Expl oring electric field sensing for solid -state nanopore s Muhammad Sajeer P Manoj M.Varma Centre for Nanoscience and Engineering Indian Institute of Science Bangalore 560012

2025-05-06 0 0 699.1KB 10 页 10玖币

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Exploring electric field sensing for solid-state nanopores

Muhammad Sajeer P, Manoj M.Varma

Centre for Nanoscience and Engineering, Indian Institute of Science, Bangalore, 560012

Corresponding email:muhammads@iisc.ac.in

Abstract

Solid-state nanopores have received substantial attention in the past years owing to their

simplicity and potential applications expected in genomics, sensing, archival information

storage, and computing. The underlying sensing technique of nanopore technology is the

analysis of modulations in the ionic current while molecules are electrophoretically driven

through the nanopore. This current blockade-based sensing is presently well recognized and

commercially used for applications such as DNA sequencing. However, this ionic current-

based method has limitations and increased complexity for futuristic applications such as single

molecular protein sequencing, where diverse charges and shape distributions are involved. A

high throughput readout method that can be used in extreme environments and has improved

sensitivity to the mixed charge profiles and shape of the analytes is required. In this work, we

present an exploratory finite element simulation study on the feasibility of using electric-field

modulations instead of ionic current blockades for nanopore translocation measurements. This

electric field sensing technique has further advantages over ionic current blockade

measurements. For instance, Electric field sensing is capable of size and charge discretion with

lesser noise and does not mandate the presence of an electrolyte solution. This technique can

be used in extreme environments and developed for defense and space applications such as

detecting air-born particles and future mars, moon, and Europa missions. We hope this work

will be a starting point for developing electric field sensing for nanopore applications and

opening the field of nanopore electrometry.

1. Introduction

Solid-state nanopores have received significant attention in the past years owing to their

simplicity, relatively lower cost, and potential applications in genomics1, single-molecule

sensing2, DNA-based information storage3, and computing4. The solid-state nanopores also

have substantial advantages, such as chemical, mechanical, and thermal stability and easy

integration with semiconductor processes, over their biological counterparts. In the nanopore

translocation measurement setup, the nanopore is situated between two chambers containing

an electrolyte, typically potassium chloride (KCl) solution. The target molecules are

electrophoretically driven from one chamber to the other through the nanopore. The movement

of target molecules through the pore, referred to as translocation, causes transient blockades of

the ionic current through the nanopore, which is recorded. These signals can be deciphered to

correlate with the charge, size, and concentration of target molecules. This current blockade-

based measurement techniques are now well-established and commercially used for DNA

sequencing using biological nanopores. Here, features in the raw ionic current traces are used

to map them to one of the four canonical bases using machine learning-based approaches5. One

can extend this mapping to include modified bases as well, but even with their inclusion, the

number of distinct entities that the current must be mapped onto is of the order of five or six.

On the other hand, emerging applications such as single-molecule protein sequencing require

mapping the nanopore current blockades to 20 amino acids. Also, proteins exhibit orders of

magnitude higher sequence diversity than DNA or RNA. For instance, mammalian cells have

about 30,000 fold more protein molecules than mRNA6. Single-molecule protein sequencing

thus presents significant challenges compared to DNA sequencing, as discussed in the

perspective article by Savlov et al6. Thus, aside from the problem of mapping current signals

to a larger number of independent entities, more challenging throughput requirements are also

there to decode the abundant proteins. Other applications, such as DNA based information

storage, may also require considerably faster readout than the ~ 500 bases/sec speed offered by

the current blockade-based readout. For instance, a readout method that is sensitive to

inhomogeneities in charge distributions and geometry, as opposed to current blockades, which

are predominantly determined by the total volume and charge, may provide a more effective

method to handle the complexities presented by single-molecule protein sequencing.

With these considerations in mind, we explored the feasibility of using electric-field

modulations instead of ionic current blockades to measure nanopore translocations. Electric

field-based sensing has several potential advantages. The local electric field is inherently

sensitive to the charge distribution of the target molecule and, therefore, potentially encodes

richer information about the molecule. Another aspect of electric-field sensing is that it can be

done without using an electrolyte, even in vacuum. Thus, this approach may have potential

benefits in the direct monitoring of air-borne particles as well as in extreme environments such

as outer space or hot and freezing conditions. Electric field sensing is presently widely used in

macroscale in proximity and object identifier sensors7–10. On the other hand, nanopore signal

readout using electric-field modulations will require highly localized measurements. We

expect that the recent development of nano11 and micro-scale12 electric field sensors, nanoscale

electric field imaging using nitrogen-vacancy centere13 and single spins14, and the development

of electric field imaging technology using polarized neutrones15 can possibly be modified for

electric field measurements in solid-state nanopores. In this study, we performed finite element

simulations of translocations of a particle through an hourglass-shaped silicon nitride nanopore

(Fig 1A). We used these simulations to compare the ionic current and local electric field

modulations caused by the translocating particle under various conditions, such as the size of

the particle and magnitude and polarity of charge, as described in the subsequent sections. We

hope this work will be a starting point of for developing electric field sensing techniques for

exciting nanopore-related applications and opening the field of nanopore electrometry.

2. Methods

The finite element simulation is conducted by solving the Poisson-Nernst-Plank (PNP)

equation in COMSOL (Version 5.5) software. The Poisson equation provides information on

the electric potential distribution, and Nernst-Plank equation solves for the diffusion of ions

under external voltage bias16 (refer to supplementary information). An hourglass-shaped

silicon nitride nanopore is defined using the 2D axisymmetric model in COMSOL. The

nanopore defined here has a length of 10 nm, an opening diameter of 5nm, and a centre

constriction of 3nm (Figure 1A). The particle, which is represented by a sphere, is translocated

through the center of the pore along the Z-axis to avoid off-axis effects16. The translocation is

done step by step in a time-independent manner. A voltage bias of 1V is applied across the

pore, and figure 1(b-c) shows the simulated voltage distribution in the nanopore system. Figure

1(d) indicates that the voltage drop's significant share occurs near the pore region. The details

of the simulation, such as the parameters, geometry, and reliability, are discussed in the

supplementary information.

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Exploringelectricfieldsensingforsolid-statenanoporesMuhammadSajeerP,ManojM.VarmaCentreforNanoscienceandEngineering,IndianInstituteofScience,Bangalore,560012Correspondingemail:muhammads@iisc.ac.inAbstractSolid-statenanoporeshavereceivedsubstantialattentioninthepastyearsowingtotheirsimplicityandpotent...

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Expl oring electric field sensing for solid -state nanopore s Muhammad Sajeer P Manoj M.Varma Centre for Nanoscience and Engineering Indian Institute of Science Bangalore 560012

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