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
Affiliations
Zhikang Li
State Key Laboratory for Manufacturing Systems Engineering, the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi’an Jiaotong University, Xi’an 710049, China; Xi’an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System, Yantai 264003, China; School of Instrument Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710049, China; Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing, Yantai 265503, China; Corresponding authors.
Yihe Zhao
State Key Laboratory for Manufacturing Systems Engineering, the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi’an Jiaotong University, Xi’an 710049, China; Xi’an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System, Yantai 264003, China; School of Instrument Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710049, China; Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing, Yantai 265503, China; Bio/CMOS Interfaces Laboratory, Institute of Electrical and Microengineering, School of Engineering, École Polytechnique F éd érale de Lausanne, Neuchâtel 2000, Switzerland
Gian Luca Barbruni
Bio/CMOS Interfaces Laboratory, Institute of Electrical and Microengineering, School of Engineering, École Polytechnique F éd érale de Lausanne, Neuchâtel 2000, Switzerland
Jie Li
College of Mechanical and Electrical Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China
Zixuan Li
State Key Laboratory for Manufacturing Systems Engineering, the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi’an Jiaotong University, Xi’an 710049, China; Xi’an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System, Yantai 264003, China; School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710049, China
Jiawei Yuan
State Key Laboratory for Manufacturing Systems Engineering, the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi’an Jiaotong University, Xi’an 710049, China; Xi’an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System, Yantai 264003, China; School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710049, China
Ping Yang
State Key Laboratory for Manufacturing Systems Engineering, the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi’an Jiaotong University, Xi’an 710049, China; Xi’an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System, Yantai 264003, China; School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710049, China
Libo Zhao
State Key Laboratory for Manufacturing Systems Engineering, the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi’an Jiaotong University, Xi’an 710049, China; Xi’an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System, Yantai 264003, China; School of Instrument Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710049, China; Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing, Yantai 265503, China; Corresponding authors.
Zhuangde Jiang
State Key Laboratory for Manufacturing Systems Engineering, the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi’an Jiaotong University, Xi’an 710049, China; Xi’an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System, Yantai 264003, China; School of Instrument Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710049, China; Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing, Yantai 265503, China
Sandro Carrara
Bio/CMOS Interfaces Laboratory, Institute of Electrical and Microengineering, School of Engineering, École Polytechnique F éd érale de Lausanne, Neuchâtel 2000, Switzerland
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.
