A Wireless Battery-Free Probe-Free Disposable Electrical-Digital-PCR Chip

As the most fundamental and widely-used technique in molecular diagnostics, polymerase chain reaction (PCR) plays a crucial role across various applications including epidemic surveillance and medical diagnosis. For the numerous epidemics such as COVID-19, the massive and frequent detection has challenged the PCR equipment in system miniaturization and hardware cost efficiency as well as rapid and precise detection. In conventional methods, fluorescence-PCR requires huge costly optical instruments, and the DNA-Probe-PCR can only detect a corresponding sample. In addition, both the fluorescence-PCR and DNA-Probe-PCR suffer from complex pre-label or modification procedure, further increasing the fabrication cost. In this work, we demonstrate the first probe-free electrical-digital-PCR (EdPCR) chip based on impedance detection: 1) A sensor-on-circuit structure is proposed to replace the bulky costly optical instrument with a single CMOS chip, enabling the PCR equipment to be portable and disposable. 2) A harmonic-voting method is proposed to reduce the testing pixel error rate (PER). The system is implemented in 55nm CMOS process, and in-vitro PCR experiment is conducted in various samples. The on-chip sensing array of the proposed PCR chip achieves a pixel density of 1111 pixels/mm², which is the highest in the state of the arts. Additionally, the proposed harmonic-voting method reduces the measured PER of impedance judgment by 35%, achieving an average PER of 12.2%.