A graphene-based physiometer array for the analysis of single biological cells

Geraldine L C Paulus; Justin T. Nelson; Katherine Y. Lee; Qing Wang; Nigel F. Reuel; Brittany R. Grassbaugh; Sebastian Kruss; Markita P. Landry; Jeon Woong Kang; Emma Vander Ende; Jingqing Zhang; Bin Mu; Ramachandra R. Dasari; Cary F. Opel; K. Dane Wittrup; Michael S. Strano

doi:10.1038/srep06865

A graphene-based physiometer array for the analysis of single biological cells

Geraldine L C Paulus, Justin T. Nelson, Katherine Y. Lee, Qing Wang, Nigel F. Reuel, Brittany R. Grassbaugh, Sebastian Kruss, Markita P. Landry, Jeon Woong Kang, Emma Vander Ende, Jingqing Zhang, Bin Mu, Ramachandra R. Dasari, Cary F. Opel, K. Dane Wittrup, Michael S. Strano

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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.

Original language	English (US)
Article number	6865
Journal	Scientific reports
Volume	4
DOIs	https://doi.org/10.1038/srep06865
State	Published - Oct 31 2014

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Paulus, G. L. C., Nelson, J. T., Lee, K. Y., Wang, Q., Reuel, N. F., Grassbaugh, B. R., Kruss, S., Landry, M. P., Kang, J. W., Ende, E. V., Zhang, J., Mu, B., Dasari, R. R., Opel, C. F., Wittrup, K. D., & Strano, M. S. (2014). A graphene-based physiometer array for the analysis of single biological cells. Scientific reports, 4, Article 6865. https://doi.org/10.1038/srep06865

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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.",

author = "Paulus, {Geraldine L C} and Nelson, {Justin T.} and Lee, {Katherine Y.} and Qing Wang and Reuel, {Nigel F.} and Grassbaugh, {Brittany R.} and Sebastian Kruss and Landry, {Markita P.} and Kang, {Jeon Woong} and Ende, {Emma Vander} and Jingqing Zhang and Bin Mu and Dasari, {Ramachandra R.} and Opel, {Cary F.} and Wittrup, {K. Dane} and Strano, {Michael S.}",

note = "Funding Information: This work was supported in part by the U. S. Army Research Laboratory and the U. S. Army Research Office through the Institute for Soldier Nanotechnologies, under contract number W911NF-13-D-0001. Fluorescence activated cell sorting was partially funded by Cancer Center Support (core) Grant P30-CA14051 from the NCI. The higher-sensitivity Raman work was supported by the NIH National Institute of Biomedical Imaging and Bioengineering, grant P41EB015871-27 and by the MIT SkolTech initiative. We thank Professor Tom{\'a}s Palacios and Benjamin Mailly-Giacchetti for useful discussions about the pH dependence of graphene.",

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AU - Paulus, Geraldine L C

AU - Nelson, Justin T.

AU - Lee, Katherine Y.

AU - Wang, Qing

AU - Reuel, Nigel F.

AU - Grassbaugh, Brittany R.

AU - Kruss, Sebastian

AU - Landry, Markita P.

AU - Kang, Jeon Woong

AU - Ende, Emma Vander

AU - Zhang, Jingqing

AU - Mu, Bin

AU - Dasari, Ramachandra R.

AU - Opel, Cary F.

AU - Wittrup, K. Dane

AU - Strano, Michael S.

N1 - Funding Information: This work was supported in part by the U. S. Army Research Laboratory and the U. S. Army Research Office through the Institute for Soldier Nanotechnologies, under contract number W911NF-13-D-0001. Fluorescence activated cell sorting was partially funded by Cancer Center Support (core) Grant P30-CA14051 from the NCI. The higher-sensitivity Raman work was supported by the NIH National Institute of Biomedical Imaging and Bioengineering, grant P41EB015871-27 and by the MIT SkolTech initiative. We thank Professor Tomás Palacios and Benjamin Mailly-Giacchetti for useful discussions about the pH dependence of graphene.

PY - 2014/10/31

Y1 - 2014/10/31

N2 - 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.

AB - 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.

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A graphene-based physiometer array for the analysis of single biological cells

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