Development of an Integrated CMUTs-Based Resonant Biosensor for Label-Free Detection of DNA with Improved Selectivity by Ethylene-Glycol Alkanethiols
Zhikang Li , Yihe Zhao , Gian Luca Barbruni , Jie Li , Zixuan Li , Jiawei Yuan , Ping Yang , Libo Zhao , Zhuangde Jiang , Sandro Carrara
Engineering ›› 2024, Vol. 41 ›› Issue (10) : 244 -255.
Development of an Integrated CMUTs-Based Resonant Biosensor for Label-Free Detection of DNA with Improved Selectivity by Ethylene-Glycol Alkanethiols
Gravimetric resonant-inspired biosensors have attracted increasing attention in industrial and point-of-care applications, enabling label-free detection of biomarkers such as DNA and antibodies. Capacitive micromachined ultrasonic transducers (CMUTs) are promising tools for developing miniaturized high-performance biosensing complementary metal-oxide-silicon (CMOS) platforms. However, their operability is limited by inefficient functionalization, aggregation, crosstalk in the buffer, and the requirement for an external high-voltage (HV) power supply. In this study, we aimed to propose a CMUTs-based resonant biosensor integrated with a CMOS front-end interface coupled with ethylene-glycol alkanethiols to detect single-stranded DNA oligonucleotides with large specificity. The topography of the functionalized surface was characterized by energy-dispersive X-ray microanalysis. Improved selectivity for on-chip hybridization was demonstrated by comparing complementary and non-complementary single-stranded DNA oligonucleotides using fluorescence imaging technology. The sensor array was further characterized using a five-element lumped equivalent model. The 4 mm2 application-specific integrated circuit chip was designed and developed through 0.18 μm HV bipolar-CMOS-double diffused metal-oxide-silicon (DMOS) technology (BCD) to generate on-chip 20 V HV boosting and to track feedback frequency under a standard 1.8 V supply, with a total power consumption of 3.8 mW in a continuous mode. The measured results indicated a detection sensitivity of 7.943 × 10−3 μmol∙L−1∙Hz−1 over a concentration range of 1 to 100 μmol∙L−1. In conclusion, the label-free biosensing of DNA under dry conditions was successfully demonstrated using a microfabricated CMUT array with a 2 MHz frequency on CMOS electronics with an internal HV supplier. Moreover, ethylene-glycol alkanethiols successfully deposited self-assembled monolayers on aluminum electrodes, which has never been attempted thus far on CMUTs, to enhance the selectivity of bio-functionalization. The findings of this study indicate the possibility of full-on-chip DNA biosensing with CMUTs.
Capacitive micromachined ultrasonic transducers (CMUTs) / DNA detection / Self-assembled monolayer (SAM) / Ethylene-glycol alkanethiols / Application-specific integrated circuit (ASIC)
THE AUTHOR
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