WO2017143357A1 - Low temperature module for a 3d biological printer deposition system and build platform - Google Patents

Low temperature module for a 3d biological printer deposition system and build platform Download PDF

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Publication number
WO2017143357A1
WO2017143357A1 PCT/US2017/021271 US2017021271W WO2017143357A1 WO 2017143357 A1 WO2017143357 A1 WO 2017143357A1 US 2017021271 W US2017021271 W US 2017021271W WO 2017143357 A1 WO2017143357 A1 WO 2017143357A1
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WO
WIPO (PCT)
Prior art keywords
filament
bioactive
extruded bioactive
extruded
solution
Prior art date
Application number
PCT/US2017/021271
Other languages
French (fr)
Inventor
Wei Sun
Qudus Hamid
Original Assignee
Sunp Biotech, Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sunp Biotech, Llc filed Critical Sunp Biotech, Llc
Publication of WO2017143357A1 publication Critical patent/WO2017143357A1/en

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/10Processes of additive manufacturing
    • B29C64/106Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/205Means for applying layers
    • B29C64/209Heads; Nozzles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30Auxiliary operations or equipment
    • B29C64/364Conditioning of environment
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00Processes of additive manufacturing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00Apparatus for additive manufacturing; Details thereof or accessories therefor
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus

Definitions

  • 3D printers There is a significant rise in three-dimensional fabrication devices. These are commonly referred to 3D printers.
  • 3D printers Presently, there are a limited amount of 3D printers that have the abilities to print living biologies, such as, but not limited to human cells.
  • the technology and techniques to print a three-dimensional construct is well established.
  • the abilities to print various forms of materials are limited. For examples, many 3D printers today would only print some form of a hard plastic. This plastic would be fed thru a nozzle, heated, and extruded. This works well, however, the temperature is usually well above what cells can survive.
  • Reverse polymers are one in which at room temperature are solid or gel-like. However, at colder temperature it becomes more liquid-like. A cold fabrication head on a 3D biologies printer would expand the library of materials that can be used to fabricate physiologically relevant tissue constructs.
  • This article presents a low temperature module for a biological printer's deposition system and build platform.
  • This module is designed to be adaptive and integrative to current biological printer while providing the abilities to maintain a "cold" environment within the fabrication head.
  • a "cold” environment is defined as changing and maintain the temperature within the printer's fabrication system of at least one degrees Celsius (1°C) below ambient temperature.
  • Figure 1 depicts the cold-body of the low temperature module for the fabrication head and its components
  • FIG. 1 depicts the Schematic of the heat exchanger showing the heat fins
  • FIG. 3 depicts a photo of the Thermoelectric Peltier Cooler (TEC) used
  • Figure 4 depicts the system components of the low temperature module for the printer's fabrication system
  • Figure 5 depicts the low temperature module is mounted on the fabrication system of an existing 3D biological printer
  • Figure 6 depicts a schematic of the low temperature module for the build platform
  • This low temperature module has two components, namely; 1) the fabrication head module, and 2) the build platform module.
  • the fabrication head module will only cool the materials in the fabrication head ( Figure 1) while the build platform is primarily responsible for the build/fabrication process' integrity ( Figure 6).
  • the fabrication head module is designed to operate integratively with the 3D printer's deposition system.
  • This low temperature module has a proportional-integral - derivative (PID) temperature control unit, thermocouple, relay system, comprehensive heat exchanger ( Figure 2), a Thermoelectric Peltier Cooler (TEC) ( Figure 3), cold-body, and mounting apparatus.
  • PID proportional-integral - derivative
  • thermocouple thermocouple
  • relay system comprehensive heat exchanger
  • TEC Thermoelectric Peltier Cooler
  • the PID temperature control unit is integrated with the biological printer such that all settings and processes can be controlled by the end-user and/or with the printer's control system.
  • the PID system provides a unique feedback control system that reduces error and over-shooting temperature settings. Over-shooting temperature can create an environment that is too hot or cold, hence causing cell dead or damaging the material in the fabrication system. Coupled with the PID system is the relay system. Together these two systems provides and maintain thermal equilibrium (set by the end user).
  • the TEC is an electrical device that has the unique ability to produce a thermal difference between its faces. On one side of the TEC device it's hot, while the other feels cold. Since this system is designed to harvest the energy on the cold face, a heat exchange is incorporated to remove the heat from the other face.
  • the TEC device is controlled with the PID controller and a thermocouple provides a feedback to the control unit. The cold face of the TEC device is pushed against the "cold-body" which conducts and transfer the cold energy onto the fabrication system.
  • the heat exchanger's objective is to remove unwanted heat from the TEC to optimize a thermal difference to maintain a cold-body on the fabrication head.
  • the heat exchanger is a liquid cooling system which operates with a pump, radiator reservoir, and heat fins. The heat fins are pushed/mounted on the hot side of the TEC and collects the unwanted energy from the TEC unit. This unwanted energy is then transferred onto the fluid flowing between the fins. The fluid then goes to the radiator where a convection cooling technique removes the unwanted energy (heat) from the fluid and distributes it into the environment. The chilled fluid returned back to the fins, where this process begins again.
  • the "cold-body” is defined as the device in which cold energy is collected and maintains a frigid environment for the printer's deposition system.
  • the cold-body is design with 200 proof ethanol to enhance the unit's potential to maintain a frigid environment.
  • the ethanol surround the deposition head, hence, maintain a constant temperature setting.
  • the cold-body has a mount apparatus to ensure a tight and secure fit onto the fabrication system.
  • Figure 4 shows the system components while Figure 5 shows the low temperature module mounted on an existing printer's fabrication head.
  • the low temperature module for the fabrication head is used to apply and maintain a cold environment for the material within the printer's deposition head. For many reverse polymers, at cooler/low temperature, the material becomes more liquid- like. While at room temperature the material is more rigid. These types of materials are of great interest in the field for tissue engineering, bio-printing. In order to fabricate any three-dimensional constructs, the fabrication device must be able to manipulate the deposited material. When using cells to print any tissue construct, there cannot be any material/chemicals present that may harm the cells. Reverse polymers are great for cell printing, because they do not require any chemical cross-linking to retain their fabricated architecture. Also, since cells are survive sub-zero conditions, printing them within a cold nozzle should not significantly cause death. This low temperature module for the fabrication head will provide a new opportunity to fabricate more physiologically relevant tissue constructs.
  • the low temperature module for the fabrication head there is a low temperature module for the build platform.
  • the end-user may not want to cool the material in the print head, but at the build platform where the fabrication process is occurring.
  • This module provides a low temperature environment similar to that of the low temperature module of the fabrication head.
  • the module for the build platform can be using with or independent of the module with the fabrication head. When used with the fabrication head, it is maintaining a constantly cold environment from the fabrication head until the fabrication process is 100% complete.
  • the build platform module can also present varying temperature to help with the gelation of the printed material.
  • the build platform is design to maintain the temperature within the build platform of at least one degrees Celsius (1°C) below ambient temperature.
  • the build platform operates integratively with the printer's deposition system.
  • This build platform module has a proportional-integral-derivative (PID) temperature control unit, thermocouple, relay system, a thermal heating element (TEC), comprehensive heat exchanger, and a cold- body. Together these components creates cold environment for cell printing.
  • PID proportional-integral-derivative
  • TEC thermal heating element

Abstract

This article presents a low temperature module for a biological printer's deposition system and build platform. This module is designed to be adaptive and integrative to a current biological printer while providing the ability to maintain a "cold" environment within the fabrication head. A "cold" environment is defined as changing and maintaining the temperature within the printer's fabrication system of at least one degrees Celsius (1 degree C) below ambient temperature.

Description

LOW TEMPERATURE MODULE FOR A 3D BIOLOGICAL PRINTER DEPOSITION SYSTEM AND BUILD PLATFORM
BACKGROUND
There is a significant rise in three-dimensional fabrication devices. These are commonly referred to 3D printers. Presently, there are a limited amount of 3D printers that have the abilities to print living biologies, such as, but not limited to human cells. The technology and techniques to print a three-dimensional construct is well established. However, the abilities to print various forms of materials are limited. For examples, many 3D printers today would only print some form of a hard plastic. This plastic would be fed thru a nozzle, heated, and extruded. This works well, however, the temperature is usually well above what cells can survive. There are materials that be printed at room temperature with cells. However, these materials are very limited and does not always provides the best conditions for cells to attached, generate, and/or regenerate. Since cells can survive very low temperate conditions (cold), they can be printed where there print head is cold. There are lots of bio-materials that are commonly referred to reverse- polymers. Reverse polymers are one in which at room temperature are solid or gel-like. However, at colder temperature it becomes more liquid-like. A cold fabrication head on a 3D biologies printer would expand the library of materials that can be used to fabricate physiologically relevant tissue constructs.
This article presents a low temperature module for a biological printer's deposition system and build platform. This module is designed to be adaptive and integrative to current biological printer while providing the abilities to maintain a "cold" environment within the fabrication head. A "cold" environment is defined as changing and maintain the temperature within the printer's fabrication system of at least one degrees Celsius (1°C) below ambient temperature.
BRIEF DESCRIPTION OF THE DRAWINGS
For a fuller understanding of the nature and desired objects of the present invention, reference is made to the following detailed description taken in conjunction with the accompanying drawing figures wherein like reference characters denote corresponding parts throughout the several views and wherein:
Figure 1 depicts the cold-body of the low temperature module for the fabrication head and its components;
Figure 2 depicts the Schematic of the heat exchanger showing the heat fins;
Figure 3 depicts a photo of the Thermoelectric Peltier Cooler (TEC) used;
Figure 4 depicts the system components of the low temperature module for the printer's fabrication system;
Figure 5 depicts the low temperature module is mounted on the fabrication system of an existing 3D biological printer;
Figure 6 depicts a schematic of the low temperature module for the build platform
DETAILED DESCRIPTION
This low temperature module has two components, namely; 1) the fabrication head module, and 2) the build platform module. The fabrication head module will only cool the materials in the fabrication head (Figure 1) while the build platform is primarily responsible for the build/fabrication process' integrity (Figure 6).
The fabrication head module is designed to operate integratively with the 3D printer's deposition system. This low temperature module has a proportional-integral - derivative (PID) temperature control unit, thermocouple, relay system, comprehensive heat exchanger (Figure 2), a Thermoelectric Peltier Cooler (TEC) (Figure 3), cold-body, and mounting apparatus.
The PID temperature control unit is integrated with the biological printer such that all settings and processes can be controlled by the end-user and/or with the printer's control system. The PID system provides a unique feedback control system that reduces error and over-shooting temperature settings. Over-shooting temperature can create an environment that is too hot or cold, hence causing cell dead or damaging the material in the fabrication system. Coupled with the PID system is the relay system. Together these two systems provides and maintain thermal equilibrium (set by the end user).
The TEC is an electrical device that has the unique ability to produce a thermal difference between its faces. On one side of the TEC device it's hot, while the other feels cold. Since this system is designed to harvest the energy on the cold face, a heat exchange is incorporated to remove the heat from the other face. The TEC device is controlled with the PID controller and a thermocouple provides a feedback to the control unit. The cold face of the TEC device is pushed against the "cold-body" which conducts and transfer the cold energy onto the fabrication system.
The heat exchanger's objective is to remove unwanted heat from the TEC to optimize a thermal difference to maintain a cold-body on the fabrication head. The heat exchanger is a liquid cooling system which operates with a pump, radiator reservoir, and heat fins. The heat fins are pushed/mounted on the hot side of the TEC and collects the unwanted energy from the TEC unit. This unwanted energy is then transferred onto the fluid flowing between the fins. The fluid then goes to the radiator where a convection cooling technique removes the unwanted energy (heat) from the fluid and distributes it into the environment. The chilled fluid returned back to the fins, where this process begins again.
The "cold-body" is defined as the device in which cold energy is collected and maintains a frigid environment for the printer's deposition system. The cold-body is design with 200 proof ethanol to enhance the unit's potential to maintain a frigid environment. The ethanol surround the deposition head, hence, maintain a constant temperature setting. The cold-body has a mount apparatus to ensure a tight and secure fit onto the fabrication system. Figure 4 shows the system components while Figure 5 shows the low temperature module mounted on an existing printer's fabrication head.
The low temperature module for the fabrication head is used to apply and maintain a cold environment for the material within the printer's deposition head. For many reverse polymers, at cooler/low temperature, the material becomes more liquid- like. While at room temperature the material is more rigid. These types of materials are of great interest in the field for tissue engineering, bio-printing. In order to fabricate any three-dimensional constructs, the fabrication device must be able to manipulate the deposited material. When using cells to print any tissue construct, there cannot be any material/chemicals present that may harm the cells. Reverse polymers are great for cell printing, because they do not require any chemical cross-linking to retain their fabricated architecture. Also, since cells are survive sub-zero conditions, printing them within a cold nozzle should not significantly cause death. This low temperature module for the fabrication head will provide a new opportunity to fabricate more physiologically relevant tissue constructs.
In addition to the low temperature module for the fabrication head, there is a low temperature module for the build platform. In some cases, the end-user may not want to cool the material in the print head, but at the build platform where the fabrication process is occurring. This module provides a low temperature environment similar to that of the low temperature module of the fabrication head. The module for the build platform can be using with or independent of the module with the fabrication head. When used with the fabrication head, it is maintaining a constantly cold environment from the fabrication head until the fabrication process is 100% complete. The build platform module can also present varying temperature to help with the gelation of the printed material.
The build platform is design to maintain the temperature within the build platform of at least one degrees Celsius (1°C) below ambient temperature. The build platform operates integratively with the printer's deposition system. This build platform module has a proportional-integral-derivative (PID) temperature control unit, thermocouple, relay system, a thermal heating element (TEC), comprehensive heat exchanger, and a cold- body. Together these components creates cold environment for cell printing.

Claims

1. A method of changing and maintain the temperature within a 3D biological printer's fabrication system of at least one degrees Celsius (1 °C) below ambient temperature.
2. A method of changing and maintain the temperature within a 3D biological printer's build platform of at least one degrees Celsius (1 °C) below ambient temperature.
3. The method of claim 1, wherein the low temperature module for the fabrication
system maintains a constantly cold environment of at least one degrees Celsius (1 °C) below ambient temperature for the fabrication head until the fabrication process is complete.
4. The method of claim 2, where in the low temperature module for the build platform maintains a constantly cold environment of at least one degrees Celsius (1 °C) below ambient temperature from the fabrication head until the fabrication process is complete.
5. The method of claim 1, wherein the extruded bioactive filament maintains cell
viability of at least 70%.
6. The method of claim 1, wherein the extruded bioactive filament includes one or more selected from the group consisting of: a polymer, a solution, a cell-lade solution, a chemically reactive solution, an aqueous solution, sodium alginate solutions, a sacrificial support material, a cell, alginate, a cross-linker, a cross-linking solution, a calcium chloride solution, and a hydrogel.
7. The method of claim 1, wherein the extruded bioactive filament is produced by
uniform mass flow rate.
8. The method of claim 1, wherein the extruded bioactive filament is produced by a gradient mass flow rate.
9. The method of claim 1, wherein the extruded bioactive filament is produced by
backwards mass flow rate.
10. The method of claim 1, wherein the extruded bioactive filament in-part comprised of one or more living cells.
11. The method of claim 1, wherein the extruded bioactive filament has no living
biologies.
12. The method of claim 1, wherein the extruded bioactive filament is symmetrical along a longitudinal axis
13. The method of claim 1, wherein the extruded bioactive filament is asymmetrical along a longitudinal axis.
14. The method of claim 1, wherein the extruded bioactive filament has one-dimensional pattern.
15. The method of claim 1, wherein the extruded bioactive filament has two-dimensional pattern.
16. The method of claim 1, wherein the extruded bioactive filament has three- dimensional pattern.
17. The method of claim 1, wherein the extruded bioactive filament has a largest cross- sectional dimension less than about 1 mm.
18. The method of using one of more fabrication head using the method in claim 1 : producing methods of claim 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16.
19. The method of claim 1, wherein the bioactive filament is used to produce:
microfluidic tissue constructs, tissue scaffolds, tissue-on-chip, organ-on-a-chip.
20. The method of claim 2, wherein the extruded bioactive filament maintains cell
viability of at least 70%.
21. The method of claim 2, wherein the extruded bioactive filament includes one or more selected from the group consisting of: a polymer, a solution, a cell-lade solution, a chemically reactive solution, an aqueous solution, sodium alginate solutions, a sacrificial support material, a cell, alginate, a cross-linker, a cross-linking solution, a calcium chloride solution, and a hydrogel.
22. The method of claim 2, wherein the extruded bioactive filament is produced by
uniform mass flow rate.
23. The method of claim 2, wherein the extruded bioactive filament is produced by a gradient mass flow rate.
24. The method of claim 2, wherein the extruded bioactive filament is produced by
backwards mass flow rate.
25. The method of claim 2, wherein the extruded bioactive filament in-part comprised of one or more living cells.
26. The method of claim 2, wherein the extruded bioactive filament has no living biologies.
27. The method of claim 2, wherein the extruded bioactive filament is symmetrical along a longitudinal axis
28. The method of claim 2, wherein the extruded bioactive filament is asymmetrical along a longitudinal axis.
29. The method of claim 2, wherein the extruded bioactive filament has one-dimensional pattern.
30. The method of claim 2, wherein the extruded bioactive filament has two-dimensional pattern.
31. The method of claim 2, wherein the extruded bioactive filament has three- dimensional pattern.
32. The method of claim 2, wherein the extruded bioactive filament has a largest cross- sectional dimension less than about 1 mm.
33. The method of using one of more fabrication head using the method in claim 2: producing methods of claim 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16.
34. The method of claim 2, wherein the bioactive filament is used to produce:
microfluidic tissue constructs, tissue scaffolds, tissue-on-chip, organ-on-a-chip.
35. A method wherein the methods of claims 1 and 2 can be used dependently and
independently.
PCT/US2017/021271 2016-01-25 2017-03-08 Low temperature module for a 3d biological printer deposition system and build platform WO2017143357A1 (en)

Applications Claiming Priority (2)

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US201662286510P 2016-01-25 2016-01-25
US62/286,510 2016-01-25

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CN110126254A (en) * 2019-04-15 2019-08-16 南方医科大学 A method of based in gel without support 3D printing biomimetic scaffolds
CN113769161A (en) * 2021-09-13 2021-12-10 国科温州研究院(温州生物材料与工程研究所) Near-infrared light-responsive bionic vascular stent for bone tissue regeneration and preparation method thereof

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US6372178B1 (en) * 1998-02-09 2002-04-16 Arizona Board Of Regents Acting For And On Behalf Of Arizona State University Method for freeform fabrication of a three-dimensional object
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Publication number Priority date Publication date Assignee Title
CN110126254A (en) * 2019-04-15 2019-08-16 南方医科大学 A method of based in gel without support 3D printing biomimetic scaffolds
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