Figure 1: MIMETAS OrganoPlate gel lane is in red and a perfusion lane is in blue.
Dr. Paul Vulto is the President and Co-Founder of MIMETAS and Member of MANCEF
Jos Joore is the Co-Founder and Executive Director of MIMETAS
Dr. Steven Wwalsh is Distinguished and Regents Professor at UNM, Institute Professor of Entrepreneurial Renewal of Industry, University of Twente, Past President of MANCEF
MEMS and nano technology based micro arrays have moved from being pushed onto the pharmaceutical research and development marketplace just a few short years ago to becoming a mainstay for industry. In the early days of micro fluidics technologies many firms employing small technologies to provide value to the pharmaceutical industry simply tried to take traditional pharmaceutical-based testing and developing procedures and duplicate them and in the process make them much better, much faster and much cheaper. The substitution of a superior MEMS-based technique eventually, and some would say inevitably replaced the traditional technologies.
These early MEMS pioneers made products to help reduce the cost of drug development in the pharmaceutical industry. Then, as now, more than 75% of new drugs failed during development. Further, these new drugs fail after over 80% of the development costs have been incurred. The pharmaceutical industry would like to closely emulate the dictum: “Fail fat and fail cheap” but it lacks the technology to select favourable compounds earlier with confidence. With the average cost of drug development at $1 billion (The Pharmaceutical Landscape; one of the series of MANCEF Roadmaps), early indication of drug failure is critical to this process.
Yet the currently available models for testing drugs are mostly two-dimensional cell culture and laboratory animals. They have proven themselves poor predictors of compound behaviour in man. Demonstrably better predictors are cell culture models based on three dimensional (3D) cultures. Unfortunately, 3D cultures are still complicated to use, expensive and lacking versatility, hampering their widespread application. The next generation of small technology based micro array devices holds great promise to change this.
Today the next generation of micro titer, micro array and other micro fluidics and nano fluidics manufacturers are again moving the industry forward. These firms are increasingly using the three- dimensional (3D) properties of their technologies for bio and pharmaceutical applications. These firms are using passive fluidics techniques to derive a variety of new technology product
platforms. These 3D array technologies are responding to one of the drivers of the pharmaceutical industry growth, the movement towards personalized medicine.
Today’s full embrace of the 3D aspects of micro fluidics combined with nano coatings and other technologies are allowing the current leading technology based firms to portend the next generation devices. One of these these leading firms, MIMETAS, is utilising the 3D aspects of its device platforms to develop ‘organ-on-a-chip’ technology for testing of new medicines. These miniaturised organ models have better predictability compared to laboratory animals and conventional cell culture models and are derived by utilising the three dimensional effects of their micro fluidics based technologies. Below we provide a discussion of one firm’s effort to improve micro titer arrays technology through fully utilising its 3D capabilities — the product platform is called MIMETAS OrganoPlates.
These micro titer plates are comprised of up to 96 tissue chambers, each of which can be individually interrogated. Specifically, each chamber can be unique in terms of co-culture and chemical gradient attributes. This allows for the next generation of array products creating unique capabilities:
■ Long term culture and compound exposure on long-living 3D tissues
■ Stable and controlled differentiation of stem cells
■ Complex (co-)culture conditions including multi-organ culturing and air-liquid interfacing
■ Drug response testing on primary patient material.
Like their early small tech based array technologies cousins, these 3D culture platforms are fully compatible with common laboratory and industry standards. Already a range of models have been implemented, including stem cell derived neurons, gut, liver, kidney, pancreas, (micro) vasculature and a range of cancer models (gut, breast, glioma). MIMETAS OrganoPlates and other like technologies can enable 21th century precision and personalised medicine as well as help to identify effective drugs earlier in the process. Figure 1 shows the MIMETAS OrganoPlate with its gel lane in red and a perfusion lane in blue.
The contributors to the MANCEF pharmaceutical landscape have identified over 18 drivers that detail how the pharmaceutical based therapeutics and diagnostics in the 21st century will differ and improve greatly over those offered in the 20th century. Personalised medicine is one of those drivers. 20st century medicines were characterised by blockbuster drugs, based on a ‘one size fits all’-concept, the 21st century will see drugs that are tailored to specific patient subgroups, and precision medicine. The MANCEF Pharmaceutical Landscape also predicts that the single root technology pharmaceutical therapy tradition will move to a much more complex four to five root technology product platform. Products like MIMETAS OrganoPlate are leading this effort. MIMETAS was a winner of a Young Technology award at last year’s COMS conference in Enschede, Netherlands.
Dr. Paul Vulto (Dordrecht, 1977) is a scientist and entrepreneur, who held positions in the Netherlands, Germany, Italy and Japan. He worked as an engineer for the high-tech company Silicon Biosystems in Bologna and headed the Diagnostic Microsystems group at IMTEK, the University of Freiburg. Paul holds a cum laude Masters degree in Biomedical Engineering and a cum laude PhD degree in Microsystems Engineering. Paul is co-author of 12 international patent applications and over 20 peer reviewed journal publications. He works as group leader at the Leiden Academic Centre for Drug Research on nano and micro fluidics for metabolomics, massive parallel screening and 3D cell & tissue culturing. He is co-founder and CTO of the company MIMETAS that markets organ and tissue models on-a-chip for development of new medicines.
Dr. Steven Walsh is a Distinguished professor at UNM where also holds the Regents professor at UNM’s Anderson School of Management. He also is the Institute Professor for Entrepreneurial Renewal of Industry at the University of Twente. He has received many business service awards, including the Lifetime Achievement Award for Commercialization of Micro and Nano Technology Firms from MANCEF. He has also been named as a Tech All Star from the State of New Mexico Economic Development Department and has been recognised by Albuquerque the magazine as a leader in service to the economic community. He is a serial entrepreneur that has helped attract millions of dollars in venture capital to these firms.