examples, the average fluid velocity of the channels of the bioreactor (e.g., a DG bioreactor) can be greater than or equal to about 1 pm / sec, 3 pm / sec, 5 pm / sec, 10 pm / sec, 15 pm / sec, 20 pm / sec, 50 pm / sec, 100 pm / sec, 200 pm / sec, or more. For example, the DG structure can provide suitable and optimized media and gas diffusion compared to some other bioreactor systems. In some examples, the velocity of the liquid media flowing through the channels within the DG can be greater than the free fall velocity of the cells flowing through the same channels.

[0324] The DG structure of the micro modules can provide increased surface area compared to many other shape selections, and this increased surface area can provide surface area for cell growth as well as improved liquid media flow, mixing, and gas exchange. When L is equal to LI, the surface of each component can be described as Y = 3258.6.XE(-1), where Y is square millimeters / microliters and X is equal to the radius defined by LI.

[0325] In some examples, the micro module structures of the bioreactor (e.g., a DG structure or a structure including any shape provided elsewhere herein) can be assembled together to constitute a macro structure or macro shape that makes up a production bioreactor. The macro structure or macro shape can include any shape, any geometry, any geometric representation, any size, and / or any combination thereof. In some examples, the macro structure can be a cube, a pyramid, a sphere, a cylinder, a multi-dimensional geometry, and / or any combination thereof. As an example, the macro structure can be a hollow pyramid, a layered pyramid, a checkerboard arrangement, a round log, a sphere, or a different shape.

[0326] In some examples, the macrostructure shape and the number of micro-modules within the production bioreactor can be tailored for various factors, such as the rate of cell division of the cells to be grown, the speed of the regulated liquid medium, gas exchange, movement of the cells through the bioreactor, and other factors. Each macrostructure can provide different possibilities for interaction with the cells, and can be selected according to the particular process the production bioreactor intends to perform.

[0327] Example bioreactors can include macrostructure shapes. For example, a plurality of micro-modules can be assembled to form a macrostructure. The macrostructure can have various shapes. The macrostructure can be a sphere, a pyramid, a hollow pyramid, a layered or other shape, structure, or topology, such as the macrostructure shapes and / or topologies provided elsewhere herein.

[0328] In some examples, the reactor can include a pyramid or hollow pyramid macrostructure shape. Such a structure can enable a suitable environment for growth while maintaining a constant velocity and cell density throughout the bioreactor. More sensitive strains can require more intervention over time, in which case a hollow pyramid can provide this capability.

[0329] In some examples, the bioreactor can include a layered pyramid macrostructure shape. Such a macrostructure shape can provide a suitable environment for growth and development, such as by maintaining a uniform (e.g., substantially constant) velocity and density. In some cases, suitable access to a subset of cells or, in some cases, to each cell can be provided at a given duration of time, in some cases, at each point in time. Layered pyramid microstructures can also enable direct intervention and treatment.

[0330] In one example, the bioreactor can include a checkerboard macrostructure shape or a log arrangement shape. The checkerboard and log arrangement can provide suitable access (e.g., in some cases, full access) to a subset of cells, in some cases, to each cell of the bioreactor at a given duration of time, in some cases, at each point in time of the process. In some examples, the checkerboard and / or log arrangement can provide or facilitate control of uniform velocity and / or density of fluid and / or cells in the bioreactor. In some examples, cells can enter at a given point or location in the bioreactor (e.g., the top of the macrostructure), and a cell collection device can be present at a given location of the bioreactor (e.g., at the bottom of the macrostructure).

[0331] In one example, the bioreactor can include a spherical macrostructure shape. Figure 47An example of a spherical bioreactor 4700 is shown in FIG. 47. The spherical bioreactor can be a bubble-free spherical bioreactor. For example, a bioreactor can be manufactured using the methods of the present disclosure and can include minimal to substantially no bubbles. In some cases, there can be some bubbles in the bioreactor. In some examples, the spherical bioreactor 4700 can include a plurality of symmetry planes (symmetry planes). For example, the bioreactor can include one or more units that can repeat the structure of the bioreactor. As an example, the spherical bioreactor shown in 4700 includes three symmetry planes (e.g., planes 4740, 4750, and 4760). The symmetry planes can divide the structure of the spherical bioreactor into a plurality of 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 the spherical bioreactor 4700, the repeating unit can be one-eighth of a sphere. One example of such a repeating unit 4698 is shown in FIG. 48. The repeating unit 4698 can form one-eighth of the volume of the bioreactor 4700. Stated another way, the eight repeating units can be at least somewhat similar to the repeating unit 4698 can repeat (e.g., be symmetric in volume) to form the spherical bioreactor 4700. In some examples, the repeating units can be completely similar or identical. In some examples, the repeating units can be somewhat similar. In some examples, the repeating units can be somewhat different and can include some differences from one another. Similar concepts and / or methods can be used to construct bioreactors having different macrostructure shapes and / or topologies. Figure 46A

[0332] A bioreactor (e.g., a spherical bioreactor) can include one or more channels. The channels of the bioreactor can include one or more collection drain channels 4710 that can be used to collect cells. The channels of the bioreactor can include one or more gas intake channels 4720. The gas intake channels can be used to inject gas into the bioreactor, such as a gas chamber (e.g., 4620 or 4840). The channels can include one or more liquid (e.g., media) intake channels 4730 that can be used to inject a liquid supply (e.g., growth media) into the bioreactor. The liquid supply can be provided to any bioreactor macrostructure according to the methods and systems provided anywhere herein. In each structure or configuration, the overall system can be optimized and appropriate adjustments can be made.

[0333] ​In some examples, the various gas intake passages 4710 of a bioreactor can be similar to one another to some extent. In some examples, the various gas intake passages of a bioreactor can be different from one another to some extent. For example, gas intake passages can be provided, each of which can include an opening for injection of a gas to supply the gas to a given region of the bioreactor, which can be a given distance from the center of the sphere. In some examples, gas intake passages for delivering 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 applications.

[0334] A cross-sectional view of an example spherical bioreactor is provided in Figure 46A and Figure 46B . Figure 46A A media intake passage 4600 that can be used to inject a liquid supply into a bioreactor is shown. The liquid supply can include a media. The liquid supply can include additional components. The liquid supply or media can be according to the supplies and media provided elsewhere herein or combinations thereof.

[0335] As an example, Figure 46B A cross-sectional view of a cross-section of an example spherical bioreactor according to the methods and systems provided herein is shown. The bioreactor can include one or more passages, such as a plurality of passages. The passages can include a harvest passage 4696. In some cases, the harvest passage can be according to the passages provided elsewhere herein. The bioreactor can also include a harvest layer 4610, one or more gas chambers, one or more culture layers, and other components and / or modules. The harvest passage and harvest layer can be used to harvest liquid media and cells from the bioreactor. In some examples, the bioreactor can also include a similar harvest passage for gas (not shown in the figure) to harvest used gas from the bioreactor. In Figure 46B In the example shown, the bioreactor includes 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 spherical bioreactor, or any other bioreactor including any macro-structural shape, can include any number of layers, any number of passages, such as any number of culture layers, any number of gas chambers, and / or other components, modules, passages, or chambers, any configuration thereof, and any combination thereof.

[0336] A bioreactor (e.g., a spherical bioreactor, such as Figure 46BA bioreactor (e.g., a production bioreactor or a production volume or layer of a bioreactor) can include one or more cultivation layers and / or one or more production layers or production volumes. A cultivation layer (e.g., 4630, 4650, 4670, 4690, and / or other cultivation layers) can be a layer of a bioreactor that can cultivate cells. In some examples, a production volume can be in a cultivation layer. For example, a cultivation layer of a bioreactor can include a production layer. A production layer can include a plurality of channels therein, an example of which is shown as production channels 4690. Production channels 4690 can be saturated. For example, a large number of channels (e.g., a high density of channels) can be installed in a relatively small volume. Alternatively, the channels can not be saturated. A cross-sectional view of production channels 4695 is shown as an example in Figure 46B

[0337] A bioreactor containing macrostructures of a given shape, such as any of the macrostructure shapes provided elsewhere herein, such as a pyramid, a hollow pyramid, a checkerboard, a log, a sphere, a cube, a cylinder, or any other macrostructure provided herein, can include a plurality of micro-modules that can be assembled to form the macrostructure. Arranging micro-modules (e.g., DG micro-modules or micro-modules of any shape, such as any of the micro-modules provided anywhere herein) into a macrostructure can provide a mechanism for determining and optimizing liquid media and gas flow within the bioreactor. In some examples, a macrostructure is composed of levels or tiers of micro-modules. In some examples, the micro-modules can be arranged in tiers or levels, and the velocity of the liquid media in each tier can be substantially the same. Alternatively or additionally, the velocity of the liquid media in each tier or level can vary. For example, the velocity of the liquid media can increase or decrease between tiers or levels. The velocity of the liquid media can vary from micro-module to micro-module, or can be substantially the same between or across micro-modules.

[0338] In some examples, a bioreactor (e.g., a production bioreactor or a production volume or layer of a bioreactor) can also include a liquid media input device. The liquid media device can be configured to provide liquid media to the micro-modules of each tier within the macrostructure. In some examples, the volume of liquid media provided to each tier can maintain a substantially constant cell density in each tier.

[0339] A bioreactor can include one or more micro-channels. Micro-channels can include various dimensions. In some cases, a micro-channel radius can be associated with a cell radius, a cell density, or other parameters (e.g., filamentous arrangement, chain-like arrangement, etc.). In some examples, a cell density can be from 1 x 10 6 cells / ml to 1 x 10 12 ​The speed of the liquid medium through each micro module can be determined by the cell division rate, in some examples, such that the time for a cell to pass through an individual micro module or micro module stage can be substantially the same as or can be proportional to the cell division rate, such that a cell can divide greater than or equal to 1, 2, 3, 4, 5, or more times during transport. In some examples, a first stage can include an example volume of "x" of the liquid medium, such that for a given number of cells, the density is x, and a second stage with a volume of 2x of the liquid medium, and the number of cells doubles (e.g., a subset of the cells (e.g., each cell) can divide on average once) over the duration of time that the cells transition from the first stage to the second stage, so the density of the second stage can remain x (e.g., constant cell density between stages).

[0340] Additional optimization can be achieved by determining an expected number of cells at the bottom of a macrostructure, which cells and / or biological products reach the terminal end of the macrostructure before exiting the structure through an output to a collection vessel. The expected number of cells can also be determined for different levels of a macrostructure. Based on the expected number of cells at the base level and different levels, the flow of gas and liquid medium can be adjusted for each level to compensate for increased gas and liquid medium demand as the number of cells increases with cell division, cell movement, and accumulation of cells as they progress through the bioreactor toward the bottom of the structure.

[0341] Liquid medium supply in a bioreactor

[0342] A bioreactor can include one or more components to supply 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 equipment, a reservoir, a pump, a bubble sensor, and a bubble trap. The culture medium formulator can generate liquid medium for the bioreactor by mixing components of the medium and water appropriate for the cells to be grown in the modules. The electroporator can be interconnected with the medium generator, for example, to clean the medium and provide sterile starting medium to supply to one or more modules for growing cells. The bubble sensor and bubble trap can be included to detect and / or remove any bubbles in the liquid medium that can be introduced in the medium generation, cleaning, or any other reason.

[0343] In some examples, a system (e.g., a bioreactor) can include one or more reservoirs for holding storage media, for example, prior to its supply to a module or micro-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. Reservoirs can be filled asynchronously, such that one reservoir is being filled while another, already fully filled, reservoir is available to supply liquid media to a bioreactor and / or its modules. Isolating reservoirs in this way can be advantageous to isolate the cell growth modules of a system (e.g., a bioreactor) from the connection of an example electrical current. A filled reservoir can be exposed to an electrical current that can flow from an upstream component (e.g., an electroporator). The filled reservoir can be isolated from the electrical current such that it does not transmit the electrical current to downstream components and modules of the system (e.g., a bioreactor). In some examples, the volume of a reservoir can be associated with the production of a production bioreactor over a cell division time selected for the process. In some examples, multiple reservoirs can be installed in parallel and isolated from one another. In some examples, multiple reservoirs can be installed in series. In some examples, multiple reservoirs can be installed in a combination of series and parallel configurations, another configuration, and / or any combination thereof.

[0344] In some examples, a liquid media supply component of a system (e.g., a bioreactor system) can also include one or more sensors. Sensors can measure parameters including the pH and temperature of the media. Sensors can be inline sensors or can be connected to a sampling device that intermittently samples media from a mineral component of the liquid media supply. A supply system can provide liquid media at a range of rates depending on the use, scale, and operation of the system. In some examples, a liquid media supply can provide about 100 microliters to about 1000 liters per hour to a bioreactor or its modules (e.g., chambers for cell growth). In some examples, a liquid media supply can provide about 0.5 liters to 1000 liters per hour to a bioreactor or its modules, channels, or chambers (e.g., cell growth chambers). In some examples, a liquid media supply can provide about 0.5 liters to 5 liters per hour to a bioreactor or its modules, components, channels, or chambers. In some examples, a liquid media supply can provide about 10 liters to 80 liters per hour to a bioreactor or its modules, components, channels, or chambers (e.g., channels or chambers for cell growth). In some examples, a liquid media supply can provide about 100 liters to 1000 liters per hour to a bioreactor or its modules, components, channels, or chambers (e.g., channels or chambers for cell growth).

[0345] The liquid media supply assembly can include one or more pumps for flowing media from a reservoir or media preparation to a component of the bioreactor system, such as a cell chip, a sandbox bioreactor, or a production bioreactor. In some examples, the system (e.g., bioreactor system) can include greater than or equal to 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.

[0346] 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, the system (e.g., bioreactor system) can include three pumps, two syringe pumps to supply a cell chip and a sandbox reactor, and a peristaltic pump to supply a production bioreactor. The pumps can work in tandem or individually. In some examples, all three pumps can work in tandem. One or more pumps can supply media (e.g., with high volume and rate accuracy) to the bioreactor or a module or component thereof, such as a module downstream of the pump (e.g., a downstream module). The downstream module can be a downstream module provided elsewhere herein. In some examples, the accuracy can be within 1, 2, 3, 4, or 5 nanoliters.

[0347] Gas supply and gas composition in bioreactor

[0348] In some examples, the systems provided herein (e.g., bioreactor systems) can be used with cells that can be compatible with or require specific gas compositions, such as cells that can require oxygen for growth and / or survival. Materials used to construct the bioreactor modules can include glass, acrylic, collagen, polydimethylsiloxane (PDMS), polyethylene glycol (PEGDA), poly(D,L-lactide), silk, cellulose, GelMA, alginate, ceramic, and / or other biocompatible polymers that can allow for media oxidation. In some examples, the systems (e.g., bioreactor systems) can also include a controller that can control the diffusion of oxygen and other gas solutions in the bioreactor or its modules. In some examples, the gas solutions can be formulated from pure component gases, such as from gas tanks or other supply mechanisms, for example, to create mixtures or pure gas solutions of various concentrations and flow rates. Alternatively or additionally, the gas mixtures can be provided from a purified air mixture. The gas solutions can be used to provide aeration and can control pH. The gas solutions can provide carbon, nitrogen, phosphorous, sulfur, and / or other media components to the liquid phase. In some examples, the systems can have more than one gas controller or mechanism, such that different gas solutions can be provided to different modules, components, parts, channels, or chambers within the system (e.g., within a given portion of the bioreactor).

[0349] In some examples, 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 aspect can include a laminar bioreactor, a hollow pyramidal reactor, or a bioreactor comprising another macroscopic structure. In such examples, in some cases, the flow can be described based on the average displacement on the single axis.

[0350] With reference to Figure 46A and Figure 46B In some examples, in a spherical bioreactor, the channels for delivering liquid supplies (e.g., channel 4600), the channels for injecting gas (e.g., gas chambers 4620, 4640, 4660, 4680, and 4692), and one or more inoculation channels (not shown) can reach appropriate points through the production structure (e.g., production volume 4694, which can be inside culture layers 4630, 4650, 4670, and 4690), respectively. The direction and / or rate of liquid and gas supplies in the bioreactor can affect the growth rate of cells or microorganisms in the bioreactor. For example, Figure 46Achannels 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 spherical bioreactor). The direction of liquid flow 4697 can be an angular direction, for example Figure 46A shown in FIG. 46B. In some examples, the direction of liquid flow can be angular, radial (the radial direction of liquid flow is not shown in the figure), and / or a combination of the two. Liquid media can flow into the bioreactor, for example, in its layers, and can deliver culture media to cells to be grown in 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 them with nutrients to survive and / or grow. The topology and macrostructure of the bioreactor, and the direction and method of injection and flow of liquid and gas therein, can all affect the growth rate of the cells.

[0351] In some examples, a bioreactor, for example, Figure 46A , Figure 46B and / or Figure 47 shown in FIG. 46B. In some examples, the direction of liquid flow can be angular, radial (the radial direction of liquid flow is not shown in the figure), and / or a combination of the two. Liquid media can flow into the bioreactor, for example, in its layers, and can deliver culture media to cells to be grown in 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 them with nutrients to survive and / or grow. The topology and macrostructure of the bioreactor, and the direction and method of injection and flow of liquid and gas therein, can all affect the growth rate of the cells.

[0352] Figure 48 Views of channels and chambers within bioreactors provided herein are schematically shown, as well as the flow of gas and liquid supply (e.g., culture media, water, nutrients, etc.) therein. Figure 48 The bioreactor shown can include any macrostructure shape and any micro module shape. In one example, Figure 48 The bioreactor shown in FIG. 46B can be a spherical bioreactor, for example Figure 47 bioreactor 4700 shown in FIG. 46B.

[0353] Gas (e.g., gas flow 4830) can pass through openings (e.g., Figure 47The injected gas can include a fresh gas feed having suitable composition (e.g., according to the gas composition provided elsewhere herein). In some cases, after the gas has passed through some regions of the bioreactor and can have reached cells within the bioreactor, the gas can be exhausted or removed from the bioreactor using a gas intake channel or another intake channel that can be substantially similar to the gas intake channel 4720. In some examples, different methods can be used to exhaust gas from the bioreactor. Examples of such methods can include using an outer layer or shell (e.g., a membrane around the bioreactor) that can be exposed to an external environment. Such an outer layer or membrane can be porous and can allow gas to be exhausted from the bioreactor. Alternatively or additionally, the bioreactor can include a gas harvest layer (not shown) and / or a gas harvest channel (not shown) that can be similar to and / or different from the harvest channel 4690 and the harvest layer 4610 to some extent. For example, the gas harvest channel can be located in a different region than the harvest channel 4696, it can be configured to have a gas flow therein, and it can be used to exhaust gas from the bioreactor after such gas has passed through a subset of the regions of the bioreactor. Any of these methods can be used to exhaust gas from the bioreactor. In some cases, similar methods can be applied to bioreactors other than the spherical bioreactor 4700.

[0354] Liquid can be injected into the bioreactor through an opening (e.g., an opening of the liquid intake channel 4730) and flow in a liquid flow channel (e.g., the liquid flow channel 4810). The liquid can include a media or ingredients listed elsewhere herein, which can be supplied to the bioreactor to aid in cell growth. The liquid can flow through the structure of the bioreactor. The liquid can include a media. In some cases, the liquid can include cells suspended therein. The liquid composition can be according to the liquid composition provided elsewhere herein.

[0355] Within the bioreactor, there can be multiple micro-modules. The micro-modules can be micro-modules of the bioreactor. The micro-modules themselves can be composed of smaller units. In some cases, multiple monomers can be assembled into a micro-module, e.g., a micro-module. In some examples, a micro-module (e.g., a micro-module such as the building block 4860) can include at least one liquid flow channel 4810 and one gas flow channel 4820, into which a gas flow (e.g., the gas flow 4830) can be injected and subjected to flow. The micro-modules (e.g., the building block 4860) can be repeated throughout the structure of the bioreactor. While Figure 48Gas and liquid flow in a spherical bioreactor is illustrated as an example, but similar schemes can be used for other bioreactor topologies and structures.

[0356] The bioreactor can also include a gas chamber 4840 (e.g., similar to gas chambers 4620, 4640, 4660, 4680, and 4692). In example bioreactors of any shape and / or structure, the gas chamber 4840 can have any topology and / or structure. In the spherical bioreactor 4700, the gas chamber can be a hollow spherical chamber. For example, in some cases, as shown in FIG. 48, the gas chamber 4840 can be a hollow sphere with a diameter of 10 cm, and the gas flow channel 4820 and the liquid flow channel 4810 can not cross or pass through the spherical hollow gas chamber (e.g., 4810). The hollow gas chamber 4840 can contain a plurality of culture channels 4850 in which cells or microorganisms can be cultured. In some cases, as shown in FIG. 49, the culture channels 4850 can be inside the gas chamber 4840. Figure 48 Figure 48

[0357] Gas flow and liquid flow can flow through their respective channels (e.g., channels 4810 and 4820) in the micro-modules (e.g., building blocks 4860), and when these channels reach the gas chamber 4840, the gas flow and the liquid flow can enter and pass through the culture channels 4850 contained in the gas chamber. Thus, the culture channels 4850 can be provided with both gas supply and liquid supply, which can help cell growth and / or survival. In some examples, the channels can be tubes.

[0358] The macrostructure or topology of a bioreactor can be selected based on the target characteristics of the application and process (e.g., cell growth). In some cases, a spherical bioreactor can be more suitable than other geometrical shapes, and can provide some advantages over other bioreactor topologies and / or macrostructure shapes (e.g., layered, pyramidal, hollow pyramidal, or other structures of bioreactors). One example feature of a spherical bioreactor is that the volume of the sphere or the volume of the example shell (the volume between two respective radii of the sphere) follows a cubic relationship with respect to its radius (e.g., V = (4πr 3 ) / 3, where V = volume, r = radius). An example graph showing this is in FIG. 50. Figure 45 ​​The volume of the bioreactor or its spheroid can correspond to or include the volume in which cells or microorganisms are grown. Thus, the volume in which cells are grown can increase cubically, for example, based on a linear increase in radial distance from the center of the spheroid relative to the radius of the spheroid. This can be different in bioreactors that include pyramidal or layered structures. This feature can be advantageous because the increased growth trend or rate (e.g., cubic) can be more similar to the trend of the proliferation rate (e.g., natural growth rate) of example microorganisms or cells that can be grown in the bioreactor, which can be beneficial in many cases. For example, it can be convenient, efficient, and / or feasible to maintain consistent and / or uniform pressure, fluid flow, cell growth, and cell concentration in a spherical bioreactor, and can provide suitable conditions for growing cells. In examples, apoptosis due to over-proliferation of cells in a given region can be prevented.

[0359] Methods of using bioreactors

[0360] In some examples, the reaction vessels or bioreactors provided herein can be used to produce or grow cells. Figure 44 Example methods of producing cells using the reaction vessels or bioreactors provided herein are shown. 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 its modules. In some examples, cells can be collected within the bioreactor or its modules, and can be further stored in the bioreactor or its modules, for example, storing cells within a cell chip module of the bioreactor.

[0361] In some examples, the bioreactor can be used to produce a biological product (e.g., from cells), such as a small molecule, a protein, an antibody, a metabolite, or other product produced by cells grown in the bioreactor. The biological product can be collected through the output channel of the bioreactor and separated from the grown cells, for example, by diffusion through a porous membrane or by filtration or using another technique. In some examples, the biological product can be inside the cells. To harvest the biological product, the cells can be collected and / or lysed, and then the biological product can be further purified if / as needed. In some examples, the biological product can be secreted from the cells and can be collected without harvesting or lysing the cells.

[0362] The bioreactors and systems including such bioreactors described herein have flexibility to optimize growth and scale-up of a variety of cell types. In some examples, the bioreactor of the system is a production bioreactor for scaling up cell growth, producing large volumes or cells, or growing cells under conditions to produce and harvest a biological product 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 for initial growth of cells and / or for storing cells to provide a particular type of cell to a production bioreactor, where such production bioreactor is then used to scale up growth or production of cells and / or production of a biological product. Another example of an additional module can include a sandbox module. In some examples, the system can include a sandbox module with a production bioreactor module (with or without a cell chip module as part of the system), for example in series or in any other configuration, where such sandbox module is included to test, analyze, and / or optimize cell growth conditions prior to scaling up in the bioreactor production module.

[0363] Systems including bioreactors can be used to produce a variety of cell types and biological products. For example, a system including a bioreactor described separately elsewhere herein or with one or more cell chip modules and / or sandbox modules (also referred to as sandbox bioreactors elsewhere herein) can accommodate production of stem cells and / or other types of cell therapy, including autologous and allogeneic production. The system can accommodate production of stem cells and other types of cell therapy, including autologous and allogeneic production. In some examples, it can perform expansion, gene delivery, or activation of t-cells for personalized chimeric antigen receptor t-cell (CAR-T) therapy. In some examples, the stem cells can be undifferentiated, growing, and / or differentiated.

[0364] In some examples, the cells to be grown in the system can be prokaryotic cells, such as bacterial cells. In some examples, the cells to be 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 a culture medium or can be adherent cells that can adhere 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 a biological product, such as a heterologous protein, an antibody, a small molecule, and / or a metabolite.

[0365] In some examples, a system including a bioreactor described herein can accommodate production of viruses, bacteriophages, and / or antigens thereof.

[0366] In some examples, systems including bioreactors described herein can accommodate the production of non-naturally occurring organisms, non-naturally occurring viruses, synthetic organisms, and / or xenobots.

[0367] In some examples, systems, devices, and methods described herein can be used under zero gravity or microgravity conditions, such that cells are grown under zero gravity or microgravity conditions.

[0368] Methods and materials for constructing bioreactor modules

[0369] Systems, components, and modules herein can be made from a variety of materials, and these materials can be tailored to the cells being grown and the cellular environment being employed. In some examples, components and modules, or portions thereof, can be manufactured 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 ultraviolet (UV) curable biocompatible polymers. In some examples, each micro-module shape can be discretely designed in a virtual environment. In some examples, components and modules can be provided from commercially available components that can be combined and arranged together as described herein. In some examples, the biological materials used can include a combination of three sub-components, a biocompatible polymer, a photoinitiator, and a UV absorber.

[0370] 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 that can employ stereolithography. Such a method can include providing a container with a resin that includes a photoinitiator and one or more polymer precursors. For example, a preprogrammed design or structure can be drawn into the surface of the container with resin using a light source (e.g., an ultraviolet (UV) laser or any other suitable light). The resin can be a photopolymer that photochemically cures upon contact with light (e.g., a UV laser) to form a single layer. Additional resin can be added and cured 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 construct objects and / or modules in any direction. In some examples, stereolithography can be used to construct modules in an additive, top-down, or bottom-up manufacturing method.

[0371] In some examples, constructing a reactor, bioreactor, or module thereof can include self-assembly of polymers (e.g., block copolymers) to form 3D structures (e.g., a spirochete, a geometric shape, or a construct of any shape, form, geometry, or dimension) or subtractive manufacturing methods.

[0372] Subtractive manufacturing methods can include chemical or mechanical removal of sacrificial material. For example, sacrificial material can be formed using binder jetting with a sintering laser. The sacrificial material can be submerged, immersed, or otherwise coated in a biocompatible polymer. The sacrificial material can then be dissolved or mechanically removed to form a 3D shape or structure (e.g., a helix) from the biocompatible polymer.

[0373] Example 3D-printed bioreactor

[0374] A bubble-free bioreactor can be printed using the 3D printing apparatus and methods described elsewhere herein. Figure 57A An example printing process is shown. 3D modeling can be used to configure the tubing and matrix of the bioreactor as well as auxiliary structures. The 3D model can be converted to a slicer for 3D printing. Prior to printing, the biopolymer resin can be formulated and the printer controller can be prepared. The bioreactor can then be printed using the 3D printing apparatus, and post-processing can be performed on the bioreactor after printing. Figure 57B Digital renderings and cross-sectional views as a function of position height of a 3D-printed bioreactor are shown. A first cross-sectional view shows the inlet and outlet of the reactor. A second cross-sectional view shows the internal structure of the helix shape. A third cross-sectional view shows the main channel of the reactor connected to the helix channel.

[0375] An example 3D printer apparatus and printed bioreactor are shown in Figure 58 The printed bioreactor includes a double helix crystal with a total void volume of about 500 milliliters (mL). The helix channel has a diameter of 500 pm and an intermembrane thickness of 300 pm. In other examples, the intermembrane thickness can be less than about 300 pm. For example, the intermembrane thickness can be less than about 275, 250, 225, 200, 175, 150, 125, 100, 75, or less pm. The example 3D printer apparatus includes a print bed 5804 with a draft tube 5801. The material within the print bed 5804 is pumped within the print bed 5804 by a recirculation system. The recirculation system includes a reservoir 5806 containing a photocurable biopolymer resin, a magnetic stirrer 5805 for mixing the biopolymer resin, and a recirculation peristaltic pump 5807 for pumping the biopolymer resin into the print bed 5804. The bioreactor can be seated between the print bed 5804 and a print platform 5802. The print platform 5802 can be connected to a circulating ball screw 5803 configured to raise the print platform 5802.

[0376] Example

[0377] In some examples, executable instructions provided herein can include methods for constructing a space or structure from a plurality of units, micro-modules, monomers, and elements according to methods provided elsewhere herein. Such methods can include assembling a plurality of micro-modules to construct a macro-structure. The macro-structure can include any shape provided elsewhere herein, such as a sphere, a pyramid, a hollow pyramid, a layered, a checkerboard, or any other macro-structure. In some examples, the macro-structure can form a bioreactor. The bioreactor can be constructed from a plurality of micro-modules assembled using methods provided herein. The method can include providing a mathematical model and one or more operators and / or operations to manipulate the micro-modules (e.g., crystalline units or crystals) using a computer-implemented method (e.g., software (e.g., a computer system provided elsewhere herein)).

[0378] Provided herein are structures that can be used as bioreactors. Methods of constructing such structures are also provided. In some examples, the structures can be 3D printed using methods provided herein. Methods of constructing the structures can include stereolithography and / or crystallography. In some examples, computer readable instructions can include methods of constructing a space using a plurality of micro-modules and methods of constructing a structure, such as a bioreactor.

[0379] In one example, a structure (e.g., a pipe or any other structure) can be manufactured using methods provided herein. In some cases, a monomer can be defined or simulated from a distribution of lattice points within a body of a monomer or lattice structure. The points can be elements. The body can be a body of a crystal or monomer. The elements can be in the monomer. For example, in a monomer or lattice, the arrangement of points can represent the location or positioning of atoms. For example, the points can represent atoms of a lattice. Due to the balance (e.g., balance of electrostatic forces) that can connect the atoms and / or that can hold them in place, the atoms in the lattice can be able to vibrate in such a way as to minimize the total surface of the lattice. In some cases, a structure can be defined by the minimized surface that forms due to the placement of the points or elements. Alternatively or additionally, in some cases, it can be suitable and / or convenient to manufacture and / or define a structure (e.g., a pipe or another structure) based on a trajectory that can connect a subset of lattice points.

[0380] The structure that can be built and used according to the method of the present disclosure can include one or more micromodules.In some examples, a micromodule can be the building block of a bioreactor. A micromodule can include one or more external micromodules (e.g., building blocks) and / or one or more internal micromodules (e.g., building blocks). In some examples, external and / or internal micromodules (e.g., building blocks) can include one or more pipelines. Example can include external pipelines, such as pipelines in the external micromodule of a bioreactor provided herein. The function of the external micromodule can include, for example, feeding one or more internal micromodules with liquid and / or gas from an external source such as a reservoir. The reservoir can be the reservoir of a bioreactor system provided elsewhere herein. In some examples, the external micromodule can be a bioreactor feeding system provided elsewhere herein, such as a system for supplying gas and liquid to a bioreactor or a part thereof.

[0381] In some examples, the method of manufacturing an internal micromodule or its components (e.g., tubing of an external micromodule) can be somewhat similar and / or somewhat different from the method of manufacturing an internal micromodule or its components (e.g., a component inside a bioreactor, an internal channel, an internal tubing, or another component of an internal micromodule of a bioreactor). For example, in some cases, the internal micromodule can include or be a monomer. The monomer can be symmetrical. In some examples, the external micromodule (e.g., a building block for making an external feeding system (e.g., external tubing)) may not be a monomer and / or may not be symmetrical. In some cases, a mathematical or crystallographic representation of the external micromodule may reside in the input and / or output links (e.g., building blocks) of the micromodule.

[0382] The micromodule or building block may include a transition micromodule or building block. In some examples, the transition micromodule may be connected to facilitate communication between the internal micromodule and the external micromodule. In some cases, the characteristics of the transition micromodule may depend on or be related to the internal and external micromodules and / or an external source (e.g., an external unit, such as another external component of a reservoir or bioreactor system). In one example, one or more pipes and / or channels may pass through one or more internal micromodules of multiple adjacent volumes (e.g., two adjacent volumes). The transition micromodule may connect one or more pipes or facilitate communication between them. For example, the transition micromodule may facilitate the flow of fluid between one pipe to another pipe.

[0383] Fluid flow within a micro-module of a bioreactor can include features involving fluid mechanics (e.g., flow regime), thermal distribution, composition distribution, and fluid delivery, thermal delivery, and mass delivery between various fluids and regions. In some examples, these features and / or characteristics can be considered, designed, and / or controlled. In some cases, the design and / or construction of a transition micro-module can take into account the aforementioned features.

[0384] The method of construction of a transition building block can be performed by a user that can provide instructions (e.g., any kind of executable instructions and / or computer-implemented methods). In some examples, a user can perform a manual design using an example drafting tool (e.g., AUTOCAD or any other drafting tool) and provide it to the computer-implemented methods provided elsewhere herein to complete the design and / or construction of a micro-module (e.g., an internal micro-module, an external micro-module, and / or a transition micro-module). In some cases, such design and construction by a user can be time consuming. Alternatively or additionally, the design of a building block (e.g., a transition micro-module) can be completed or facilitated by an artificial intelligence driven generative design that can automate, at least to some extent, the design and / or construction of a micro-module. In some cases, the artificial intelligence driven generative design can improve characteristics such as fluid mechanics (e.g., flow regime), thermal distribution, composition distribution, and fluid delivery, thermal delivery, and mass delivery between various fluids and regions in a micro-module. In some examples, two micro-modules that need to be connected can be labeled. Alternatively or additionally, a plurality of external variables of the structure can also be labeled. The labeling process can be used to provide a set of training data that can train a deep learning algorithm. In some examples, the algorithm can include a neural network. Examples of the algorithm and / or neural network can include a generative adversarial network and a variational autoencoder.

[0385] In some examples, a structure can be represented mathematically. The structure can include or be an internal and / or external micro-module. In one example, the structure to be represented can be a pipe. The pipe can be internal or external. An example of a mathematical representation of a pipe driven by a lattice point (e.g., element) is provided in Figure 49. The mathematical representation of the conduit 4900 can include one or more curves (e.g., parametric curves) 4910. The curve 4910 can be mathematically represented or formulated using a polynomial equation. Polynomials may be suitable for such representation, for example, because of their simplicity and performance. Polynomials can include the flexibility to represent the curve as and / or where desired in various applications (e.g., for building micromodules and structures). In some examples, various mathematical equations can be used to represent the curve, and examples of mathematical equations that can be used can include polynomials, sines, cosines, logarithms, exponentials, and / or any other suitable mathematical equations. In some examples, Bezier curves can be used (e.g., in 3D). In some cases, lattice points can be used as control points and / or extremes of the curve. Examples of extreme points can include Figure 49 Points A, B, C, D, and E in . Examples of control points may include Figure 49 Point C in A1 、C A2 、C B1 、C B2 、C C1 、C C2 、C D1 and C D2 .

[0386] Methods for mathematical representation of chambers are provided herein. In some examples, the chambers may be within micromodules. In some examples, the chambers may be shapes derived from the intersection of paths through lattice points. The representation may vary depending on the type and structure of the chamber and other factors. In some examples, pipes or channels may generate chambers, for example, from collision paths through lattice points. The design in each case may depend on the characteristics of the bioreactor in which such pipes and / or chambers may be used. Example representations of this are provided in Figure 50 In this figure, C P1 and C P3 is the control point of A. C P1 and C P2 is the control point of C. C P2 and C P3 is the control point of B.

[0387] In some cases, a function, such as a mathematical function or mathematical operator, can be used to generate the chamber. For example, a chamber can be generated by an intersection function applied to a curve (e.g., a 3D curve). In some cases, further modeling may not be required to complete the representation and / or construction of the chamber. Alternatively, in some cases, further modeling may be appropriate, helpful, or necessary to perform at least a subset of the steps of the process. Figure 51AAn example representation 5100 of an example structure is shown. The representation 5100 can be an implicit chamber. In some examples, when two or more paths (e.g., curves such as 2D or 3D curves such as curve 5110) can reach the same point (e.g., intersect at the same point, e.g., at intersection point 5120), an intersection mathematical function or operator can couple, connect, and / or unify the two curves or paths, thereby forming a shape such as a structure. Depending on the intersection function used to establish the connection between the curves, the intersection point can be smooth (e.g., intersection point 5120) or it can be sharp, e.g., an edge of a pyramid or other structure (example not shown). The resulting structure (e.g., representation 5100) can be any structure. For example, the curves can be pipes and / or channels, they can intersect at a point, the intersection function can connect and / or couple them and can make some further modifications to them to generate a structure such as a chamber. As an example, the intersection function used to generate representation 5100 is an exact intersection function. Another example of a structure generated using this method is shown in Figure 51B . A similar method can be employed to generate Figure 51B representation 5130 shown. As an example, the intersection function used to make representation 5130 is an exponential smoothing intersection function. Representation 5130 can be an implicit chamber.

[0388] In some examples, 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 properties of the resulting micro module or structure (e.g., a bioreactor). In some cases, a structure such as a chamber or its representation can be parameterized. The result can differ depending on the method used to generate the structure (e.g., chamber).

[0389] In some examples, multiple monomers can be assembled to generate a micro module. For example, monomers can be used as voxels to voxelize a structure of a micro module such as a bioreactor or an entire bioreactor. A micro module can be a building block of an entire structure. In some cases, a micro module or building block can inherit some properties from the monomers that can be used to generate the micro module. For example, in some cases, the opposite faces of a monomer can be parallel to each other. In some cases, adjacent faces of two micro modules or building blocks can connect equivalent links. In some cases, an example monomer can be used as a voxel to construct a voxelized structure (e.g., an upper voxelized structure). A monomer can include any shape listed herein, e.g., a cube or other shape (e.g., provided in Table 1.1).

[0390] Examples of fabricating structures through assembly of monomers are shown in Figure 52A 3D sphere and its voxelated representation using cubic cells is shown. In some examples, the first step of the method can be defining the shape of the structure to be constructed. For example, the shape of the structure can be defined by a mathematical equation (e.g., parametric equation) and a mix of constructive solid geometry. The shape of the structure (e.g., macrostructure) can be defined as a 3D object (e.g., a perfect 3D shape), in some cases, regardless of the shape of the cells or voxels used to construct it. In some examples, the structure to be constructed can be a macrostructure, such as a bioreactor. In some cases, the structure to be constructed can be a micro module. As an example, once the geometry of the macrostructure (e.g., sphere 5200) is defined, voxelation can be performed to represent the macrostructure as a collection of multiple cells or voxels (e.g., cells or voxels 5210). In some cases, voxelation can be performed according to the type of cell (e.g., see Table 1.1). In some examples, the arrangement of lattice points within a cell can be ignored for the purposes of voxelation. During this process, micro modules and / or building blocks can be created. The entire macrostructure can include multiple such micro modules or building blocks. Such micro modules and / or building blocks can include internal, external, transitional, and / or any of the kinds of micro modules or building blocks provided elsewhere herein.

[0391] The next step can include incorporating conduits in the structure, for example, within the micro modules and / or building blocks. The properties of the conduits can be accurate and can become uniform (e.g., according to the methods described elsewhere herein). The conduits can include elongated conduits that can carry gases and liquids throughout the structure of the bioreactor.

[0392] External connectors

[0393] In some examples, the structure can include multiple external connectors. For example, the structure can include Figure 47 The structure, such as a bioreactor (e.g., bioreactor 4700), can include multiple intake channels (e.g., channels 4720 or 4730) as shown. 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 can be suitable to have a relatively small number of intake channels, or in some cases, to minimize the number of intake channels. The structure can also include multiple channels, such as internal channels (e.g., channels 4810 and 4820) as shown in FIG. 48. Figure 48 The channels can be conduits. The external connectors (e.g., intake channels, such as channels 4720 or 4730) can feed the internal channels (e.g., channels 4810 and 4820). The channels can be conduits (e.g., Figure 19The structure can have any number of conduits. In some examples, the structure can include from one to several million conduits (including any number in between). Between the channels and / or conduits, in some cases, between all of the channels of a bioreactor, it can be appropriate to generate an appropriate (e.g., uniform) distribution of gas and / or liquid. In some cases, it can be appropriate to have multiple intake channels so that controlling them can become more convenient and efficient. In some cases, the method of constructing the structure (e.g., the programming) can include tracking intake channels from external building blocks or micro-modules and / or connecting conduits into different kinds of external connectors. In some cases, the connectors can have been pre-tested to ensure that intake and output channels can be evenly distributed into flow through the channels (e.g., conduits) of the structure.

[0394] Tree-shaped connectors

[0395] The structures provided herein can include one or more connectors. The structures can be bioreactors 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. Examples of connectors can include tree-shaped connectors. Examples of tree-shaped connectors are shown in Figure 53

[0396] Examples of different shaped connectors can include tree-shaped connectors, single-sided connectors, and other shaped connectors. In some examples, the shape of a single-sided connector can vary in different designs. In a single-sided connector, an 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 external micro-modules (e.g., external building blocks). In some examples, to facilitate even and / or uniform distribution of fluid between the conduits, for example, once the chamber is filled, the width of the connector, chamber, and / or conduits can be adjusted to allow a target amount of fluid to be filled into the conduits.

[0397] Architectural design and methods of architectural design of structures (e.g., bioreactors) are provided herein. In some examples, the method can include functionalizing micro-modules (e.g., building blocks). In some examples, the building blocks and / or micro-modules can be linked (e.g.,​Figure 19 The links 1915 shown in FIG. 19 can connect to each other. Figure 19 The unit cell shown in FIG. 19 can be an example of a micro module that includes multiple faces (e.g., faces 1910 and 1920) and multiple conduits (e.g., conduit 1905). Such a unit cell or micro module can be connected to other monomers, micro modules, or building blocks through links (e.g., links 1915). In some examples, the links (e.g., links 1915) can be external links and can be located in one or more faces (e.g., face 1910) of the micro module. A micro module can be denoted as a unit cell. In some cases, an example of a micro module can be a repeating unit, such as Figure 48 The building block 4860 shown in FIG. 48. In some cases, a link can be positioned over an edge of two or more faces, such as in Figure 19 a side of the geometry (e.g., a cube or other shape) of the monomer shown in FIG. 48. In some examples, a link can be shared by two or more faces, such as three or more faces, and it can be positioned on a vertex of the building block, such as in Figure 19 a vertex of a cubic unit cell shown in FIG. 48, or on any other shape or kind of unit cell. In some examples, two or more adjacent blocks (e.g., adjacent micro modules or adjacent unit cells) can be matchable (e.g., connectable) if they share the same location in a face to be connected and if the links attached to them share the same cross-sectional shape. That link can then connect to the two adjacent micro modules.

[0398] In some examples, the design of a bioreactor can include different numbers of phase volumes that can be connected to each other. In some cases, the phase volumes can be important for macro-structures that are composed of multiple internal micro-modules (e.g., building blocks). For example, in some cases, the method for connecting micro-modules and / or building blocks can include considering the medium inside such micro-modules. For example, a micro-module can be configured to allow a fluid, such as a gas or a liquid, to flow therein. An example of such a micro-module can be a pipe or a channel or another structure (e.g., of a bioreactor). For example, a consistent unified pipe can be constructed as a result of connecting two adjacent pipes, and the medium transported in these pipes can also match. Such a match can be accomplished by labeling the pipes (e.g., within a phase volume) used in the building blocks or micro-modules. In some examples, such labels can also be associated with attributes such as pressure, heat, fluid composition, etc. In some examples, it can be desirable to preserve such attributes. For example, these attributes can not be destroyed as a result of connecting building blocks or micro-modules. In one example, two pipes can be connected to each other, each pipe can have a fluid flowing therein, each fluid can include a set of characteristics, such as flow rate, temperature, pressure, composition, etc. The pipes can be connected while taking into account these characteristics, such that as a result of connecting the pipes, these characteristics will be preserved or maintained under suitable conditions. This can be accomplished by the labeling scheme described herein. In some examples, many such considerations are tested, researched, and / or validated, for example, prior to finalizing the design of the structure.

[0399] A micro-module or building block can include a transition micro-module and / or building block. A transition micro-module can include a transition phase volume. The transition phase volume of a micro-module can take into account suitable characteristics of the phase volume composed of the transition micro-modules to be connected and the adjacent phase volumes of those transition micro-modules.

[0400] In some examples, a connector can be configured to carry a medium (e.g., a fluid, such as a gas or a liquid) from outside of a bioreactor to an input pipe or intake channel (e.g., an intake channel, such as intake channels 4720 or 4730) in an external building block or micro-module of the bioreactor, in some cases to all intake channels. A connector can include multiple levels. A connector can include a lower level connector. In some examples, a lower level connector (e.g., a first level connector) can include a structure that can transform a pipe into a larger intake channel, which can gradually create multiple intake channels (e.g., intake channels 4720 or 4730) outside of a bioreactor (e.g., bioreactor 4700).

[0401] Connectors can also include advanced or higher-level connectors. Higher-level connectors can build larger intake channels from lower-level connectors stepwise (e.g., layer by layer). Such connectors can be external connectors, tree connectors, and / or single-sided connectors, which can function according to information provided elsewhere herein.

[0402] Simulation and modeling

[0403] Provided herein are methods for modeling and / or simulating monoliths (e.g., unit cells) and their behavior and / or functionality. Such simulations can be helpful in determining design characteristics based on intended applications and / or expected results regarding generated bioreactors. Simulations can include computational simulations and / or numerical simulations. Examples of simulations or models can include integral simulations, Lattice Boltzmann simulations, finite element simulations, functional microfluidic feedback and correction (e.g., at second and / or third order), phase continuity, and other methods.

[0404] As an example, finite element analysis (FEA) can be used to solve problems related to designing and / or constructing structures of the present disclosure. In some examples, FEA can be used to predict, model, and / or simulate the behavior of 3D or 3D models with respect to various factors, including external forces, heat, fluid flow, and other factors, e.g., physical phenomena. In some cases, simulations can be used during product development as feedback to improve design quality. In some cases, FEA can start with subdividing an object into a plurality of finite elements (e.g., millions of finite elements). This can be an important process for the efficiency and accuracy of the predictions. In some cases, performing FEA can be time-consuming, e.g., due to the topology of the crystal structure. The way the structure is divided into finite elements can be important for the efficiency and / or accuracy of the model.

[0405] In some examples, modeling or simulation can include a Lattice Boltzmann method. In some examples, Lattice Boltzmann simulations can be compatible with implicit representations of models or structures. The method can also include using a function to improve the performance and / or accuracy of Lattice Boltzmann simulations. In some examples, such a function can be a mathematical function or operator, e.g., a signed distance function.

[0406] The simulation method of the crystal structure can include pre-computation of building blocks. In some examples, the building blocks or micro-modules can be substantially similar, in some cases, identical. Classification of micro-modules with a limited number (e.g., a small number of samples) of samples can be performed. For example, pre-computation experiments can be performed on a subset of samples or all samples using different numbers of input variables. Pre-computation can be used to speed up the simulation of the bioreactor. Pre-computation can be performed on a subset (e.g., samples) of the structure. In some examples, the design of internal and external micro-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 considered.

[0407] In some examples, the methods and systems can include a database of simulations and methods of manufacturing and using simulations. For example, simulations that are computed and performed 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 the simulation can be increased by using previous computations. In some cases, a faster approximation can be provided. For example, such an approximation can be based on information stored in the database of simulations or other computations stored elsewhere. This can make the computational cost of the simulation lower.

[0408] 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 (e.g., an AI-driven platform based on deep learning). The purpose of doing so can include generating faster and / or better predictions and simulations. In some examples, tagging micro-modules or building blocks can facilitate storing previous simulations and / or meta-information derived from experiments or pre-computations. In some examples, a database of simulations can be used to store such data. The training data can be used to train a model. The platform (e.g., an AI-driven platform) can provide information by performing simulations that are faster, more efficient, and / or more accurate. This can be part of a product development cycle according to the methods provided herein. A method can include simulations performed by a user, simulations performed by AI, and / or a combination thereof. The method can include an iterative process. Using AI can improve the speed, efficiency, and / or accuracy of the iterations. The resulting design and / or production configuration can include constructional considerations and functional considerations as well as other factors. Example design properties can include mechanical strength, industrial compatibility, and the like.

[0409] While preferred embodiments of the subject matter have been shown and described herein, it is to be understood that the embodiments are merely examples in accordance with the principles of the subject matter. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the subject matter. It should be understood that various alternatives to the embodiments of the subject matter described herein can be employed in practicing the subject matter.

Claims

1. A computer-implemented system comprising: At least one processor, memory, and instructions executable by the at least one processor to create a process modeling application, the process modeling application comprising: a) An interface that allows the user to perform at least the following operations: i. Define at least one volume in the scene, ii. identifying a crystallization unit for said at least one volume, iii. identifying the symmetry of the crystallographic unit, and iv. Edit the properties of the crystallization unit; b) a presentation module configured to: i. replicating the identified crystallographic unit cell according to the identified symmetry to generate a three-dimensional lattice, the three-dimensional lattice being functionalized and fluidically interconnected to provide at least one microchannel or chamber; ii. using one or more mathematical equations to represent the scenario, and iii. Rendering the scene; c) a simulation editor that allows the user to configure one or more simulations of the scenario; d) a simulation module configured to perform the one or more simulations in the scenario; e) a print editor that allows the user to configure printing scenarios; and f) a printing module configured to transmit instructions to a 3D printer. 2 . The system of claim 1 , wherein the interface further allows the user to configure one or more microchannels in the at least one volume.

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

4. The system of claim 1, wherein the properties of the crystallization unit include links for connecting to one or more adjacent crystallization units and pipes connecting the links.

5. The system of claim 1, wherein the crystallization unit comprises a spiral.

6. The system of claim 5, wherein the lattice comprises spiral geometric shapes spatially distributed in a periodic manner.

7. The system of claim 1 , wherein the process modeling application further comprises a deep learning algorithm trained to predict: a) transition volumes between different functionalized volumes, and b) a transitional crystalline unit of the transitional volume.

8. The system of claim 7, wherein the deep learning algorithm comprises one or more neural networks (NNs).

9. The system of claim 8, wherein the one or more NNs comprise one or more generative adversarial networks (GANs) or one or more variational autoencoders (VAEs).

10. The system of claim 1, wherein the one or more simulations comprise finite element analysis (FEA).

11. The system of claim 1 , wherein the one or more simulations assess microfluidic continuity of the at least one microchannel or chamber.

12. The system of claim 1, wherein performance of the procedural modeling application does not degrade as the size of the scene or the detail of the scene increases.

13. The system of claim 1, wherein the at least one processor comprises a plurality of graphics processing units (GPUs).

14. The system of claim 1, wherein the at least one processor comprises a cloud computing platform.

15. The system of claim 1, wherein the interface comprises a viewport.

16. The system of claim 1, wherein the rendering module further comprises a configuration for rendering the scene using ray marching.

17. The system of claim 1, wherein the rendering module allows the user to save the scene to a scene library.

Images