TABLE I.

Summary of different scaling methods.

Methods	Direct scaling	Residence time-based scaling	Allometric scaling	Functional scaling	Multifunctional scaling
Main principles	Multiplication of organ sizes by a scaling factor	Match the fluid (blood) residence time for each organ	Physiological parameters should follow allometric power laws at microscale	Define major functional parameter for each organ	Specify multiple objective parameters and numerically derive design parameters
Pros	• Very simple	• Ensures physiologically realistic dynamics between organs	• Plenty of literature sources for allometric relationship for various parameters	• Mathematically robust and easy to apply once data is provided	• Works well for a specific purpose (for example, PK study)
Cons	• Likely to cause imbalance between organ functions at microscale	• Each organ module should have physiological level of intrinsic activity	• Allometric scaling law may not hold at microscale	• Issues with organs with multiple functions	• Can be mathematically complex when the system becomes larger
	• Ignores flow rates or circulation time	• Mass transfer within the tissue needs to be considered	• Often requires further refinement by considering cell number, flow rates, etc.	• Difficult to define quantitative parameters for some organ functions