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  • br PSA br Saliva br Serum br


    Signal-off immunosensor 
    In this study, a simple and lable-free voltammetric immunosensor was successfully developed for the ultrasensitive detection of prostate specific antigen (PSA). To do this, multiwalled carbon nanotube (MWCNT)/L-histidine functionalized reduced graphene oxide (His-rGO) was demonstrated as a bifunc-tional nanoplatform for covalently attaching thionine redox indicator and anti-PSA antibody (Ab). The MWCNT enhanced electrical conductivity and facilitated the electron transfer between thionine and the glassy carbon electrode. While, the presence of anti-PSA antibody blocked the electron transfer of thionine and decreased redox signals. The principle response of proposed immunosensor was based on the selective interaction of PSA with thionine-NH2 -GO−COOH-Ab. This selective interaction led to further decrease of response current of attached electrochemical probe. The liner calibration curve for tumor marker determination was 10 fg mL−1 –20 ng mL−1 (R2 = 0.996). Under optimized conditions, the immunosensor was able to selectively detect PSA with a limit of detection (LOD) of 2.8 fg mL−1 at 3 . The relative standard deviations (RSDs) for single-electrode repeatability and electrode-to-electrode repro-ducibility were less than 2.9% and 5.7% (n = 5), respectively. Furthermore, the as-proposed immunosensor showed excellent performance in detection of PSA in the human serum and saliva samples, which implies that the current strategy has a promising feature for the clinical assessment of tumor marker status in patients with prostate cancer.
    Published by Elsevier B.V. This is an open access article under the CC BY license (http://
    1. Introduction
    Prostate-specific antigen (PSA), a single-chain glycoprotein secreted by the epithelial TUDCA of the prostate gland, is present in blood serum of healthy men, but cancer increases serum levels of PSA and is therefore used as a non-invasive biomarker by clini-cians. The typical PSA cutoff level in serum regarding to suspicious prostate cancer is 4 ng mL−1 [1]. However, there is a controversy over this cutoff with demands to use age- and even race-specific thresholds. Findings from the Prostate Cancer Prevention Trial (PCPT), identified many men with PSA levels <4.0 ng mL−1 who had cancer [2]. This finding has resulted in urgent damands to lower cutoffs up to 2.5 ng mL−1 or even lower. In addition to prostate cancer, a number of benign (not cancerous) conditions may cause
    ∗ Corresponding authors. E-mail addresses: [email protected], [email protected] (L. Farzin),
    [email protected] (M. Shamsipur). 
    a rise in PSA level. The most frequent benign prostate conditions that cause an elevation in PSA level are prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH) (enlargement of the prostate). Therefore, early and accurately detection of this biomarker plays a critical role in the treatment of different types of prostate problems, especially prostate cancer. Several method-ological improvements have been made in the field of PSA detection such as enzyme-linked immuno-sorbent assay (ELISA) [3], radioim-munoassay [4] and sensing methods [1]. Most of the biosensing devices for PSA detection are based on aptamers (aptasensors) [1,5] and antibodies (immunosensors) [1].
    A variety of immunosensing technologies including fluo-rescence immunosensors [6], surface plasmon resonance (SPR) immunosensors [7], surface-enhanced Raman scattering-based immunoassays [8] and electrochemical immunosensors [1] have been developed for the quantitative analysis of PSA. Among these, electrochemical immunosensors have received enough interest without some drawbacks such as being time-consuming, needing expensive instruments as well as skillful operators. Electrochemical
    0731-7085/Published by Elsevier B.V. This is an open access article under the CC BY license (
    techniques are the most desired systems with excellent sensitivity, rapidity, portability and ease of handling. Currently, electrochem-ical immunosensing technology has been spread worldwide in a fairly mature way. In this field, signal amplifying strategies and new nanoplatforms for immobilization of antibody are of great value. The signal amplifying platforms can directly determine such biosensing properties as including sensitivity, precision and ease of preparation.
    Graphene oxide (GO) is a novel type of two-dimensional nano-materials with honeycomb crystal lattices that are based on a form like the benzene six-membered ring [9]. It has been considered as a “rising star” carbon nanosheet in the biosensing devices because of its high surface area (theoretically 2630 m2 g−1 for single-layer graphene), strong mechanical strength, low density and good elec-trical conductivity [10]. Because of high conductivity arising from free movement of electrons in the graphene planes and a wide potential window, the use of graphene derivatives in modified elec-trodes can promote the electron transfer [11]. This charecteristic leads to platforms with excellent electrocatalytic properties.