Engineering organs-on-a-chip via multi-channel microfluidics.

Conventional in vitro physiological models, relying on animal studies and 2D/3D cell cultures, are fundamentally limited by interspecies biological discrepancies, ethical constraints, or inadequate replication of human physiology. Organ-on-a-chip (OoC) technology overcomes these challenges through emulating organ-specific microphysiological systems. The transformative power of this innovation lies in multi-channel microfluidic chips. These chips facilitate the formation of 3D cellular organizations and tissue interfaces via integrated porous membranes, micropillar arrays, or perfusable vascular microchannels, simultaneously allowing for precise and dynamic modulation of chemical, biological, and physical factors. Rapid technological evolution has yielded functional models of lung alveoli, the blood-brain barrier, cardiac tissues, etc., thereby advancing drug testing and disease modeling accuracy. This review systematically examines the development of OoC technology through the lens of multi-channel microfluidics by focusing on four pivotal domains: (1) the biomimetic design overview for OoCs, (2) fabrication methods including soft lithography and 3D printing, (3) applications in pathophysiological investigations, preclinical drug evaluation, and toxicological assessment, and (4) current challenges and perspectives in structural design, materials and fabrication, biological applications, and other development directions. This review is intended to provide a reference for the technological iteration and interdisciplinary application of multi-channel microfluidic chip systems.