A CMOS Molecular Sensor for Personalized Diagnostics Featuring Enzyme-Free Reading and Encoding of Viral Variants at Single-Nucleotide Resolution

This paper introduces a CMOS electrochemical molecular sensor array, specifically designed for personalized diagnostics. For the first time, it facilitates highly sensitive and time-effective detection of viral variants on CMOS at single-nucleotide polymorphism (SNP) resolution and demonstrates on-chip DNA reading and molecular-level digital encoding capabilities. The SARS-CoV-2 RNA and its D614G mutation are used to validate the CMOS molecular sensor performance. The sensor array comprises 4096 three-electrode electrochemical pixels with a pitch size of $36 \times 36 ~ \mu\mathrm{m}^{2}$ using 40 nm CMOS technology. Within each sensor pixel, the array integrates an ultra-compact current input continuous-time sigma-delta ADC (I- $\Sigma \Delta$ ADC) for direct current-to-digital conversion, ensuring robustness against environmental noise and interference during personalized diagnostic applications. Each CMOS sensor pixel consumes only $21.4 \mu\mathrm{W}$.