title: Label-Free Single-Molecule Imaging with Numerical-Aperture-Shaped Interferometric Scattering Microscopy.
abstract: Our ability to optically interrogate nanoscopic objects is controlled by the difference between their extinction cross sections and the diffraction-limited area to which light can be confined in the far field. We show that a partially transmissive spatial mask placed near the back focal plane of a high numerical aperture microscope objective enhances the extinction contrast of a scatterer near an interface by approximatelyT-1/2, whereTis the transmissivity of the mask. Numerical-aperture-based differentiation of background from scattered light represents a general approach to increasing extinction contrast and enables routine label-free imaging down to the single-molecule level.
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford , South Parks Road, OX1 3QZ Oxford, U.K.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cole
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford , South Parks Road, OX1 3QZ Oxford, U.K.
authors.forename: Gavin
authors.initials: G
authors.lastname: Young
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford , South Parks Road, OX1 3QZ Oxford, U.K.
authors.forename: Alexander
authors.initials: A
authors.lastname: Weigel
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford , South Parks Road, OX1 3QZ Oxford, U.K.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Sebesta
authors.affiliation: Physical and Theoretical Chemistry Laboratory, University of Oxford , South Parks Road, OX1 3QZ Oxford, U.K.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kukura
keywords: biosensing; interferometric scattering; label-free; single-molecule imaging