W2
Chip-based disease models: Biomedical applications of organ-on-a-chip technologies
Prof. Peter Ertl, Technical University Vienna
Austria Wirtschaftsservice
Challenge
In 2004, the FDA estimated that 92 percent of drugs which pass preclinical tests, including mandatory animal tests, fail to proceed to the market – a situation that has not markedly improved over the last decade. Animal trials are not only controversial due to ethical considerations but also costly to perform, creating the demand for ethically responsible and economic research methods. As a result in vitro 2D cell cultures and cell-based assays have been extensively used in biomedical research, pharmaceutical development and toxicity testing in the last decades. Although studying in vitro cell cultures is an essential aspect of cell biology, its technological advancement has fallen dramatically behind compared to progress made in the fields of genomics, proteomics and high-throughput testing of biochemicals. In contrast, one new and promising research field which simultaneously addresses the fundamental need to develop alternative methods for animal tests, improve validity of the assay and throughput capability is called organ-on-a-chip technology. Organ-on-a-chips are 3D human living cell cultures that are cultivated in a dynamic microchip environment under controlled condition that maintain human tissue functionality or mimic organ dysfunction. Since disease-specific human cell types can be used to establish individual microtissues with physiologic cellular behavior, organ-on-a-chip technology can also be used for in vitro disease modeling.
Technology
Organs-on-chips technology is still in its infancy. To date no technological solutions exist that allow automation, standardization and miniaturization of cell-based assays to ensure high degree of reproducibility by simultaneously reducing manual labor steps, material costs as well as sample and media requirements. In our laboratory, we have developed four research platforms targeting (1) the inner lining of the joint capsule (synovium on a chip) to study the onset of rheumatic arthritis, (2) cartilage-on-chip and subsequently pathogenesis of osteoarthritis (OA), and (3) placenta-on-a-chip as well as (2) iPSC derived midbrain organoids-on-chip recreating naturally occurring Parkinson’s disease.
Commercial Opportunity
Collaboration with:
- industrial clients with R&D activities in the mentioned diagnostic field
- industrial R&D partners
Development Status
Alpha-prototypes developed and proof-of-concepts established
Patent Situation
Two patents filed (EP Priority 4/16 - Microfluididc device, 8/17 - Artificial cartilage and method for its production) and two patents in preparation.
Further Reading
www.tuwien.ac.at/aktuelles/news_detail/article/124941/
Sticker D et al. Microfluidic migration and wound healing assay based on mechanically inducing injuries of defined and highly reproducible areas. Anal Chem, 2017, 89 (4), 2326-2333
Ehgartner J et al. Simultaneous determination of oxygen and pH inside microfluidic devices using core-shell nanosensors. Anal Chem, 2016, 88 (19), 9796-9804
Rothbauer M et al. Recent advances and future applications of microfluidic live-cell microarrays. Biotech Adv 2015, 33(6), 948-961
Sticker D et al. Multi-layered, Membrane-integrated Microfluidics based on Replica Molding of a Thiol-ene Epoxy Thermoset for Organ-on-a-Chip Applications. Lab Chip, 2015, 15, 4542-4554
Rothbauer et al. Crystalline Protein Nanolayers as Multifunctional Biointerfaces for Simultaneous Cultivation of Adherent and Non-Adherent Cells in Microfluidic Devices. Adv Mater Interf, 2015, 2(1)
Ertl P et al. Lab-on-a-Chip Technologies for Stem Cell Research. Trends Biotechnol, 2014, 32 (5) 245-253
Organ-on-a-chip system containing embedded 3D hydrogel microtissues