Thiolate self-assembled monolayers on monolithic CMOS-MEMS resonators as a tunable platform for VOCs classification in biosensing applications

This paper presents monolithically integrated sub-micron CMOS-MEMS resonators operating in oscillator mode as inertial mass sensors that are dip-cast individually functionalized with thiolate self-assembled monolayers for gas sensing in the biomedical domain. Multi-sensor-arrayed devices decorated with three distinct organothiols (octadecanethiol, 2-phenylethanethiol, and perfluorodecanethiol) are manufactured and experimentally demonstrated. These devices form a six-channel VOC multi-sensor array designed for human breath pattern recognition towards non-invasive disease diagnosis. The mechanical structures were fabricated using a commercial 0.35-µm CMOS technology, followed by an in-house post-CMOS process for mechanical parts release and gold surface coating via electroless nickel immersion. This ensures an innovative batch-compatible dip-cast functionalization strategy, maintaining fabrication compatibility across all post-processing steps. Organothiols self-assembly and surface anchoring on gold was verified by contact angle measurements and infrared spectroscopy. Experimental evidence from VOCs caption dynamics and static imprint characteristics demonstrates cross-reactive sensing and unique pattern recognition of representative VOCs (toluene, ethanol, hexane, and acetone) across all thiol-anchored active receptors. An ethanol cross-sensitivity of 9:1 and 5:1 was observed on octadecanethiol-perfluorodecanethiol and 2-phenylethanethiol-perfluorodecanethiol, respectively, while 2-phenylethanethiol showed a 7:1 cross-sensitivity towards toluene versus acetone. The main novelty of this approach relies on adopting a fully batch-compatible self-assembly solution-cast functionalization in line with advanced technological trends for Lab-on-Chip CMOS-compatible devices. The organothiol approach provides exceptional design flexibility that can be seamlessly extended to complementary organic compounds with analogous anchoring mechanisms, paving the way for low-cost versatile CMOS-compatible biochemical sensing platforms. • CMOS-MEMS resonators with thiolate self-assembled monolayer functionalization. • Multi-sensor array with distinctive functional groups for 6-channel fingerprint. • VOCs classification and pattern recognition thanks to cross-reactive sensing. • Sensing devices are fabricated with a commercial CMOS technology. • Fully batch compatible functionalization in line with Lab-on-Chip compatibility.