Whole-tissue level spatial proteomics investigation offers powerful insights into biological regulation, disease mechanisms, and drug delivery. However, achieving high spatial resolution in whole-tissue mapping has long been a technical barrier. The Micro-scaffold Assisted Spatial Proteomics (MASP) method, developed by Dr. Jun Qu’s team, required micro-scaffolds capable of dissecting tissue into precisely defined compartments. Conventional 3D printing technologies lacked the resolution and reliability needed to produce such intricate structures, limiting both accuracy and reproducibility.
To overcome these challenges, the University at Buffalo research team turned to Boston Micro Fabrication’s (BMF) micro-precision 3D printers. By developing new printing protocols using BMF’s Projection Micro Stereolithography (PµSL) technology, the team successfully fabricated hexagonal micro-scaffolds with micro-wells as small as 50 µm, enabling robust and complete tissue micro-compartmentalization—the first critical step in the MASP workflow.
These ultra-fine scaffolds supported a multi-step proteomics pipeline:
- Tissue compartmentalization using BMF-printed micro-scaffolds for precise sampling.
- Micro-scale sample preparation and digestion for LC-MS analysis.
- Protein mapping and data analysis to generate high-resolution proteome distributions.
With the upgraded MASP platform powered by BMF’s high-resolution scaffolds, the team generated whole-tissue maps of more than 10,000 proteins and >30,000 phosphorylation sites from the healthy mouse brain with thoroughly validated mapping accuracy. The enhanced resolution revealed fine spatial patterns that had previously been obscured, leading to the discovery of numerous novel, regionally enriched proteins across different brain structures.
The improved MASP method also enabled new pharmaceutical research applications—allowing researchers to visualize the intra-brain distribution of antibody drugs and uncover novel insights into drug transport and local tissue responses.
According to Dr. Qu’s team, only BMF’s printers were capable of fabricating the necessary high-fidelity scaffolds. Competing systems failed to achieve the required precision and reproducibility. BMF’s printers stood out for their robust performance, consistent success rates, and ability to deliver micro-scale accuracy at sub-50 µm levels—making them the only viable platform for advancing MASP to its current level of sophistication.
Impact
The new MASP workflow, powered by BMF technology, represents a significant step forward for high-resolution, whole-tissue spatial proteomics. The ability to map protein distributions with such precision opens new frontiers in biological and pharmaceutical research, paving the way for deeper understanding of tissue heterogeneity and drug action.
“The precision and reliability of BMF’s printers have enabled us to map protein spatial information across entire tissues with unprecedented depth and accuracy. With BMF’s support, our team was able to develop new protocols pushing the boundaries of spatial biology, anticipating new insights into tissue heterogeneity for both biological and pharmaceutical research.”
— Dr. Jun Qu, University at Buffalo
