Constant distance mode mass spectrometry imaging with a confocal sensor

Mass spectrometry imaging in constant distance mode is critical for analyzing samples with complex topography, achiev-ing high spatial resolution, and a robust imaging platform. Variations in sample height during an imaging experiment can cause signal instability, regardless of the ionization technique employed. In this work, we present the use of a confocal distance sensor for non-contact, real-time control of the sample height in MSI experiments. The confocal sensor offers sub-micron distance resolution and compatibility with a wide variety of surface optical properties. Although we demon-strate the performance of the sensor for constant distance mode nanospray desorption electrospray ionization (nano-DESI) experiments, the sensor is expected to be compatible with other MSI techniques, making it a versatile solution for challenging MSI applications.