High resolution and high efficiency biomolecular sensing using solid-state and hybrid bilayer MoS2 nanopores

  • Author / Creator
    Sen, Payel
  • Solid-state nanopores have emerged as stable label- and amplification- free biosensors for rapid detection of charged biomolecules. Analytes are electrophoretically pulled through nanopores and are detected using the characteristic blockade current due to the translocation. However, despite their stability and scalability, solid-state nanopores have few limitations which need to be overcome for achieving a versatile and efficient biosensor. One of the primary challenges of nanopore sensing is single molecule detection which requires both spatially and temporally resolved signals.
    Monolayer molybdenum disulphide (a 2D material) due to its favourable surface charge, monolayer thickness, and stability in electrolytic medium have been used for single molecule sensing due to their superior spatial resolution. However, their ultra-thinness reduces analyte/nanopore surface charge interaction and makes translocation too fast to temporally resolve the signals, thereby reducing statistical confidence and efficiency of detection.
    In this work, both simulation and experimental data demonstrate that bilayer MoS2 nanopores (~ 1 nm thick) can detect single molecules (nucleotides in this study) with 5 times higher detection rate and 4% higher sensing efficiency by slowing down DNA translocation (i.e., improving temporal resolution) while maintaining a good spatial resolution.
    Another limitation of solid-state nanopores is its charge versatility. Solid-state nanopores despite showing good sensitivity towards charged biomolecules, fail to show good neutral molecule detection sensitivity; the latter demanding increased signal-to-noise ratio and dwell times at the nanopore. A biological nanopore due to a chemically sensitive interface manifests minor charge alterations with higher resolution, thus helping in neutral molecule sensing as well. However, biological pores alone are prone to thermo-mechanical instabilities and are unsuitable for manufacturing portable sensors.
    Hybrid nanopores formed by incorporating biological pore in a solid-state nanopore can be suitable for both charged and uncharged molecule sensing. A hybrid of engineered outer membrane porin G (eOmpG) and bilayer MoS2 nanopore was constructed. This hybrid nanopore demonstrated 1.9 times better signal-to-noise ratio and 8 times better dwell times for polynucleotide sensing as compared to solid-state BL MoS2 nanopore, due to unique size controllability, gating properties and improved local-charge sensitivity of eOmpG. This hybrid nanopore was able to detect a change as low as 1 pM of delta-9-THC level, which is a neutral molecule, in saliva. The study on THC detection can also help in real-time monitoring of marijuana toxicity in users as well as predict consequences due to its toxicity. The eOmpG in hybrid nanopore also helped in obtaining THC orientation-specific information which can act as means to differentiate toxic and non-toxic elements of marijuana in future.
    The study demonstrates that 2D material like MoS2 is suitable for fabricating solid state nanopores which are repeatable and stable. Nanopores with different number of layers MoS2 were studied and due to the inter layer interaction bilayer MoS2 was found to be the optimum one for measurement of single nucleotides effectively and efficiently. Additionally, these BL MoS2 were used to form hybrid nanopores using barrel protein OmpG which demonstrated reduction of the noise in the nanopore measurement. This hybrid nanopore was used for THC molecule detection which is normally not conducted using a nanopore. Hence, the work has opened the path for layered materials and their applications for nanopores.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.