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Digitally encoded DNA nanostructures for multiplexed, single-molecule protein sensing with nanopores
Abstract
The simultaneous detection of a large number of different analytes is important in bionanotechnology research and in diagnostic applications. Nanopore sensing is an attractive method in this regard as the approach can be integrated into small, portable device architectures, and there is significant potential for detecting multiple sub-populations in a sample. Here, we show that highly multiplexed sensing of single molecules can be achieved with solid-state nanopores by using digitally encoded DNA nanostructures. Based on the principles of DNA origami, we designed a library of DNA nanostructures in which each member contains a unique barcode; each bit in the barcode is signalled by the presence or absence of multiple DNA dumbbell hairpins. We show that a 3-bit barcode can be assigned with 94% accuracy by electrophoretically driving the DNA structures through a solid-state nanopore. Select members of the library were then functionalized to detect a single, specific antibody through antigen presentation at designed positions on the DNA. This allows us to simultaneously detect four different antibodies of the same isotype at nanomolar concentration levels.
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In the citing paper
“Conversely, in regards to nanopore reads of labeled DNA, each label is read in [10–1; 101] ms.”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [21]
In the citing paper
“The authors used conical quartz nanopores with diameters of ∼14 nm for a 3-bit barcode that could be assigned with 94% accuracy.”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [21]
In the citing paper
“The use of nanopores to read out digital information encoded in DNA nanostructures was demonstrated by Bell and Keyser, who fabricated “DNA barcodes” to capture proteins.21”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [21]
In the citing paper
“More recently, through the use of long DNA backbones as in DNA origami, the organization of DNA protrusions has been used to produce three-dimensional DNA barcodes21 or hard drives that may be read using solid-state nanopores.”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [21]
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Metadata
- Authors
- Bell, N. A. W., & Keyser, U. F.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Bell, Nicholas A. W.
- Keyser, Ulrich F.
- Venue
- Nature Nanotechnology
- Published
- 2016-04-04
- Volume
- 11
- Issue
- 7
- Pages
- 645-651
- ISSN
- 1748-3387 (ISSN-L)
- 1748-3395
- OpenAlex
- W2329887558
- Cited by
- 345
- References
- 45
- Citations by year
- 2026: 28 · 2025: 37 · 2024: 24 · 2023: 38 · 2022: 39 · 2021: 30 · 2020: 34 · 2019: 39 · 2018: 40 · 2017: 25 · 2016: 10
- FWCI
- 18.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (acceptedVersion)
- Funders
- Engineering and Physical Sciences Research Council
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanopore and Nanochannel Transport Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Physical Sciences › Chemistry › Analytical Chemistry › Electrochemical sensors and biosensors
- Keywords
- DNA nanostructures, DNA origami, solid-state nanopores, nanopore sensing, multiplexed protein detection, single-molecule detection, DNA barcodes, antibody detection, antigen presentation
- MeSH terms
- Binding Sites, DNA, Proteins, Nanotechnology, Nanostructures, Nanopores
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