3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention
The development of continuous bioprocesses—which require cell retention systems in order to enable longer cultivation durations—is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for gre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Micromachines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-666X/12/9/1060 |
| _version_ | 1797518185297084416 |
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| author | Anton Enders John-Alexander Preuss Janina Bahnemann |
| author_facet | Anton Enders John-Alexander Preuss Janina Bahnemann |
| author_sort | Anton Enders |
| collection | DOAJ |
| description | The development of continuous bioprocesses—which require cell retention systems in order to enable longer cultivation durations—is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for greater focusing in specific channel regions), which in turn facilitates the development of small continuous cell separation systems. However, previously published systems did not allow for separation control. Additionally, the focusing effect of these systems requires constant, pulsation-free flow for optimal operation, which cannot be achieved using ordinary peristaltic pumps. As described in this paper, a 3D printed cell separation spiral for CHO-K1 (Chinese hamster ovary) cells was developed and evaluated optically and with cell experiments. It demonstrated a high separation efficiency of over 95% at up to 20 × 10<sup>6</sup> cells mL<sup>−1</sup>. Control over inlet and outlet flow rates allowed the operator to adjust the separation efficiency of the device while in use—thereby enabling fine control over cell concentration in the attached bioreactors. In addition, miniaturized 3D printed buffer devices were developed that can be easily attached directly to the separation unit for usage with peristaltic pumps while simultaneously almost eradicating pump pulsations. These custom pulsation dampeners were closely integrated with the separator spiral lowering the overall dead volume of the system. The entire device can be flexibly connected directly to bioreactors, allowing continuous, pulsation-free cell retention and process operation. |
| first_indexed | 2024-03-10T07:26:36Z |
| format | Article |
| id | doaj.art-f0b94a8707654a6faa9a76fb0173f655 |
| institution | Directory Open Access Journal |
| issn | 2072-666X |
| language | English |
| last_indexed | 2024-03-10T07:26:36Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micromachines |
| spelling | doaj.art-f0b94a8707654a6faa9a76fb0173f6552023-11-22T14:16:03ZengMDPI AGMicromachines2072-666X2021-08-01129106010.3390/mi120910603D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell RetentionAnton Enders0John-Alexander Preuss1Janina Bahnemann2Institute of Technical Chemistry, Leibniz University Hannover, 30167 Hannover, GermanyInstitute of Technical Chemistry, Leibniz University Hannover, 30167 Hannover, GermanyInstitute of Technical Chemistry, Leibniz University Hannover, 30167 Hannover, GermanyThe development of continuous bioprocesses—which require cell retention systems in order to enable longer cultivation durations—is a primary focus in the field of modern process development. The flow environment of microfluidic systems enables the granular manipulation of particles (to allow for greater focusing in specific channel regions), which in turn facilitates the development of small continuous cell separation systems. However, previously published systems did not allow for separation control. Additionally, the focusing effect of these systems requires constant, pulsation-free flow for optimal operation, which cannot be achieved using ordinary peristaltic pumps. As described in this paper, a 3D printed cell separation spiral for CHO-K1 (Chinese hamster ovary) cells was developed and evaluated optically and with cell experiments. It demonstrated a high separation efficiency of over 95% at up to 20 × 10<sup>6</sup> cells mL<sup>−1</sup>. Control over inlet and outlet flow rates allowed the operator to adjust the separation efficiency of the device while in use—thereby enabling fine control over cell concentration in the attached bioreactors. In addition, miniaturized 3D printed buffer devices were developed that can be easily attached directly to the separation unit for usage with peristaltic pumps while simultaneously almost eradicating pump pulsations. These custom pulsation dampeners were closely integrated with the separator spiral lowering the overall dead volume of the system. The entire device can be flexibly connected directly to bioreactors, allowing continuous, pulsation-free cell retention and process operation.https://www.mdpi.com/2072-666X/12/9/1060microfluidics3D printinginertial microfluidicscontinuous cultivationcell retentionCHO cells |
| spellingShingle | Anton Enders John-Alexander Preuss Janina Bahnemann 3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention Micromachines microfluidics 3D printing inertial microfluidics continuous cultivation cell retention CHO cells |
| title | 3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention |
| title_full | 3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention |
| title_fullStr | 3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention |
| title_full_unstemmed | 3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention |
| title_short | 3D Printed Microfluidic Spiral Separation Device for Continuous, Pulsation-Free and Controllable CHO Cell Retention |
| title_sort | 3d printed microfluidic spiral separation device for continuous pulsation free and controllable cho cell retention |
| topic | microfluidics 3D printing inertial microfluidics continuous cultivation cell retention CHO cells |
| url | https://www.mdpi.com/2072-666X/12/9/1060 |
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