A Low-Power Sensing System of VEGF Concentration With Noise Reduction Using Subsampling Technique for Cancer Diagnosis

This article presents a monolithic low-power sensing system for early cancer detection. The system uses a CMOS microelectromechanical system (MEMS) capacitive transducer with a gold interdigitated electrode (IDE) and deoxyribonucleic acid (DNA) aptamers to sense the concentration of vascular endothelial growth factor (VEGF). When the DNA aptamer is immobilized with the VEGF sensor, it generates an electric double-layer capacitance. The low-noise front-end circuits amplify this capacitance change and convert the signal into the frequency domain. To solve the wide input dynamic range and reduce power consumption, a two-step time-to-digital converter (TDC) is utilized. The proposed subsampling (SS) technique provides a higher conversion gain to reject noise interference and overcome the increase in noise floor introduced from the decoder due to lower supply voltage. The SS delay-locked loop (SSDLL), combined with the calibration circuit, enhances TDC linearity and noise performance while preventing calibration noise from degrading conversion accuracy. Finally, the time-based information is converted into digital codes with high power efficiency for early cancer analysis. The system is fabricated in TSMC 0.35- $\mu \text{m}$ MEMS CMOS process with electroplated gold. Measurement results show that the power consumption of the readout circuit and the overall system is only 18 and $60.65~\mu \text{W}$ , respectively. The proposed system improves jitter by 49% and achieves 0.725-mV/pg-mL sensitivity.