Graphene Interfaced with Biological Cells: Opportunities and Challenges Phong Nguyen and Vikas Berry* Department of Chemical Engineering, Kansas State University, Manhattan, Kansas 66506, United States ABSTRACT: By interfacing the quantum mechanical properties of nanomaterials with the complex processes in biology, several bio/nano systems have evolved with applications in biosensors, cellular devices, drug delivery, and biophotoluminescence. One recent breakthrough has been the application of graphene, a two-dimensional (2-D) sheet of sp 2 hybridized carbon atoms arranged in a honeycomb lattice, as a sensitive platform for interfacing with biological cells to detect intra- and extracellular phenomena, including cellular excretion and cell mem- brane’s potential modulation. In this Perspective, we discuss the recent results on graphene/cell interfacial devices and the principles defining the modulation of charge-carrier properties in graphene and its derivatives via interaction with cellular membranes. Graphene’s high sensitivity in these applications evolves from the π-carrier cloud confined within an atom-thick layer, quantum-capacitance-induced doping enhancement, closely spaced electronic bands, and a large surface area. We discuss the effect of the electronegativity of the cell wall and the dynamic changes in its chemical potential on doping specific carriers into graphene. Finally, we discuss the challenges and opportunities of graphene-interfaced biocellular systems. S ince the 1990s, several studies have originated on interfacing nanomaterials with biocomponents, with the goal of detecting biocomponents or biological phenomena. 1-6 Until 2004, the research community was primarily applying zero-dimensional (0-D) and one-dimensional (1-D) nano- materials (semiconducting nanoparticles, silicon nanowires), which are excellent for interfacing with biomolecules (DNA, proteins) and nanoscale biocomponents (viral particles, lipid micelles). These interfaces have led to the development of valuable tools and devices for biodiagnostics and biomedi- cine. 1,3,4,5 The 2004 experiments on graphene 7 led to the evolu- tion of 2-D nanotechnology. Owing to a unique combination of its crystallographic and electronic structure, 8 graphene exhibits several superior and atypical properties, including weakly scat- tered (λ scattering > 300 nm) ballistic transport of its charge carriers at room temperature, 7,9,10 gate-tunable band gap in bilayers, 11 a chemically 12,13 and geometrically 14 controllable band gap, quantum Hall effect at room temperature, 15,16 quantum interference, 17 exceptional mechanical strength, 18 and mega- hertz characteristic frequency. 19 Due to these properties, graphene has emerged as an attractive candidate for several unique applications, including ultrafast nanoelectronic devi- ces, 8,10 single-molecule detectors, 20 ultracapacitors, 21 optoelec- tronics, 22 and nanomechanical devices. 19,23 In comparison to 0-D nanoparticles 1,2 and 1-D nanowires, 3-5 including their 2-D networks, 6 the 2-D graphene sheets possess a large and continuous sensing/interfacing area. 2 Therefore, graphene can provide a stable interface for microbes and mammalian cells, which too have large surface area (Figure 1). Although several impedance-modulation mechanisms have been developed for cellular detection, these have primarily focused on the change in conduction through the cells. By interfac- ing with the cell, graphene provides an avenue to (a) change its own carrier properties via events on the cell wall, (b) interface strongly with the cell and interact with the cell wall by large surface area, (c) enable single-cell studies, and (d) maintain the cell’s viability during measurements. 24 The mechanism of the graphene/cell detection systems is based on carrier doping via the cell wall’s electronegativity or dipole moment. Graphene’s interface with the cell is via the cell wall or Received: January 9, 2012 Accepted: March 29, 2012 Graphene provides a sensitive platform for interfacing with biological cells to detect intra- and extracellular phenomena. Figure 1. A generalized schematic for a graphene device interfaced with a biological cell. Perspective pubs.acs.org/JPCL © XXXX American Chemical Society 1024 dx.doi.org/10.1021/jz300033g | J. Phys. Chem. Lett. 2012, 3, 1024-1029