skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Noise in nanopore sensors: Sources, models, reduction, and benchmarking
Label-free nanopore sensors have emerged as a new generation technology of DNA sequencing and have been widely used for single molecule analysis. Since the first α-hemolysin biological nanopore, various types of nanopores made of different materials have been under extensive development. Noise represents a common challenge among all types of nanopore sensors. The nanopore noise can be decomposed into four components in the frequency domain (1/f noise, white noise, dielectric noise, and amplifier noise). In this work, we reviewed and summarized the physical models, origins, and reduction methods for each of these noise components. For the first time, we quantitatively benchmarked the root mean square (RMS) noise levels for different types of nanopores, demonstrating a clear material-dependent RMS noise. We anticipate this review article will enhance the understanding of nanopore sensor noises and provide an informative tutorial for developing future nanopore sensors with a high signal-to-noise ratio.  more » « less
Award ID(s):
1710831 1912410
PAR ID:
10589293
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
American Institute of Physics
Date Published:
Journal Name:
Nanotechnology and Precision Engineering
Volume:
3
Issue:
1
ISSN:
1672-6030
Format(s):
Medium: X Size: p. 9-17
Size(s):
p. 9-17
Sponsoring Org:
National Science Foundation
More Like this
  1. 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. 
    more » « less
  2. null (Ed.)
    Solid-state nanopore sensors have broad applications from single-molecule biosensing to diagnostics and sequencing. Prevalent nanopore sensors are fabricated on silicon (Si) substrates through micromachining, however, the high capacitive noise resulting from Si conductivity has seriously limited both their sensing accuracy and recording speed. A new approach is proposed here for forming nanopore membranes on insulating sapphire wafers by anisotropic wet etching of sapphire through micro-patterned triangular masks. Reproducible formation of small membranes with an average dimension of ~10 μm are demonstrated. For validation, a sapphire-supported (SaS) nanopore chip, with a 100 times larger membrane area than silicon-supported (SiS) nanopore, showed 130 times smaller capacitance (10 pF) and ~2.5 times smaller rootmean-square (RMS) noise current (~20 pA over 100 kHz bandwidth). Tested with 1k bp double-stranded DNA, the SaS nanopore enabled sensing at microsecond speed with a signal-to-noise ratio of 21, compared to 11 from a SiS nanopore. This SaS nanopore presents a manufacturable platform feasible for biosensing as well as a wide variety of MEMS applications. 
    more » « less
  3. ABSTRACT Detection of ultra‐short peptides is one of the critical steps toward deeper understanding of proteins and the sequencing of amino acids using solid‐state nanopores. The ability of solid‐state nanopores to detect these ultra‐short peptides can help us reveal their hydrodynamic state under different conditions like the concentrations and the external voltage, which may further guide the future development in this field for deeper investigation and possible improvement. In this study, we fabricate SixNynanopores by CDB with various pore sizes and use them to detect ultra‐short peptides comprised of five different amino acids. The peptide translocation events are extracted under various external voltages. Optimal experimental conditions such as the concentration of electrolytes and analytes, and the range of external voltage are investigated and compared. The statistical results based on volume exclusion analysis indicate that a significant portion of peptides exist in aggregation form. Due to the limitations of SixNynanopores such as the thickness and the noise, most of the single peptide signals are masked under the baseline noise. In addition, the results show that peptide–pore interactions are dependent upon the diameter of the nanopore. Higher voltage may also influence the degree of peptide aggregations. This study serves to further comprehend the physical and chemical properties of peptides, find possible ways to improve the performance of solid‐state nanopores in the area of protein and peptide detections, and indicate the potential improvements in solid‐state nanopore‐based peptide sequencing. 
    more » « less
  4. Abstract In this review, recent research efforts that aimed at developing nanopore sensors for detection of metal ions, which play a crucial role in environmental safety and human health, are highlighted. Protein pores use three stochastic sensing‐based strategies for metal ion detection. The first strategy is to construct engineered nanopores with metal ion binding sites, so that the interaction between the target analytes and the nanopore can slow the movement of metal ions in the nanochannel. Second, large molecules such as nucleic acids and especially peptides can be utilized as external selective molecular probes to detect metal ions based on the conformational change of the ligand molecules induced by the metal ion–ligand chelation/coordination interaction. Third, enzymatic reactions can also be used as an alternative to the molecule probe strategy in the situation that a sensitive and selective probe molecule for the target analyte is difficult to obtain. On the other hand, by taking advantage of steady‐state analysis, synthetic nanopores mainly use two strategies (modification and modification‐free) to detect metals. Given the advantages of high sensitivity and selectivity, and label‐free detection, nanopore‐based metal ion sensors should find useful application in many fields, including environmental monitoring, medical diagnosis, and so on. 
    more » « less
  5. DNAs have been used as probes for nanopore sensing of noncharged biomacromolecules due to its negative phosphate backbone. Inspired by this, we explored the potential of diblock synthetic polyelectrolytes as more flexible and inexpensive nanopore sensing probes by investigating translocation behaviors of PEO-b-PSS and PEO-b-PVBTMA through commonly used alpha-hemolysin ( α -HL) and Mycobacterium smegmatis porin A (MspA) nanopores. Translocation recordings in different configurations of pore orientation and testing voltage indicated efficient PEO-b-PSS translocations through α -HL and PEO-b-PVBTMA translocations through MspA. This work provides insight into synthetic polyelectrolyte-based probes to expand probe selection and flexibility for nanopore sensing. 
    more » « less