The sandwich method is derived from the fast-evaporation method and the overlayer method. It was reported for the first time by Liang Li and collaborators in 1996 [ ], and used for the analysis of single mammalian cell lysates by mass spectrometry. The report also included the description of a Microspot MALDI sample preparation to reduce the sample presentation surface to a minimum.
In the sandwich method the sample analyte is not premixed with matrix. A sample droplet is applied on top of a fast-evaporated matrix-only bed as in the fast-evaporation method, followed by the deposition of a second layer of matrix in a traditional (non-volatile) solvent. The sample is basically sandwiched between the two matrix layers.
The method is not widely utilized so it is not described in detail here.