Mass Spectrometry has been playing a central role in proteomics and disease biomarker discovery.Nevertheless, there are still many major obstacles to be overcome in order to expand its capacity beyond present horizon.These include (1) low sensitivity in detecting very large biomolecules with the mass higher than 100,000 Da (2) Low dynamic range so that trace amount of proteins not detectable and (3) time consuming in proteomic analysis so that high throughput biomarker search cannot be achieved.We have been trying to develop the following three novel technologies to overcome the above barriers.They are (1) a detector which can detect a single large biomolecular ion with 100% efficiency even with the mass-to-charge-ratio going beyond 1,000,000.Indeed, the mass of the ion is not a limitation any more.(2) a biomolecular ion enrichment device to achieve dynamic range beyond six orders of magnitude for detection of trace proteins and proteins with post-translation modification and (3) a novel biomarker search platform to increase the proteomic analysis speed by more than one order of magnitude so that biomarkers of many diseases can be discovered in a much shorter time.Applications to a few different cancers will be presented in the meeting.