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, achieving high spatial resolution, and providing a robust imaging platform. Regardless of the ionization technique employed, variations in sample height during an imaging experiment can cause signal instability. In this work, we present the use of a confocal distance sensor for noncontact, real-time control of the sample height in MSI experiments. The confocal sensor offers submicrometer distance resolution and compatibility with a wide variety of surface optical properties. Although we demonstrate 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.