In-Memory Sensing: a Novel Biosensing Platform Combining Silicon Nanowires and Microfluidics

This Master’s Thesis presents the development of a biosensing platform that leverages the memristive properties of silicon nanowires for detecting Prostate-Specific Antigen (PSA), a critical biomarker for early-stage prostate cancer diagnosis. The platform integrates three key components: silicon nanowires with nickel silicide (NiSi) pads as the core biosensors, gold electrodes for electrical measurements, and a PDMS-based microfluidic platform, which guides the sample to the active sensing area, optimizing reagent usage, and ensuring the necessary humidity conditions for biological reactions. The core of the biosensing device consists of two-terminal, vertically stacked Schottky barrier silicon nanowire structures, fabricated through electron beam lithography and Bosch etching processes. These nanowires are anchored between NiSi pads, and when a potential difference is applied, exhibit memory-like behavior characteristic of memristors, with electrical contact established through two Schottky barriers. This memristive behavior is essential to the platform's sensing capabilities, as it manifests in a hysteresis loop in the current-voltage (I-V) characteristics. Upon surface activation and functionalization of the nanowires for antigen-antibody interactions, antigen binding results in a measurable shift in the voltage gap of the I-V curve, allowing for label-free detection. The microfluidic platform, fabricated from PDMS using the SU-8 molding technique, incorporates finely designed channels that control the delivery of reagents, such as antibodies, antigens, and washing solutions. This approach offers several advantages over traditional drop-casting methods, including precise reagent concentration within the active sensing area, minimized reagents waste, and optimal humidity control for biological reactions. Furthermore, it simplifies reagent transport and storage. Different bonding techniques were explored and tested to ensure stable, leak-free integrations between the microfluidic platform and the silicon chip with nanowires and electrodes. The metal electrodes, patterned using photolithography and the lift-off method, extend from the NiSi pads to enable reliable electrical measurements without damaging the sensitive biosensor surfaces and pads. Additionally, the electrodes are fundamental for integrating the microfluidic system; without them, the NiSi pads would be covered by the PDMS structure, making it impossible to access the nanowires for electrical measurements. Electrode characterization and performance testing confirmed reliable conductivity and stable integration, without introducing significant series resistance that could mask the memristive behavior. Design requirements and decisions are critically discussed, along with microfabrication processes carried out in the cleanroom facilities at the Center of MicroNanoTechnology (CMi) of École Polytechnique Fédérale de Lausanne (EPFL), which led to the successful realization of the entire device. Comprehensive experimental results demonstrated successful PSA detection in most cases, though challenges and potential areas for improvements are also critically analyzed. Finally, potential future developments are explored, particularly in enhancing multiplexing capabilities, which would broaden the platform's applications in biomedical diagnostics. For instance, the integration of rotary valves could lead to more advanced fluidic control mechanisms, optimizing the microfluidic system’s efficiency and adaptability.