Novel biosensor platform using CMOS fringe-field capacitive sensing and PNA-labelled beads for detection and quantification of viral RNA and antibodies

Abstract We report a new platform for digital biosensing of HIV-1 RNA and antibodies. The detection assay is implemented on an 0.35‑µm standard complementary metal-oxide semiconductor (CMOS) chip using fringe‑field capacitive sensing of peptide nucleic acid (PNA)‑tethered beads. The sensing capacitors are composed of interdigitated electrodes in the top aluminium metal layer and are protected by SiO₂/Si₃N₄ passivation. A self‑zooming, second‑order sigma-delta (ΣΔ) capacitive‑to‑digital converter achieves attofarad resolution in digitizing sensor outputs across a wide dynamic range. The CMOS sensor is leveraged for the detection of beads specifically tethered to PNA probes on the sensor surface. The physical signal transduction mechanism in combination with the novel CMOS sensor allowed direct detection of antibodies in HIV-1 or HIV-2 positive plasma and detection of femtomolar concentrations of HIV viral DNA. The semi-automated platform incorporated endpoint RT-PCR amplification and correctly detected HIV-1 viral RNA in pre-clinical studies of HIV positive patient plasma from 379 copies/mL to over 500,000 copies/mL with further testing of contrived samples down to 50 copies/mL. This system provides a manufacturable, compact, low‑cost platform for digital biosensing, and eliminates the need for optical detection. Performing viral‑load and serological measurements on the same detection platform could improve point‑of‑care applications.