A Personal Perspective on the Technological and Commercial Development of Nanospray and Nanobore LC-MS

Flow-rate-minimized electrospray ionization, commonly referred to as nanoelectrospray or, more simply, nanospray, has evolved into an essential foundational technology in the development and proliferation of mass spectrometric-based proteomic analysis. Historically, nanospray was an offline technique, termed herein as static nanospray. Static nanospray paired well with the leading protein purification method of the day: two-dimensional polyacrylamide gel electrophoresis (PAGE). The demands of analyzing ever more complex samples have evolved rapidly with the introduction of LC-based methodologies. The introduction of shotgun proteomics technology, taking inspiration from the development of shotgun-based genomic sequencing, enabled the analysis of whole-cell protein digests in a single LC-MS run. As mass spectrometry continued to improve in both sensitivity and speed over the decades, concomitant advances in nanobore LC column technology and emitter performance have occurred. Over the past 30 years, we have been fortunate to see sensitivity gains progress from isolated PAGE gel bands to single-cell proteomics. Here, I offer a personal perspective on the evolution of nanospray and nanobore LC-MS technology and on the journey of bringing these tools from the bench to the global scientific community through commercialization.