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Microfluidic Immuno-Biochip for Detection of Breast Cancer Biomarkers Using Hierarchical Composite of Porous Graphene and Titanium Dioxide Nanofibers
journal contribution
posted on 2016-07-21, 00:00 authored by Md. Azahar Ali, Kunal Mondal, Yueyi Jiao, Seval Oren, Zhen Xu, Ashutosh Sharma, Liang DongWe 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.
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Breast Cancer BiomarkersnTiO 2 yieldsanatase nTiO 2EDCGFelectrochemical impedance spectroscopynTiO 2electrochemical sensor applicationsreceptor tyrosine kinasesTitanium Dioxide Nanofiberstarget ErbB 2 antigenmicrofluidicepidermal growth factor receptor 2gold counter electrodeEGFRsurfacebreast cancer biomarkerscharge transfer resistance