Microfabricated Physiological Models for In Vitro Drug Screening Applications

Abstract

Microfluidics and microfabrication have recently been established as promising tools for developing a new generation of in vitro cell culture microdevices. The reduced amounts of reagents employed within cell culture microdevices make them particularly appealing to drug screening processes. In addition, latest advancements in recreating physiologically relevant cell culture conditions within microfabricated devices encourage the idea of using such advanced biological models in improving the screening of drug candidates prior to in vivo testing. In this review, we discuss microfluidics-based models employed for chemical/drug screening and the strategies to mimic various physiological conditions: fine control of 3D extra-cellular matrix environment, physical and chemical cues provided to cells and organization of co-cultures. We also envision future directions for achieving multi-organ microfluidic devices.

Keywords: drug screening; microfluidics; organ-on-chips; physiological models.

Figure 1

(a) Geometrical 3D arrangement of a liver lobule-on-a-chip. An hydrogel patterning technique is employed by Ma et al. to obtain radially distributed hepatocytes (green) in a network of endothelial cells (red). Adapted from [42] with permission; (b) 3D sketch of a blood–brain barrier microdevice model with upper compartment hosting endothelial monolayer culture on a microporous membrane and lower compartment for collection of transported nanoparticles. Electrical measurements across the endothelial monolayer provide information on barrier integrity; (c) Pictures of blood–brain barrier microdevices with fluidic and electical connections (adapted from [52] with permission).

Figure 2

Cardiovascular organs-on-a-chip. (a) Exploded view of heart-on-a-chip device. Adapted from [96] with permission from The Royal Society of Chemistry; (b) Scanning electron micrograph of the microphysiological system. Red rectangular boxes show the 2 mm endothelial-like barrier and the weir gap. Adapted with permission from [103]; (c) Schematic of the 3D beating heart-on-a-chip microdevice. The polydimethylsiloxane (PDMS) membrane between compartments deforms, compressing the 3D cell construct. Adapted from [87] with permission from The Royal Society of Chemistry; (d) Schematic showing top and side view of the microfluidic device for inducing platelet aggregation at four distinct high shear stenotic regions. Adapted with permission from [104].

Figure 3

Biological barrier microfluidic models applied for kidney and lung organs. Kidney platform: (a) sketch of the fabrication process involving the sandwich assembly of the porous membrane between two PDMS layers; (b) schematic of the chip operating principle; and (c) picture of the device connected to a syringe pump through silicon tubing. Adapted from [137] with permission. Human lung on a chip: (d) schematic of the epithelial and endothelial cells co-cultured on opposite sides of the porous membrane, stretched applying vacuum in the side channels to mimic alveolar deformation during normal breathing; and (e) picture of a microdevice filled with color dyes. Adapted from [121] with permission.