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Rapid production and recovery of cell spheroids by automated droplet microfluidics
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.ORCID iD: 0000-0001-5232-0805
2019 (English)In: bioRxivArticle in journal (Refereed) Published
Abstract [en]

Droplet microfluidics enables high throughput cell processing, analysis and screening by miniaturizing the reaction vessels to nano- or pico-liter water-in oil droplets, but like many other microfluidic formats, droplet microfluidics have not been interfaced with or automated by laboratory robotics. Here we demonstrate automation of droplet microfluidics based on an inexpensive liquid handling robot for the automated production of human scaffold-free cell spheroids, using pipette actuation and interfacing the pipetting tip with a droplet generating microfluidic chip. In this chip we produce highly mono-disperse 290μm droplets with diameter CV of 1.7%. By encapsulating cells in these droplets, we produce cell spheroids in droplets and recover them to standard formats at a throughput of 85000 spheroids per microfluidic circuit per hour. The viability of the cells in spheroids remains high after recovery only decreased by 4% starting from 96% after 16 hours incubation in nanoliter droplets. Scaffold-free cell spheroids and 3D tissue constructs recapitulate many aspects of functional human tissue more accurately than 2D or single cell cultures, but assembly methods for spheroids, e.g. hanging drop micro-plates, has had limited throughput. The increased throughput and decreased cost of our method enables spheroid production at the scale needed for lead discovery drug screening and approaches the cost where these micro tissues could be used as building blocks for organ scale regenerative medicine.

Place, publisher, year, edition, pages
Cold Spring Harbor Laboratory , 2019.
National Category
Pharmaceutical Biotechnology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Medical Laboratory and Measurements Technologies
Identifiers
URN: urn:nbn:se:kth:diva-250382DOI: 10.1101/552687OAI: oai:DiVA.org:kth-250382DiVA, id: diva2:1307878
Note

QC 20190624

Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-06-24Bibliographically approved

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Publisher's full texthttps://www.biorxiv.org/content/10.1101/552687v2

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Langer, KrzysztofJönsson, Håkan

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