Nanopore-Based Optofluidic Devices for Single Molecule Sensing - Nanofluidics: Nanoscience and Nanotechnology - page 139

CHAPTER 7
Nanopore-Based Optofluidic Devices for
Single Molecule Sensing

GUILLAUME A. T. CHANSIN 1,2 , JONGIN HONG 1,2 , ANDREW J. D E MELLO 1
& JOSHUA B. EDEL 1,2
1

Department of Chemistry, Imperial College London, South Kensington, London,
SW7 2AZ, United Kingdom

2

Institute of Biomedical Engineering, Imperial College London, South
Kensington, London, SW7 2AZ, United Kingdom

7.1 INTRODUCTION

One of the primary motivations behind the development of miniaturised analysis
devices has been to create new tools for modern day genomic and genetic analysis. 1 At
present, much effort is directed towards designing faster and more efficient DNA analysis
devices that could potentially identify the genes responsible for specific diseases. 2-4 One
increasingly popular approach is confinement and detection of single analyte molecules
within nanofluidic structures. Such devices, have at least one dimension of the channel
measuring less than a few hundred nanometres. 5 One of the main advantages of
nanofluidics is in the ability to confine single molecules within a well defined space in
order to be efficiently detected. Importantly, probing molecules at the single molecule level
is essential if one wants to measure fluctuations usually lost in ensemble averaged
techniques.
Although there are many approaches in combining single molecule detection with
nanofluidics , a promising approach over the past decade has been in the use of nanopores.
In the 1990s, much effort was made to recreate and engineer nanopores outside of the
living cell. 6 Of particular interest was the -hemolysin pore, a protein that opens a 1.5 nm-
wide channel when inserted inside a lipid bilayer membrane. 7 In 1996, Kasianowicz et al.
demonstrated the application of -hemolysin to measure the length of single-stranded DNA
molecules. 8 The authors could detect the blockage of the ionic current during the
translocation of the molecules inside the channel. This milestone opened a new field of
research through the motivation that nanopores could be used to sense and analyse nucleic
acids 9 (ibid. Chapter 6). In recent years, different approaches have been used to create
nanopores with standard micro and nano-fabrication processing techniques as opposed to a
biologically driven approach. 10,11 Such devices are made using the same materials used in
the semiconductor industry and thus integrate well with other top-down technologies. In
this chapter, we will focus our attention on these solid-state nanopores and their potential
use in fluorescence spectroscopy of single molecules.
Nanopore-based platforms are suitable for the study of single molecules as they
provide a level of confinement that allows for perfect detection efficiency. This level of
confinement results in an entropic barrier being overcome by the biopolymers as the
molecule is unfolded when driven inside the pore. This concept can be easily explained for

139