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In developing solid-state nanopore sensors for single molecule detection, comprehensive evaluation of the nanopore quality is important. Existing studies typically rely on comparing the noise root mean square or power spectrum density values. Nanopores exhibiting lower noise values are generally considered superior. This evaluation is valid when the single molecule signal remains consistent. However, the signal can vary, as it is strongly related to the solid-state nanopore size, which is hard to control during fabrication consistently. This work emphasized the need to report the baseline current for evaluating solid-state nanopore sensors. The baseline current offers insight into several experimental conditions, particularly the nanopore size. Our experiments show that a nanopore sensor with more noise is not necessarily worse when considering the signal-to-noise ratio (SNR), particularly when the pore size is smaller. Our findings suggest that relying only on noise comparisons can lead to inaccurate evaluations of solid-state nanopore sensors, considering the inherent variability in fabrication and testing setups among labs and measurements. We propose that future studies should include reporting baseline current and sensing conditions. Additionally, using SNR as a primary evaluation tool for nanopore sensors could provide a more comprehensive understanding of their performance.
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Surveying silicon nitride nanopores for glycomics and heparin quality assurance
Abstract Polysaccharides have key biological functions and can be harnessed for therapeutic roles, such as the anticoagulant heparin. Their complexity—e.g., >100 monosaccharides with variety in linkage and branching structure—significantly complicates analysis compared to other biopolymers such as DNA and proteins. More, and improved, analysis tools have been called for, and here we demonstrate that solid-state silicon nitride nanopore sensors and tuned sensing conditions can be used to reliably detect native polysaccharides and enzymatic digestion products, differentiate between different polysaccharides in straightforward assays, provide new experimental insights into nanopore electrokinetics, and uncover polysaccharide properties. We show that nanopore sensing allows us to easily differentiate between a clinical heparin sample and one spiked with the contaminant that caused deaths in 2008 when its presence went undetected by conventional assays. The work reported here lays a foundation to further explore polysaccharide characterization and develop assays using thin-film solid-state nanopore sensors.
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- Award ID(s):
- 1150085
- PAR ID:
- 10153467
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 9
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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