A new way to detect noncovalently bonded complexes of biomolecules from liquid micro-droplets by laser mass spectrometry

A new version of laser mass-spectrometry is presented, which allows the quantitative analysis of specific biocomplexes in native solution. On-demand micro droplets, injected into vacuum, are irradiated by mid IR-laser pulses. Above a certain intensity threshold they explode due to the transmitted energy, setting free a fraction of the charged biomolecules which are then mass-analyzed. Amounts of analyte in the attomolar range may be detected with the ion intensity being linear over a wide range of molarity. Evidence is given that this method is soft, tolerant against various buffers, reflects properties of the liquid phase, and suitable for studying noncovalently bonded specific complexes. This is highlighted by results from antibiotics specifically binding into the minor groove of duplex DNA.