Mass spectrometry is a standard analytical technique widely used in research and from which other complementary devices have been developed for more specific purposes. The mass spectrometry (MS) technique measures the mass-to-charge ratio of charged particles to identify unknown compounds, quantify known materials, and unravel the structure and chemical properties of the molecules within a sample. Similarly, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS) takes the challenge to the next level, as it estimates the mass-to-charge ratio of ions from measuring the ion's time-of-flight when advancing to a detector. The soft ionization employed in the technique enables the characterization of specimens susceptible to fragmentation, thus serving as a valuable tool for identifying biological species, evaluating enzymatic activity, and for various applications. This chapter reviews both techniques from the perspective of their history, basic principles of their operation mechanism, advantages and disadvantages, and applications in the biosensing area. In addition, the chapter includes a troubleshooting section addressing the typical errors, causes, and solutions of the techniques mentioned above.
