A Low-Cost, High-Resolution Thermoplastic Microfluidic Probe for Mass Spectrometry Imaging of Biological Tissue Samples

Mass spectrometry imaging (MSI) using nanospray desorption electrospray ionization (nano-DESI) has been extensively used for label-free mapping of hundreds of molecules in biological samples with minimal sample pretreatment. While both nano-DESI probes made of two fused silica capillaries and glass microfluidic probes (MFP) have been developed for imaging biological tissues with high spatial resolution, MFPs significantly enhance the robustness and throughput of nano-DESI MSI experiments. Despite their advantages, the fabrication of glass microfluidic devices is costly and requires specialized equipment or cleanroom facilities. Meanwhile, plastic microfluidic devices often suffer from limited solvent compatibility and low fabrication precision, restricting their achievable spatial resolution. To overcome these limitations, we have developed a low-cost microfluidic probe made from cyclic olefin copolymer (COC), a widely used thermoplastic material known for its excellent chemical resistance. The probe is fabricated using wire imprinting and thermal bonding in a standard laboratory setting. We estimate the achievable spatial resolution of the COC-MFP of 5-7 μm and demonstrate its robustness by imaging a large (20.0 mm × 9.5 mm) human kidney tissue section with high sensitivity. This affordable thermoplastic probe makes high spatial resolution nano-DESI MSI more accessible, broadening its applications in the scientific community.