If direct infusion (MeCN , no FA) is not ionizing you analyte and if your LC/MS eluent contains FA and is efficient for ionization, I conclude that FA is necessary to protonate you analyte. Is analyte a weak base, leading to inefficient ionization ?

You may try other solvents, like MeOH, mixtures, etc.

For the formation of Na formate clusters, what is needed is FA and Na+ (ubiquitous ion in samples) ; evidently if you use pure sodium formate as calibrant, FA is probably not necessary.

You do need a proton donor to ionize the molecules. This can be formic acid, acetic acid, or even phenol (I've used it with good results for peptides). You want a proton donor that is itself volatile. You also want something that has a pKa below that of the amines being ionized, yet not so strong an acid that they form salts. For example TCA, TFA and HCl don't work well in ESI-MS(+). TFA does work better in MALDI than acetic acid, however. Some argue that it is a gas phase pKa issue. Some argue that it is a liquid phase pKa issue. The sweet spot is generally acetic or formic acid.

I think you can use Ammonium Fluoride at 0.5 mM. This help you to ionize your molecula better than AF in posite mode. The maxima concentration for this ammonium fluoride could be 2 mM. Good luck.

Just a remark : Ammonium Fluoride is potentially dangerous, it is corrosive to glass and silicates in general. It is used mostly in negative mode of ESI. See attached file for some uses of NH4F.

Other volatile ammonium salts have also been used (e.g., (NH4)2SO4, (NH4)CO3, and ammonium phenolate) in low concentrations. Ammonium equilibrates to volatile ammonia, donating a proton. Sulfate will equilibrate with water to form H2SO4, which will decompose to SO2 +H2O. Similar for the carbonate salt. Pyridinium salts (e.g., pyridium acetate) as additives also work, but smell really noxious once sprayed.

Thank you for all answers. They are very helpful for my research.