Closed-Loop Nanopatterning of Liquids with Dip-Pen Nanolithography

The ability to reliably manipulate small quantities of liquids is the backbone of high-throughput chemistry, but the continual drive for miniaturization necessitates creativity in how nanoscale samples of liquids are handled. Here, we describe a closed-loop method for patterning liquid samples on pL to sub-fL scales using scanning probe lithography. Specifically, we employ tipless scanning probes and identify liquid properties that enable probe-sample transport that is readily tuned using probe withdrawal speed. Subsequently, we introduce a novel two-harmonic inertial sensing scheme for tracking the mass of liquid on the probe. Finally, this is combined with a fluid mechanics-based iterative control scheme that selects printing conditions to meet a target feature mass to enable closed-loop patterning with better than 1% accuracy and ∼4% precision in terms of mass. Taken together, these advances address a pervasive issue in scanning probe lithography, namely, real-time closed-loop control over patterning, and position scanning probe lithography of liquids as a candidate for the robust nanoscale manipulation of liquids for advanced high-throughput chemistry.