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  • Rapid Manufacturing of Multilayered Microfluidic Devices for Organ on a Chip Applications.

Rapid Manufacturing of Multilayered Microfluidic Devices for Organ on a Chip Applications.

Sensors (Basel, Switzerland) (2021-03-07)
Roberto Paoli, Davide Di Giuseppe, Maider Badiola-Mateos, Eugenio Martinelli, Maria Jose Lopez-Martinez, Josep Samitier
ABSTRACT

Microfabrication and Polydimethylsiloxane (PDMS) soft-lithography techniques became popular for microfluidic prototyping at the lab, but even after protocol optimization, fabrication is yet a long, laborious process and partly user-dependent. Furthermore, the time and money required for the master fabrication process, necessary at any design upgrade, is still elevated. Digital Manufacturing (DM) and Rapid-Prototyping (RP) for microfluidics applications arise as a solution to this and other limitations of photo and soft-lithography fabrication techniques. Particularly for this paper, we will focus on the use of subtractive DM techniques for Organ-on-a-Chip (OoC) applications. Main available thermoplastics for microfluidics are suggested as material choices for device fabrication. The aim of this review is to explore DM and RP technologies for fabrication of an OoC with an embedded membrane after the evaluation of the main limitations of PDMS soft-lithography strategy. Different material options are also reviewed, as well as various bonding strategies. Finally, a new functional OoC device is showed, defining protocols for its fabrication in Cyclic Olefin Polymer (COP) using two different RP technologies. Different cells are seeded in both sides of the membrane as a proof of concept to test the optical and fluidic properties of the device.

MATERIALS
Product Number
Brand
Product Description

Supelco
Chloroform, analytical standard
Supelco
Cyclohexane, analytical standard
Sigma-Aldrich
Paraformaldehyde, reagent grade, crystalline
Sigma-Aldrich
Gelatin from porcine skin, powder, gel strength ~300 g Bloom, Type A, BioReagent, suitable for electrophoresis, suitable for cell culture
Sigma-Aldrich
Collagen, Type I solution from rat tail, BioReagent, suitable for cell culture, sterile-filtered
Sigma-Aldrich
Sodium azide, purum p.a., ≥99.0% (T)
Sigma-Aldrich
Blood-Brain Barrier hCMEC/D3 Cell Line, The hCMEC/D3 BBB cell line has been extensively characterized for brain endothelial phenotype and is a model of human blood-brain barrier (BBB) function.
Sigma-Aldrich
Triton X-100, for molecular biology