Novel microfluidic device integrated with a fluidic‐capacitor to mimic heart beating for generation of functional liver organoids

Abstract

Liver organoids hold a great potential to understand liver development and contribute for drug screening and toxicological testing. However, conventional methods to generate organoids provide insufficient liver functions and less reproducibility, due to lack of controllability of cellular microenvironmental cues. To tackle these issues, we focus on one of the environmental cues, pressure stimuli by heart beating, and develop a microfluidic‐based cell culture platform integrating a fluidic capacitor to produce pressure stimuli with hydrostatic pressure. Furthermore, we demonstrate a numerical simulation based on equivalent circuit model for designing the device parameters with sufficient accuracy. This device concept will provide insights into physical micro‐environmental regulation on organoid development.

Automated cellular stimulation with integrated pneumatic valves and fluidic capacitors

“…27,28 These components have been used, for example, in frequency-specific flow control in microfluidic devices 27 and to produce pressure stimuli that mimic heartbeats in a microfluidic cell culture platform. 29…”

“…27,28 These components have been used, for example, in frequency-specific flow control in microfluidic devices 27 and to produce pressure stimuli that mimic heartbeats in a microfluidic cell culture platform. 29 The possibility of incorporating one capacitor before the islet chamber for both perfusion inlets was considered. This would simplify the fabrication process, but it would increase the volume, and increase the time, required to change stimulants when the valves were switched.…”

One-Stop Microfluidic Assembly of Human Brain Organoids To Model Prenatal Cannabis Exposure

“…[24][25][26][27][28][29] Moreover, the microstructure-based perfusion chip design also allows for robust generation of organoids and precise control of medium perfusion, and this device has been adopted to fabricate liver, pancreas and glomerulus organoids and even full embryoids on chip. [30][31][32][33][34][35][36][37][38][39][40][41][42][43] Body-on-a-chip designs feature interconnected modular organoids to mimic inter-organ crosstalk. [44][45][46][47][48] To address the challenges in human brain organoid culture, the Qin group recently has developed a series of microfluidic chips to simplify the brain organoid fabrication process and minimize transferring loss of brain organoids.…”

“…Organoids-on-a-chip technologies provide advantages to recapitulate organ physical structures, chemical environment, and gas exchange as well as mechanical cues. − Ingber’s group has developed a lung-on-a-chip device consisting of two cell culture channels and an interface membrane, and this device design can precisely control fluidic flow and mechanical deformation to mimic lung breathing as well as intestinal epithelium stretching. − Moreover, the microstructure-based perfusion chip design also allows for robust generation of organoids and precise control of medium perfusion, and this device has been adopted to fabricate liver, pancreas, and glomerulus organoids and even full embryoids on-chip. − Body-on-a-chip designs feature interconnected modular organoids to mimic inter-organ crosstalk. − To address the challenges in human brain organoid culture, the Qin group recently has developed a series of microfluidic chips to simplify the brain organoid fabrication process and minimize transferring loss of brain organoids. Micropillar array devices have been used for the in situ generations of human brain organoids .…”

PDMS membrane-based flexible bi-layer microfluidic device for blood oxygenation

“…The previous works [29][30][31][32][33] broadly investigated the influence of PDMS thickness on the mechanical properties and have also studied gas diffusion permeability characteristics for different mixing ratios [28,34,35]. The effect of mixing ratios on the membrane deformation and consequently the gas diffusion characteristics have also been studied in the literature [36][37][38][39]. Despite the above developments, the effect of membrane thickness and the flow rates of blood and oxygen across the gas exchange has not been attempted.…”