Organs-on-Chips in Drug Development: Engineering Foundations, Artificial Intelligence, and Clinical Translation

Area of Science:

• Biomedical Engineering
• Microfluidics
• Cellular Engineering

Background:

• Organ-on-a-chip (OoC) technologies, or microphysiological systems (MPSs), integrate microfluidics, biomaterials, and biosensors to mimic human physiology.
• These systems aim to provide quantitative, time-resolved physiological data at the microscale.

Purpose of the Study:

• To review literature from 2010-2025 on OoC technologies, focusing on sensing, standardization, and analytics for clinical and regulatory applications.
• To synthesize advances in materials, fabrication, organ-specific models, and translational benchmarks.

Main Methods:

• Literature review of OoC technologies, materials, fabrication, microfluidic design, and organ-specific case studies.
• Analysis of translational benchmarks aligning chip outputs with clinical pharmacokinetic and toxicological data.
• Synthesis of advancements in biosensing modalities (impedance, electrochemical, optical) and integration of vascularization and immune components.

Main Results:

• Cardiac OoCs achieve AUROC ≥ 0.85 for torsadogenic risk classification; renal chips improve prediction of transporter-mediated clearance.
• Platforms increasingly incorporate vascularization, immune components, and organoid hybrids with real-time measurements.
• Biosensor-enabled OoCs demonstrate progress toward quantitatively benchmarked platforms for safety pharmacology, ADME/PK-PD, and precision medicine.

Conclusions:

• Sensing, standardized sampling, and analytics in OoC technologies are crucial for clinical concordance and regulatory acceptance.
• Advances in AI, multi-omics, and digital-twin workflows are poised to further automate analysis and integrate OoC data with in silico models.
• OoC technology is advancing towards validated, fit-for-purpose platforms for drug development and personalized medicine.