Institute of Microelectronics, Tsinghua University, Beijing 100084, China; Tsinghua National Laboratory for Information and Science Technology (TNList), Tsinghua University, Beijing 100084, China.
Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China.
Biosens Bioelectron. 2015 Sep 15;71:261-268. doi: 10.1016/j.bios.2015.04.043. Epub 2015 Apr 15.
An atomic resolution ultra-high sensitivity surface acoustic wave (SAW) biosensor for DNA sequences and cells detection is proposed. Interdigitated transducers (IDTs) fabricated on LiNbO3 substrate achieve a high quality factor (Q) of over 4000 at a frequency of 6.4 GHz (third-order harmonic mode) using an optimized design and process. The biosensor shows excellent linear responses to target DNA in the range from 1 μg/ml to 1 ng/ml with a high sensitivity of 6.7 × 10(-16)g/cm(2)/Hz, hence the difference of a single hybridized DNA base can also be distinguished. With such a high mass resolution, the biosensor is capable of quantitative detection of living cancer cells. The frequency responses of single mouse mammary adenocarcinoma (EMT6) cell and mouse fibroblast (3T3) cell are studied. The interferences in the experiments show insignificant influence on the frequency shift, which verifies the high selectivity of the biosensor. The biosensor is also able to repeat the sensing ability after rough cleaning, therefore cost reduction is achieved from the recycling process in practical applications. The detection limit is defined from the noise analysis of the device, atomic resolution is realized according to the calculation, thereby initiating a potential tool for high-precision medical diagnoses and phenomena observation at the atomic-level.
提出了一种用于 DNA 序列和细胞检测的原子分辨率超高灵敏度体声波（SAW）生物传感器。在 LiNbO3 衬底上制造的叉指换能器（IDT）通过优化的设计和工艺实现了超过 4000 的高品质因数（Q），频率为 6.4GHz（三阶谐波模式）。该生物传感器在 1μg/ml 至 1ng/ml 的范围内对目标 DNA 表现出优异的线性响应，灵敏度高达 6.7×10^(-16)g/cm^2/Hz，因此也可以区分单个杂交 DNA 碱基的差异。由于具有如此高的质量分辨率，该生物传感器能够对活癌细胞进行定量检测。研究了单个鼠乳腺腺癌（EMT6）细胞和鼠成纤维细胞（3T3）细胞的频率响应。实验中的干扰对频率偏移的影响可以忽略不计，这验证了生物传感器的高选择性。该生物传感器在粗糙清洁后也能够重复感应能力，因此在实际应用中通过回收过程实现了成本降低。检测极限是从器件的噪声分析中定义的，根据计算实现了原子分辨率，从而为高精度医疗诊断和原子级现象观察提供了一种潜在的工具。
