ORGAN-ON-CHIP

Towards precision medicine in future healthcare

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.

Societal impact 

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.

 

Relevance for the Electronic Components and Systems (ECS) industry

Despite its great promise, the maturity of Organ-on-Chip technology, with a few exceptions, at present remains mainly stuck at the academic level. Handmade PDMS molded devices, interfaced with a multitude of tubes to external pumps are not compatible with the standardized work flow in biology and pharmaceutical labs. The ECS industry can play an important role in maturing the Organ-on-Chip concept by developing:

  • Technology platforms for the large volume, low cost fabrication of Organ-on-Chip devices utilizing the enormous infrastructure available for the production of microfabricated and microfluidic devices;

  • Platform “packaging” concepts that bring the Organ-on-Chip devices into the standard well plate format used by biologist and the pharmaceutical industry. These “smart well plates” need to contain unobtrusive perfusion and (wireless) electrical interfaces to let them blend in in standard work flows;

  • Readout equipment that collects the large amounts of data generated by the integrated electrodes and sensors and uses AI to assist in date interpretation.

 

Enabling technology platforms

The essential capabilities underlying the Organ-on-Chip field are primarily embedded microfluidics and the processing of polymers in a microfabrication environment.  Ideally the industry should formulate one or more open technology platforms that will allow for the production of a range of different Organ-on-Chip devices on a foundry service base. Additionally, the industry should come to standardization of the microfluidic, and when applicable electronic interfaces on Organ-on-Chip devices to allow individual Organ-on-Chip devices to  be applied in larger systems that are compatible with standard work flows (smart well plates). Smart sensors can be used as readout devices while edge AI will be essential in data interpretation and reduction.

Further Reading:
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