Category:Oroboros Ecosystem: Difference between revisions

The Oroboros Ecosystem

Medical fields from neurology to pharmacology are permeated by mitochondrial problems. Modern studies highlight the crucial role of mitochondria in the progression of many diseases and in maintaining health, with the number of mitochondrial publications increasing exponentially. For 10 years, the Oroboros O2k has been established worldwide as the leading measuring instrument for mitochondrial functional analysis.

Mitochondria - the powerhousesof the cell - generate electrical energy in a molecular combustion process and regulate the oxygen consumption of cellular respiration. Mitochondrial physiology is part of our lives: mitochondrial fitness is crucial for the quality of life and function of every organ - from muscle to brain. Moreover, mitochondrial fitness makes us resistant to preventable and age-related degenerative diseases: diabetes, heart failure, Alzheimer's, several types of cancer, and more. Heredity, age, gender, lifestyle and environmental factors all influence mitochondrial fitness as a set of complex molecular functions.

Mitochondrial functional analysis represents a current challenge in biomedical diagnostics. No other instrument has been able to analyze the most important parameters of cellular respiration under comparable conditions. This explains the high demand for a reliable, accurate and efficient instrument for the simultaneous measurement of cell respiration and other mitochondrial functions: all-in-one. However, the planning of experiments optimally adapted to specific problems requires a deep understanding of mitochondrial physiology and biochemistry. Additionally, raw data needs to be analyzed and interpreted by experts. These requirements created barriers that stood in the way of broad applications of O2k technology outside specialized research laboratories.

The Oroboros Ecosystem responds to the needs of biomedical research and expands the market leadership of Oroboros Instruments worldwide. It has developed in a sequence of three phases:

1) The Tyrolean life science company Oroboros Instruments developed the O2k-FluoRespirometer in cooperation with a network of SMEs and university institutes. This innovation was supported by the K-Regio project 'MitoCom' and was awarded the Houska Prize "Light in the Powerhouse of the Cells" in 2012.

2) The further development of the innovation and marketing strategy and the corporate concept of Oroboros led to the project "Oroboros Ecosystem". ‘MitoFit’ as a second K-Regio project in series and the project 'O2k-Innovation' referred to the Houska Prize 2012. The synergistic effects of the cooperation between the university and industry as well as the further development of quality management with our partner WGT Elektronik GmbH & Co KG were recognized. MitoFit led to the ISO13485 certification of WGT (2016). Stemming from innovative technical developments the further scientific and economic success was rooted in the concept "Oroboros Ecosystem":

a) Establishment (2013) and expansion of the Oroboros O2k research laboratory, where a scientific elite has been developed to support and advise our customers.

b) Intensified cooperation with academic institutes and companies in Austria as well as the establishment of international networks, e.g., the H2020 COST Action Project 'MitoEAGLE' chaired by E. Gnaiger, which led to a publication with 621 co-authors.

c) Innovative business model with worldwide O2k-Network, O2k-Open Support, and Open innovation management.

d) Sustainable initiatives, in particular the scientific website Bioblast with MitoPedia, the 'Blue Book' as a textbook of mitochondrial physiology - which leads researchers and students to the O2k technology as a basis for courses at numerous universities - and a mitochondrial preprint server (MitoFit Preprints. The Oroboros Ecosystem combines these building blocks into a mosaic that integrates innovation, research, development and worldwide cooperation in a business-oriented company to form a modern image of mitochondrial respiratory physiology (Fig. 1). The comprehensive mitochondrial functional analysis to determine vitality is ultimately intended to improve our health system. Did you know about the connection between pandemic obesity, loss of mitochondrial fitness and degenerative diseases? - Body Mass Excess, BME - bme.oroboros.at

3) Oriented towards the Oroboros Ecosystem including innovation, marketing and project management, Oroboros received its so far largest grant (EU H2020 SME NextGen-O2k) with €1.7 mill for two years. Again we emphasized the encouragement by the Houska Prize 2012. The all-in-one O2k-concept got extended by additional modules. These enable O2k applications in photosynthesis and environmental technology, and thus add a new market segment to the Oroboros Ecosystem.

Innovation

While the focus in 2011-2014 was on instrument development and the market launch of the O2k, Oroboros Instruments now stands out even more sharply from the competition thanks to the innovative Oroboros Ecosystem concept. In the Oroboros O2k-Laboratory, a team of experts with 20 O2k instruments develops application protocols that are fed into the O2k-Software, tests new developments, conducts collaborative research, advises customers and trains guest scientists. With efficient access to mitochondrial research, new customers can be rapidly introduced to the complex field of mitochondrial physiology and expand their experimental work with new O2k-Modules.

The Oroboros Ecosystem attaches great importance to the continuing education of our team and the training of O2k-Customers: international O2k-Workshops; O2k-Network laboratories with O2k-Training centers; training schools (COST Action CA15203 MitoEAGLE, Chair: E. Gnaiger). New features of our device-specific software are crucial for quick implementation of O2k-Technology. A ticket system in connection with the scientifically oriented website (Bioblast / MitoPedia) is the backbone of our customer service (O2k-Open Support).

Continuous innovation is our sustainable strategy: The newly offered 'Small Volume O2k-Module' enables a fourfold saving of sample quantity, especially for blood cell diagnostics. MiR05-Kit and MitoKit-CII are quality controlled chemical sets that simplify the use of O2k-Technology.

Our technical-scientific expertise offers internationally recognized service, which is integrated in the selling price of the O2k and helps users to enrich the mitochondrial research field with reproducible results and innovative findings in a sustainable way. We make a contribution to research on aging and preventive medicine in order to develop forward-looking solutions for the healthcare system.

Research

The O2k is applied in basic research, ageing research and a wide range of research areas in bioenergetics, mitochondrial physiology, medicine, sports medicine and pharmacology (Fig. 2). Mitochondrial function and disorders of cellular respiration are relevant for many areas of medicine, from diabetes, metabolic syndrome, cancer and Alzheimer's research to organ transplantation. With lifestyle diseases, such as obesity or cardiovascular diseases, and the associated preventive medicine, insights into the cellular energy balance are essential.

Oroboros is internationally known among mitochondrial researchers. Our high-quality product is considered a reference for high-resolution respirometry. We have participated in expeditions in the far north of Greenland and up to altitudes of 5300 m at the Everest Basecamp, as good publicity to prove the reliability of O2k under extreme conditions and to publish spectacular results also relevant for intensive care medicine. The O2k-Network for scientific information exchange between 677 network laboratories is represented globally. Well over 1000 researchers have contributed to >3800 O2k-Publications.

As a long-term strategy, we are working with preclinical and clinical laboratories to develop a diagnostic tool as an in-vitro medical device for researching mitochondrial status in various diseases and, in a further step, to introduce it as an in-vitro diagnostic tool. The NextGen-O2k project also aims to expand the scientific scope to enter the field of photosynthesis with the O2k-PhotoBiology Module and to gain the corresponding clientele in the environmental technology sector.

Mitochondrial Respiration

Our research focus is mitochondrial respiration. By integrating fluorometry into the O2k, H2O2 production (oxidative stress), mitochondrial membrane potential, ATP production, Ca2+, pH, H2S or NO can be measured simultaneously with oxygen consumption.

The Q-Redox module further compliments the 'all-in-one' concept of the O2k. Adding a photo-[CG1] biology module for measuring photosynthesis opens up the environmental technology market. The complexity of the possible applications required the development and quality control of standardized protocols with detailed descriptions in publications and on the homepage (MitoPedia: SUIT) to support our customers in generating reproducible and universally interpretable data. An open access software (SUITbrowser) selects the optimal SUIT protocol for a specific question and application in our new DatLab 7.4 Software (suitbrowser.oroboros.at).

For quality control a worldwide unique proficiency test for mitochondrial respirometry has been developed based on an optimized cryopreservation procedure of HEK cell cultures. Chemical sets were developed and distributed as the foundation for quality management of chemical solutions. Video clips support the O2k-users in the preparation of tissue homogenates and permeabilized muscle fibers as well as in the operation of the O2k. The new Small-Volume O2k-Module was tested with mitochondria and HEK cells with applications for fresh and cryopreserved human blood cells, fibroblasts and sperm cells from patients. Quality control and data management are now a key component of O2k-Technology.

These methodological developments have been successfully applied in several dissertations and scientific collaborations in cancer research, neurology, sports science and altitude medicine and have contributed to numerous publications.

Publications

1. Oemer G, Lackner L, Muigg K, Krumschnabel G, Watschinger K, Sailer S, Lindner H, Gnaiger E, Wortmann SB, Werner ER, Zschocke J, Keller MA (2018) The molecular structural diversity of mitochondrial cardiolipins. Proc Nat Acad Sci U S A 115:4158-63. - »Bioblast link«
2. Doerrier C, Garcia-Souza LF, Krumschnabel G, Wohlfarter Y, Mészáros AT, Gnaiger E (2018) High-Resolution FluoRespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle, and isolated mitochondria. Methods Mol Biol 1782:31-70. - »Bioblast link«
3. Horscroft JA, Kotwica AO, Laner V, West JA, Hennis PJ, Levett DZH, Howard DJ, Fernandez BO, Burgess SL, Ament Z, Gilbert-Kawai ET, Vercueil A, Landis BD, Mitchell K, Mythen MG, Branco C, Johnson RS, Feelisch M, Montgomery HE, Griffin JL, Grocott MPW, Gnaiger E, Martin DS, Murray AJ (2017) Metabolic basis to Sherpa altitude adaptation. Proc Natl Acad Sci U S A 114:6382–7. - »Bioblast link«
4. Lemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers. Sci Rep 7:2840. - »Bioblast link«
5. Gnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. Scand J Med Sci Sports 25 (Suppl 4):126–34. - »Bioblast link«

Presentations

1. Gnaiger E: High-resolution respirometry and innovations in the Oroboros O2k-technology. Nature Conference Cellular Metabolism. 2019 Apr 8-11; Xiamen CN. - »Bioblast link«
2. Gnaiger E: The protonmotive force under pressure: an isomorphic analysis. 20th European Bioenergetics Conference. 2018 Aug 25-30; Budapest, Hungary. - »Bioblast link«
3. Doerrier C: High-resolution respirometry, two techniques combined in one to explore mitochondrial function in health and disease. 52nd Annual Scientific Meeting of the European Society for Clinical Investigation. 2018 May 30–Jun 01; Barcelona, Spain. - »Bioblast link«
4. Gnaiger E: Electron transfer at the Q-junction: new perspectives from combined measurement of mitochondrial O2 flux, H2O2 flux, and coenzyme Q redox state. AussieMit. 2018 Nov 29 - Dec 01; Melbourne, Australia. - »Bioblast link«
5. Gnaiger E: Oxidative phosphorylation and mitochondrial function differ between human prostate tissue and cultured cells. Mitochondrial Medicine. 2016 Jun 15-18; Seattle, WA, USA. - »Bioblast link«

PhD Theses

1. Kohlegger (früher Düregger) Andrea (2015) Perspectives of the chemopreventive effects of natural compounds in the adjuvant treatment of prostate cancer. Med Univ Innsbruck.
2. Burtscher Johannes (2016) Neurochemical characterization of epileptogenesis: the role of endogenous enkephalin. Med Univ Innsbruck.
3. Schoepf Bernd (2016) Mitochondrial markers for prostate cancer prognosis and therapy. Med Univ Innsbruck.
4. Weber Anja (2018) Metabolic reprogramming of prostate cancer cells. Med Univ Innsbruck.
5. Volani Chiara (2019) Regulatory mechanisms between homeostasis, mitochondrial function and metabolic pathways. Med Univ Innsbruck.

The Economic Factor

Successes of the Oroboros Ecosystem project are the result of a user-tailored communication concept with direct customer contact and a global network. Together with our sophisticated instrument, the Oroboros Ecosystem offers complete solutions based on R&D and builds a symbiotic relationship between developers and users with feedback analogous to the Oroboros logo. The Oroboros Ecosystem links threads into interrelated networks - experimental planning, sample preparation, instrumental application, data evaluation and interpretation - focused on scientific relevance and reproducibility. The Oroboros Ecosystem concept is an open model for continuous innovation.

O2k-Workshops with a contribution to travel expenses are included in the O2k basic price. Project-related revenues thus result largely from O2k sales, which, since the 2012 Houska Award, have increased 1.7 and 2.15 times in four and eight years (2011: 54; 2015: 94; 2019: 116 devices; Fig. 3). Direct revenue per O2k increased from €25,293 (2011) to €36,111 (2019) thanks to the all-in-one concept. The revenues generated directly with the O2k sales have therefore more than doubled from €1.4 million (2011) to €3.0 million (2015), and tripled to €4.2 million (2019). To date, the high-quality Oroboros products have been sold to customers in the public and private sectors in 49 countries and generated revenues of more than €28 million.

Oroboros has been successful with national and EU project funding: K-Regio project MitoFit, O2k-Innovation project, several Marie Curie networks. As consistent continuation of our project management, we were able to obtain the highest funding budget to date in the competitive H2020 SME funding scheme with €1.7 million for two years, which, in line with the Oroboros Ecosystem, is oriented towards synergy of innovation and marketing. Oroboros was consequently recognized as one of the most innovative SMEs in Austria.

Distribution

The B2C concept in 45 countries and annual training courses for our distributors (China, Taiwan, Korea and Japan) promote personal customer contact with our sales and research teams, enabling tailor-made advice and scientific support.

In 2016-2019, alongside on-site training and distributor meetings, we organized 36 O2k-Workshops with 20 to 28 international participants each. Although these workshops are mainly attended by working groups already registered as customers, new interested parties also join to assess O2k-Technology.

Our customers are the Oroboros Ecosystem Ambassadors, who communicate our concept - without expensive marketing. The scientific elite and open-minded students appreciate that the financial resources are used sustainably for R&D, optimization of our products and research support. As part of our marketing strategy, our research results are published on open-access platforms.

The unique technical selling point of the O2k, which as a 'sole-source' instrument surpasses its competitors in every public tender worldwide, enables direct marketing in many countries around the globe by Oroboros as developers and scientific experts. Manufactured by the Ecosystem Partner WGT Elektronik in Kolsass, Tyrol, the O2k is shipped directly to customers following quality control by WGT and the Oroboros O2k-Laboratory. The direct distribution ensures strong customer loyalty and feedback to optimize our products. Thus, ideas and observations of the customers flow into the development of the instrument and our customers receive optimal technical and scientific support. The expansion in the Asian market requires the integration of national distributors into the Oroboros Ecosystem.

Austrian Business Location

The structure of the Oroboros Ecosystem aims at maximum added value and a strong link to its roots in Austria. Even production is carried out regionally by WGT with suppliers mainly from Austria. The indispensable DatLab software for O2k-Technology is continuously optimized in cooperation with local businesses and since 2017 with the Innsbruck-based start-up software company HTech, with an investment of €1 million contributed by Oroboros partly through project funding. As the international sales are mostly handled directly, our products can be offered at an economical and competitive price without compromising product quality.

In 2018, a turnover of €4.6 million (without project funding) was achieved through exports, with a significant proportion in theUSA and China. Through the international presence of Oroboros Instruments, Tyrol as a business location and the reputation of Austria as a promoter of innovation in the life science sector are strengthened. In addition, Oroboros has raised more than €2.7 million in EU project funding from 2016-2019 for Austria as a business location.

With the introduction of our quality management, two full-time academic positions were created in 2019. Oroboros currently provides 25-27 high-quality jobs in Innsbruck. The internationally positioned team brings know-how to Austria and creates an attractive and challenging working environment for young domestic scientists. In addition, 10-12 jobs at WGT and Htech are integrated into the Oroboros Ecosystem. Newly acquired biomedical research projects and expansion into the environmental technology (photosynthesis) sector will create additional jobs in the near future.

As a side effect of the O2k-Workshops, training courses and congresses organized by Oroboros in Austria, the local tourist industry is given a boost, especially in the off-season.

Revenues

The life science instrumentation market is expected to grow at a rate of 6.7% (2017-2022) to reach a global value of $75.2 billion by 2022. North America, Europe and China, as Oroboros' main markets, account for the largest share of market growth. Further countries in Asia, South America and Australia are important markets.

Since Oroboros introduced high-resolution respirometry to the market in 1992, the company has been constantly working on continuous development. Enhanced by the newly developed Q-Redox sensor, the NextGen-O2k is a revolutionary part of the Oroboros Ecosystem and responsible for an immense competitive advantage. Applications of high-resolution respirometry will play an important role especially in the clinical areas of age research, Alzheimer's, diabetes, Parkinson's or for preliminary examinations of cancer treatments and genetic diseases. Furthermore, the market potential of O2k-Technology will be significantly increased by entering the medical fields of diagnostics and the testing of therapeutic interventions.

Prototypes of the NextGen-O2k are already being tested in laboratories in Europe and USA. The market launch is being prepared for 2021. It is expected to generate €46 million cumulative revenue and €17 million profit with an ROI of 3.5 during the first five years of commercialization.

Furthermore, the application of the PhotoBiology-Module for measuring photosynthesis in microalgae will open up a new market for Oroboros in botanical research and environmental technology. The corresponding world market in 'Green Technology' is estimated to reach $3 billion in 2025. The prototype development of the PhotoBiology-Module has been completed and a significant increase in sales can be expected in this field as well.

Sustainability

Oroboros has proven sustainability in the sense of lasting economic success since its foundation. Lean management supports the growing team and strengthens partner networking in the Oroboros Ecosystem. Quality management requirements were organically integrated into the project landscape.

Oroboros and WGT attach great importance to the sustainability and durability of the O2k with high-quality materials and quality-assured production processes. Carefully designed to conserve resources and maintain low operating costs, the O2k-Technology is customer-friendly.

Our Open Innovation IP strategy is based on publishing R&D results without expensive international patents for highly specialized high-tech products. These resources are invested in innovation and leading laboratories are involved in first applications. Copying could never compete with the innovation dynamics appreciated by the expanding customer base. “Cooperation and feedback in science” is our advertising strategy.

Enthusiastic customers are the most efficient advertising medium. We avoid expensive advertising campaigns that do not create added value for a product. Instead, we invest in training, innovation and quality. The Oroboros Ecosystem focuses on sustainability and interconnecting business and science. E. Gnaiger is chairman of the international Mitochondrial Physiology Society, which underlines the technical appreciation of the Oroboros Ecosystem and ensures sustainable networking with the scientific clientele. The website Bioblast with MitoPedia (high-resolution terminology - matching measurements at high-resolution) is regarded as a mitochondrial textbook. Out of the MitoFit project came the preprint server MitoFit Preprints, which promotes the Open Access preprint concept with scientific quality and reproducibility.

The project NextGen-O2k will create 12 new jobs at Oroboros by 2025.

The Oroboros Ecosystem concept

Oroboros pursues a strategy independent of investors. WGT Elektronik is the key partner in development and production, with numerous jointly completed projects. IP and commercial risk remain with Oroboros. The Oroboros Laboratories emphasize synergy between university and industry research with a clear distinction between the company-owned Oroboros O2k-Laboratory and the DSL-Oroboros Research Lab (Med Univ Innsbruck), which was equipped by us with 8 O2k devices for clinical research.

Besides global marketing, we focus on research and development to continuously expand the market with innovations and protect our brand. Following the demand for a medical device, Oroboros Holding GmbH was founded in 2018 as the supporting organization of the Oroboros Ecosystem. In contrast to the innovation-oriented Oroboros Instruments GmbH, Oroboros Diagnostics GmbH will specialize in standardization and in vitro diagnostics, for which a financing concept with patent protection (8-chamber HRR) and possible investor participation is being considered.

The O2k has an optimal price-performance ratio with low operating costs. In the 'all-in-one' O2k, several mitochondrial functions can be analyzed in one instrument, which previously required different devices. High reproducibility is our unique selling point. Scientific consulting by the Oroboros team in the international O2k-Network and at O2k-Workshops serve to strengthen customer loyalty and function as a marketing tool.

The close cooperation with distribution companies in Asia resulted in a large increase in sales. We sell directly in another 45 countries. Particularly with regard to a medical product, the establishment of Oroboros sales companies in the USA and China is being pursued in cooperation with national organizations. Information on the Oroboros Ecosystem business model is summarized in Fig. 4-7.