Drop-coating silanization of silicon substrates as a step towards the fabrication of CMOS-based MEMS biosensors

MEMS-(Micro-electro-mechanical-systems)-based biosensors are a promising new platform for the delivery of diagnostic services close to the point of care, where issues like reliability, ease of use, and low cost are of primary importance. The intrinsically parallel nature of MEMS fabrication, derived from integrated circuit technology, allows for very low unitary cost of elementary MEMS components. As an added benefit, the reuse or modification of standard Complementary MOS (CMOS) technologies allows the coexistence on the same silicon chip of MEMS components and the driving and conditioning circuitry, making the design of smart sensors possible without significant increase in cost. This approach can be pursued for biosensors as well, as long as the specific issues related to the bio-activation of the sensor surface and its compatibility with on-chip MEMS and electronics are taken into account. While standard procedures to prepare bioactive surfaces on glass or silicon substrates normally involves dip-coating (immersion) of the sample with the required solutions, this approach may not be feasible for silicon chips containing mechanically sensitive MEMS components. Moreover, the bio-coating technique must be compatible with the package used to allow proper handling of the sensor and access to the electrical signals through metal wires. An alternative to this approach can be the use of single droplets of the reagents (drop-coating). In this work, the use of drop-coating as a substitute to immersion for the creation of bioactive surfaces on MEMS sensors is investigated. The target sensor platform is a CMOS-based resonant sensor based on the microbalance principle. Preliminarily, a test to verify the effectiveness of the functionalization protocol was performed: test silicon dioxide surfaces were cleaned in an ammonia-based hydroxylation solution, and silanized through drop-coating with an aqueous-based APTES (amino-propyl-triethoxysilane) solution as the preliminary step towards the deposition of a bioactive layer. The surfaces were studied by means of conventional and angle resolved x-ray photoelectron spectroscopy (ARXPS). The spectroscopic characterization confirmed that the resulting surface chemical composition was not significantly different upon the two alternative processing approaches. Subsequently, a sample containing several MEMS resonators underwent a similar procedure. The amino coated resonators were then exposed to a drop of solution containing an oligonucleotide specifically designed to link to a portion of human MGMT (methylguanine-DNA methyltransferase) mRNA, and subsequently to its FITC fluorescent labeled complementary target (again in drop form). The fluorescence signal confirms the occurrence of a specific binding between probe and target.