Simulationsgestützte Charakterisierung von Transportprozessen und Affinitätsreaktionen an Festphasen in der zentrifugalen Mikrofluidik
Zusammenfassung der Projektergebnisse
In the project CentriPhase, affinity-based separation in centrifugal microfluidic systems was studied and an integration strategy for lateral flow strips (LFS) was developed. In addition to the extensively studied porous solid phase of the LFS, the binding to a planar solid phase was analysed. Here, the effect of Coriolis force mixing on surface based affinity reactions in a centrifugal microfluidic channel was investigated. A Streptavidin-Biotin system was used as model assay. A centrifugal cartridge (LabDisk) was compared with a pressure driven setup. The binding of analyte to the binding sites on the channel walls was significantly (p<0.01) enhanced of more than 30 % in the centrifugal system. This difference can be attributed to the induced Coriolis mixing inside the microfluidic channel. Since considerable potential was seen in the enhancement of the restricted capillary driven flow through LFSs, our focus was on the studying of the porous solid phase. A flow control for LFSs using centrifugal microfluidics was developed. The flow is controlled only by centrifugal force, thus it is independent of membrane wetting properties and permeability. The flow rate can be decreased and increased, enabling control of incubation times for a wide variety of samples. We deduced a formula as a guideline for the integration of chromatographic membranes into centrifugal microfluidic disks to ensure that all the sample liquid flows through the membrane, hence safely avoiding bypass flow around the membrane. We verified the calculated operation conditions using different membranes, different flow rates, and different sample viscosities and published these results in a peer reviewed journal. Nevertheless, the viscosity bias of LFSs remain a significant challenge. Therefore, we developed a centrifugal-pneumatic flow control for the porous solid phase to exclude the viscosity bias. Key feature is balancing the sample flow into the cassette of the stripe with the air flow out of the cassette. A viscosity independent flow rate of 3.42 ± 0.16 µl/min (± 5%) was demonstrated with samples with viscosities ranging by a factor 20 from 1.3 mPa*s to 25 mPa*s. Signal deviations of a model human IgG lateral flow assay caused by varying sample viscosities from 1.3 mPa*s to 2.5 mPa*s could be reduced from nearly 40 percentage points to less than 6 points. We also developed a LabDisk for a commercial available insulin-like growth factor I (IGF-I) lateral flow assay with integrated sample preparation. We could automate the blood plasma separation, the acidification of the sample, the neutralisation of the sample as well as the resuspension of gold nanoparticles on the LabDisk. Initial results are very encouraging and show the potential of centrifugal microfluidic point of care tests. The high level of interest shown by our partners and potential costumers has enabled us to launch further projects to turn the basic principles developed in CentriPhase into a final product.
Projektbezogene Publikationen (Auswahl)
- Total flow control for later flow tests with centrifugal microfluidics, Poster at MicroTAS 2018
Daniel M. Kainz, Susanna M. Früh, Tobias Hutzenlaub, Roland Zengerle and Nils Paust
- Flow control for lateral flow strips with centrifugal microfluidics, Lab on a Chip 19 (2019), 2718
Daniel M. Kainz, Susanna M. Früh, Tobias Hutzenlaub, Roland Zengerle and Nils Paust
(Siehe online unter https://doi.org/10.1039/c9lc00308h) - Flow profile through exposed porous media in centrifugal microfluidics, Poster at MicroTAS 2019
Daniel M. Kainz, Susanna M. Früh, Tobias Hutzenlaub, Roland Zengerle and Nils Paust
- Tailormade Immunological Reactions in Lateral Flow Strips Enabled by Total Flow Control, Poster at Wissenschaftsforum Chemie 2019
Susanna M. Früh, Daniel M. Kainz, Tobias Hutzenlaub, Roland Zengerle and Nils Paust
- Viscosity independent flow for planar chromatographic immunoassays by centrifugal microfluidics, Poster at MicroTAS 2020.
Daniel M. Kainz, Susanna M. Früh, Tobias Hutzenlaub, Roland Zengerle and Nils Paust
