title: Cancer Cell Hyperactivity and Membrane Dipolarity Monitoring via Raman Mapping of Interfaced Graphene: Toward Non-Invasive Cancer Diagnostics.
abstract: Ultrasensitive detection, mapping, and monitoring of the activity of cancer cells is critical for treatment evaluation and patient care. Here, we demonstrate that a cancer cell's glycolysis-induced hyperactivity and enhanced electronegative membrane (from sialic acid) can sensitively modify the second-order overtone of in-plane phonon vibration energies (2D) of interfaced graphene via a hole-doping mechanism. By leveraging ultrathin graphene's high quantum capacitance and responsive phononics, we sensitively differentiated the activity of interfaced Glioblastoma Multiforme (GBM) cells, a malignant brain tumor, from that of human astrocytes at a single-cell resolution. GBM cell's high surface electronegativity (potential ∼310 mV) and hyperacidic-release induces hole-doping in graphene with a 3-fold higher 2D vibration energy shift of approximately 6 ± 0.5 cm-1than astrocytes. From molecular dipole-induced quantum coupling, we estimate that the sialic acid density on the cell membrane increases from one molecule per ∼17 nm2to one molecule per ∼7 nm2. Furthermore, graphene phononic response also identified enhanced acidity of cancer cell's growth medium. Graphene's phonon-sensitive platform to determine interfaced cell's activity/chemistry will potentially open avenues for studying activity of other cancer cell types, including metastatic tumors, and characterizing different grades of their malignancy.
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Bijentimala
authors.initials: B
authors.lastname: Keisham
authors.affiliation: Department of Neurosurgery, University of Illinois at Chicago , Chicago, Illinois 60612, United States.
authors.forename: Arron
authors.initials: A
authors.lastname: Cole
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Phong
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Department of Neurosurgery, University of Illinois at Chicago , Chicago, Illinois 60612, United States.
authors.forename: Ankit
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Vikas
authors.initials: V
authors.lastname: Berry
mesh_terms: D001253:Astrocytes / Q000166:cytology; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000473:pathology; D016764:Cell Polarity / Q000502:physiology; D005909:Glioblastoma / Q000473:pathology*; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D060787:Neoplasm Grading; D013059:Spectrum Analysis, Raman / Q000295:instrumentation* / Q000379:methods*
chemical_list: D006108:Graphite
keywords: GBM; Raman; cancer; graphene; phonon