A major problem in developing new medicines is the limited availability of human model systems for preclinical research on disease target identification, drug efficacy and toxicity. Laboratory animals or cells in standard tissue cultures, even if they are human, often do not respond to medication in the way cells in intact human organs in the body do. Organ-on-Chip technology based on human cells may present solutions to this challenge of creating near-human test systems.
In an Organ-on-Chip the smallest functional unit of an organ is replicated. A typical Organ-on-Chip comprises the following elements:
- Multiple cell types in a 3D culture, with the cells interacting with each other as they would do in the real organ. The cells are derived from individuals with iPSC technology and thus have the genetic characteristics of a particular individual (patients-on-chips);
- A microfluidic device that contains the cells and that provides perfusion and other physiological relevant stimuli such as: stretch, shear stress and chemical gradients;
- A readout which can simply be optical, but also electrical for electrically active cells, and that can include a whole range of chemical and physical sensors.
Organs-on-chips can significantly reduce the costs of healthcare, because they will allow drug development to become better, safer, faster and cheaper. Presently the development of a new drug from start-to-market takes about 12 years, and costs minimally 1 billion euro per drug. This is due to inefficient drug development pipelines, with too many drugs failing late in development. Organs-on-chips will:
- Speed up the development time of new drugs, thereby reducing costs;
- Enable precise screening of drugs for unwanted side effects and toxicity (clinical trials on a chip);
- Greatly reduce animal testing supporting the 3Rs guiding principles of reduction, refinement and replacement of animal experiments.
In Moore4Medical “smart multiwell plate” platforms will be developed to seamlessly integrate multiple organ-on-chip technologies from different manufacturers into existing workflows, comprising:
- A smart multiwell plate that works as an autonomous system. It will contain micropumps and a microfluidic infrastructure that provide perfusion, as well as the electronics to drive the micropumps and integrated readout sensors;
- A high definition electrophysiology (HD e-Phys) multiwell plate to bridge the gap between advanced high electrode count CMOS ASICs and the world of biology and pharma by means of advanced microfluidic fan-out technologies integrated into the well plate;
- A smart multiwell plate lid that can be used in combination with ordinary, as well as the smart multiwell plates. The non-disposable lid contains micropumps and sensors that monitor in situ and in a parallel fashion monitor the medium of cell cultures in incubators.
The proposed platforms will be validated in a realistic setting with relevant cell cultures. The universal nature of the smart multiwell plate will be demonstrated with three different organ-on-chip devices from three different manufacturers.
In an innovation track, sensors and organ-on-chip devices will be developed to ensure continuous innovation by bringing advanced sensing and complex organ and disease models to future smart multiwell plates. Furthermore, the “DEPArray” technology of Menarini for the isolation of 100% pure single live cells from heterogeneous samples will be improved by a dedicated sensing platform for the detection and classification of rare cells, such as, but not limited to circulating tumor cells.
- Organ-on-Chip white paper, an hDMT publication
- Towards an organ-on-chip roadmap, an ORCHID publication
- Impact of organ-on-a-chip technology on pharmaceutical R&D costs, N. Franzen et al. Drug Discovery Today, Volume 24, Issue 9, September 2019, Pages 1720-1724