Elsevier

Biosensors and Bioelectronics

Volume 97, 15 November 2017, Pages 278-284
Biosensors and Bioelectronics

Near-infrared photoluminescence biosensing platform with gold nanorods-over-gallium arsenide nanohorn array

https://doi.org/10.1016/j.bios.2017.06.009Get rights and content

Highlights

  • The well-defined nanohorn-like GaAs array was developed using etching technique.

  • The GaAs array provided an improved PL signal and high biorecognition activity.

  • The ultrasensitive near-infrared PL detection of DNA and thrombin was realized.

Abstract

The near-infrared (NIR) optical detection of biomolecules with high sensitivity and reliability have been expected, however, it is still a challenge. In this work, we present a gold nanorods (AuNRs)-over-gallium arsenide nanohorn-like array (GaAs NHA) system that can be used for the ultrasensitive and specific NIR photoluminescence (PL) detection of DNA and proteins. The fabrication of GaAs NHA involved the technique of colloidal lithography and inductively coupled plasma dry etching, yielding large-area and well-defined nanostructural array, and exhibiting an improved PL emission compared to the planar GaAs substrate. Importantly, we found that the DNA-bridged AuNRs attachment on NHA could further improve the PL intensity from GaAs, and thereby provide the basis for the NIR optical sensing of biological analytes. We demonstrated that DNA and thrombin could be sensitively and specifically detected, with the detection limit of 1 pM for target DNA and 10 pM for thrombin. Such ultrasensitive NIR optical platform can extend to the detection of other biomarkers and is promising for clinical diagnostics.

Introduction

Ultrasensitive, specific and reliable detection of biomarkers is of great importance in gene profiling, drug screening, and clinic diagnostics, because of their close association with various biological processes and diseases. In this regard, many molecular detection approaches have been developed, such as electrochemistry, colorimetry, fluorescence, surface plasmon resonance (SPR) and electric signals, etc. (Homola, 2008, Liu et al., 2009, Gopinath et al., 2014, Howes et al., 2014, Song et al., 2014, Lim and Gao, 2016, Smith et al., 2017). Among them, fluorescence (including photoluminescence, PL)-based assays are among the most preferred techniques in the development of biosensing systems, owing to their simple and great convenience and reliability (Homola, 2008, Hilderbrand and Weissleder, 2010, Howes et al., 2014). Extensive studies have focused on the integration with signal amplification strategies, and the improving on the sensing capability in the complex fluids (e.g., the rapid detection of biomarkers in blood at pM concentrations), but there are still several important roadblocks that limit their practical applications. First, many analytes in real-life samples are in the complicated biological fluids (e.g., blood, serum), while the fluorescence detection in complex fluid relies on extensive sampling pretreatment (e.g., concentration and separation) because of the nonspecific binding, which significantly reduce the testing efficiency and accuracy (Song et al., 2014). Second, the most current state-of-the-art amplification strategies, including various isothermal amplification techniques, can offer high sensitivity and in some cases high selectivity, but often are costly, laborious and time-consuming (Connolly and Trau, 2010, Guo et al., 2015). Additionally, most of the biosensors for the fluorescence detection of biomarkers were fabricated by using sandwich-type methods, in which the process are complicated and the insufficient limit of detection (LOD) significantly limit the practical applications (Gopinath et al., 2014). It is thus very interesting and valuable to seek for a simple and robust biosensing platform for ultrasensitive detection of biomarkers.

Currently, considerable interest has focus on the near-infrared (NIR) fluorescent biosensing platforms for biological imaging and detection, as the NIR spectral range within 700–1700 nm is referred to as the “biological window”, in which the light absorbance, scattering and auto-fluorescence of tissues, blood and water are at a minimum (Hilderbrand and Weissleder, 2010, Malic et al., 2011, Hong et al., 2017). Thus, the biosensors operating in the NIR region can avoid interference from biological media and thereby facilitate relatively interference-free sensing. However, only a limited number of organic fluorophores, such as IRDye78, Cy7 and indocyanine green, are suitable in this range, and they also have some drawbacks such as relatively low quantum yield, easy photobleaching and broad emission spectra, which significantly limit their effectiveness in bioassays (Resch-Genger et al., 2008, Hong et al., 2017). Semiconductor nanostructures (including quantum dots, quantum nanowires and quantum nanowells) are promising fluorescent materials for biosensors, because of their many advantages over conventional organic fluorophores such as high PL efficiency, tunable emission wavelengths narrower emission bandwidths and photostability (Boghossian et al., 2011, Gao et al., 2004, Rosini and Magri, 2010). However, so far the applications of NIR semiconductor nanomaterials in biosensing and clinic diagnostics field still encounter a number of scientific and engineering challenges, such as in the controllable and reproducible detection of biomarkers with low abundance.

Owing to their excellent NIR PL and controllable surface modification, we earlier utilized gallium arsenide (GaAs) as biosensing platform to monitor the DNA hybridization events, and integrated with the DNA-decorated gold nanoparticles (AuNPs) to modulate the PL emission of GaAs, achieving the detection of nM concentration of target DNA (Tang et al., 2013). More recently, we further depicted that the use of DNA scaffold as a bridge to control the distance of AuNPs away from GaAs, enabling a DNA length-dependent PL enhancement from GaAs (Yu et al., 2016). Actually, the integration of surface plasmons (SPs) from plasmonic nanoparticles with semiconductor nanomaterials is of interest for both fundamentals study and potential applications in optics, devices and catalytic reactions. In our case, it is expected that the AuNPs would increase the density of states and the spontaneous emission in the GaAs because of the metal-enhanced fluorescence effect (Okamoto et al., 2004, Jin and Gao, 2009, Zhou et al., 2009). Despite these progresses, the planar GaAs substrates have not fulfilled their promise as NIR optical sensing platform as their limited PL emission efficiency and thereby insufficient sensitivity for the detection of trace biomarkers (Tang et al., 2013). As reported, the nanostructured semiconductors normally have a higher quantum efficiency, and thus are potentially serve as a more sensitive biosensing platforms. For example, the GaAs nanowires had been synthesized and the investigation on their emission properties suggested that the higher quantum efficiency could enhance the PL emission of the semiconductor (Fortuna et al., 2008, Rosini and Magri, 2010). Furthermore, compared to the flat surfaces or micron-scale pores/channels, semiconducting nanostructures with a higher porosity with submicron or nano-sized features were more favorable to loading more active biomolecules. Therefore, a three-dimensional (3D) nanostructured GaAs surface would be ideally suited for this biosensing system (Barnes et al., 2003). To the best of our knowledge, however, little effort has been expended on the demonstration of enhanced PL emission with plasmonic NPs on the above GaAs substrates, and the further NIR optical biosensing application remains to be further explored (Barnes et al., 2003, Okamoto et al., 2004, Shahbazyan, 2012, Guo et al., 2015).

In this work, we report a gold nanorods (AuNRs)-over-GaAs nanohorn-like arrays (NHA) system for specific and ultrasensitive detection of targets of DNA and proteins. A large-area well-defined GaAs NHA nanostructure has been designed and fabricated using the colloidal NPs array-templated dry etching technique. We also demonstrated the nanostructured GaAs array possessed an enhanced the PL emission compared to the planar GaAs substrate, and importantly the attachment of AuNRs could further improve the PL intensity. In addition, this well-ordered and uniform nanostructured GaAs platform could provide reproducible PL signals and had high bio-recognition activity for target biomarkers. Based on these findings, we proposed the AuNRs-over-GaAs NHA systems (i.e., DNA-bridged AuNRs attachment on GaAs NHA) for enhancing the NIR PL emission, and explored their biosensing performance for biological analytes (e.g., DNA and thrombin) even in the serum samples.

Section snippets

Materials

The single-crystal n+-GaAs (100) substrates used in the study were purchased from AXT, Inc. Tetrachloroauric (III) acid trihydrate (HAuCl4·3H2O, 99.999%), L-ascorbic acid (99%), tris(2-carboxyethyl)phosphine hydrochloride (TCEP) and mercaptohexanol (MCH) were purchased from Sigma-Aldrich (China). Monodisperse silica nanospheres (NSs) with diameters of ~ 500 nm were obtained from Base Line Co. (2.5% w/v, coefficient of variation less than 5%). Thrombin (from human plasma), bovine serum albumin

Fabrication and characterization of GaAs nanohorn array

The GaAs nanohorn-like array was fabricated by the combination of colloidal lithography and inductively coupled plasma (ICP) dry etching, as described in the experimental section and schematically represented in Fig. 1A. Typically, the silica NSs assembly on GaAs wafer had iridescent color under different angles of view (Fig. 1B). The specific light diffraction indicates the formation of a periodic array on the GaAs substrate. Fig. 1C presents the typical corresponding scanning electron

Conclusion

To sum up, we have demonstrated that the AuNRs-over-GaAs NHA system using DNA scaffold as a bridge can be employed as NIR optical biosensing platform for the specific and sensitive detection of the biomarkers, such as DNA and thrombin. Compared to other conventional optical sensing systems, this AuNRs-over-GaAs NHA platform possesses several unique features, resulting in the improved sensing performance. First, the AuNRs-over-GaAs NHA system provides reproducible and significantly improved PL

Notes

The authors declare no competing financial interest.

Acknowledgment

This work was financially supported by National Natural Science Foundation of China (No. 61405176), Natural Sciences Fund of Zhejiang Province (No. LY14B050004) the Scientific Research Start-up Fund of Zhejiang Agriculture and Forestry University (No. 2015FR012), the Scientific and Technology Project for Analysis and Test of Zhejiang Provincial Department of Technology (No. 2015C37071) and the Fundamental Research Funds for the Central Universities (No. 2016QNA5001). Y.M.Z. and T.J. contributed

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