Blood-brain barrier; TEER; drug discovery; high throughput screening; lung; microfluidics; organ-on-chip; shear stress; skin; vascular barriers; Humans; Models, Biological; Electric Impedance; Blood-Brain Barrier/metabolism; Lab-On-A-Chip Devices; Biochemistry; Histology; Cell Biology
Abstract :
[en] The development of new therapies is hampered by the lack of predictive, and patient-relevant in vitro models. Organ-on-chip (OOC) technologies can potentially recreate physiological features and hold great promise for tissue and disease modeling. However, the non-standardized design of these chips and perfusion control systems has been a barrier to quantitative high-throughput screening (HTS). Here we present a scalable OOC microfluidic platform for applied kinetic in vitro assays (AKITA) that is applicable for high, medium, and low throughput. Its standard 96-well plate and 384-well plate layouts ensure compatibility with existing laboratory workflows and high-throughput data collection and analysis tools. The AKITA plate is optimized for the modeling of vascularized biological barriers, primarily the blood-brain barrier, skin, and lung, with precise flow control on a custom rocker. The integration of trans-epithelial electrical resistance (TEER) sensors allows rapid and repeated monitoring of barrier integrity over long time periods. Together with automated liquid handling and compound permeability testing analyses, we demonstrate the flexibility of the AKITA platform for establishing human-relevant models for preclinical drug and precision medicine's efficacy, toxicity, and permeability under near-physiological conditions.
Disciplines :
Biotechnology
Author, co-author :
Nguyen, Hoang-Tuan ; Finnadvance Ltd, Oulu, Finland ; Faculty of Biochemistry and Molecular Medicine, and Biocenter Oulu, University of Oulu, Oulu, Finland
Rissanen, Siiri-Liisa; Finnadvance Ltd, Oulu, Finland
Peltokangas, Mimosa; Finnadvance Ltd, Oulu, Finland
Laakkonen, Tino; Finnadvance Ltd, Oulu, Finland
Kettunen, Jere; Finnadvance Ltd, Oulu, Finland
Barthod, Lara; Finnadvance Ltd, Oulu, Finland
Sivakumar, Ragul; Finnadvance Ltd, Oulu, Finland
Palojärvi, Anniina; Finnadvance Ltd, Oulu, Finland
Junttila, Pauliina; Finnadvance Ltd, Oulu, Finland
Talvitie, Jussi; Finnadvance Ltd, Oulu, Finland
BASSIS, Michele ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Developmental and Cellular Biology > Team Jens Christian SCHWAMBORN
NICKELS, Sarah Louise ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology
Kalvala, Sara; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Ilina, Polina; Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
Tammela, Päivi; Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
Lehtonen, Sarka; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland ; Neuroscience Center, University of Helsinki, Helsinki, Finland
SCHWAMBORN, Jens Christian ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology
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