Mixing in centrifugal microfluidics
Medical Physics, Biomedical Technology
Final Report Abstract
In the project CentriMix, a batch‐mode mixing for centrifugal microfluidics operated at fixed rotational frequency was developed. Gas is generated by the disk integrated decomposition of hydrogen peroxide (H2O2) to liquid water (H2O) and gaseous oxygen (O2) and inserted into a mixing chamber. There, bubbles are formed that ascent through the liquid in the artificial gravity field and lead to drag flow. Additionally, strong buoyancy causes deformation and rupture of the gas bubbles and induces strong mixing flows in the liquids. Buoyancy driven bubble mixing is quantitatively compared to shake mode mixing, mixing by reciprocation and vortex mixing. To determine mixing efficiencies in a meaningful way, the different mixers are employed for mixing of a lysis reagent and human whole blood. Subsequently, DNA is extracted from the lysate and the amount of DNA recovered is taken as a measure for mixing efficiency. Relative to standard vortex mixing, DNA extraction based on buoyancy driven bubble mixing resulted in yields of 92 ± 8 % (100 s mixing time) and 100 ± 8 % (600 s) at 130⋅g centrifugal acceleration. Shake mode mixing yields 96 ± 11 % and is thus equal to buoyancy driven bubble mixing. An advantage of buoyancy driven bubble mixing is that it can be operated at fixed rotational frequency, however. The additional costs of implementing buoyancy driven bubble mixing are low since both the activation liquid and the catalyst are very low cost and no external means are required in the processing device. Furthermore, buoyancy driven bubble mixing can easily be integrated in a monolithic manner and is compatible to scalable manufacturing technologies such as injection moulding or thermoforming. We consider buoyancy driven bubble mixing an excellent alternative to shake mode mixing, in particular if the processing device is not capable of providing fast changes of rotational frequency or if the low average rotational frequency is challenging for the other integrated fluidic operations. In the next step, the bubble mixer was developed to function without prestorage of a chemical. Instead temperature and a specific arrangement of channels and chambers were used to pump air through a liquid filled chamber thus mixing the liquid. Finally, the developed bubble mixer was applied to mix beads and liquids in a next generation sequencing library preparation workflow automated by centrifugal microfluidics. Here we see considerable potential to transfer the technology to a successful product.
Publications
- Rigorous buoyancy driven bubble mixing for centrifugal microfluidics, Lab on a Chip 16, 261 – 268 (2016)
S. Burger, M. Schulz, F. von Stetten, R. Zengerle and N. Paust
(See online at https://doi.org/10.1039/c5lc01280e) - Temperature change rate actuated bubble mixing for homogeneous rehydration of dry prestored reagents in centrifugal microfluidics, Lab on a Chip 18, 362 – 370 (2018)
S. Hin, N. Paust, M. Keller, M. Rombach, O. Strohmeier, R. Zengerle and K. Mitsakakis
(See online at https://doi.org/10.1039/c7lc01249g) - LabSlice XL – a centrifugal microfluidic cartridge for the automated bio‐chemical processing of industrial process water, Doktorarbeit 2019
S. Burger
(See online at https://doi.org/10.6094/UNIFR/17481) - Review on pneumatic operations in centrifugal microfluidics, Lab on a Chip 22, 3745 – 3770 (2019)
J. F. Hess, S. Zehnle, P. Juelg, T. Hutzenlaub, R. Zengerle and N. Paust
(See online at https://doi.org/10.1039/c9lc00441f)
