Journal: Nature Reviews. Genetics

Article Title: Human organs-on-chips for disease modelling, drug development and personalized medicine

doi: 10.1038/s41576-022-00466-9

Figure Lengend Snippet: a | An optically clear, two-channel, mechanically actuable, organ chip fabricated from polydimethylsiloxane (PDMS) using soft lithography with two parallel channels separated by a flexible microporous membrane (now sold by Emulate ). Different tissue cells are cultured on the top and bottom of the central extracellular matrix (ECM)-coated membrane with micrometre-sized pores to recreate a tissue–tissue interface that permits cell transmigration, and air can be introduced above the epithelium to create an air–liquid interface (for example, in lung) or fluid can be perfused through this channel. Application of cyclic suction to hollow side chambers results in rhythmic distortion of the flexible membrane and attached tissues, thereby mimicking organ-level mechanical distortions (such as breathing motions). b | A multiplexed array of three-channel plastic (polystyrene) chips that contain a thick ECM gel in the central channel, which lacks solid sidewalls and instead restrains the gel using a phase guide. Cells can be cultured in one or both of the flow channels as well as within the ECM gel (now sold by Mimetas ). c | One or more hollow channels are created within a thick 3D ECM gel material by removing cylindrical mandrels after gelling has occurred, and cells can be cultured on the inner surface of the channels as well as within the ECM gel in these plastic devices (now sold by Nortis ). d | A multiplexed PDMS microfluidic device containing two endothelium-lined channels separated by a third diamond-shaped chamber filled with ECM gel that can be used to support capillary ingrowth and 3D microvascular network formation surrounded by cells such as tumour cells in the gel (now sold by Aracari Biosciences ). e | A plastic, multiwell-format organ chip system that incorporates multiple bioreactor chambers, each with a rigid porous membrane and lower microfluidic chamber linked to a fluid reservoir that can be cultured individually under flow or fluidically linked together through the lower compartment. Tissue–tissue interfaces are created by plating different cell types on either side of the membrane, and air or fluid can be included in the upper chamber (now sold by CN Bio Innovations ). f | A higher-throughput (384-well) format plastic organ chip that includes two parallel channels separated by a rigid microporous membrane, and air or fluid can be introduced into the upper channel. g | Organ chips created using 3D printing to deposit sacrificial material in a cylindrical form in any desired pattern within an ECM gel with or without embedded cells. Once gelation is complete, the material is removed and epithelial or endothelial cells are cultured on the inner surface of the channel. h | A plastic multi-chamber organ chip system in which multiple mini-bioreactor chambers positioned on a flat plate can be cultured individually or fluidically coupled through a shared underlying fluidic channel. The cells may be cultured at bottom of the chamber in the flow path (left) or on top of the rigid porous membrane within a Transwell insert that placed within a chamber (right) so that they are separated from the flow path (now sold by TissUse ). Part a adapted with permission from ref. , AAAS. Part e adapted with permission from ref. , RSC. Part g adapted with permission from ref. , CC BY 4.0 ( https://creativecommons.org/licenses/by/4.0/ ). Part h adapted with permission from ref. RSC.

Article Snippet: Cells can be cultured in one or both of the flow channels as well as within the ECM gel (now sold by Mimetas ). c | One or more hollow channels are created within a thick 3D ECM gel material by removing cylindrical mandrels after gelling has occurred, and cells can be cultured on the inner surface of the channels as well as within the ECM gel in these plastic devices (now sold by Nortis ). d | A multiplexed PDMS microfluidic device containing two endothelium-lined channels separated by a third diamond-shaped chamber filled with ECM gel that can be used to support capillary ingrowth and 3D microvascular network formation surrounded by cells such as tumour cells in the gel (now sold by Aracari Biosciences ). e | A plastic, multiwell-format organ chip system that incorporates multiple bioreactor chambers, each with a rigid porous membrane and lower microfluidic chamber linked to a fluid reservoir that can be cultured individually under flow or fluidically linked together through the lower compartment.

Techniques: Cell Culture, Transmigration Assay

Journal: Nature Reviews. Genetics

Article Title: Human organs-on-chips for disease modelling, drug development and personalized medicine

doi: 10.1038/s41576-022-00466-9

Figure Lengend Snippet: Human disease states and clinical responses replicated in single organ chips

Article Snippet: Cells can be cultured in one or both of the flow channels as well as within the ECM gel (now sold by Mimetas ). c | One or more hollow channels are created within a thick 3D ECM gel material by removing cylindrical mandrels after gelling has occurred, and cells can be cultured on the inner surface of the channels as well as within the ECM gel in these plastic devices (now sold by Nortis ). d | A multiplexed PDMS microfluidic device containing two endothelium-lined channels separated by a third diamond-shaped chamber filled with ECM gel that can be used to support capillary ingrowth and 3D microvascular network formation surrounded by cells such as tumour cells in the gel (now sold by Aracari Biosciences ). e | A plastic, multiwell-format organ chip system that incorporates multiple bioreactor chambers, each with a rigid porous membrane and lower microfluidic chamber linked to a fluid reservoir that can be cultured individually under flow or fluidically linked together through the lower compartment.

Techniques: Drug Transport Assay, Plasmid Preparation, Infection, Expressing, Filtration, High Throughput Screening Assay, Mutagenesis, Isolation