Table 1.

Summary of various viral infection-on-a-chip studies.

No.	Organ-on-chip model	Design considerations	Study	Experimental assay	Virus	Culture type	Cell type used	Ref.
1.	Liver sinusoids	Perfused bioreactor, collagen-coated scaffold for cell adherence	Host/pathogen interactions. Recapitulation of all steps of the HBV life cycle	Expression of innate immune receptors cytokine responses	Hepatitis B virus (HBV)	Co-culture	Primary human hepatocyte (PHH) Non-parenchymal cells	[57]
2.	Three-layer microfluidic chip	Low shear stress. Tree-like concentration gradient generator using Nocodazole	Infection and proliferation characteristics of GFP-PrV. Molecular biology of herpes viruses. concentration	Tracking the fluorescence intensity of GFP. Determining the one-step growth curve.	Recombinant Pseudorabies virus (GFP-PrV)	Monoculture	African green monkey kidney (Vero) cells	[102]
3.	Microfluidic device combined with a light modulation system	Array of glass microwells deposited with Pt(II) octaethylporphine (PtOEP) as the oxygen-sensitive luminescent layer. Pneumatically actuated lids set above the microwells to controllably seal the microwells of interest	Quantitatively monitor the viral infection process in real time Real-time monitoring of cellular oxygen consumption rates (OCRs).	Determine the antiviral activities of carrageenan	Dengue virus (DENV)	Monoculture	Baby hamster kidney-21 (BHK-21) fibroblast cells	[68]
4.	Microfluidic chip with Dielectrophoretic (DEP) force	Optical tweezers To trap concentrated virus. Dielectrophoretic (DEP) force: To concentrates the virus. To avoid virus adhesion to the glass substrate.	Manipulation of the single virus. DEP concentration of viruses	Single cell infection to a specific cell using DEP virus concentration	Influenza virus	Monoculture	H292 cell	[25]
5.	Microfluidic chamber system	Composed of small PDMS piece with compartments connected by microgrooves	Directs growth of axons into a fluidically isolated environment. Uses substantially smaller amounts of virus inoculum and media.	Neuron-to-cell spread of infection. Viral transport in axons.	Pseudorabies virus (PRV)	The swine kidney epithelial cells (PK15) in the axonal compartm ent Neurons from the superior cervical ganglia (SCG) in the somal compartm ent	PK15 Neurons	[42]
6.	Microphysiological System	Fluidic flow Drain reservoir Medium reservoir Primary infection Bystander infection	Evaluated the spreading of oncolytic viruses [58]. Real-time monitoring of oncolytic activity. Evaluating the bystander infection of OVs in 3D multicellular tumoroids.	Identify cell death as oncolytic cytopathogenesis. Gene expression of the cytoplasmic VSV-related Proteins (VSV-glycoprotein (VSV-G) and interferon-beta (IFNβ). Immune Response to VSV-GFP Infection	Vesicular stomatitis virus (VSV)-green fluorescence protein (GFP)	3D multicellul ar tumoroids	A549 MRC-5 HUVECs	[65]
7.	Distal renal tubule-on-a-chip (DTC)	Three-layered microfluidic chip. Distal renal barrier structure. Na+ reabsorption in distal renal tubules.	Pathogenesis of virus-related renal dysfunctions,	Na+ reabsorption function evaluation. Electrolytes regulation Reabsorption barrier Polarized distribution of the functional proteins (Na+-K+-ATPase)	Pseudorabies Virus (PrV)	Monoculture	MDCK cells	[103]
8.	Intestinal tubules in the OrganoPlate platform	Single microfluidic channel network. Comprising three channels that join in the center membrane-free manner. ECM-gel. Perfused epithelia tubules.	Real-time interrogation of drugs effects on barrier integrity. Studying exposure concentration response. Studying exposure time response.	Assessing the barrier integrity of 40 leak-tight, polarized epithelial gut tubes. Over 350 gut tubes Over 20,000 datapoints		Seeded in the top medium channel	Human colon adenocarcinoma cell line Caco-2	[58]
9.	Gut-on-a-chip	Fluid flow, peristalsis-like motions, vascular channel and epithelial channel	Study human enterovirus infection. Investigating mechanisms of enterovirus pathogenesis.	Viral titers. Detecting cytopathic effects (CPEs). Caspase-3 assay. Cytokine analysis	Coxsackievirus B1 (CVB1)	Human Caco2 intestinal cells seeded into the top channel	Human Caco2 intestinal cells	[44]
10.	Human alveolus chip	Upper alveolar epithelial channel. Lower Pulmonary microvascular endothelial channel. Porous PDMS membrane. The alveolar-capillary interface. Fluidic flow	Pathological changes of epithelium-endothelium interface. Inflammatory responses. Anti-viral therapy	RNA-seq analysis, western blot, immunostaining, analysis, permeability assay, inflammatory cytokines analysis and drug treatment	SARS-Cov-2	Co-culture	Alveolar epithelial cells (HPAEpiC) pulmonary microvascular endothelial cells (HULEC-5a)	[31]