A Graphene-Based Physiometer Array for the Analysis of Single Biological Cells

A significant advantage of graphene as a biosensor is its potential to display a continuum of independent and aligned sensors at a specific interface. Here, we demonstrate a nanoscale version of a micro-physiometer – a device that measures cellular metabolic activity from the local acidification rate.  Graphene can function as an array of independent pH sensors enabling subcellular and spatiotemporal detection of single biological cells.  Raman spectroscopy shows that aqueous protons (H⁺) p-dope graphene – in agreement with established doping trajectories, and that graphene displays two distinct pKa values (2.9 and 14.2). The cell physiometer allows micron spatial resolution of cellular acidification, differentiating immunoglobulin (IgG) producing human embryonic kidney (HEK) cells from non-IgG-producing control cells.  Graphene also allows single cell counting in a population for mapping phenotypic diversity, variances in metabolic rate, and cellular adhesion. Finally we show the proposed platform can be extended to the detection of other analytes, e.g. dopamine. This work motivates the application of graphene as a unique biosensor array for cellular and sub-cellular interrogation.