{"title":"利用乙二醇烷硫醇开发基于 CMUTs 的集成式共振生物传感器,用于无标记检测 DNA 并提高其选择性","authors":"","doi":"10.1016/j.eng.2023.12.015","DOIUrl":null,"url":null,"abstract":"<div><div>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 mm<sup>2</sup> 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<sup>−3</sup> μmol∙L<sup>−1</sup>∙Hz<sup>−1</sup> over a concentration range of 1 to 100 μmol∙L<sup>−1</sup>. 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.</div></div>","PeriodicalId":11783,"journal":{"name":"Engineering","volume":"41 ","pages":"Pages 231-241"},"PeriodicalIF":10.1000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Development of an Integrated CMUTs-Based Resonant Biosensor for Label-Free Detection of DNA with Improved Selectivity by Ethylene-Glycol Alkanethiols\",\"authors\":\"\",\"doi\":\"10.1016/j.eng.2023.12.015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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 mm<sup>2</sup> 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<sup>−3</sup> μmol∙L<sup>−1</sup>∙Hz<sup>−1</sup> over a concentration range of 1 to 100 μmol∙L<sup>−1</sup>. 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.</div></div>\",\"PeriodicalId\":11783,\"journal\":{\"name\":\"Engineering\",\"volume\":\"41 \",\"pages\":\"Pages 231-241\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2095809924002522\",\"RegionNum\":1,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Engineering","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2095809924002522","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
受重力共振启发的生物传感器在工业和护理点应用中吸引了越来越多的关注,它可以对 DNA 和抗体等生物标记物进行无标记检测。电容式微机械超声换能器(CMUT)是开发微型高性能生物传感互补金属氧化物硅(CMOS)平台的理想工具。然而,由于功能化效率低、聚集、缓冲器串扰以及需要外部高压(HV)电源,它们的可操作性受到了限制。在本研究中,我们旨在提出一种基于 CMUTs 的共振生物传感器,该传感器集成了 CMOS 前端接口和乙二醇烷硫醇,可检测具有高度特异性的单链 DNA 寡核苷酸。能量色散 X 射线显微分析对功能化表面的形貌进行了表征。通过使用荧光成像技术比较互补和非互补单链 DNA 寡核苷酸,证明了芯片杂交选择性的提高。该传感器阵列使用五元素叠加等效模型进行了进一步表征。通过 0.18 μm HV 双极-CMOS-双扩散金属氧化物-硅(DMOS)技术(BCD)设计和开发了 4 mm2 特定应用集成电路芯片,在标准 1.8 V 电源下产生片上 20 V HV 升压并跟踪反馈频率,在连续模式下总功耗为 3.8 mW。测量结果表明,在 1 至 100 μmol∙L-1 的浓度范围内,检测灵敏度为 7.943 × 10-3 μmol∙L-1∙Hz-1。总之,在带有内部高压供应商的 CMOS 电子设备上使用频率为 2 MHz 的微加工 CMUT 阵列,成功地演示了在干燥条件下对 DNA 的无标记生物传感。此外,乙二醇烷硫醇成功地在铝电极上沉积了自组装单层,这是迄今为止在 CMUT 上从未尝试过的,从而提高了生物功能化的选择性。这项研究的结果表明了利用 CMUT 实现全芯片 DNA 生物传感的可能性。
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.
期刊介绍:
Engineering, an international open-access journal initiated by the Chinese Academy of Engineering (CAE) in 2015, serves as a distinguished platform for disseminating cutting-edge advancements in engineering R&D, sharing major research outputs, and highlighting key achievements worldwide. The journal's objectives encompass reporting progress in engineering science, fostering discussions on hot topics, addressing areas of interest, challenges, and prospects in engineering development, while considering human and environmental well-being and ethics in engineering. It aims to inspire breakthroughs and innovations with profound economic and social significance, propelling them to advanced international standards and transforming them into a new productive force. Ultimately, this endeavor seeks to bring about positive changes globally, benefit humanity, and shape a new future.