Large-Scale Stereolithography Precision Manufactured Solid Cone-Jet Emitters for Electrospray Mass Spectrometry.

An electrospray emitter is a crucial component for sample introduction at the front-end of ESI-MS. Its development plays a key role in enhancing analytical sensitivity and pushing forward biological discoveries. Herein, based on stereolithography printing, a high-throughput approach for large-scale precision manufacture of solid cone-jet emitters (SCONE) was developed. As opposed to classical tapered-tip emitters, the SCONE emitter has a solid cone inside, supporting an enhanced ionization efficiency and high electrospray stability. Based on stereolithography printing's precision, flexible and fine-tuning manufacturing capability, the conicity of SCONE emitters has been comprehensively evaluated from 1:0.25 to 1:4. With the optimized conical geometry, SCONE emitters exhibit enhanced ion current (340 nA), good reproducibility (RSD = 5.2%, n = 20), and broad operational range (2.6-3.0 kV), realizing significant improvements in analytical sensitivity. For small-molecule drugs, peptides, and proteins, ionization efficiencies are enhanced by 1.7-3.98-fold compared to that achievable on classical tapered-tip emitters. Additional experiments show that SCONE emitters maintain consistent performance over extended use without noticeable degradation, even in challenging matrix environments (e.g., Hank's balanced salt solution). Apart from its manufacturing robustness, the current technology enables large-scale (12,000 units/plate) and high-throughput (72,000 units/h) production of MS emitters. More importantly, emitters manufactured from different batches show excellent emitter-to-emitter reproducibility (RSD < 6%, n = 100, 5 batches), demonstrating SCONE emitters' potential in a high-throughput application scenario. Powered by stereolithography, the current study provides a new approach and perspective for efficient, scalable, and economical precision manufacturing of microdevices, supporting high-performance analyses of low-abundance entities.