# Advanced Parallel Readers for DNA Sequencing Through a 2D Nanopore

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $273,277

## Abstract

Project Summary
To improve DNA and RNA sequencing with respect to accuracy, robustness and speed, this NIH
R21 project focuses on using a two-layer design with two parallel solid-state SiN-2D nanopores
on low-noise all-glass chips, towards DNA sequencing and direct RNA sequencing. The basic
concept behind nanopores involves using an applied voltage to drive single-stranded DNA
molecules through a narrow nanopore, which separates chambers of electrolyte solution. This
voltage also drives a flow of electrolyte ions through the pore, measured as an electric current.
When molecules pass through the nanopore they modify the flow of ions, and structural
information can be extracted by analysis of the duration and magnitude of the resulting current
reductions. Nanopore in ultrathin SiN membranes, as well as 2D membranes, improve the signal-
to-noise ratio for molecular detection and analysis because the resistance to the ionic flow through
a nanopore increases linearly with the nanopore thickness, so both the magnitudes of the ionic
current and the blocked current with a translocating molecule increase with decreasing nanopore
height. Specifically, we seek to make solid-state ionic-current based nanopore sequencing
possible by combining several important components: we propose to demonstrate a two-layer on-
chip solid-state SiN-2D-pore system that limits the range of DNA motion through two parallel
proximal pores that are electrically independently addressable. We create devices containing a
second layer with one silicon nitride (SiN) pore, parallel to a primary layer containing the
atomically-thin 2D pore that confine ssDNA within a device to a restricted geometry, yet allow the
free motion of salt ions to maintain a high signal-to-noise ratio. We propose a specific two-layer
concept, where the two layers are in close proximity, with two independent electrical connections,
and corresponding chip device architecture to achieve this goal. In this method, there is a central,
highly sensitive 2D pore which we refer to as the main sensing/sequencing 2D nanopore. A
secondary layer has a second pore sharing the same electrode pair as the sensing pore, but also
having its own independent electrode pair to be probed separately. Although we have two pores,
they can operate as a continuous system due to their proximity. We outline the 3D finite element
analysis modeling and practical implementation (two versions) of these concepts with Si-based
technology, including advantages and challenges involved for DNA (and biomolecule) sequencing
(analysis) in solution. Our approach eliminates the need for any enzymes and enables DNA and
biomolecules to be guided through robust and long-lasting nanopores, facilitated by the custom-
designed chip combining the best of what the SiN and 2D pores can currently offer.
Illustration 1: Proposed two-layer
device concept for this NIH R21
proposal, relying on minimization of
DNA entropic motion using two
proximal, parallel SiN-2D po...

## Key facts

- **NIH application ID:** 10437327
- **Project number:** 1R21HG012395-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Marija Drndic
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $273,277
- **Award type:** 1
- **Project period:** 2022-08-04 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437327

## Citation

> US National Institutes of Health, RePORTER application 10437327, Advanced Parallel Readers for DNA Sequencing Through a 2D Nanopore (1R21HG012395-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10437327. Licensed CC0.

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