title: Macroporous mesh of nanoporous gold in electrochemical monitoring of superoxide release from skeletal muscle cells.
abstract: Real-time monitoring of metabolically relevant biochemicals released in minuscule amounts is of utmost diagnostic importance. Superoxide anion as a primary member of reactive oxygen species, has physiological and pathological effects that depend on its concentration and release rate. Here we present fabrication and successfully testing of a highly sensitive electrochemical biosensor featuring a three-dimensional macroporous mesh of nanoporous gold tailored to measure the dynamics of extracellular superoxide concentration. Wide and accessible surface of the mesh combined with high porosity of the thin nanoporous gold coating enables capturing the analyte in pico- to nano-molar ranges. The mesh is functionalized with cytochrome-c (cyt-c) and incorporated as a working electrode to measure the release rate of drug-induced superoxides from C2C12 cells through a porous membrane. The device displays a considerably improved superoxide sensitivity of 7.29nAnM-1cm-2and a low level of detection of 70pM. Such sensitivity is orders of magnitude higher than any similar enzyme-based electrochemical superoxide sensor and is attributed to the facile diffusion of the analyte through the well-spread nanofeatured gold skin. Superoxide generation rates captured from monolayer myoblast cultures containing about 4×104cells, varied from 1.0 to 9.0nMmin-1in a quasi-linear fashion as a function of drug concentration. This work provides a platform for the development of highly sensitive molecular electrochemical biosensors.
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai, 980-8577 Japan; Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139 USA.
authors.forename: Ramin
authors.initials: R
authors.lastname: Banan Sadeghian
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai, 980-8577 Japan.
authors.forename: Jiuhui
authors.initials: J
authors.lastname: Han
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai, 980-8577 Japan.
authors.forename: Serge
authors.initials: S
authors.lastname: Ostrovidov
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai, 980-8577 Japan.
authors.forename: Sahar
authors.initials: S
authors.lastname: Salehi
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139 USA; Department of Electrical Engineering, Faculty of Engineering, Majlesi Branch, Islamic Azad University, Esfahan, 86316-56451 Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Bahraminejad
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai, 980-8577 Japan.
authors.forename: Samad
authors.initials: S
authors.lastname: Ahadian
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai, 980-8577 Japan.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai, 980-8577 Japan; Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02139 USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115 USA; Department of Physics, Faculty of Science, King Abdulaziz University, Jeddah, 21569 Saudi Arabia; College of Animal Bioscience and Technology, Department of Bioindustrial Technologies, Konkuk University, Hwayang-dong, Kwangjin-gu, Seoul, 143-701 Republic of Korea. Electronic address: alik@bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation*; D002460:Cell Line; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism; D055664:Electrochemical Techniques / Q000295:instrumentation*; D004566:Electrodes; D004800:Enzymes, Immobilized / Q000737:chemistry / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D051379:Mice; D032446:Myoblasts / Q000737:chemistry* / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D016062:Porosity; D013481:Superoxides / Q000032:analysis* / Q000378:metabolism
chemical_list: D004800:Enzymes, Immobilized; D013481:Superoxides; D006046:Gold; D045304:Cytochromes c
keywords: Hierarchical nanostructure; Noninvasive electrochemical biosensor; Reactive oxygen species; Skeletal muscle cells; Superoxide anion monitoring