Details
| Original language | English |
|---|---|
| Article number | 1060 |
| Journal | Micromachines |
| Volume | 12 |
| Issue number | 9 |
| Early online date | 31 Aug 2021 |
| Publication status | Published - Sept 2021 |
Abstract
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 × 106 cells mL−1 . 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.
Keywords
- 3D printing, Cell retention, CHO cells, Continuous cultivation, Inertial microfluidics, Microfluidics
ASJC Scopus subject areas
- Engineering(all)
- Control and Systems Engineering
- Engineering(all)
- Mechanical Engineering
- Engineering(all)
- Electrical and Electronic Engineering
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In: Micromachines, Vol. 12, No. 9, 1060, 09.2021.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - 3d printed microfluidic spiral separation device for continuous, pulsation-free and controllable cho cell retention
AU - Enders, Anton
AU - Preuss, John Alexander
AU - Bahnemann, Janina
N1 - Funding Information: Funding: This research was funded by German Research Foundation (DFG) via the Emmy Noether Programme, grant number 346772917. The publication of this article was funded by the Open Access Fund of the Leibniz Universität Hannover.
PY - 2021/9
Y1 - 2021/9
N2 - 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 × 106 cells mL−1 . 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.
AB - 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 × 106 cells mL−1 . 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.
KW - 3D printing
KW - Cell retention
KW - CHO cells
KW - Continuous cultivation
KW - Inertial microfluidics
KW - Microfluidics
UR - http://www.scopus.com/inward/record.url?scp=85114476079&partnerID=8YFLogxK
U2 - 10.3390/mi12091060
DO - 10.3390/mi12091060
M3 - Article
AN - SCOPUS:85114476079
VL - 12
JO - Micromachines
JF - Micromachines
SN - 2072-666X
IS - 9
M1 - 1060
ER -