Non‐binary Encoded Nucleic Acid Barcodes Directly Readable by a Nanopore

A large collection of unique molecular barcodes is useful in the simultaneous sensing or screening of molecular analytes. Though the sequence of DNA has been widely applied to encode for molecular barcodes, decoding of these barcodes is normally assisted by sequencing. We here demonstrate a barcode...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-05, Vol.61 (20), p.e202116482-n/a
Main Authors: Yan, Shuanghong, Wang, Liying, Wang, Yuqin, Cao, Zhenyuan, Zhang, Shanyu, Du, Xiaoyu, Fan, Pingping, Zhang, Panke, Chen, Hong‐Yuan, Huang, Shuo
Format: Article
Language:English
Subjects:
Antibodies
Bar codes
DNA - metabolism
DNA probes
MicroRNA
miRNA
MspA
Mycobacterium smegmatis
Nanopores
Nodes
Nucleic Acid Barcode
Nucleic acids
Nucleic Acids - metabolism
Nucleotide sequence
Porins - metabolism
Proteins
Sequences
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Summary:A large collection of unique molecular barcodes is useful in the simultaneous sensing or screening of molecular analytes. Though the sequence of DNA has been widely applied to encode for molecular barcodes, decoding of these barcodes is normally assisted by sequencing. We here demonstrate a barcode system based solely on self‐assembly of synthetic nucleic acids and direct nanopore decoding. Each molecular barcode is composed of “n” distinct information nodes in a non‐binary manner and can be sequentially scanned and decoded by a Mycobacterium smegmatis porin A (MspA) nanopore. Nanopore events containing step‐shaped features were consistently reported. 14 unique information nodes were developed which in principle could encode for 14n unique molecular barcodes in a barcode containing “n” information nodes. These barcode probes were adapted to detect different antibody proteins or cancer‐related microRNAs, suggesting their immediate application in a wide variety of sensing applications. An extremely simple molecular barcoding strategy is proposed based on self‐assembly of synthetic DNA oligomers and direct nanopore decoding. The composition of the barcode probe is highly programmable, and in principle 14n unique step‐shaped barcode patterns can be generated without nanopore sequencing. Different protein and microRNA targets were identified using this strategy, showing its generality in single molecule sensing.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202116482