The screening of large cell libraries is an important process in pharmaceutical discovery and R&D, e.g. to define drug targets or develop effective medicines. The goal of this project is the implementation of a screening platform based on 3D cultivation of primary human mesothelioma cells encapsulated in alginate hydrogels. To this end, new hydrogel compositions will be designed, tested and finally utilized in the Nanoliter Reactor (NLR) cultivation system that enables high throughput analysis of 3D cell cultures

Bono, Epifania

Felley-Bosco, Emanuela

Hund, Corinna

Meyer, Andreas

Pelleaux, René

Picenoni, Armin

Rimann, Markus

ZHAW digitalcollection

Business Potential• New market entry from microbial library screening(industrial biotechnology) to mammalian libraryscreening (pharmaceutical industry)• High throughput compatible matrix-based 3D cellculture technology• Primary cell line developmento Patient-derived cancer (stem) cell lines• Phenotypic high throughput screeningo Enrichment of cancer-derived cell subpopulationsfor targeted therapyo Discovery of novel biologics and efficacy and toxicology studies with small moleculesAcknowledgementsWe gratefully thank the innovation promotion agency (CTI, Switzerland) for finacial support of the project and technical guidanceDevelopment of a matrix-based technology platformfor the high throughput analysis of 3D cell culturesProject Number: CTI 18364.2 PFLS-LSMain Applicant: ZHAW, Dr. Markus Rimann, Dr. Epifania Bono, Armin PicenoniResearch Partner: University Hospital Zurich, Dr. Emanuela Felley-BoscoMain Industrial Partner: FGen GmbH, Dr. Andreas Meyer, René Pellaux, Corinna HundStart: 01.01.2017, Duration: 24 monthsProject goalThe screening of large cell libraries is an important process inpharmaceutical discovery and R&D, e.g. to define drug targets ordevelop effective medicines. The goal of this project is theimplementation of a screening platform based on 3D cultivation ofprimary human mesothelioma cells encapsulated in alginatehydrogels (Fig. 1) . To this end new hydrogel compositions will bedesigned, tested and finally utilized in the Nanoliter Reactor(NLR) cultivation system (Fig. 2) that enables high throughputanalysis of 3D cell cultures.Key Findings• Successful manual cell encapsulation of mesothelioma cell lineZL55SPT into alginate beads (Fig. 1A)• Life/dead staining of encapsulated ZL55SPT cells (Fig. 1B)Scientific Innovation• 3D cell culture of mammalian cells in Ca-alginate hydrogels offering different microenvironments:o Blending of alginate with natural environment mimicking compounds o Modification of the hydrogel stiffness to adapt to native tissue • Implementation of the modified Ca-alginate hydrogel in the NLR-technology to produce reliable monodisperse capsules at high reproducibility.• Development of a novel method to generate patient-derived primary mesothelioma cell lines in 3D (e.g. cell subpopulations, like cancer stem cells) from a biopsy in a high throughput manner using the NLR-technology. • Retain the encapsulated mesothelioma cells in their native state to use them for drug development/treatment to gain predictive drug responses. • Comparison of in vitro to in vivo and come up with strategies to develop personalized drug treatment regimes.Fig. 1: Mesothelioma cell line ZL55SPT encapsulated in alginate beads. A) Cellgrowth and spheroid formation after 9 days of incubation. B) Life/Dead staining(green/red) of cells after 21 days of incubation.Fig. 2: NLR technology schemeCultivation106 NLRs/100 mLEncapsulation0.7 - 3.5 kHzCell library105 – 107 cells Ø: 20 – 600 µmNLRs with cellsPhenotypic Assay NLRs with clusters>200 cells/clusterFluorescent hits3 fluorescent signalsCharacterizationSecondary assaysAnalysis/Selection10 – 250 HzIsolation from NLR A B

Development of a matrix-based technology platform for the high throughput analysis of 3D cell cultures

ZHAW Zürcher Hochschule für Angewandte Wissenschaften

Business Potential
• New market entry from microbial library screening
(industrial biotechnology) to mammalian library
screening (pharmaceutical industry)
• High throughput compatible matrix-based 3D cell
culture technology
• Primary cell line development
o Patient-derived cancer (stem) cell lines
• Phenotypic high throughput screening
o Enrichment of cancer-derived cell subpopulations
for targeted therapy
o Discovery of novel biologics and efficacy and 
toxicology studies with small molecules
Acknowledgements
We gratefully thank the innovation promotion agency (CTI, 
Switzerland) for finacial support of the project and technical guidance
Development of a matrix-based technology platform
for the high throughput analysis of 3D cell cultures
Project Number: CTI 18364.2 PFLS-LS
Main Applicant: ZHAW, Dr. Markus Rimann, Dr. Epifania Bono, Armin Picenoni
Research Partner: University Hospital Zurich, Dr. Emanuela Felley-Bosco
Main Industrial Partner: FGen GmbH, Dr. Andreas Meyer, René Pellaux, Corinna Hund
Start: 01.01.2017, Duration: 24 months
Project goal
The screening of large cell libraries is an important process in
pharmaceutical discovery and R&D, e.g. to define drug targets or
develop effective medicines. The goal of this project is the
implementation of a screening platform based on 3D cultivation of
primary human mesothelioma cells encapsulated in alginate
hydrogels (Fig. 1) . To this end new hydrogel compositions will be
designed, tested and finally utilized in the Nanoliter Reactor
(NLR) cultivation system (Fig. 2) that enables high throughput
analysis of 3D cell cultures.
Key Findings
• Successful manual cell encapsulation of mesothelioma cell line
ZL55SPT into alginate beads (Fig. 1A)
• Life/dead staining of encapsulated ZL55SPT cells (Fig. 1B)
Scientific Innovation
• 3D cell culture of mammalian cells in Ca-alginate hydrogels 
offering different microenvironments:
o Blending of alginate with natural environment mimicking 
compounds 
o Modification of the hydrogel stiffness to adapt to native 
tissue 
• Implementation of the modified Ca-alginate hydrogel in the 
NLR-technology to produce reliable monodisperse capsules 
at high reproducibility.
• Development of a novel method to generate patient-derived 
primary mesothelioma cell lines in 3D (e.g. cell 
subpopulations, like cancer stem cells) from a biopsy in a 
high throughput manner using the NLR-technology. 
• Retain the encapsulated mesothelioma cells in their native 
state to use them for drug development/treatment to gain 
predictive drug responses. 
• Comparison of in vitro to in vivo and come up with 
strategies to develop personalized drug treatment regimes.
Fig. 1: Mesothelioma cell line ZL55SPT encapsulated in alginate beads. A) Cell
growth and spheroid formation after 9 days of incubation. B) Life/Dead staining
(green/red) of cells after 21 days of incubation.
Fig. 2: NLR technology scheme
Cultivation
106 NLRs/100 mL
Encapsulation
0.7 - 3.5 kHz
Cell library
105 – 107 cells Ø: 20 – 600 µm
NLRs with cells
Phenotypic 
Assay 
NLRs with clusters
>200 cells/cluster
Fluorescent hits
3 fluorescent signals
Characterization
Secondary assays
Analysis/Selection
10 – 250 Hz
Isolation 
from NLR 
A B


https://digitalcollection.zhaw.ch/bitstream/11475/5403/1/SwissMedtechDay_2017_Poster_final.pdf

Development of a matrix-based technology platform for the high throughput analysis of 3D cell cultures

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