{"title":"三维打印的可高压灭菌的生物相容性生物可降解生物反应器容器,带有聚乳酸制成的集成喷射器。","authors":"Lena Achleitner , Martina Winter , Peter Satzer","doi":"10.1016/j.jbiotec.2024.06.001","DOIUrl":null,"url":null,"abstract":"<div><p>3D printing has become widespread for the manufacture of parts in various industries and enabled radically new designs. This trend has not spread to bioprocess development yet, due to a lack of material suitable for the current workflow, including sterilization by autoclaving. This work demonstrates that commercially available heat temperature stable poly-lactic acid (PLA) can be used to easily manufacture novel bioreactor vessels with included features like harvest tubes and 3D printed spargers. Temperature responsiveness was tested for PLA, temperature stable PLA (PLA-HP) and glass for temperatures relevant for insect and mammalian cell culture, including temperature shifts within the process. Stability at 27 °C and 37 °C as well as temperature shifts to 22 °C and 32 °C showed acceptable performance with slightly higher temperature overshoot for 3D printed vessels. A stable temperature is reached after 2 h for PLA, 3 h for PLA-HP and 1 h for glass reactors. Temperature can be maintained with a fluctuation of 0.1 °C for all materials. A 3D printed sparger design directly integrated into the vessel wall and bottom was tested under three different conditions (0.3 SLPH and 27 °C, 3 SLPH and 37 °C and 13 SLPH and 37 °C). The 3D printed sparger showed a better <em>k</em><sub><em>L</em></sub><em>a</em> than the L-Sparger with more pronounced differences for higher flowrates. An insect cell culture run in the novel vessel exhibited the same growth behavior as that in standard glass vessels, reaching the same maximum cell concentration. Being 3D printed from biodegradable materials, these bioreactors offer design flexibility for novel bioreactor formats. Additionally, their autoclavability allows seamless integration into standard workflows.</p></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"391 ","pages":"Pages 33-39"},"PeriodicalIF":4.1000,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168165624001585/pdfft?md5=84eaa92ae8eab00368f5f0b282323f19&pid=1-s2.0-S0168165624001585-main.pdf","citationCount":"0","resultStr":"{\"title\":\"3D printed autoclavable biocompatible biodegradable bioreactor vessels with integrated sparger made from poly-lactic acid\",\"authors\":\"Lena Achleitner , Martina Winter , Peter Satzer\",\"doi\":\"10.1016/j.jbiotec.2024.06.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>3D printing has become widespread for the manufacture of parts in various industries and enabled radically new designs. This trend has not spread to bioprocess development yet, due to a lack of material suitable for the current workflow, including sterilization by autoclaving. This work demonstrates that commercially available heat temperature stable poly-lactic acid (PLA) can be used to easily manufacture novel bioreactor vessels with included features like harvest tubes and 3D printed spargers. Temperature responsiveness was tested for PLA, temperature stable PLA (PLA-HP) and glass for temperatures relevant for insect and mammalian cell culture, including temperature shifts within the process. Stability at 27 °C and 37 °C as well as temperature shifts to 22 °C and 32 °C showed acceptable performance with slightly higher temperature overshoot for 3D printed vessels. A stable temperature is reached after 2 h for PLA, 3 h for PLA-HP and 1 h for glass reactors. Temperature can be maintained with a fluctuation of 0.1 °C for all materials. A 3D printed sparger design directly integrated into the vessel wall and bottom was tested under three different conditions (0.3 SLPH and 27 °C, 3 SLPH and 37 °C and 13 SLPH and 37 °C). The 3D printed sparger showed a better <em>k</em><sub><em>L</em></sub><em>a</em> than the L-Sparger with more pronounced differences for higher flowrates. An insect cell culture run in the novel vessel exhibited the same growth behavior as that in standard glass vessels, reaching the same maximum cell concentration. Being 3D printed from biodegradable materials, these bioreactors offer design flexibility for novel bioreactor formats. 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引用次数: 0
摘要
三维打印技术已广泛应用于各行各业的零件制造,并带来了全新的设计。由于缺乏适合当前工作流程(包括高压灭菌)的材料,这一趋势尚未蔓延到生物工艺开发领域。这项工作证明,市面上热温稳定的聚乳酸(PLA)可用于轻松制造新型生物反应器容器,其中包括采收管和 3D 打印喷嘴等功能。测试了聚乳酸、温度稳定聚乳酸(PLA-HP)和玻璃在昆虫和哺乳动物细胞培养相关温度下的温度响应性,包括过程中的温度变化。在 27 °C 和 37 °C 温度下的稳定性,以及在 22 °C 和 32 °C 温度下的温度变化,都显示出可以接受的性能,但 3D 打印容器的温度过冲稍高。聚乳酸反应器在 2 小时后达到稳定温度,聚乳酸-热塑性聚乳酸反应器在 3 小时后达到稳定温度,玻璃反应器在 1 小时后达到稳定温度。所有材料的温度波动均可保持在 0.1 °C。在三种不同条件下(0.3 SLPH 和 27 °C、3 SLPH 和 37 °C、13 SLPH 和 37 °C),对直接集成到容器壁和底部的三维打印喷射器设计进行了测试。与 L 型分流器相比,3D 打印分流器显示出更好的 kLa,在流速较高时差异更为明显。在新型容器中进行的昆虫细胞培养表现出与在标准玻璃容器中相同的生长行为,达到相同的最大细胞浓度。这些生物反应器由生物可降解材料三维打印而成,为新型生物反应器的设计提供了灵活性。此外,它们的高压灭菌性允许无缝集成到标准工作流程中。
3D printed autoclavable biocompatible biodegradable bioreactor vessels with integrated sparger made from poly-lactic acid
3D printing has become widespread for the manufacture of parts in various industries and enabled radically new designs. This trend has not spread to bioprocess development yet, due to a lack of material suitable for the current workflow, including sterilization by autoclaving. This work demonstrates that commercially available heat temperature stable poly-lactic acid (PLA) can be used to easily manufacture novel bioreactor vessels with included features like harvest tubes and 3D printed spargers. Temperature responsiveness was tested for PLA, temperature stable PLA (PLA-HP) and glass for temperatures relevant for insect and mammalian cell culture, including temperature shifts within the process. Stability at 27 °C and 37 °C as well as temperature shifts to 22 °C and 32 °C showed acceptable performance with slightly higher temperature overshoot for 3D printed vessels. A stable temperature is reached after 2 h for PLA, 3 h for PLA-HP and 1 h for glass reactors. Temperature can be maintained with a fluctuation of 0.1 °C for all materials. A 3D printed sparger design directly integrated into the vessel wall and bottom was tested under three different conditions (0.3 SLPH and 27 °C, 3 SLPH and 37 °C and 13 SLPH and 37 °C). The 3D printed sparger showed a better kLa than the L-Sparger with more pronounced differences for higher flowrates. An insect cell culture run in the novel vessel exhibited the same growth behavior as that in standard glass vessels, reaching the same maximum cell concentration. Being 3D printed from biodegradable materials, these bioreactors offer design flexibility for novel bioreactor formats. Additionally, their autoclavability allows seamless integration into standard workflows.
期刊介绍:
The Journal of Biotechnology has an open access mirror journal, the Journal of Biotechnology: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
The Journal provides a medium for the rapid publication of both full-length articles and short communications on novel and innovative aspects of biotechnology. The Journal will accept papers ranging from genetic or molecular biological positions to those covering biochemical, chemical or bioprocess engineering aspects as well as computer application of new software concepts, provided that in each case the material is directly relevant to biotechnological systems. Papers presenting information of a multidisciplinary nature that would not be suitable for publication in a journal devoted to a single discipline, are particularly welcome.