Piezoresistive Micropillar Sensors for Nano-Newton Cell Traction Force Sensing

Several studies demonstrate that large variations in biologically cell-generated forces are strong indicators of diseases in the body. To realize the full potential of single-cell biomechanical properties as label-free, non-invasive biomarkers in cell-based disease diagnoses, we need high-throughput test platforms that interrogate single cells individually while allowing measurement of thousands of cells at a time. This work presents a piezoresistive sub- $\mu \text{N}$ lateral force sensing approach using vertical pillars as structural elements and silicon-based, N-type piezoresistors embedded underneath the pillars for stress-sensing. Experimental testing of the first generation of sensors developed shows excellent $\text{F}_{\mathrm {x}}$ sensing resolution down to $\sim $ 70 nN. Measured sensitivities of devices with different pillar geometries range from $\Delta \text{R}$ /R = 0.05% to 0.14% $\mu \text{N}^{-1}$ and are varied by simply scaling pillar geometry. While having a comparable resolution to existing MEMS in-plane sensors, the sensor design sets itself apart from existing approaches with its 3D printed pillar-based approach, which is combined with traditional nanofabrication to achieve 500 nm to $3 \, \mu \text{m}$ width, in-substrate piezoresistors. Effective device footprint is a compact few $\mu \text{m}^{2}$ on substrate which makes the sensor design ideal for implementation in large, dense sensing arrays with $\mu \text{m}$ -scale sensor-to-sensor pitches in both in-plane axes. [2023-0190]