Customizable Microfluidic Origami Liver‐on‐a‐Chip (oLOC)

Abstract

The design and manufacture of an origami‐based liver‐on‐a‐chip device is presented, together with demonstrations of the chip's effectiveness at recapitulating some of the liver's key in vivo architecture, physical microenvironment, and functions. Laser‐cut layers of polyimide tape are folded together with polycarbonate nanoporous membranes to create a stack of three adjacent flow chambers separated by the membranes. Endothelial cells are seeded in the upper and lower flow chambers to simulate sinusoids, and hepatocytes are seeded in the middle flow chamber. Nutrients and metabolites flow through the simulated sinusoids and diffuse between the vascular pathways and the hepatocyte layers, mimicking physiological microcirculation. Studies of cell viability, metabolic functions, and hepatotoxicity of pharmaceutical compounds show that the endothelialized liver‐on‐a‐chip model is conducive to maintaining hepatocyte functions and evaluation of the hepatotoxicity of drugs. The unique origami approach speeds chip development and optimization, effectively simplifying the laboratory‐scale fabrication of on‐chip models of human tissues without necessarily reducing their structural and functional sophistication.

Rapid Prototyping of Thermoplastic Microfluidic 3D Cell Culture Devices by Creating Regional Hydrophilicity Discrepancy

“…This is consistent with previous publications suggesting that dynamic 3D culture improves hepatocyte long‐term viability and metabolic competence. [ 33–35 ] Our model also predicted the cytotoxic effects of troglitazone, a known hepatotoxic drug. [ 22 ] Corroborating findings from other dynamic 3D liver models, [ 8,34,36,37 ] 3D liver‐on‐a‐chip model exhibits enhanced metabolic function relative to 2D cultures of hepatocytes, more closely mimicking gene expression patterns associated with hepatic drug uptake, accumulation, metabolism, and clearance, and allowing drugs dosed in a physiologically‐relevant manner.…”

Organoids: The current status and biomedical applications

“…Organ‐on‐a‐chip is a microfluidic cell culture device that allows accurate control of the biophysical and biochemical environment for cell growth and simulates both cellular and microenvironmental conditions, as well as inter‐tissue and multiorgan interactions 105 . A variety of organ‐on‐a‐chips have been created to simulate corresponding organs in vitro, which are used for disease modeling and to study the function of related organs 106–108 …”

“…105 A variety of organ-on-achips have been created to simulate corresponding organs in vitro, which are used for disease modeling and to study the function of related organs. [106][107][108] Although organ-on-a-chip has fundamental differences from organoids, the organoids-on-a-chip generated from the combination of organoid technologies and organ-on-achip can compensate for the shortcomings of the two technologies, and thus better serve as more effective preclinical models for simulating key features of target organ tissues. Cells in organoids-on-a-chip are randomly and spontaneously self-organized into 3D structures, which differs from the carefully designed organ-on-a-chip.…”

“… 105 A variety of organ‐on‐a‐chips have been created to simulate corresponding organs in vitro, which are used for disease modeling and to study the function of related organs. 106 , 107 , 108 …”

Variable Stiffness Fibers Enabled Universal and Programmable Re‐Foldability Strategy for Modular Soft Robotics

“…By incorporating flat rigid facets and well‐defined fold lines, origami can readily realize complex kinematic behavior and flat folding. These inherent advantages have led to its wide application across various fields such as DNA synthesis, [ 1 , 2 ] microfluidics, [ 3 ] medical devices, [ 4 , 5 ] batteries, [ 6 ] robotics, [ 7 , 8 , 9 ] manufacturing, [ 10 ] and space structures. [ 11 , 12 ] Recently, the integration of origami techniques into soft materials has simplified the design of soft actuators, [ 13 , 14 , 15 , 16 , 17 ] endowing them with a variety of programmable functionalities, ranging from contraction, twisting, and bending, to radial morphing.…”