The Molecular Structure of Biopolymers: Developing Nanopores as Probes

A hallmark of modern science has been the continual development of experimental strategies to observe individual atomic scale ‘events’. These strategies ultimately rely on significantly amplifying the consequences of a selective microscopic interaction, for example the chemical development of a silver halide grain in a photographic emulsion, or the charge amplification in electron multiplier devices. Research performed by members of the nanopore research group at Harvard has shown that individual polymers associated with replication and regulation of life, DNA and RNA, can be registered and characterized singly with a new kind of detector, a nanopore.

A nanopore can be a protein channel in a lipid bilayer or an extremely small isolated ‘hole’ in a thin, solid-state membrane. For a nanopore to be useful as a single molecule detector, its diameter must not be much larger than the size of the molecule to be detected — just a few tens of Angstroms across. When a single molecule enters a nanopore in an insulating membrane, it causes changes in the nanopore’s electrical properties that are readily detected with modern electronic devices and circuits. The mission of the Nanopore Group at Harvard is to study the science of single molecules in nanopores. Our aim is to use this knowledge to develop an ultra high-speed method for sequencing DNA, but we are also developing a number of other important, but less demanding, applications that utilize the extraordinary sensitivity and speed of nanopore probing. On the path to achieving sequencing, we are modeling the physics of DNA polymer movement through the confined space of a nanopore, coordinating the application of material science tools to fabricate solid-state nanopores, and developing the associated biochemistry, molecular biology, electronics, and signal processing to effect molecular recognition.

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