Abstract

Designing a Bioreagent-Compatible Material for a 3D-Printed Molecular Design System

Noah Malmstadt, Professor of Chemical Engineering and Materials Science, University of Southern California

While stereolithographic 3D printing (SLA) is a promising method for the rapid prototyping and manufacturing of microfluidic systems, the bioadhesive properties of cured SLA resins are poorly characterized. Adhesion of biomolecules to microfluidic channels is an issue in nearly all biological applications, but it becomes a particular problem in applications that require precise and reproducible control of reaction conditions. Over the past several years, we have deployed SLA-printed modular microfluidic components to automate the biochemical workflow of mRNA display. mRNA display is a selection technology that harnesses a massive oligonucleotide-peptide hybrid library to identify molecules that bind to protein targets; automating the mRNA display workflow is a route towards the rapid development of novel cancer protein binding agents. A major roadblock to the microfluidic automation of mRNA display is the nonspecific adhesion of the many required enzyme, peptide, and oligonucleotide reagents to the channel surfaces.

To minimize or eliminate this adhesion, we have explored a range of SLA resin formulations based on vinyl monomers with various functional groups. After examining the achievable resolution and mechanical properties of each formulation, we characterized peptide, oligonucleotide, and protein adhesion and determined the degree to which adhered enzymes retained enzymatic activity. Low-adhesion SLA-printed modules were assembled to construct an automated system capable of producing new mRNA display binding ligands.