Biosensor based on a silicon nanowire field-effect transistor functionalized by gold nanoparticles for the highly sensitive determination of prostate specific antigen
Introduction
During the past decades significant improvements in miniaturization of biomedical systems resulted in the establishment of nanoscale bioelectronic devices (Zhang and Lieber, 2016). Among these devices, semiconductor nanowire field-effect transistors (NW FETs) have been attracted a particular attention due to unique electronic properties, ultra small dimensions and label-free detection in real-time mode (Cui and Lieber, 2001, Zhang et al., 2009, Noor and Krull, 2014). The use of silicon for nanosensors has the advantages provided by its features: biocompatibility, unique electronic, optical, and mechanical properties (Peng et al., 2014). The sensitivity of such biosensors is extremely high, it can reach the level from micromoles (Lin et al., 2010) to amol (Maki et al., 2008) and even allows to achieve the detection of single molecules (Hahm and Lieber, 2004, Wang et al., 2005) or particles (Patolsky et al., 2004). NW based biosensors show the advantages in the registration of proteins at extremely low concentrations which is of great importance for early diagnostics of cancer, acute myocardial infarction, and other disorders (Azmi et al., 2014, Zhang et al., 2012, Kong et al., 2012).
Despite the fact that the use of NWs for biosensors is increasingly widespread, only a few of them were applied for the detection of analytes in real biological samples like blood (A. Kim et al., 2009; Stern et al., 2010). High ionic strength of biological fluids reduces the efficiency of conductivity detection on the surface of NWs. Gao et al. (2015) have recently shown that specific modification of silicon NW by a polymer layer of polyethelene glycol increases the effective screening length of the sensor and enables detection of biomolecules in high ionic strength solutions in real-time. In this paper, we report about a new functionalization technique for silicon by small size gold nanoparticles (GNPs) for the improvement of NW FETs electrical performance as peculiar properties of GNPs such as high surface-to-volume ratio, high surface energy, and conductivity were shown to facilitate an electron transfer between biospecific layer and the electrode surface (Liu et al., 2003). In our method we used 5 nm GNPs for the covalent immobilization of half-fragments of antibodies on gold through their own thiol groups. New functionalization method was compared with chemical modification by different organo-silanes. We have utilized NW FETs for the determination of prostate specific antigen (PSA), which is a molecular marker of prostate cancer. NW FET functionalized by GNPs showed the improved sensing performance and the widest detection range for PSA detection. Application of NW FET biosensors on the serum samples showed good correlation with the standard ELISA while significantly simplifying and reducing the analysis time.
Section snippets
Materials
Inorganic chemicals, 3-aminopropyltrimethoxysilane (APTMS), ethylendiaminetetraacetic acid (EDTA), 3-glycidopropyltriethoxysilane (GOPS), GOPS with thiol groups (GOPS-SH), 1,4-phenylendiizothiocyanate (PDITC), tetrachloroauric (III) acid, 3,3′5,5′-tetramethylbenzidine (TMB), Tween 20, bovine serum albumin (BSA), casein were purchased from Sigma (St. Louis, USA). PSA and two clones of mouse monoclonal antibodies (mAbs) to PSA were provided by JSC “NVO Immunotek” (Moscow, Russia). MAbs and PSA
Functionalization of silicon by covalently immobilized mAbs
The small size of nanodevices imposes certain requirements on the density and uniformity of the biorecognition layer. In order to achieve optimal density and uniform distribution of chemical groups for the covalent attachment of mAbs we compared different approaches for silane functionalization of silicon by: (a) aminopropyltrimetoxysilane (APTMS) in a combination with bifunctional reagent 1,4-phenylene diisothiocyanate (PDITC), (b) 3-glycidopropyltriethoxysilane (GOPS), (c) GOPS-SH followed by
Conclusions
We developed a label-free and fast assay based on the NW FETs for determination of PSA in human serum. NWs functionalization was performed by a new method using GOPS-SH and 5 nm GNPs, which provides covalent oriented attachment of antibody half-fragments via their thiol groups. The use of the GNPs results in improved electrical performance of the transistor and its higher sensitivity to pH. NW FETs demonstrated low limit of analyte detection together with the widest dynamic concentration range.
Acknowledgments
We thank Ivan Bozhiev for assistance in sample fabrication. The work was supported by the Russian Foundation for Basic Research (RFBR), Russia (Grants 13-04-01137 and 16-29-03266).
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