title: Label-free cell-substrate adhesion imaging on plasmonic nanocup arrays.
abstract: Cell adhesion is a crucial biological and biomedical parameter defining cell differentiation, cell migration, cell survival, and state of disease. Because of its importance in cellular function, several tools have been developed in order to monitor cell adhesion in response to various biochemical and mechanical cues. However, there remains a need to monitor cell adhesion and cell-substrate separation with a method that allows real-time measurements on accessible equipment. In this article, we present a method to monitor cell-substrate separation at the single cell level using a plasmonic extraordinary optical transmission substrate, which has a high sensitivity to refractive index changes at the metal-dielectric interface. We show how refractive index changes can be detected using intensity peaks in color channel histograms from RGB images taken of the device surface with a brightfield microscope. This allows mapping of the nonuniform refractive index pattern of a single cell cultured on the plasmonic substrate and therefore high-throughput detection of cell-substrate adhesion with observations in real time.
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, 306 N Wright St, Urbana, IL 61801, USA; Miro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 N Wright St, Urbana, IL 61801, USA.
authors.forename: L P
authors.initials: LP
authors.lastname: Hackett
authors.affiliation: Miro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 N Wright St, Urbana, IL 61801, USA; Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green St, Urbana, IL 61801, USA.
authors.forename: S
authors.initials: S
authors.lastname: Seo
authors.affiliation: Miro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 N Wright St, Urbana, IL 61801, USA; Department of Bioengineering, University of Illinois at Urbana-Champaign, 1270 Digital Computer Laboratory, Urbana, IL 61801, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, 306 N Wright St, Urbana, IL 61801, USA; Miro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 N Wright St, Urbana, IL 61801, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Goddard
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, 306 N Wright St, Urbana, IL 61801, USA; Miro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, 208 N Wright St, Urbana, IL 61801, USA; School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 43007, China.
authors.forename: G L
authors.initials: GL
authors.lastname: Liu
keywords: (100.2960) Image analysis; (170.0180) Microscopy; (170.1530) Cell analysis; (170.3880) Medical and biological imaging; (240.6680) Surface plasmons; (280.1415) Biological sensing and sensors