TABLE II.

Summary table of CULTIVATION: Organism-on-a-Chip part.

Format	Microorganism	Material used	Fabrication techniques	Dimensions	Comment	Reference
Multiplexed microbioreactor	E. coli	PMMAPDMS	Milling Hermetical sealing	150 μl reactor chamber	OD, DO and pH measuring 4 parallel microbial fermentation	41
Microbioreactor	E. coli	PMMAPDMS PAA	CNC milling Thermal bonding	150 μl reactor chamber	OD, DO, pH measuring Reinforced cultivation time and prevented wall growth of the cells	42
3D microfluidic chip	HeLa E. coli	PMMAPC	Laser cutter Wax bonding	2 mm width and 500 μm height of chamber	PCR, HeLa cell EP and E. coli culturing Effect of ciprofloxacin concentration on E. coli	43
Microfluidic chip	Pseudomonas aeruginosa	PMMAPDMS	Laser ablation Adhesive tape for sealing	150 μm thick cell culture chamber	Chip allows the gas transition Active oxygen depletion examination	44
Microfluidic chip	E. coli Shigella flexneri Shigella boydii Shigella sonnei Uropathogenic E. coli	PMMA	CO2 laser cutter glue bonding	5 mm in diameter and 800 μm in the height of reservoir	Drug resistance testing of several bacterial strains Comparison of the microfluidic system and 96-well microtiter plates	45
PMMA made microchannels	E. coli K12	PMMA	Hot embossing UVO-assisted thermal bonding	42 μm height, 1 mm width and 20 mm length of microchannels	Positively charged nanofibers were better than negatively charged ones	46
Microfluidic chip	Cordyceps militaris	PMMA	CO2 laser machine Screw binding	NA	Monodispersed agar beads for cultivation	47
Milliliter-scale bioreactor	Lactobacillus paracasei S. cerevisiae	PMMAPDMS	CNC machining PDMS for sealing glue for bonding	0.5–2 ml bioreactor	OD, DO, pH measuring. Aeration and mixing capability	48
Microfluidic chip	S. cerevisiae	PC	Ultrasonic hot embossing Ultrasonic welding	Microchannels with a depth between 50 μm and 1 mm and a width between 100 μm and 3 mm	eGFP tagged protein monitoring with a supply of the inducer galactose 22 h operation in the device	49
3D multilayer microfluidic system	Zebrafish (Danio rerio)	PMMA	Infrared laser machine Thermal bonding	Conical traps of 2 mm in diameter at the top and 1.6 mm in diameter at the bottom planes	One embryo in one trap 100% trapping of the cells 72 h experiments	50, 51
Microfluidic chip	Zebrafish (Danio rerio)	PMMA	High-speed infrared CO2 laser cutting Thermal bonding	0.75 mm in diameter and 0.5 mm in height of microwells	ESEM imaging Damaged tissues under a low vacuum environment	52
3D microfluidic chip	Zebrafish (Danio rerio)	PMMA	Infrared laser machine Thermal bonding	1.7 mm × 1.5 mm × 55 mm of main channel	Rapid and automated manipulation of zebrafish cells for drug discovery	53
Microfluidic chip	Zebrafish (Danio rerio)	PMMA	CO2 laser cutting	36 circular microwells (0.75 mm in diameter and 0.5 mm in depth	Microwells for keeping zebrafish yolk revealing morphological features of zebrafish via ESEM imaging	54
3D multilayer microfluidic chip	Zebrafish (Danio rerio)	PMMA	Infrared laser micromachining Thermal bonding	Suction manifold of 0.5 mm width and 1.8 mm height	Analyzing, sorting and dispensing of cells	55
3D multilayer microfluidic chip	Zebrafish (Danio rerio)	PMMA	Laser micromachining Thermal bonding	20 miniaturized traps and 1.7 mm × 1.5 mm × 55 mm of main channel	Making automatic immobilization, culture and treatment of cells	56
3D multilayer microfluidic chip	Zebrafish (Danio rerio)	PMMA	Infrared laser micromachining Thermal bonding	96-well microtiter plate 21 miniaturized traps of 1.5 mm × 1 mm	FET assay performing Rapid loading separating immobilizing of cells and continuous perfusion Anti-angiogenesis drug tests	57
3D multilayer microfluidic chip	Zebrafish	PMMA	Infrared laser micromachining	18 embryo traps of 1.5 mm × 1 mm	FRIM technology for kinetic quantification of the aqueous oxygen gradients	58
Small-animal Nutritional Access Control (SNAC) chip	Drosophila melanogaster	PMMA	CNC machining Thermal fusion bonding	Behavior chamber of 20 mm × 15 mm × 2 mm Feeding alcove of 400 μm width	Studying the actions of flies	59
Microfluidic chip	HepG2	PMMAPS PC COC	Hot embossing Thermal bonding	3.5 μl culture chambers	Investigation of biocompatible materials	60
Microfluidic coculture chip	Human U937 and MG-63 cell lines	PMMA	CO2 laser scriber Thermal bonding	Trenches of 200 μm in height and width	Studying coculture behavior	61
Microbioreactor	HT 1080	PMMA	Milling Double sided adhesive tape	Culture channel of 4 cm × 300 μm × 300 μm	DO level and shear-stress acting on the cells investigation	62
Microfluidic chip	HEK-293T	PDMS PMMA	PDMS: silicon wafer mold + high frequency generator PMMA: CO2 laser etching	Microchannels of 40 μm H × 0.4 mm W Microchannels of 40 μm H × 100 μm W	Revealing optimum conditions for growth under several experimental conditions	63
Hard-soft hybrid material microfluidic chip	HepG2 C2C12	PETG COC PS	Hot embossing Soft lithography Argon and oxygen plasma	X region of 200 μm height	Combination of hard and soft materials Cell culturing ∼100% cell survival rate	64
Microfluidic chip	HEK293 U-2 OS PC12	PTFE	CNC machining Stainless steel clamping	Fluidic input channels of 500 μm2, opening out of 1000 μm2	Encapsulation of living, therapeutically active cells within monodisperse alginate microspheres	30
Microfluidic chip	IMR-90 fetal lung fibroblast Human neutrophils	PS PDMS	Thermal scribing	Microchannel of 500 μm width, 250 μm height and 25 mm length	Understanding the mechanism of neutrophil culture systems	65
Microfluidic chip	Human colorectal adenocarcinoma cells	PDMS PMMA	CNC machining Replica molding Oxygen plasma	36 microbioreactors of 1.5 mm in diameter and 1 mm in height	High-throughput 3D cell culture and chemosensitivity assay	68
Microfluidic chip	Human oral cancer cell line	PDMS PMMA	CNC machining Replica molding Oxygen plasma	30 microbioreactors of 3 mm in diameter and 2.5 in height	High-throughput 3D cell culture system Chemosensitivity assay DNA content detection Viability experiments	69
Micro-scaffold array chip and Drug laden chip	NIH3T3 fibroblasts Human fibrosarcoma cells Human hepatocellular carcinoma cells Human non-small lung cancer cells	PMMA	CO2 laser system	96 microwell array of 2 mm in diameter	3D cell culture Drug administration Quantitative in situ assays	70
Microbioreactor	Human lung adenocarcinoma epithelial cell line (A549)	PMMA	Micromilling Screw binding	Rectangle obstacles of 0.35 mm × 1.2 mm in microchannel of 0.8 mm × 0.35 mm	Cell viability and cell toxicity tests Drug testing experiments	71
Microfluidic chip	K562 human erythroleukemia cells	PMMA	machining Thermal bonding	Microchannel of 254 μm W × 150 μm H	NP study to examine the Bcl-2 down-regulation at the mRNA and protein levels	73
Semi-continuous flow electroporation (SFE) chip	K562 cells	PMMA	Hot embossing Lamination	Channels of 2 mm width	Increasing the transmission of exogenous oligonucleotides in vitro	74
Single field chip (SFC) and multi-field electrostatic chip (MFC)	CL1-5 and CL1-0 lung cancer cell lines	PMMA	CO2 laser ablation Double sided adhesive tape	SFC: microchannel of 3000 μm × 70 μm × 15 mm MFC: microchannel of 24 mm in length with 5000, 1667, 1000 μm in width segments	Electrotaxis study Distinct electric fields applications for cellular response	76
Microfluidic chip	MDA-MB-231 human breast cells	PMMA	NA	Barrier thickness of 60 μm ± 40 μm	Multilayer contactless dielectrophoresis system	77
Sensor chip	HEK293 cells	PMMA	Hot embossing FIB milling	Micropore of 1.5–2 μm in diameter	Cell trapping	78
Microfluidic chip	HepG2 cells	PMMA	CO2 laser ablation Double-sided adhesive tape Hot-press bonding	Rectangular cell culture chamber of 8 mm × 6 mm	Monitoring cell growth Cytotoxicity experiments	79
Parallel microfluidic cytometer (PMC)	Chinese hamster ovary cells Jurkat cells Jurkat T-cells	PMMA	Deep reactive-ion etching	Microchannel of 40 μm × 150 μm	Cell screening assays	80
Micro-optical tweezers (μOT)	RBC Tumor cells	Glass PMMA	Micromilling Solvent assisted bonding	Channels of 60 μm × 1 mm × 2 cm	Mechanical and chemical spectroscopic analysis	81
Nanotopography	Primary human osteoprogenitor cells	PMMA	Colloidal lithography Polymer demixing Embossing	10 nm size topographies	Cell morphology, cell cytoskeleton, adhesion formation, cell growth and differentiation studies	85
Spheroid microarray chip (SM chip)	Hepatocytes	PMMA	Micromilling Press bonding	Cylindrical cavities of 300 μm	Production of spheroids by hepatocytes	86
Microfluidic chip	Schwann cells Fibroblast cells	PMMA	CO2 laser machining Screw bonding	Microchannel width of 200 μm, depth of the chip is 1.5 mm	Can be used as scaffold for cell cultures	87
Surface modification	Human corneal limbal epithelial cells (HCLEs) Human keratocytes	PMMA	Surface modifications with chemicals	NA	Adhesion of collagen gel studies	88
Microengineering vascular structures	Human umbilical vein cell (HUVEC)	PMMA	Gelatin methacrylate hydrogel photopatterning	NA	More complex, vascularized tissue constructs for regenerative medicine and tissue engineering applications with the combination of SAM-based cell transfer and hydrogel photocrosslinking	89
Helical and straight microchannels	NIH 3T3	PMMA	Agarose solution for hydrogel fabrication Laser etcher	Chamber: 24 mm × 12 mm × 5 mm Wire diameter: 300 μm	Helical and straight microchannels comparison Better perfusion ability and oxygen and nutrient delivery to cells in helical microchannels	90
Surface modification	MC3T3-E1	PS	Anodization Hot embossing Nickel electroforming	Nanopore structure with a diameter of 200 nm, depth of 500 nm	Studying the topographical effects of surfaces on MC3T3-E1 cells	91
Surface modification	MC3T3-E1	PS	Injection molding	Several patterns with 2,3,4 μm diameter holes	Bone replacement operations Microtopography, pillar diameter, aspect ratio and spacing evaluations Micro-pillared surfaces are better than flat surfaces	92
3D microfluidic structures	Liver tissue cultures Mesothelial cells	PMMA	Engraving machine UV photo polymerization	PEGDA structures of 60 μm height	PEGDA microstructures with mesothelial cells for contribution of adhesive surface and tissue repair	93
Microfluidic chip	Primary human alveolar bone osteoblast (PHABO)	PMMA	NA	300 μm cubic cavities 10 mm × 10 mm device	PHABO morphogenesis investigation in both microchip-based 3D-static conditions and 3D-fluid flow-mediated biomechanical stimulation in perfusion bioreactors	94
Mechanical microconnector system (mMS)	Spinal cord stumps	PMMA	Vacuum application	Thickness of 350 μm and outer diameters of 1.7 mm and 2.7 mm	Regulation of retracted spinal cord stumps Axonal regrowth was achieved after 2, 5 and 19 weeks with the mMS.	95
Microfluidic chip	C3H10T1/2 stem cells	PMMA	CO2 laser etching Thermal bonding	170 μm width, 200 μm height and 1.5 cm length	Application of click chemistry Bio-orthogonal chemical group generation in a rapid, straightforward and flexible way	96
Microvascular network	Endothelial cell Mesenchymal stem cells	PMMA	Laser cut Silicone glue bonding	2 × 2 × 2 mm3 and 2 × 2 × 5 mm3 masks	Parameter effects on the vascularization of bone-mimicking tissues Creation a link in between the macroscale and microscale tissue engineering studies	97
Microfluidic chip	Human umbilical vein endothelial cells (HUVEC) Blood neutrophil	PS COP	Hot embossing Thermal bonding	3 different aspect ratios: 10, 20 and 50 Height: 10 μm	HUVEC culturing in one application and blood neutrophil culturing under chemoattactant in another PS can be used for long term studies	98
Microfluidic chip	Human microvascular endothelial cells (hMVECs)	COC	Hot embossing Oxygen plasma Roller-lamination	50 mm × 4 mm × 100 μm (L×W×H)	No adverse effect of COC material on cells	99
MOTiF biochip	Endothelial cells	COC	Injection molding Surface oxidation	140 μm thick	Nutrient medium supply, catabolic cell metabolites removal and shear stress applications	100
Body-on-a-chip	A549 Caco2 HepG2 C3A Meg01 HK2	PC Silicone PMMA	Milling Screwing	2.5 μl volume	Imitation the drug distribution and metabolism processes in the body Building, managing and cultivating of multi-organ microphysiological system	101
Microwell and patterned chip	Embryoid bodies from mouse embryonic stem cells	PMMA	Micromilling Microcontact printing	270 microwells of 600 μm in diameter and depth, 270 gelatin spots of 200 μm in diameter	The proliferation and differentiation of EB variation from design to design	102
Spheroid transfer chip (ST chip)	Mouse ES cells, 3T3 cells, HepG2 cells and primary hepatocytes	PMMA PDMS	Micromilling	270 microwells of 600 μm in diameter, depth and pitch	Spheroid production Cell proliferation and cell viability in the spheroid and spheroid size monitoring	103
Microfluidic chip	L929 mouse fibroblast	PMMA	Automated nanodispensing or microcontact printing Double side sticky pressure-sensitive adhesive	Microgel coatings of 200 μm	Cultivation of L929 mouse fibroblast Studying cell detachment	104
Surface modification	MG-63	PS	Nano-injection molding UV photolithography electroforming	The width and spacing of microgroove patterns: 50 μm	Cell attachment and alignment using PMS-NPS PMS-NPS are better than flat PS surfaces	105
Surface modification	MG-63	PS	Nano-injection	Nanopore array: 20 mm × 20 mm	Cell attachment and proliferation study on NES Nanopore surface is better than flat surface	106