Table 8. Microfluidic Concepts for Engineering Neuronal Circuits or Neural Tissues.
3D model | cell source | scaffold material | microfluidic device | functional study | key findings |
---|---|---|---|---|---|
layered cortical circuits39 | cortex E19a rat | agarose–alginate | device with four inlets converging on a single channel | microscopic imaging | 3D multilayered cortical networks were formed in two cell-hydrogel layers separated by cell-free hydrogel layers in a single channel. |
neuronal cell blocks424 | hippocampus E18 rat hiPSC-derived neurons | collagen | multiple microwells for loading cell-matrix mixtures; gelling to form cell blocks | MEA electrophysiology, calcium imaging | Aligned collagen fibers guided axons between 3D neuronal cell blocks. Bidirectional functional connectivity was confirmed by MEA electrophysiology. |
aligned cortical circuits425 | cortex E17 rat | Matrigel | device with pre- and postsynaptic compartments, and a gel-alignment compartment | calcium imaging | Matrigel aligned by applying hydrostatic pressure from presynaptic side. 3D cortical circuits with functional connectivity between pre- and postsynaptic modules. |
anisotropically organized hippocampal circuits426 | hippocampus CA3 and CA1b neurons E18.5 mouse | collagen | device with 3 inlets merging on a single channel | patch-clamp electrophysiology, calcium imaging | Collagen was aligned by stretch and release to guide axons between CA3 and CA1 populations. Synaptic contact between CA3 and CA1 neurons confirmed by microscopy and patch clamp. |
neurospheroid blocks, cortical–hippocampal circuit423 | cortex and hippocampus E17–E18 rat | scaffold-free | PDMS-based neuronal blocks used to mold neuronal spheroids | calcium imaging, microscopy | Synaptic contact between cortical and hippocampal spheroid networks confirmed by oscillations in calcium signals detected by microscopy. |
neurospheroid-on-a-chip449 | cortex E16 rat | scaffold-free self-assembly | multiple microwells and low interstitial level fluidic flow | High-throughput spheroid platform for modeling β-amyloid-induced Alzheimer’s disease. | |
brain organoid-on-a-chip450 | hiPSCs | Matrigel | parallel organoid chambers and media perfusion channels | microscopy of organoid growth on chip | Perfusion of brain organoids improved cortical development compared to static organoid cultures. |
motor unit-on-a-chip452 | myoblast and mESCc-derived motor neurons (MNs) | collagen–Matrigel hydrogel | parallel gel channels flanked by medium channels assembled on top of a PDMS membrane with two sets of capped pillars | patch clamp, optogenetic stimulation of MNsd, measurement of contraction forces | Functional 3D neuromuscular junction. Capped pillars in myoblast compartment measured their contraction force. Optical stimulation of MNs induced myoblast contraction. |
ALSe motor unit-on-a-chip453 | MNs from ALS patient iPSC-derived skeletal muscle cells | collagen–Matrigel hydrogel | device with multiple compartments for MN, muscle cells, and neurite elongation; pillars on muscle cell compartment | electrical and optical stimulation of MNs, measurement of contraction forces in the muscle cells | Functional 3D motor unit derived from ALS patient compared with a motor unit from a healthy subject. Optically or electrically induced contraction forces were measured. |
neurovascular unit458 | cortex E18 rat astrocytes P0–P2f rat HUVECsg | collagen type I | parallel compartments for medium, neuron-hydrogel, astrocyte-hydrogel, and an endothelial cell monolayer separated by trapezoidal structures | calcium imaging, permeability assay | Functional 3D-engineered neuronal network with vascular unit. Compound selectivity of the endothelial monolayer was used to analyze the effect of different compounds and factors on neuronal growth and maturation. |
BBB-on-a-chip459 | cortex E17–E18 rat motor neurons, E12 mouse Schwann cells P4, mouse HBMECsh | collagen type I | A 96-well plate-format device with hydrogel injection ports, media reservoirs, hydrogel channels, and micropost arrays. | calcium imaging, permeability testing, quantification of protein expression levels | High-throughput 3D-engineered cortical circuits, BBBi and myelinated MNs. |
brain organoid-on-a-chip450 | hiPSCs | Matrigel | parallel organoid chambers and supporting media channels with interconnecting apertures | immunolabeling of cortical markers | Brain organoids benefited from an improved nutrient exchange. Enhanced expression of cortical markers compared to static cultures. |
brain organoid-on-a-chip451 | hiPSCs | brain ECMj mixed with Matrigel | multicompartment device with 3D assembled microchannels and rocker-system driven flow | immunostaining, calcium imaging, patch-clamp electrophysiology | Improved and reproducible corticogenesis, complex structural organization, diverse and mature neuronal identities, and enhanced electrophysiological properties. |
retinal organoid-on-a-chip463 | hiPSCs | HyStem-Ck | 2-layer structure: top layer (organoids) and lower layer (vasculature system) with a porous membrane in between | immunostaining, drug testing, calcium imaging | Replicated the interaction of mature photoreceptors and RPEl. Enhanced retinal outer segment formation. Modeling key processes of the visual cycle. |
Embryonic day.
CA1 and CA3 subregions of hippocampus.
Mouse embryonic stem cell.
Motor neurons.
Amyotrophic lateral sclerosis.
Postnatal day.
Human umbilical vein endothelial cells.
Human brain microvascular endothelial cells.
Blood–brain barrier.
Extracellular matrix.
A hyaluronic acid-based hydrogel.
Retinal pigment epithelium.