Vibrational spectroscopy is a group of optical measurement techniques increasingly popular in process analytical chemistry because of the ability to directly provide molecular-specific information about a given sample under investigation. The application of ultrasonic standing wave (USW) particle manipulation has long been intensively investigated for reliable sample concentration to enhance sensor applications including exploitation for diagnostic purposes in medical environments. An important step to proliferate this is the establishment of in-line sensing approaches. The aim was to compare the Raman signal of homogeneously suspended theophylline crystals with measurements of agglomerates brought about by the USW. The radiation forces direct solid particles like cells toward the pressure nodes of the USW regions of vanishing sound pressure. The combination of a USW for particle manipulation and confocal Raman microspectroscopy is a novel approach to increase selectivity and sensitivity of on-line Raman measurements of suspensions.