Automated Microcontact Bioprinting for High-Throughput Manufacturing of Lubricant-Infused Microarrays

Microarrays are widely used for detecting target analytes and biomarkers, with fabrication methods ranging from non-contact to contact bioprinting techniques. Microcontact bioprinting (μCP), which utilizes elastomeric stamps to transfer biorecognition molecules (bioinks) onto substrates, offers advantages such as customizability, cost-effectiveness, and versatility in handling bioinks with high viscosities. Despite its prevalent use in laboratory settings, μCP faces challenges in achieving the repeatability and reproducibility required for industrial manufacturing. In this study, we address these limitations by developing and optimizing a μCP protocol using industrial techniques. A key innovation in our approach is the combination of microcontact printing with fluorosilanization, enabling the use of lubricant-infused surfaces to prevent non-specific attachment. Additionally, we enhance biomolecule immobilization through covalent attachment using a modified bioink formulation. We identify and mitigate high-risk failure modes including bioink formulation, application and removal, environmental conditions, and force application during stamping. Furthermore, we integrate an automated syringe pump and a standardized force application system, taking critical steps toward industrial scalability. Using lubricant-infused substrates, our optimized μCP protocol demonstrates significant improvements in repeatability and reproducibility, achieving intra-assay and inter-assay coefficients of variance below 10% and signal-to-noise ratios exceeding 15. These advancements validate our μCP method for high-throughput, scalable microarray fabrication, paving the way for its implementation in industrial manufacturing.