학술논문

Mikrofluidik-Chip-Architekturen für eine Zell-Sortieranlage basierend auf der Elektrowetting-Technologie
Document Type
research-article
Source
tm - Technisches Messen. 83(5):274-288
Subject
Mikrofluidik
Elektrowetting
CMOS Technologie
Fluoreszenzanalyse
Zellsortierung
Zytometrie
FACS
Sorterarchitektur
physikalischer Sortieralgorithmus
fluiddynamische Simulationen
Microfluidics
electrowetting
CMOS technology
fluorescence analysis
cell sorting
cytometry
sorter architecture
physical sorting
computational fluid dynamics
Beiträge
Language
German
ISSN
0171-8096
2196-7113
Abstract
In this contribution we present the development of various physical sorting algorithms, each of which is represented by a corresponding sorter topology for a microfluidic-based cell sorter chip using electrowetting on dielectric (EWOD) as transport mechanism. One of the main tasks of this novel cell sorter is devoted to the study of specific cell mechansims using cell selection in the research on tumor genesis with respect to e. g. the development of leukemias or lymphomas. The development of the multi-layer chip has been carried out in the framework of the EU founded (EFRE) joint research project „MINAPSO“ (Mikrochip Navigierte Parallel Sortier-Anlage) and encompasses a control chip in standard CMOS technology together with the corresponding mictrofluidic packaging. The hereby realized sorter topology consists of an optimized so-called „2-3-Sequential-Divider-Sorter“ with a numerically estimated performance (i. e. cell throughput) between 0.6 bis 1.85 cells/clock (future chip architectures such as the so-called „Smart-Diffusion-Sorter“ achieve even higher cell throughputs up to 5 cells/clock). For the modeling and optimization of the sorter architectures (aka sorter algorithms) a simulation platform has been developed and implemented in MATLAB. Here the EWOD-based droplet manipulations and subsequent operators have been represented and handled within a sort of data paradigm in order to closely conform to the essentials of digital microfluidics. To estimate the characteristic time delays and the impact of the EWOD-based operators on the overall cell throughput together with the quest for hidden optimization potentials the previous numerical logistic analysis is paralleled by extensive computational fluid dynamics (CFD) simulations using COMSOL Multiphysics as well as by corresponding droplet actuation experiments. It's worth noting that the presented cell sorter stands – to the best of our knowledge – for the currently most complex EWOD microfluidic chip.