Table 2.
Overview of representative human organoids-on-a-chip.
| Organ types | Cell sources | ECM | Chip design | Applications |
|---|---|---|---|---|
| Brain | hESCs[71] | Matrigel | A two-dimensional compartment constructed with an upper membrane connected to a media reservoir and a lower coverslip forming its base | Modeling the physics of the folding brain |
| hiPSCs[56,57,62,84,85,162] | Matrigel | A high throughput micropillar array chip[57,85] A perfusable chip system contained parallel multichannels[56,62] Microfluidic fabricated hollow alginate fiber[84,162] |
Modeling biological events during early brain development in vitro Covering the impact of prenatal exposure to environmental factors |
|
| Spinal cord | hESCs[163] | Laminin | A resin chip comprises a 3D-printed organoid holder and a polycarbonate (PC) membrane | Exploring nociceptive circuits for the development of pain therapeutics |
| Retina | hESCs[164] | Matrigel | A micro-millifluidic bioreactor is designed to be free from shear stress, comprising a series of linear, single-sided chambers alongside serpentine, alternating side chambers that enhance the mixing and distribution of cellular components within the system[164] | Exploring the impact of drug candidates on retinal health and validating the efficacy of AAV vectors for gene delivery in retinal treatments |
| hiPSCs[98,165] | Matrigel | A chip contains an upper structure with four distinct tissue compartments interconnected through a microchannel, while the bottom is equipped with a perfused channel that is partitioned by a thin, porous membrane, facilitating the exchange of nutrients and waste products between the compartments[98,165] | ||
| Liver | hiPSCs[57,58,166] | Nore, fibrinogen, and chitosan | A perfusable micropillar chip system[57,58] A perfusable chip system with C-trap architecture[167] All-aqueous droplet microfluidic device[166] |
Modeling human nonalcoholic fatty liver disease (NAFLD) |
| Kidney | hPSCs[59,168] | Gelatin, fibrin, and Matrigel | A perfusable millifluidic chip by 3D bioprinting | Modeling the processes of glomerular vascular development and the morphogenesis of kidney organoids, investigate mechanisms of kidney diseases |
| hASCs[169] | Collagen I | A three-lane OrganoPlate platform with parallel chips | Simulate BK virus infection and hereditary kidney diseases in a personalized manner | |
| Lung | Tumor tissue[170] | Matrigel | A microwell array chip | Integrating in situ cryopreservation technology to preserve organoid viability for the drug sensitivity testing |
| Tumor-free tissue[171] | Collagen I | A sandwiched chip with PET membrane | Development of more representative human preclinical models of the (diseased) alveolar compartment | |
| Intestine | hiPSCs[63] | Matrigel | A microengineered multilayered device that incorporates a permeable membrane and supports the cultivation of epithelial cells harvested from intestinal organoids under dynamic flow conditions | Studying intestinal epithelial responses to external stimuli, such as cytokines |
| hASCs[88,172,173] | Collagen I and Matrigel | A multilayer chip with a porous membrane enables cyclic deformation and supports the culture of epithelial cells within a microfluidic system[172] A microchip system equipped with crypt-like microcavities and a hydrogel scaffold supports the generation of epithelial organoids and the perfusable design allows the continuous removal of cellular debris[88] A tailored 384-well IFlowPlate with an innovative “open-well” design supports the perfusion and vascularization of colon organoids without requiring external pumps[173] |
Mimicking the human duodenum in vivo, enabling the study of intestinal function such as nutrient digestion, mucus secretion, and barrier integrity Simulating in vivo crypt-villus architecture for host-microbe interaction studies Studying inflammation by stimulating immune responses with inflammatory cytokines |
|
| Breast | Colorectal liver metastasis tissue[108] | Fibrinogen and Matrigel | A multiplexed platform contains AngioTube scaffolds for vascular network formation and is integrated with a 96-well base plate for high-throughput analysis | Simulating of physiological drug delivery to tumors through a vascular network, providing a platform for investigating therapeutic responses in a clinically relevant timeframe |
| Pancreas/islet | hiPSCs[174] | 3D alginate and hydrogel | A perfusable multilayer chip comprises a top microwell array, a polycarbonate porous membrane, and a bottom PDMS layer | Recapitulating the key cellular composition and functions of islet, such as more sensitive glucose-stimulated insulin secretion and higher Ca2+ flux |
| Pancreatic ductal adenocarcinoma cancer tissues[105] | Matrigel | A two-layer chamber chip, which can be reversibly clamped, features a 200-well array and an upper layer consisting of fluidic channels | Automated dynamic and combinatorial drug screening | |
| Stomach | hPSCs[72] | Matrigel | A central compartment designed for organoid cultivation, accompanied by two adjacent chambers for media storage and exchange | Replicating the peristaltic movements in a manner that closely mimics in vivo conditions |
3D: three-dimensional; AAV: adeno-associated virus; BK virus: human polyomavirus 1; ECM: Extracellular matrix; hESCs: human embryonic stem cells; hiPSCs: human induced pluripotent stem cells; hASCs: human adipose stem cells; PDMS: Polydimethylsiloxane; PET: polyethylene terephthalate.