3D-Printed electrochemical sensor-integrated transwell systems

This work presents a 3D-printed, modular, electrochemical sensor-integrated transwell system for monitoring cellular and molecular events in situ without sample extraction or microfluidics-assisted downstream omics. Simple additive manufacturing techniques such as 3D printing, shadow masking, and molding are used to fabricate this modular system, which is autoclavable, biocompatible, and designed to operate following standard operating protocols (SOPs) of cellular biology. Integral to the platform is a flexible porous membrane, which is used as a cell culture substrate similarly to a commercial transwell insert. Multimodal electrochemical sensors fabricated on the membrane allow direct access to cells and their products. A pair of gold electrodes on the top side of the membrane measures impedance over the course of cell attachment and growth, characterized by an exponential decrease (~160% at 10 Hz) due to an increase in the double layer capacitance from secreted extracellular matrix (ECM) proteins. Cyclic voltammetry (CV) sensor electrodes, fabricated on the bottom side of the membrane, enable sensing of molecular release at the site of cell culture without the need for downstream fluidics. Real-time detection of ferrocene dimethanol injection across the membrane showed a three order-of-magnitude higher signal at the membrane than in the bulk media after reaching equilibrium. This modular sensor-integrated transwell system allows unprecedented direct, real-time, and noninvasive access to physical and biochemical information, which cannot be obtained in a conventional transwell system. Sensors: Electrochemical measurements of cultured cells Researchers in the United States have developed a novel system which can measure cellular and molecular events in cell cultures non-invasively and in real-time. The new approach builds on transwell system and is designed to be compatible with existing protocols and tools. The team, led by Reza Ghodssi of the University of Maryland, added electrochemical sensors to the porous membrane normally found in transwell systems, enabling them to measure characteristics of the cultures. An impedance sensor is used to measure cell attachment and growth, while cyclic voltammetry sensors at the bottom measure molecular concentration. The modular platform is 3D printed from autoclavable materials, making the system reusable. With this tool, researchers will have unprecedented access to study the cellular and molecular activity in cel