The present disclosure generally provides ionization methods and devices for use in mass spectrometry. In some embodiments, the ionization methods and devices employ short laser pulses (e.g., pulses having pulsewidths in a range of about 2 fs to about 1 ps) at a high intensity (e.g., an intensity in a range of about 1 TW/cm2 to about 1000 TW/cm2) to ionize an analyte an ambient pressure greater than about 10−5 Torr (e.g., an ambient pressure in a range of about 1 atmosphere to about 100 atmospheres).