Biomedical Engineering Reference
In-Depth Information
Chapter 2
Molecular Detection and Force Spectroscopy
in Solid-State Nanopores with Integrated
Optical Tweezers
Adam R. Hall and Cees Dekker
Abstract We describe how individual biopolymer molecules can be captured,
detected and manipulated inside a solid-state nanopore using an integrated optical
tweezer system. The combination of nanopore and tweezer technologies offers
measurement capabilities like size and length discrimination similar to transloca-
tion experiments along with arbitrary position control and the ability to perform
direct force spectroscopy. We discuss the experimental setup and measurements on
two different types of molecules (bare DNA and protein-coated DNA), and we
describe a model for the force on a charged molecule in a nanopore.
Keywords Force Spectroscopy Integrated Optical Tweezers Size and length
discrimination Protein-Coated DNA Molecules
2.1
Introduction
Solid-state nanopores show great promise as a high-throughput means by which to
detect and analyze biopolymers on an individual basis [
1
,
2
]. A commonly used
method towards this end involves the use of a thin, insulating membrane with a
single fabricated pore in it (typically prepared by either a transmission electron
microscope [
3
] or a focused ion beam [
4
]) that acts as a barrier between two supplies
of ionic solution. The application of a voltage across the membrane sets up an
electric field that is strongly focused inside the pore and can be used to transport
charged molecules from one side to the other electrophoretically. Upon doing so,
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