Research & development
Our multidisciplinary R&D teams are dedicated to the development of optimal solutions for today’s biomedical laboratories. The diversity of team members and the synergy at all levels give R&D at Miltenyi Biotec an organic quality, an entity that nurtures products from concept to reality. Invention, accessibility, diversity, and dynamism are the values that drive us forward.
R&D is a dependable partner, providing competent technical support for all our customers by promoting continual growth of in-house expertise. Open communication at all levels, ongoing dialog with opinion leaders and synergism across the boundaries of individual skills are the forces that power our creativity.
We develop and provide great products that address almost all aspects of immunological research. We carry out our own front-line research and interact closely with the world’s leading immunologists, a prerequisite for unique products such as our pioneering human and mouse dendritic cell reagents. In the clinic, our concepts for cellular therapies based on adult stem cells, T cells, NK , dendritic cells, and other novel treatments are already helping patients achieve a better quality of life.
Our rapidly expanding portfolio of neuroscience products addresses tissue dissociation, cell separation and culture, and characterization of all neural cell types (neurons, astrocytes, oligodendrocytes, microglia and their precursors). We recently developed an anti-GLAST antibody, which enables the immunomagnetic isolation of astrocytes and will lead to a better understanding of this diversified cell lineage. We also place special emphasis on studying directed differentiation of pluripotent stem cells into specific neural cell types. These studies should facilitate the advancement of stem cell-based cell therapy in neurological conditions such as Parkinsonism and spinal cord trauma.
Stem cell research
Our activities address all types of stem cells, including mesenchymal, hematopoietic and cancer stem cells. By developing protocols for GMP-compliant cell separation, differentiation, expansion and formulation, we have been able to sponsor a multicenter phase III clinical trial of CD133-positive hematopoietic cell grafting during CABG surgery and its role in improving post-infarct myocardial regeneration. Currently, our emphasis is on developing great tools for the isolation, analysis, and culture of embryonic stem cells, induced pluripotent stem cells, tissue (e.g. neural, cardiac and hepatic) stem cells and cancer stem cells. Our latest developments focus on re-programming, directed differentiation and enrichment of the resulting differentiated cells.
We design integrated solutions for cancer research, from automated tissue dissociation, through isolation of tumor cell and tumor-infiltrating lymphocyte subpopulations, to analysis at both the cellular and molecular levels. Specializing in cancer stem cell (CSC) analysis, our flagship CD133 reagents represent only a part of our extensive range of antibodies to CSC surface markers. In addition to CSC, we focus on tumor-associated and tumor-induced immune suppressor cells, such as regulatory T cells, tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs).
Reproducible results depend on the quality of sample preparation; for example, an appropriate processing of the tissue is crucial prior to cell sorting. We not only develop practical tools for the gentle and efficient dissociation of different tissues, we also systematically optimize dissociation conditions for each tissue type with respect to cell viability, recovery and epitope integrity by combining tailor-made enzyme mixes and mechanical dissociation protocols. This has resulted in standardized protocols for the rapid dissociation and subsequent isolation of diverse cell types, such as astrocytes from adult brain or tumor infiltrating lymphocytes from melanoma. Some protocols are already under test for clinical applications.
Miltenyi Biotech is the recognized market leader in magnetic cell separation (MACS Technology). New reagents are being continually developed for many different cell types. We investigate unique markers as the basis for new or improved reagents, especially for the efficient enrichment of rare cells. New technologies are developed with convenience and performance in mind and our goal is to enable the translation of promising applications “from bench to bedside” and fulfil the promise of cellular therapy.
Developing innovative products for cellular therapy is one of our primary goals. Effective cellular immunotherapy of cancer and autoimmune diseases, as well as tissue regeneration, needs highly specialized cellular products. Our aim is to provide complete and versatile solutions for GMP-compliant cell manufacturing, which includes cell separation, differentiation, expansion, formulation, and cryopreservation.
Immunadsorption therapy holds promise for numerous diseases, including autoimmune diseases. Our objective is to develop smart medical devices for immune adsorption of pathogenic plasma components (e.g. autoantibodies) by immunoaffinity adsorption. The identification of ligands and development of specific matrices for each individual application are the driving forces behind this promising therapeutic approach.
Our flow cytometry group is committed to the development of reagents and instruments with outstanding quality and convenience. But we do more than that, we generate great solutions for specific applications, e.g. by designing novel assays for cell functionality, and our current developments range from innovative reagents to fully automated cell analysis robotics. Our motivation derives from the customer’s needs: how can we help the customer overcome specific scientific challenges?
The new experience in highly sensitive flow analysis, the MACSQuant family of cell analyzers has been designed and developed, and is manufactured, by our own dedicated teams in Biomedical Engineering, Production and Flow Cytometry. Their unique features, developed together with our software development group, and their compact design were prerequisites for success. The result of these innovative developments is that the concept of the Personal Flow Cytometer has been firmly established in laboratories across the world.
Antibodies represent the most important reagents in flow cytometry and cell analysis. Timely recognition of new ligands and receptors means that our antibodies are always at the forefront of research. Interaction with other departments, such as Biomedical Engineering, means that reagents are developed in parallel to the instruments. Such synergism is at the root of our innovation powers.
Cytokine detection is central to the analysis of cell-to-cell signaling and for studying intracellular and extracellular regulatory molecules. Our latest developments include reagents for intracellular staining of cytokines and the innovative MACS Staining Technology for working with low numbers of cells. Optimal solutions for cytokine analysis exemplify our commitment to providing our customers with reliable research tools.
Tumor cell analysis
In cancer research, the unequivocal identification and characterization of disseminated or minimal residual tumor cells requires extremely sensitive methods. Target cells are often found in very low numbers, below the limit of detection of most analytical methods. Our ongoing research has overcome these limitations by developing innovative reagents for the enrichment and detection of rare tumor cells. We combine the power of flow cytometry with magnetic enrichment for highly sensitive analysis and separation of rare cells.
Our aim is to develop chemically defined media for specific primary and secondary cells, including stem cells, where phenotypic stability, or population expansion, or directed differentiation, is required or the cells need to be frozen without loss of viability or functionality. The media are developed according to cell type using a fully automated facility for cell culture and cell-based high throughput screening. The optimized media are then characterized for use with a specific cell type and developed as a research grade product, or as a GMP-compliant product for clinical applications.
We develop and utilize mouse models for evaluating sorting protocols, generating antibodies and as preclinical models for cell therapy and tissue regeneration studies. One of our latest developments, a novel transgenic mouse line enables expression of an artificial cell surface antigen on target cells using Cre recombination. This enables simple MACS isolation and analysis of target cells after crossing of our model with specific Cre deleter lines and also means that the tagged cells can be used in tracking experiments.
Our portfolio of contrast reagents for small animal studies addresses all currently available imaging modalities. Ongoing development programs have resulted, for example, in magnetic particles that can be used intracellular labeling of cells for detection by magnetic resonance imaging. This represents a convenient method for tracking injected cells by MRI during cellular therapy and tissue regeneration studies.
Our nano- and micro-particle technologies include the synthesis, purification and biocompatible coating of the magnetic particles that are at the heart of MACS Technology. Development of specific precipitation protocols, ferromagnetic matrix chromatography methods and chemoselective ligation chemistries are just a few of the processes used in the optimization of our cell separation products. Novel fluorescent dyes and probes provide the backbone for our portfolio of analytical protocols with stable fluorochrome/antibody conjugates enabling state-of-the-art labeling of cells and subsequent characterization by flow cytometric analysis. Solid-phase peptide synthesis and DNA chemistry feature strongly in our skills portfolio.
The development of innovative tools for the analysis and processing of miRNA and mRNA is at the focus of our studies. Technologies have been developed for the efficient isolation, labeling and, notably, amplification of RNA, which is the key to transcriptome profiling when the sample consists of just a few cells. Many of the protocols use specific in-column enzyme reactions for even more efficiency and convenience, for example, in the generation of cDNA. Protein analysis tools are based on epitope-tagged molecules and immunoprecipitation protocols and are being continually developed as the knowledge base grows.
By applying our renowned cell separation technology to the isolation of organelles and biomolecules we have developed simple solutions for technically complex problems. An outstanding example is the recently launched Mitochondrial Isolation Kit enables the isolation of intact viable human mitochondria from cells or tissue with high yields and optimal convenience. Similar solutions for isolating mRNA and proteins are notable for their ease of use, stability and reproducibility. The trend in high-throughput robotics is reflected by our development of microplate-compatible columns and instruments.
We employ prokaryote and eukaryote technologies with proprietary vector designs, carry out fermentation in bioreactors with capacities up to 200 L, and develop dedicated purification strategies, including protein refolding, to support our concept of high product quality, process robustness and reproducibility.
Some products are produced in our fully GMP-compliant manufacturing facility in Teterow. We have developed assays of reagent bioactivity as well as for the detection of residual host protein, host DNA and endotoxin in our reagents. We also continue to improve existing processes in order to reduce animal-source components and to produce reagents in novel formats.