A Comprehensive Review of Organ-on-a-Chip Technology and Its Applications

Abstract

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell cultures due to various limitations of in vivo testing. Unfortunately, in-vitro cell culturing fails to provide an accurate microenvironment, and in vivo cell culturing is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The critical component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in-vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

Keywords: disease models; human-on-a-chip; multi-organs-on-a-chip; organ-on-a-chip.

Figure 1

Kidney-on-a-chip design [80].

Figure 2

Huh et al.’s lung-on-a-chip. (A) The microfabricated lung device replicates breathing motions through vacuum-induced mechanical stretching of PDMS membranes, forming an alveolar-capillary barrier within the compartmentalized microchannels. (B) Diaphragm contraction lowers intrapleural pressure (P_ip), stretching the alveolar-capillary interface during inhalation in living lungs [39].

Figure 3

Marsane et al.’s heart-on-a-chip. (a) The microfabricated heart-like device has two PDMS chambers with cardiac cells in a fibrin gel matrix, replenished by side channels, allowing for configurable geometries. (b) Pressurizing the bottom compartment deforms the PDMS membrane, compressing the 3D cell construct against postsgenerating cyclic pressure to mimic physiological heart phases [87].

Figure 4

Gunther et al.’s artery-on-a-chip. (a) Illustration of a resistance artery segment. (b) Illustration of the chip housing a network of microchannels, a loading well for arteries, and an inspection area for arteries. (c–e) Illustrations of reversible procedures for artery segment loading, fixation, and inspection [56].

Figure 5

Kim et al.’s intestine-on-a-chip. (a) Schematic of a gut-on-a-chip device: flexible ECM-coated membrane with gut epithelial cells spans central microchannel, flanked by full-height vacuum chambers. (b) Images show intestinal monolayers in gut-on-a-chip: with (right) or without mechanical strain (left) (30%; arrow indicated direction); suction applied to vacuum chambers causes cell distortion toward tension direction [44].

Figure 6

Uterus-on-a-chip [146].

Figure 7

Vagina-on-a-chip. (A) Image of a two-channel PDMS chip. (B) Image of a pod demonstrating the reservoirs for basal and apical channels. (C) Illustration depicting a cross-sectional view of a Vagina Chip infected with microbes [155].

Figure 8

Diagram of human-on-a-chip. This image was taken from the ELVESYS Group website (elveflow.com).