High-efficiency electrospray is critical to achieving the full potential of mass spectrometry. The CO2 can undergo phase conversion to supercritical fluid at P > 7.3 MPa and T > 31.1 oC (sCO2). The supercritical fluids provide fast analysis, high throughput, and improved resolution. Nanospraying the supercritical fluid provides efficient desolvation and therefore higher ionization efficiency. We developed a split-flow system that providing equal ionization opportunities for analytes in a complex matrix. This benefits for accurate quantification with higher metabolomic and lipidomic coverage than conventional LC.