Lanthanide Encoded Logically Gated Micromachine for Simultaneous Detection of Nucleic Acids and Proteins by Elemental Mass Spectrometry.
Lanthanide Encoded Logically Gated Micromachine for Simultaneous Detection of Nucleic Acids and Proteins by Elemental Mass Spectrometry.
复制标题
DOI：
10.1021/acs.analchem.2c04494
复制
发表时间：
2022-12
影响因子：
7.4
通讯作者：
Peng Yang;Rongxing Zhou;Jing Hu;Lijie Du;Feng Li;Junbo Chen;X. Hou
中科院分区：
文献类型：
--
作者：
Peng Yang;Rongxing Zhou;Jing Hu;Lijie Du;Feng Li;Junbo Chen;X. Hou
基于 DNA 的逻辑计算可用于分析生物标记输入和生成寡核苷酸信号输出，这引起了不同领域科学家的极大兴趣。然而，其在检测多种生物标志物方面的实际应用受到普遍性和鲁棒性的限制。在这项工作中，基于邻近分析，构建了一种镧系元素编码的逻辑门控微机器（LGM-Ln），它能够响应生物基质中的多重输入。在由输入和布尔“AND”算法触发的逻辑功能控制下，随后是放大的“ON”信号以指示分析物（输入）。在这个逻辑门控传感系统中，整个计算过程不涉及分子间反应中的链位移，并且采用无阈值设计，通过粒子内裂解生成0和1计算，这方便了计算单元，使“计算值”更加可靠。通过简单地改变输入生物识别的亲和配体，LGM-Ln还可以扩展到多输入模式，并在全人血清中产生强大的镧系元素编码输出，用于感测核酸（检测限为10 pM）和蛋白质（检测限为20 pM）。与用荧光团编码的逻辑门控微机器相比，LGM-Ln 具有更高的分辨率，并且多个输入没有光谱重叠，因此在多重分析和临床诊断中具有广阔的前景。
DNA-based logic computing potentially for analysis of biomarker inputs and generation of oligonucleotide signal outputs is of great interest to scientists in diverse areas. However, its practical use for sensing of multiple biomarkers is limited by the universality and robustness. Based on a proximity assay, a lanthanide encoded logically gated micromachine (LGM-Ln) was constructed in this work, which is capable of responding to multiplex inputs in biological matrices. Under the logic function controls triggered by inputs and a Boolean "AND" algorithm, it is followed by an amplified "ON" signal to indicate the analytes (inputs). In this logically gated sensing system, the whole computational process does not involve strand displacement in an intermolecular reaction, and a threshold-free design is employed to generate the 0 and 1 computation via intraparticle cleavage, which facilitates the computation units and makes the "computed values" more reliable. By simply altering the affinity ligands for inputs' biorecognition, LGM-Ln can also be extended to multi-inputs mode and produce the robust lanthanide encoded outputs in the whole human serum for sensing nucleic acids (with the detection limit of 10 pM) and proteins (with the detection limit of 20 pM). Compared with a logically gated micromachine encoded with fluorophores, the LGM-Ln has higher resolution and no spectral overlaps for multiple inputs, thus holding great promise in multiplex analyses and clinical diagnosis.