Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

Abstract

Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called "organ-on-a-chip" technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

Keywords: BioMEMs; body-on-a-chip; microfluidics; organ-on-a-chip; tissue engineering.

Figure 1

Illustration of the diverse microfluidic devices used to study biological processes occurring in vascular, respiratory, nervous, digestive and excretory systems. A. Biochip with subdividing interconnecting microchannels (array of pillars) that decrease in size to mimic cell flow and adhesion in microvasculature to study of vaso-occlusive processes. B. Human breathing lung-on-a-chip microdevice, a biomimetic microsystem that reconstitutes the alveolar-capillary interface of the lungs. The device uses compartmentalized chambers to form an alveolar-capillary barrier on a porous membrane and produces cyclic stretching of such membrane by vacuum actuation. C. Two-compartment microfluidic culture system bridged by microchannels. It allows the visualization of cell interactions in co-culture, namely as a model for synaptic connectivity between mixed hippocampal co-cultures in which microgrooves allow both axons and dendrites to enter and form synapses. D. Vertical cross-section representing the on-chip generation of intestinal villi obtained by villus morphogenesis of Caco-2 cells. The up-scale of this system leads to the production of gut-on-a-chip platforms to study pharmacokinetics and diffusion processes. E. Artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture to study diffusive nutrient transport in liver-mediated metabolism. This unit consists of a cord of hepatocytes fed by diffusion of nutrients across the narrow microfluidic channels from a convective transport vessel. F. Kidney proximal tubule-on-a-chip. The microfluidic device consists of an apical channel separated from a bottom reservoir by a porous membrane upon which primary human proximal tubule epithelial cells are cultured in the presence of apical fluid shear stress. This design mimics the dynamically active mechanical microenvironment of the living kidney proximal tubule and allows the study of active and passive epithelial transport.

Figure 2

Schematic representation of a BoC approach in which cell-autonomous and non-autonomous studies can be performed using a single chip.