title: Microfluidic Immuno-Biochip for Detection of Breast Cancer Biomarkers Using Hierarchical Composite of Porous Graphene and Titanium Dioxide Nanofibers.
abstract: We report on a label-free microfluidic immunosensor with femtomolar sensitivity and high selectivity for early detection of epidermal growth factor receptor 2 (EGFR2 or ErbB2) proteins. This sensor utilizes a uniquely structured immunoelectrode made of porous hierarchical graphene foam (GF) modified with electrospun carbon-doped titanium dioxide nanofibers (nTiO2) as an electrochemical working electrode. Due to excellent biocompatibility, intrinsic surface defects, high reaction kinetics, and good stability for proteins, anatase nTiO2 are ideal for electrochemical sensor applications. The three-dimensional and porous features of GF allow nTiO2 to penetrate and attach to the surface of the GF by physical adsorption. Combining GF with functional nTiO2 yields high charge transfer resistance, large surface area, and porous access to the sensing surface by the analyte, resulting in new possibilities for the development of electrochemical immunosensors. Here, the enabling of EDC-NHS chemistry covalently immobilized the antibody of ErbB2 (anti-ErbB2) on the GF-nTiO2 composite. To obtain a compact sensor architecture, the composite working electrode was designed to hang above the gold counter electrode in a microfluidic channel. The sensor underwent differential pulse voltammetry and electrochemical impedance spectroscopy to quantify breast cancer biomarkers. The two methods had high sensitivities of 0.585 μA μM(-1) cm(-2) and 43.7 kΩ μM(-1) cm(-2) in a wide concentration range of target ErbB2 antigen from 1 × 10(-15) M (1.0 fM) to 0.1 × 10(-6) M (0.1 μM) and from 1 × 10(-13) M (0.1 pM) to 0.1 × 10(-6) M (0.1 μM), respectively. Utilization of the specific recognition element, i.e., anti-ErbB2, results in high specificity, even in the presence of identical members of the EGFR family of receptor tyrosine kinases, such as ErbB3 and ErbB4. Many promising applications in the field of electrochemical detection of chemical and biological species will derive from the integration of the porous GF-nTiO2 composite into microfluidic devices.
authors.affiliation: Department of Electrical and Computer Engineering, Iowa State University , Ames, Iowa 50011, United States.
authors.forename: Md Azahar
authors.initials: MA
authors.lastname: Ali
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Kunal
authors.initials: K
authors.lastname: Mondal
authors.affiliation: Department of Electrical and Computer Engineering, Iowa State University , Ames, Iowa 50011, United States.
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Electrical and Computer Engineering, Iowa State University , Ames, Iowa 50011, United States.
authors.forename: Seval
authors.initials: S
authors.lastname: Oren
authors.affiliation: Department of Electrical and Computer Engineering, Iowa State University , Ames, Iowa 50011, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Chemical Engineering, Indian Institute of Technology Kanpur , Kanpur 208016, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Electrical and Computer Engineering, Iowa State University , Ames, Iowa 50011, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
mesh_terms: D014408:Biomarkers, Tumor; D015374:Biosensing Techniques; D001943:Breast Neoplasms; D055664:Electrochemical Techniques; D004566:Electrodes; D006108:Graphite; D006801:Humans; D044085:Microfluidics; D057139:Nanofibers; D016062:Porosity; D014025:Titanium
chemical_list: D014408:Biomarkers, Tumor; C009495:titanium dioxide; D006108:Graphite; D014025:Titanium
keywords: biosensor; cancer immunodiagnostics; carbon-doped titanium dioxide; electrochemical detection; graphene foam; microfluidics