3D Cell Culture Incubator CERO 3D
The innovative 3D Cell Culture Incubator

3D Cell Culture Bioreactor & Incubator CERO 3D

3D Cell Culture Bioreactor & Incubator CERO 3D

The CERO 3D Incubator & Bioreactor is a new, revolutionary instrument creating optimal cell culture environment. It offers a special 3D cell culture technology that monitors and controls temperature, pH and carbon dioxide levels. Indeed, this is ideal for stem cells, spheroids, organoids and even tissues.

The CERO 3D Incubator & Bioreactor provides some distinct advantages. First and foremost, it improves viability and maturation with minimized apoptosis and necrosis. The CERO 3D Incubator & Bioreactor has no shear forces, no requirement for embedding substrate, thus providing maximum homogeneity and allowing long-term cultivation for more than one year. Indeed, this will significantly reduce your running costs.

The individually controlled provide highest biomass yields. With volumes up to 50 ml, the CEROtubes, have small fins and a flat bottom allowing mild cultivation conditions in a standardized and reproducible way, with minimum handling requirements.

The CERO 3D Incubator & Bioreactor allows for simplified scale-up and automation platforms, and cost reduction. This is due to its distinct advantages of easy to set-up and simple workflows and minimum hands-on time that can be down to less than 2 minutes per day.

The CERO 3D Incubator & Bioreactor is indeed ideal for a wide variety of applications, from stem cell expansion projects in biobanks, cell-based drug discovery, toxicity testing and regenerative medicine, it is your ideal partner. For stem cells, The CERO 3D Incubator & Bioreactor is able to differentiate in 3 germ layers , provide homogeneous iPSC and ESC 3D aggregates. Your cells can be easily processed directly for differentiation such as for organoids or spheroids as a downstream application in 3D or 2D assay development and avoid technical limitations of long-term culture with high efficiency and standardization.

The CERO 3D Incubator & Bioreactor indeed is an ever-evolving a state-of-the-art dynamic culture system, accelerates your processes reduces costs and hands-on time and allows multiplexing. It provides optimal nutrition, gas diffusion thus increasing size and lifespan of your cultures.

Highlights - 3D Cell Culture Incubator CERO 3D

  • Improved viability and maturation
  • No embedding substrate required
  • Significantly reduced apoptosis & necrosis
  • No shear forces
  • Long-term cultivation for > 1 year
  • Significant reduced running cost

The CERO 3D Incubator & Bioreactor offers a unique 3D cell culture technology to boost your stem cell, spheroid, organoid and tissue research.

Highest levels of homogeneity and viability in long term cultures are just two benefits CERO 3D will provide.

Break the limits in 3D Cell Culture

The CERO 3D Incubator & Bioreactor is a new, revolutionary instrument creating optimal cell culture environment by monitoring and controlling temperature, pH and CO2 levels. 1- 4 individually controlled CEROtubes with a volume of up to 50ml provide highest biomass yields in a standardized and reproducible way, with minimum handling requirements. The CEROtubes, with small fins and a flat bottom, enable gentle cultivation conditions with reduced shear stress to your cells.

Pluripotent Stem Cells

The CERO 3D Incubator & Bioreactor provides the solution for scale-up and automation platforms, simplification and cost reduction of stem cell expansion projects in biobanks, cell-based drug discovery, toxicity testing and regenerative medicine.

  • Microcarrier-free
  • Stable pluripotency over many passages
  • Easy to set-up and simple workflow
  • Free-floating 3D aggregates
  • Able to differentiate in 3 germ layers
  • Homogeneous iPSC and ESC aggregates

Human iPSC after expansion in CERO 3D

Pluripotent stem cells are directly inoculated as single cells into the CEROtube. During the self-aggregation the cells form homogeneous aggregates which can be expanded over many passages. The biomass increases significantly while only ~2min per day hands on time is required.

The resulting stem cell 3D aggregates can be processed directly for differentiation e.g. organoids or any other downstream application in 3D or 2D assay development.

CERO 3D Cell Culture Bioreactor iPSC Pluripotency
Human iPSC after expansion in CERO 3D Incubator & Bioreactor tested for pluripotency.
CERO 3D Cell Culture Bioreactor iPSC Differentiation
Human iPSC after expansion in CERO 3D Incubator & Bioreactor tested for differentiation in three germ layers.

Pluripotent stem cells expanded in CERO 3D (former name “BioLevitator”) will maintain pluripotency and can be differentiated into all 3 germ layers, as described by Elanzev et. al. 2015; Biotechnol. J. 2015, 10, 1589–1599:

Hepatitis Virus Research Model - Spheroids

The advent of long-term three dimensional cell culture holds a great promise in disease modeling and drug discovery. The cells kept in a 3D environment have the ability to mimic tissue-like structures more efficiently than in traditional 2D monolayer cultures. However, many scientist are struggling with many technical limitations when working with spheroids in long-term cultures.

The CERO 3D Incubator & Bioreactor is a revolutionary technology enabling scientists to perform experiments they were not able to do before.

  • No necrosis and apoptosis
  • Viability in long-term culture > 80 days
  • Improved maturation
  • Long-term proliferation
  • High homogeneity
  • High yield

Spheroids from HepG2 cells (hepatocyte cell line) cultivated in CERO 3D for >80 days.

Cells Proliferation
Cells are positive for cell proliferation marker KI67
Positive Cells
Cells are negative for apoptosis marker Casp.cl.3
Cells Albumin
Cells are positive for albumin

Virus Research

CERO 3D Incubator & Bioreactor enables growth and maturation of spheroids without necrosis and apoptosis while other technologies fail. Therefore, CERO 3D allows to maintain state-of-the-art 3D cultures of Huh7 hepatic cell line (see figure below). The disposable CEROtubes with Hepa filter allow safe virus experiments.

Virus Research CERO

Spheroid from hepatocyte cell line was matured for 20 days prior to exposure to HCV. Infection spreading (rate) was controlled after 24, 48 and 72hours (brown staining)

Cultivating hepatocyte spheroids in CERO considerably improves expansion, differentiation, maturation and hepatic virus infection compared to monolayer culture. Our research takes advantage from healthy cells even from long-term cultures in CERO. Moreover, we are now able to perform 3D long-term culture of human tissue specimen in CERO - a paradigm shift.

Prof. Dr. Heikenwälder, Chronic Inflammation and Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany

Cardiac Tissue Model

Beating Cardiac Bodies – a complete workflow

Stem cell derived cardiomyocytes gain more and more attention in the field of cardiovascular research, disease modeling and drug development.

The CERO 3D Incubator & Bioreactor platform allows the workflow with stem cell expansion in homogeneous aggregates followed by direct induction into a high number of beating cardiac bodies. The expansion of pluripotent stem cells and subsequent cardiac induction/differentiation in CERO 3D results in a much higher cell quality, homogeneity, integrity and yield compared to traditional orbital shakers.

Cardiac Tissue Model

CERO 3D versus Orbital shaker – differentiation of murine embryonic stem cell derived cardiomyocytes 3, 8 and 13 days after cardiac induction.

  • Homogeneous 3D aggregates in suspension
  • Expansion and differentiation in the same CEROtube
  • Easy to handle & standardize
  • Highest yield
  • No substrate required
  • More relevance for drug treatments
  • More relevance for disease modeling

Purified and homogeneous cardiac bodies generated in CERO 3D Incubator & Bioreactor are a perfect tool for disease modeling and drug discovery. The pure cardiomyocytes can also be used in 2D downstream monolayer applications.

The overarching aim of all our studies is the identification and development of clinically relevant therapeutic agents for the treatment of human heart disease. To that end we utilize human self-organised cardiac organoids for high throughput drug screening and in vivo genetic models of human congenital disease, as our experimental platform, in combination with adeno-associated virus (AAV) and anti-sense RNAs as therapeutic agents. The CERO 3D has considerably simplified our cardiac organoid generation workflow and enabled us to scale-up organoid production significantly. Organoids generated with CERO 3D reveal improved cellular organisation, and display uniformity and consistency within and across production batches.

Prof. Dr. Jaya Krishnan, Institute of Cardiovascular Regeneration, Goethe-University Frankfurt and Co-Founder of Genome Biologics

Moreover this 3D cultivation system substantially improves viability, maturation and contractility, therefore provides a reliable tool for cardiovascular therapies.

Yvonne Eibach, group of Prof. Thomas Braun, Max Planck Institute, Bad Nauheim

Organoids as Tumor Tissue Model

From Adult Stem Cells to Organoids

The CERO 3D Incubator & Bioreactor is a revolutionary technology for production of organoids from pluripotent or adult stem cells. It offers an efficient, standardizable way to generate and maintain high yields of homogeneous organoids used as a tool in cancer research. Remarkably, the organoids have also a predictive capacity for in vivo response.

  • Reduced costs and time
  • Increase size & lifespan
  • Optimal nutrition & gas diffusion
  • Free floating, no shear forces
  • High homogeneity and yield
  • Multiplexing organoidogenesis

Increase cellular, structural and functional complexity of organoids.

Gastric Organoids
Gastric organoids (bright field) at day 7 and after splitting on day 22 expanding from small cysts that expand to bigger spheres
Staining of Gastric Organoids
HE staining of Gastric organoids (2a) showing single layer of epithelia cells composed by the different cell types found in the stomach as seen in the PCR results (2b): expression of gastric mucins MUC5AC and MUC6, trefoil factors and pepsinogen, for instance. There are also stem cells markers like Lgr5 and Sox2.

The generation of gastric organoids is a crucial step in the study of Helicobacter pylori infection and gastric carcinogenesis. The CERO 3D Incubator & Bioreactor allows the generation in a much more efficient, reproducible, physiological and cost efficient way compared to any other approach

Dr. Raquel Mejias-Luque, TUM, Germany

Personalised and precision medicine

The progress in the development of molecular target therapies has improved the outcome in “in vivo”, however it is because of the tumor heterogeneity in patients that limits the efficiency of those drugs. Thus, to increase the relevance of “in vitro” models, it is particularly important to develop a reliable platform for growing primary tumor cells in a 3D in vitro model, like patient-derived xenografts or organoids. The CERO 3D Incubator & Bioreactor evolving a state-of-the-art dynamic culture system, accelerates precision medicine of primary tumor cells. The CERO 3D offers an efficient and reproducible approach to grow and maintain viable cancer cells in a CERO 3D Incubator & Bioreactor.

Positive Cholangiocellular
CK 20 positive Cholangiocellular carcinoma cancer cells
Viable Cholangiocellular
H & E staining: Viable Cholangiocellular carcinoma cancer cells
Positive Cells
MAPAC 155 positive cells

Our group is focusing on primary tumor cells grown on 3D polymer scaffolds. For that we are using CERO 3D to develop a model of drug development and precision medicine. It is particularly important that the cells are viable and proliferating in 3D complex structures as seen in tumor tissues. With the CERO 3D we are implementing and developing tools for patient-specific tumor therapy. Furthermore, the cancer cells isolated from fresh tumor biopsies make treatment optimization possible before a therapy is initiated. Here, CERO 3D incubator & bioreactor enables us to develop personalized medicine in a 3D cell culture model.

Prof. Dr. med. Felix Rückert, Geschäftsführender Oberarzt Chirurgische Klinik, Universitätsmedizin Mannheim

Publications

“Bradley Justice, Nadia A.Badr, Robin A.Felder (2009)
3D cell culture opens new dimensions in cell-based assays
Drug Discovery Today 102-107 ”
DOI: 10.1016/j.drudis.2008.11.006

“Susan Breslin, Lorraine O’Driscoll
Three-dimensional cell culture: the missing link in drug discovery
Drug Discovery Today Volume 240-249”
DOI: 10.1016/j.drudis.2012.10.003

“Simone Allazetta, Tanja C. Hausherr, and Matthias P. Lutolf
Microfluidic synthesis of cell-type-specific artificial extracellular matrix hydrogels
Biomacromolecules 2013, 14, 4, 1122–1131”
DOI: 10.1021/bm4000162″

“Maria Mrakovcic, Markus Absenger, Regina Riedl, Claudia Smole, Eva Roblegg, Leopold F Fröhlich, Eleonore Fröhlich
Assessment of long-term effects of nanoparticles in a microcarrier cell culture system
PLoS One. 2013; 8(2);e56791. ”
DOI: 10.1371/journal.pone.0056791

“Zhen-Yu Yang, Jun-Tao Kan, Ze-Yu Cheng, Xian-Li Wang, Yi-Zhun Zhu & Wei Guo
Daphnoretin-induced apoptosis in HeLa cells: a possible mitochondria-dependent pathway
Cytotechnology volume 66, pages51–61(2014)”
DOI: 10.1007/s10616-013-9536-8

“Bernhard Ellinger, Johanna Silber, Anjali Prashar, Johannes Landskron, Jonas Weber, Sarah Rehermann, Franz-Josef Müller, Stephen Smith, Stephen Wrigley, Kjetil Taskén, Philip Gribbon, Antje Labes, and Johannes F. Imhoff
A phenotypic screening approach to identify anticancer compounds derived from marine fungi
Assay Drug Dev Technol. 2014 Apr 1; 12(3): 162–175 ”
DOI: 10.1089/adt.2013.564

“Ching-Yu Lin, Chi-Hui Huang, Yuan-Kun Wu, Nai-Chen Cheng & Jiashing Yu
Maintenance of human adipose derived stem cell (hASC) differentiation capabilities using a 3D culture
Biotechnology Letters volume 36, pages1529–1537(2014) ”
DOI: 10.1007/s10529-014-1500-y

“Simon Wuest,  Stéphane Richard, Isabelle Walther, Reinhard Furrer, Roland Anderegg, Jörg Sekler & Marcel Egli
A Novel Microgravity Simulator Applicable for Three-Dimensional Cell Culturing
Microgravity Science and Technology volume 26, pages77–88(2014)”
DOI: 10.1007/s12217-014-9364-2

“Annette Geltmeier, Beate Rinner, Dennis Bade, Katharina Meditz,Reiner Witt, Uwe Bicker, Catrin Bludszuweit-Philipp, Patrick Maier
Characterization of Dynamic Behaviour of MCF7 and MCF10A Cells in Ultrasonic Field Using Modal and Harmonic Analyses
PLOS ONE”
DOI:10.1371/journal.pone.0134999

“Andreas Elanzew, Annika Sommer, Annette Pusch-Klein, Oliver Brüstle and Simone Haupt
A reproducible and versatile system for the dynamic expansion of human pluripotent stem cells in suspension
Biotechnol. J. 2015, 10, 1589–1599”
DOI: 10.1002/biot.201400757

“Akvilė Jarmalavičiūtė, Virginijus Tunaitis, Ugnė Pivoraitė, Algirdas Venalis, Augustas Pivoriūnas
Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine–induced apoptosis
Cytotherapy Volume 17, Issue 7, July 2015, Pages 932-939”
DOI: 10.1016/j.jcyt.2014.07.013

“Aletta Schnitzler, Anjali Verma, Daniel E. Kehoe, Donghui Jing, Julie R. Murrell, Kara A. Der, Manjula Aysola, Peter J. Rapiejko, Sandhya Punreddy, Martha S. Rook
Bioprocessing of human mesenchymal stem/stromal cells for therapeutic use: Current technologies and challenges
Biochemical Engineering Journal Volume 108, 15 April 2016, Pages 3-13”
DOI: 10.1016/j.bej.2015.08.014

“Guoliang Meng, Shiying Liu, Anna Poon, and Derrick E. Rancourt
Optimizing Human Induced Pluripotent Stem Cell Expansion in Stirred-Suspension Culture
Stem Cells and Development Vol. 26, No. 24”
DOI: 10.1089/scd.2017.0090

“Yongxin Zhang, Xianghan Wang, Mao Pong, Liang Chen, Zhijia Ye
Application of Bioreactor in Stem Cell Culture
J. Biomedical Science and Engineering, 2017, Vol. 10, (No. 11), pp; 485-499”
DOI: 10.4236/jbise.2017.1011037

“Michael Gepp, Benjamin Fischer, André Schulz, Johanne Dobringer, Luca Gentile, Julio A. Vásquez, Julia C. Neubauer, Heiko Zimmermann
Bioactive surfaces from seaweed-derived alginates for the cultivation of human stem cells
Journal of Applied Phycology volume 29, pages2451–2461(2017)”
DOI https://doi.org/10.1007/s10811-017-1130-6

“Alina Čebatariūnienė, Akvilė Jarmalavičiūtė, Virginijus Tunaitis, Alina Pūrienė, Algirdas Venalis, Augustas Pivoriūnasa
Microcarrier culture enhances osteogenic potential of human periodontal ligament stromal cells
Journal of Cranio-Maxillofacial Surgery Volume 45, Issue 6, June 2017, Pages 845-854”
DOI: 10.1016/j.jcms.2017.03.009

“Benjamin Fischer, Anna Meier, Annika Dehne, Aseem Salhotra, Thao Anh Tran, Sascha Neumann, Katharina Schmidt, Ina Meiser, Julia C. Neubauer, Heiko Zimmermann, Luca Gentile
A complete workflow for the differentiation and the dissociation of hiPSCderived cardiospheres
Stem Cell Research 32 (2018) 65–72”
DOI: 10.1016/j.scr.2018.08.015

“Róbert Alföldi, József Á. Balog, Nóra Faragó, Miklós Halmai, Edit Kotogány, Patrícia Neuperger, Lajos I. Nagy, Liliána Z. Fehér, Gábor J. Szebeni andLászló G. Puskás
Single Cell Mass Cytometry of Non-Small Cell Lung Cancer Cells Reveals Complexity of In Vivo and Three-Dimensional Models over the Petri-Dish Cells 2019, 8(9), 1093”
DOI: 10.3390/cells8091093

“Alina Čebatariūnienė, Karolina Kriaučiūnaitė, Justina Prunskaitė, Virginijus Tunaitis, and Augustas Pivoriūnas
Extracellular Vesicles Suppress Basal and Lipopolysaccharide-Induced NFκB Activity in Human Periodontal Ligament Stem Cells
Stem Cells Dev. 2019 Aug 1;28(15):1037-1049.”

“Shamsul Sulaiman, Shiplu Roy Chowdhury, Mh Busra Fauzi, Rizal Abdul Rani,Nor Hamdan Mohamad Yahaya, Yasuhiko Tabata, Yosuke Hiraoka, Ruszymah Binti Haji Idrus and Ng Min Hwei
3D Culture of MSCs on a Gelatin Microsphere in a Dynamic Culture System Enhances Chondrogenesis
Int. J. Mol. Sci. 2020, 21(8), 2688”
DOI: 10.3390/ijms21082688

“Emily Fang, Tana Siboonruang, Jonathan Pache, Eugene Reznikov, Reilly Cashmore
Cell Therapy for Spinal Cord Injuries: Design of a Commercial Manufacturing Facility”
https://sites.duke.edu/emilyfang/files/2020/04/FINAL-REPORT.pdf

“Linda Elberskirch , Thorsten Knoll , Rebecca Konigsmark ¨ , Janis Renner, Nadine Wilhelm ,
Hagen von Briesen , Sylvia Wagner
Microfluidic 3D intestine tumor spheroid model for efficient in vitro investigation of nanoparticular formulations
Journal of Drug Delivery Science and Technology 63 (2021) 102496”
DOI: 10.1016/j.jddst.2021.102496

“Eleonore FRÖHLICH, Claudia MEINDL, Maria MRAKOVCIC, Gerd LEITINGER,
Ramona BAUMGARTNER, Eva ROBLEGG
IN-VITRO TESTING FOR IDENTIFICATION OF LONG-TERM EFFECTS OF NANOPARTICLES
Nanocon 2014 in Brno, CZ”

“S Allazetta, L Kolb, S Zerbib, J Bardy, MP Lutolf
Cell-Instructive Microgels with Tailor-Made Physicochemical Properties
small 2015, 11, No. 42, 5647–5656”
DOI: 10.1002/smll.201501001

“Linda Elberskirch, Ronan Le Harzic, Dietrich Scheglmann, Gerhard Wieland, Arno Wiehe, Maria Mathieu-Gaedke, Hartwig R.A. Golf, Hagen von Briesen, Sylvia Wagner
A HET-CAM based vascularized intestine tumor model as a screening platform for nano-formulated photosensitizers
European Journal of Pharmaceutical Sciences 168 (2022) 106046 ”
DOI: 10.1016/j.ejps.2021.106046

“Pascal Baumann, Jürgen Hubbuch
Downstream process development strategies for effective bioprocesses: Trends, progress, and combinatorial approaches
Eng Life Sci. 2017 Nov; 17(11): 1142–1158.”
DOI: 10.1002/elsc.201600033

“Thao Thi Thanh Ngo, Bella Rossbach, Isabelle Sébastien, Julia C. Neubauer, Andreas Kurtz, Krithika Hariharan
Functional differentiation and scalable production of renal proximal tubular epithelial cells from human pluripotent stem cells in a dynamic culture system Cell Prolif. 2022 Mar; 55(3): e13190”
DOI: 10.1111/cpr.13190

“Stange, Katja, Amir Keric, Andreas Friese, and Monika Röntgen.
Preparation of Spheroids from Primary Pig Cells in a Mid-Scale Bioreactor Retaining Their Myogenic Potential
Cells 2022; 11, no. 9: 1453.”
DOI: 10.3390/cells11091453

“Saskia Altmaier, InaMeiser, Emilie Lemesre, Benjamin Chanrion, Rachel Steeg, Lidia Elena Leonte, Bjørn Holst, Boye Schnack Nielsen, Christian Clausen, Katharina Schmidt, Anne Marie Vinggaard, Heiko Zimmermann, Julia Christiane Neubauer, Mikkel AabechRasmussen
Human iPSC-derived hepatocytes in 2D and 3D suspension culture for cryopreservation and in vitro toxicity studies,
Reproductive Toxicology. Volume 111, August 2022, Pages 68-80”
DOI: 10.1016/j.reprotox.2022.05.005

“Chee Keong Kwok, Isabelle Sébastien, Krithika Hariharan, Ina Meiser, Jeanette Wihan, Saskia Altmaier, Isabell Karnatz, Alexander Feile, Alfredo Cabrera-Socorro, Mikkel Rasmussen, Bjørn Holst, Julia C. Neubauer, Christian Clausen, Catherine Verfaillie, Andreas Ebneth, Mattias Hansson, Rachel Steeg, Heiko Zimmermann
Scalable expansion of iPSC and their derivatives across multiple lineages
Reprod Toxicol. 2022 May 17;S0890-6238(22)00068-5.”
DOI: 10.1016/j.reprotox.2022.05.007

Meet the CERO 3D

Upcoming CERO events

January
1st

3D Cell Culture Bioreactor CERO Frontview

No Stress for Cells and Staff

Webinar | On Demand Webinar | 12 am CET

Innovative session on the essentials of a 2D and 3D cell culture workflow. Follow the active dialog of the speakers talking about their experiences in cell culture and a workflow that avoids stress for your cells and yourself. They will talk about the optimized media for individual cells, how to keep cells alive during freezing & thawing cycles and how to set up a reliable quality control. And there is by far more to talk about as real-time imaging and monitoring as well as stem cell expansion, and differentiation of organoids and spheroids.


Consumables

CEROTubes (48 units)

CEROTubes (48 units)

Price on request
CEROTubes (48 units)

CEROsolution 1

CEROsolution 1

Price on request
Increases viscosity of the cell culture media and reduces 3D cell aggregate sedimentation (4x10mL)

Get in touch

Amir Keric
Sales


    Consumables


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