集成乙二醇烷硫醇的CMUT共振生物传感器用于提升DNA无标记检测选择性

Zhikang Li; Yihe Zhao; Gian Luca Barbruni; Jie Li; Zixuan Li; Jiawei Yuan; Ping Yang; Libo Zhao; Zhuangde Jiang; Sandro Carrara

doi:10.1016/j.eng.2023.12.015

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工程（英文） ›› 2024, Vol. 41 ›› Issue (10) : 231-241. DOI: 10.1016/j.eng.2023.12.015

研究论文

Article

集成乙二醇烷硫醇的CMUT共振生物传感器用于提升DNA无标记检测选择性

Zhikang Li ^a^,^b^,^c^,^d^,^e^,^* ,
Yihe Zhao ^a^,^b^,^c^,^d^,^e^,^f ,
Gian Luca Barbruni ^f ,
Jie Li ^g ,
Zixuan Li ^a^,^b^,^d ,
Jiawei Yuan ^a^,^b^,^d ,
Ping Yang ^a^,^b^,^d ,
Libo Zhao ^a^,^b^,^c^,^d^,^e^,^* ,
Zhuangde Jiang ^a^,^b^,^c^,^d^,^e ,
Sandro Carrara ^f

作者信息 +

Development of an Integrated CMUTs-Based Resonant Biosensor for Label-Free Detection of DNA with Improved Selectivity by Ethylene-Glycol Alkanethiols

Zhikang Li ^a^,^b^,^c^,^d^,^e^,^#^,^* ,
Yihe Zhao ^a^,^b^,^c^,^d^,^e^,^f^,^# ,
Gian Luca Barbruni ^f ,
Jie Li ^g ,
Zixuan Li ^a^,^b^,^d ,
Jiawei Yuan ^a^,^b^,^d ,
Ping Yang ^a^,^b^,^d ,
Libo Zhao ^a^,^b^,^c^,^d^,^e^,^* ,
Zhuangde Jiang ^a^,^b^,^c^,^d^,^e ,
Sandro Carrara ^f

Author information +

History +

Abstract

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.

Keywords

Capacitive micromachined ultrasonic transducers (CMUTs) / DNA detection / Self-assembled monolayer (SAM) / Ethylene-glycol alkanethiols / Application-specific integrated circuit (ASIC)

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Zhikang Li, Yihe Zhao, Gian Luca Barbruni. 集成乙二醇烷硫醇的CMUT共振生物传感器用于提升DNA无标记检测选择性. Engineering. 2024, 41(10): 231-241 https://doi.org/10.1016/j.eng.2023.12.015

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