Convergence of dip-pen nanolithography and acoustic biosensors towards a rapid-analysis multi-sample microsystem

The present work demonstrates for the first time patterning of a ready-to-use biosensor with several different biomolecules using Dip-Pen Nanolithography (DPN) for the development of a procedure towards more rapid and efficient multi-sample detection. The biosensor platform used is based on a Surface Acoustic Wave (SAW) device integrated with a parallel-channel microfluidic module, termed as "microfluidics-on-SAW" ("μF-on-SAW"), for reproducible multi-sample analysis. Lipids with different functionalized head groups were patterned at distinct, microfluidic-formed rectangular domains with sharp edges all located on the same sensor surface; pattern quality was verified using a fluorescent microscope. The functionality of the head groups, the efficiency of the patterning method, and the suitability of DPN for the surface modification of the acoustic device were subsequently examined through acoustic experiments. The μF-on-SAW configuration was used to detect specific binding between the pre-patterned functionalized lipids with their corresponding biomolecules. The achievement of an improved sensitivity (5-fold compared to previous acoustic configurations) and reduced preparation time by at least 2 h clearly indicates the suitability of DPN as a direct patterning method for ready-to-use acoustic sensor devices like the μF-on-SAW towards integrated, rapid-analysis, multi-sample biosensing microsystem development.