Organ-on-a-chip is a novel technology which mimics the pathology and physiology of a human organ on a chip. It does not aim to reproduce human organs or tissue as original, instead, it mimics the key cellular architecture and functionality at a smaller scale. It is used for the purpose of disease modeling, drug screening. The chip is fabricated with silicon-based polymer polydimethylsiloxane (PDMS) using soft lithography that makes it compact size and it has microchannels to precisely manipulate various fluidic and chemical parameters such as concentration gradient, pH, cell pattern, pressure, oxygen, etc.

Pharmaceutical industries have been aggressively looking for an effective drug discovery method, this organ-on-chip can create a bridge between animal studying and clinical trials involving human subjects. The current in vitro 2D or 3D cell culture and in vivo animal experimentation remains undesirable for an efficient and accurate preclinical evaluation of drug efficacy and toxicity before a clinical trial can be approved for testing in human subjects. Nearly 40% of newly discovered drug candidate fails even after clearing the preclinical evaluation with animal studies due to the species differences between human and animals. Therefore, organ-on-a-chip technology will create a great impact.

Breakthroughs and Developments

After the development of organ-on-a-chip technology, many single-organ-chip such as lung chips, heart chips, kidney chips, intestine and gut chips, pancreas chips, blood-brain-barrier chips, bone chips, bone marrow chip has been developed to investigate the efficacy and toxicity of drugs at the preclinical development stage. Like a single-organ-chip mimics the individual organ functions, a multi-organ-chip mimics different organ functions in a single chip such as a gut compartment for drug absorbance, a liver compartment for drug metabolism, kidney compartment for drug excretion. For instance, three organ chip heart-liver-screen-on-a-chip, four organs chip intestine-liver-skin-kidney-on-a-chip etc. Currently, this development has gone further, and an advanced version is termed Body-on-a-chip or Human-on-a-chip for mimicking the human body physiology using a single chip for drug pharmacokinetic and pharmacodynamic analysis. A Cartilage-on-a-chip model is developed for studying the mechanical factors involved in the pathogenesis of osteoarthritis (OA) and for the development of disease-modifying osteoarthritis drugs.  Skin and hair-on-a-chip are developed for a more extended cultural period through dynamic perfusion with the incorporation of variable mechanical shear stress. In addition to this Oral mucosa-on-a-chip is developed for analyzing the oral mucosal interactions with microbes and biomaterials.

Future prospect

The future development of Organ-on-a-Chip will be on continuous integration of novel engineering tools (e.g., automation handling, 3D printing. and in situ multi-sensors) and biological concepts (e.g., patient-specific induced pluripotent stem cells and organoids) into the Organ-on-a-Chip platform will unprecedentedly promote its biomedical applications. In the future, Organ-on-a-Chip platforms will demonstrate a physiologically relevant and spatiotemporally responsive microenvironment for solving biological and pharmaceutical problems of interest. It will require improvement and standardization of the product manufacturing process as well as categorizing of the system designs, configurable modules, and interfaces. The operation of this platform should come in a more automated, high output, and parallelized manner through a standardized user-friendly interface to enable compatibility with routine biological laboratory experiments and the work mode of the pharmaceutical industry. The OOAC platforms will be developed based on patient-derived materials, such as patient tissue, other biological materials, for personalized precision medicine where patient selection and stratification biomarkers will be critical factors leading to successful drug development.

Conclusion

The OOAC platform in the development pipeline could be more beneficial in future R&D. It is expected to fill up the gap between translational, preclinical, and clinical studies. OOAC has the potential to be used in the pharmaceutical industry and future personalized precision medicine.