Open AccessSeamless Combination of Fluorescence-Activated Cell Sorting and Hanging-Drop Networks for Individual Handling and Culturing of Stem Cells and Microtissue Spheroids
Author(s) -
Axel K. Birchler,
Mischa Berger,
Verena Jäggin,
Telma Lopes,
Martin Etzrodt,
Patrick M. Misun,
Maria Pena-Francesch,
Timm Schroeder,
Andreas Hierlemann,
Olivier Frey
Publication year - 2016
Publication title -
analytical chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.117
H-Index - 332
eISSN - 1520-6882
pISSN - 0003-2700
DOI - 10.1021/acs.analchem.5b03513
Subject(s) - spheroid , microfluidics , cell sorting , chemistry , stem cell , drop (telecommunication) , microbiology and biotechnology , nanotechnology , microfluidic chip , fluorescence , cell , biomedical engineering , biophysics , biology , materials science , in vitro , computer science , engineering , biochemistry , telecommunications , physics , quantum mechanics
Open microfluidic cell culturing devices offer new possibilities to simplify loading, culturing, and harvesting of individual cells or microtissues due to the fact that liquids and cells/microtissues are directly accessible. We present a complete workflow for microfluidic handling and culturing of individual cells and microtissue spheroids, which is based on the hanging-drop network concept: The open microfluidic devices are seamlessly combined with fluorescence-activated cell sorting (FACS), so that individual cells, including stem cells, can be directly sorted into specified culturing compartments in a fully automated way and at high accuracy. Moreover, already assembled microtissue spheroids can be loaded into the microfluidic structures by using a conventional pipet. Cell and microtissue culturing is then performed in hanging drops under controlled perfusion. On-chip drop size control measures were applied to stabilize the system. Cells and microtissue spheroids can be retrieved from the chip by using a parallelized transfer method. The presented methodology holds great promise for combinatorial screening of stem-cell and multicellular-spheroid cultures.