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 × 256 working electrodes of size 44 μm × 52 μm, along with 16 reference electrodes of dimensions 56 μm × 399 μm and 32 counter electrodes of dimensions 399 μm × 106 μm, 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.

中文翻译：

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用于大规模并行外电原筛选的 CMOS 多模式电化学和阻抗细胞传感阵列

该论文提出了一个 256 像素的 CMOS 传感器阵列，具有像素内双电化学和阻抗检测模式，用于快速、多维表征外生电。CMOS IC 具有 16 个并行读出通道，使其能够以高吞吐量执行多项测量，并使芯片能够同时处理不同的样本。该芯片共包含2×256个44μm×52μm的工作电极，16个56μm×399μm的参比电极和32个399μm×106μm的对电极，共同促进了高分辨率筛选的测试样本。该芯片采用标准的 130nm BiCMOS 工艺制造。片上电极经过额外的制造工艺，包括关键的铝蚀刻步骤，可确保 CMOS 传感器阵列在生物环境中的出色生物相容性和长期可靠性。通过检测电活性分析物 NaFeEDTA 和外生电来验证电化学传感模式希瓦氏菌MR-1 细菌，展示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。对芯片上培养的 HEK-293 癌细胞进行的阻抗测量成功捕获了电极与癌细胞之间的细胞表面粘附信息。所报告的 CMOS 传感器阵列在空间分辨率和速度方面优于用于外电原表征的传统离散设置，这表明该芯片具有从根本上加速合成生物学工程的潜力。