Achieving high sensitivity in electrospray ionization mass spectrometry (ESI-MS) is the key to effective analysis of complex biological sample. Every significant improvement in ESI-MS detection limit will enable applications otherwise impractical. Advances in ESI-MS sensitivity can also increase the dynamic range over which quantitative measurements can be performed. Currently, most sensitivity loss in ESI-MS is in the atmospheric pressure ESI interface region. The ion transmission through this interface is essentially limited by the small MS sampling inlet (typically 400 to 500 ƒÝm in diameter as required to maintain a good vacuum pressure in MS analyzer chamber) resulting in a <1% of overall ion transmission efficiency or ~99% of ion loss in the interface region. It is the primary purpose of this invention disclosure to effectively eliminate this major interface ion loss. Specifically, we disclose a novel ¡§interfaceless¡¨ concept that operates electrospray at a sufficiently reduced pressure so that sample solution can be directly sprayed into an electrodynamic ion funnel capable of completely focusing and transmitting ions into the MS analyzer.