Nanopores for detecting and sensing biological molecules

Barati Farimani, Amir

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https://hdl.handle.net/2142/89267 Copy

Description

Title

Nanopores for detecting and sensing biological molecules

Author(s)

Barati Farimani, Amir

Issue Date

2015-08-28

Director of Research (if dissertation) or Advisor (if thesis)

Aluru, Narayan R

Doctoral Committee Chair(s)

Aluru, Narayan R

Committee Member(s)

• Jakobsson, Eric
• Tajkhorshid, Emad
• Lyding, Joseph W

Department of Study

Mechanical Science & Engineering

Discipline

Mechanical Engineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Nanopore
• Deoxyribonucleic acid (DNA)
• Detection
• Protein
• DNA origami
• molybdenum Disulfide (MoS2)
• Graphene

Abstract

In spite of significant advances in the detection, separation and counting of single biological molecules (DNA, proteins, aminoacids, etc.) with solid-state nanopores, atomically-resolved scanning and detection of these molecules remains a significant challenge. In most nanopore-based DNA sequencing and single molecule detection techniques, ionic current blockade and blockade duration are the primary signatures associated with reading and scanning. Although these techniques are good enough for single molecule detection, they are not sophisticated enough to analyze and detect single DNA bases, fine structures, homologues and mutagenesis. Aside from the detection difficulties, low signal to noise ratio (SNR), fast speed of translocation, and lack of a cross-check signal are the biggest challenges of current nanopore technology. In this study, we explored different nanopore architectures and materials to find solutions to these current challenges. Using extensive atomistic simulations, we showed that a single layer molybdenum Disulfide (MoS2) nanopore is attractive pore for single base DNA detection with high SNR and multi-level conductance. We introduced and simulated MscL (Mechano-Sensitive Channel of Large Conductance) as an alternative to traditional biological nanopores (Alpha-Hemolysin, MspA) since it provides a flexible nanopore with adaptability to DNA base types. Induced tension in MscL is shown to be different and distinguishable for each DNA base type. The speed of DNA translocation is also decreased by one order of magnitude in MscL, providing a better detection resolution compared to its counterpart, e.g. MspA. Next, we explored DNA origami-graphene hybrid nanopore for DNA detection. We found that the dwell time of each base type in the hybrid pore is different and distinguishable compared to pristine graphene nanopore. The specific interaction (hydrogen bonds) between the complimentary bases at the edge of the pore and the translocating DNA bases give rise to distinguishable dwell time for each DNA. In addition to DNA sequencing studies, we also investigated the recognition of natively folded proteins using graphene nanopore. We specifically focused on the detection of Immunoglobin G subclasses since the separation and the detection of different subclasses of IgG is the signature of many diseases. These four subclasses differ only in their hinge regions and are 95% homologues. We showed that the one atom thick graphene is highly capable of distinguishing between the subclasses by using ionic current and water flux signals.

Graduation Semester

2015-12

Type of Resource

text

Permalink

http://hdl.handle.net/2142/89267

Copyright and License Information

Copyright 2015 Amir Barati Farimani

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