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.

中文翻译：

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开发基于 CMUTs 的集成共振生物传感器，用于乙二醇烷硫醇无标记检测 DNA，具有更高的选择性


受重量共振启发的生物传感器在工业和护理点应用中引起了越来越多的关注，实现了 DNA 和抗体等生物标志物的无标记检测。电容式微机械超声换能器 （CMUT） 是开发小型化高性能生物传感互补金属氧化物硅 （CMOS） 平台的有前途的工具。然而，它们的可操作性受到低效功能化、聚集、缓冲器中的串扰以及对外部高压 （HV） 电源的要求的限制。在这项研究中，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，与乙二醇烷硫醇耦合，以检测具有高度特异性的单链 DNA 寡核苷酸。通过能量色散 X 射线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的单链 DNA 寡核苷酸，证明了芯片上杂交选择性的提高。使用五元件集总等效模型进一步表征传感器阵列。这款 4 mm2 专用集成电路芯片采用 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，可在标准 1.8 V 电源下产生片上 20 V HV 升压并跟踪反馈频率，在连续模式下的总功耗为 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，在内部 HV 供应商的 CMOS 电子设备上使用具有 2 MHz 频率的微加工 CMUT 阵列成功证明了 DNA 在干燥条件下的无标记生物传感。此外，乙二醇烷硫醇成功地在铝电极上沉积了自组装的单层，这是迄今为止从未在 CMUT 上尝试过的，以增强生物功能化的选择性。本研究的结果表明，使用 CMUT 进行全芯片 DNA 生物传感的可能性。