Microfluidic Interfaces for Chronic Bidirectional Access to the Brain

Simone Marcigaglia, Robin De Plus, Charysse Vandendriessche, Eleonore Schiltz, Marie‐Lynn Cuypers, Jordi Cools, Luis D. Hoffman, Roosmarijn E. Vandenbroucke, Maarten Dewilde, Sebastian Haesler

Two-photon polymerization (TPP) is an additive manufacturing technique with micron-scale resolution that is rapidly gaining ground for a range of biomedical applications. TPP is particularly attractive for the creation of microscopic three-dimensional structures in bio-compatible and non-cytotoxic resins. Here, TPP is used to develop microfluidic interfaces which provide chronic fluidic access to the brain of preclinical research models. These microcatheters can be used for either convection-enhanced delivery (CED) or for the repeated collection of liquid biopsies. In a brain phantom, infusions with the micronozzle result in more localized distribution clouds and lower backflow compared to a control catheter. In mice, the delivery interface enables faster, more precise, and physiologically less disruptive fluid injections. A second microcatheter design enables repeated, longitudinal sampling of CSF over time periods as long as 250 days. Moreover, further in vivo studies demonstrate that the blood-CSF barrier was intact after chronic implantation of the sampling interface and that samples are suitable for downstream molecular analysis for the identification of nucleic acid- or peptide-based biomarkers. Ultimately, the versatility of this fabrication technique implies a great translational potential for simultaneous drug delivery and biomarker tracking in a range of human neurological diseases. This article is protected by copyright. All rights reserved.