Novel Tape-Based Microfluidic Chip for Surface Mass Spectrometry Analysis of Biomaterials

Abstract Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides high-resolution, label-free chemical imaging. Direct chemical characterization inside enclosed microchannels remains challenging because opening the device can alter the sample surface and spatial information. In this study, we present a tape-based microfluidic chip that enables direct ToF-SIMS analysis of biomaterials within enclosed microchannels. The chip uses a thin, polymeric membrane as a removable sealing layer, which maintains microfluidic integrity during operation and can be selectively removed by a 20 keV Ar2600+ beam to expose the sample surface. Our novel tape-based chip concept eliminates the need for cleanroom fabrication and allows a straightforward transition from microfluidic experiments to vacuum-based analysis. As a case study, the chip was validated by detecting model compounds in gelatin methacrylate (GelMA) hydrogels: moxifloxacin (MXF, ∼401 Da), an antibiotic molecule, and poly(styrene sulfonate) (PSS, Mw ≈ 70, 000), a high-molecular-weight polyelectrolyte. The design supports in situ chemical imaging of biomaterials and can be applied to investigate molecular interactions, drug transport, and tissue responses in engineered microenvironments at room temperature. Additionally, the method could be adapted for Cryo-SIMS, enabling the analysis of biological samples in a near-native state. This work presents a practical and cost-effective strategy for integrating microfluidic chips with surface-sensitive mass spectrometry, enabling new opportunities in biomaterials characterization and pharmaceutical research.