A CMOS Multi-Modal Electrochemical and Impedance Cellular Sensing Array for Massively Paralleled Exoelectrogen Screening
A CMOS Multi-Modal Electrochemical and Impedance Cellular Sensing Array for Massively Paralleled Exoelectrogen Screening
复制标题
DOI：
10.1109/tbcas.2021.3068710
复制
发表时间：
2021-04-01
影响因子：
5.1
通讯作者：
Wang, Hua
中科院分区：
文献类型：
--
作者：
Kumashi, Sagar R.;Jung, Doohwan;Wang, Hua
本文提出了一种256像素的CMOS传感器阵列，具有像素内双重电化学和阻抗检测模式，用于快速、多维地表征外源电信号。该芯片具有16个并行读出通道，使其能够以高吞吐量执行多个测量，并使芯片能够同时处理不同的样本。该芯片包括2×256个工作电极，尺寸为44微米×52微米，以及16个尺寸为56微米×399微米的参比电极和32个尺寸为399微米×106微米的对电极，这些都有助于测试样品的高分辨率筛选。该芯片采用标准的130 nm BiCMOS工艺制造。芯片上的电极经过额外的制造工艺，包括关键的铝刻蚀步骤，以确保在生物环境中CMOS传感器阵列具有良好的生物兼容性和长期可靠性。通过检测电活性分析物NaFeEDTA和外生电生单胞菌MR-1细菌，验证了电化学传感模式，说明了芯片量化产生的电化学电流和区分不同分析物浓度的能力。利用芯片上培养的HEK-293癌细胞进行的阻抗测量成功地捕捉到了电极与癌细胞之间的细胞表面黏附信息。报道的CMOS传感器阵列在空间分辨率和速度方面优于传统的离散外电极表征装置，这表明该芯片具有从根本上加速合成生物工程的潜力。
The paper presents a 256-pixel CMOS sensor array with in-pixel dual electrochemical and impedance detection modalities for rapid, multi-dimensional characterization of exoelectrogens. The CMOS IC has 16 parallel readout channels, allowing it to perform multiple measurements with a high throughput and enable the chip to handle different samples simultaneously. The chip contains a total of 2 x 256 working electrodes of size 44 mu m x 52 mu m, along with 16 reference electrodes of dimensions 56 mu m x 399 mu m and 32 counter electrodes of dimensions 399 mu m x 106 mu m, which together facilitate the high resolution screening of the test samples. The chip was fabricated in a standard 130nm BiCMOS process. The on-chip electrodes are subjected to additional fabrication processes, including a critical Al-etch step that ensures the excellent biocompatibility and long-term reliability of the CMOS sensor array in bio-environment. The electrochemical sensing modality is verified by detecting the electroactive analyte NaFeEDTA and the exoelectrogenic Shewanella oneidensis MR-1 bacteria, illustrating the chip's ability to quantify the generated electrochemical current and distinguish between different analyte concentrations. The impedance measurements with the HEK-293 cancer cells cultured on-chip successfully capture the cell-to-surface adhesion information between the electrodes and the cancer cells. The reported CMOS sensor array outperforms the conventional discrete setups for exoelectrogen characterization in terms of spatial resolution and speed, which demonstrates the chip's potential to radically accelerate synthetic biology engineering.