Modular automated microfluidic cell culture platform reduces glycolytic stress in cerebral cortex organoids

Abstract

Organ-on-a-chip systems combine microfluidics, cell biology, and tissue engineering to culture 3D organ-specific in vitro models that recapitulate the biology and physiology of their in vivo counterparts. Here, we have developed a multiplex platform that automates the culture of individual organoids in isolated microenvironments at user-defined media flow rates. Programmable workflows allow the use of multiple reagent reservoirs that may be applied to direct differentiation, study temporal variables, and grow cultures long term. Novel techniques in polydimethylsiloxane (PDMS) chip fabrication are described here that enable features on the upper and lower planes of a single PDMS substrate. RNA sequencing (RNA-seq) analysis of automated cerebral cortex organoid cultures shows benefits in reducing glycolytic and endoplasmic reticulum stress compared to conventional in vitro cell cultures.

A computer vision based optical method for measuring fluid level in cell culture plates

“…Previous work has been published laying out the design and use of a 24 well parallel microscope system using similar camera hardware and LEDs, this system is called the "Picroscope" [11,12]. The picroscope is also built to be compatible with a microfluidic cell culture feeding platform [13]. Applying this principle to this system can enable feedback control for fluid contents of the wells in this and other microfluidic "lab-on-achip" type systems.…”

“…What is advantagous about the method presented here is that it uses hardware that may be already present in the system. For instance some lab-on-a-chip microfluidic systems contain imaging modules as well as the materials to move fluids [13]. In systems like this, An overhead LED and a camera may already be present for other imaging needs.…”

IoT cloud laboratory: Internet of Things architecture for cellular biology

“… An outline of existing tools that utilize the IoT Cloud Laboratory platform described in this paper. (Device) shows Picroscope [ 32 , 33 ] for microscopy, Piphys [ 34 ] for electrophysiology recording, and Autoculture [ 35 ] for fluidic media exchange and liquid biopsy. (Infrastructure) shows the primary suite of tools introduced in Sections 3.2 , 3.4 and 3.5 .…”