title: A graphene-based physiometer array for the analysis of single biological cells.
abstract: A significant advantage of a graphene biosensor is that it inherently represents a continuum of independent and aligned sensor-units. We demonstrate a nanoscale version of a micro-physiometer - a device that measures cellular metabolic activity from the local acidification rate. Graphene functions as a matrix of independent pH sensors enabling subcellular detection of proton excretion. Raman spectroscopy shows that aqueous protons p-dope graphene - in agreement with established doping trajectories, and that graphene displays two distinct pKa values (2.9 and 14.2), corresponding to dopants physi- and chemisorbing to graphene respectively. The graphene physiometer allows micron spatial resolution and can differentiate immunoglobulin (IgG)-producing human embryonic kidney (HEK) cells from non-IgG-producing control cells. Population-based analyses allow mapping of phenotypic diversity, variances in metabolic activity, and cellular adhesion. Finally we show this platform can be extended to the detection of other analytes, e.g. dopamine. This work motivates the application of graphene as a unique biosensor for (sub)cellular interrogation.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Geraldine L C
authors.initials: GL
authors.lastname: Paulus
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Nelson
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Katherine Y
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Qing Hua
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Reuel
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Brittany R
authors.initials: BR
authors.lastname: Grassbaugh
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kruss
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Markita P
authors.initials: MP
authors.lastname: Landry
authors.affiliation: Laser Biomedical Research Center, G.R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Jeon Woong
authors.initials: JW
authors.lastname: Kang
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Vander Ende
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Mu
authors.affiliation: Laser Biomedical Research Center, G.R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Ramachandra R
authors.initials: RR
authors.lastname: Dasari
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Cary F
authors.initials: CF
authors.lastname: Opel
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: K Dane
authors.initials: KD
authors.lastname: Wittrup
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Strano
mesh_terms: D000465:Algorithms; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods*; D006108:Graphite; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008962:Models, Theoretical; D013059:Spectrum Analysis, Raman
chemical_list: D006108:Graphite