Metal coordination induced SERS nanoprobe for sensitive and selective detection of histamine in serum

Highlights

• Histamine has a strong affinity to Ni²⁺ through amino group and imidazole nitrogen.

• The method of evaporation-driven assembly of Au NPs array with high density hot spots is facile and convenient.

• NTA-Ni²⁺ functionalized Au NPs as SERS nanoprobe can realize sensitive and selective detection of HA.

• Au NPs-NTA-Ni²⁺ SERS nanoprobe allows for efficiently analysis and record of HA in complex specimen.

Abstract

Sensitivity and credibility detecting histamine (HA) as an important neurotransmitter in biofluids is of importance in analytical science and physiology. Surface-enhanced Raman spectroscopy (SERS) is able to realize the high sensitivity with single molecules level, but providing the high sensitivity for HA with a small cross section remains a challenge. Here we develop the metal complex-based SERS nanoprobe nitrilotriacetic acid-Ni²⁺ (NTA-Ni²⁺) combined with self-assemble Au NPs active substrates for sensitive detection of HA. The NTA-Ni²⁺ can capture the HA molecules close to Au NPs substrates and then amplify the Raman signals of HA owing to the formation of a complex of NTA-Ni²⁺-HA. The self-assemble Au film through the evaporation-driven method can provide the high-density hot spots substrate with high stability and reproducibility. The NTA-Ni²⁺ decorated Au NPs as nanoprobe responds to HA with 1 μM level of sensitivity. More importantly, the developed SERS nanoprobe composing of NTA-Ni²⁺ and self-assemble Au NPs can be utilized to detect and monitor the HA spiked into serum, indicating the potential prospect in analysis of HA in complex specimen.

Introduction

Neurotransmitters play pivotal roles in neurologic transmission of information, therefore the unbalance of neurotransmitter levels can cause many clinical diseases. Up to now, about 100 neurotransmitters have been known [1]. Histamine (HA) as the biogenic amines, synthesized from histidine by histidine decarboxylase, is associated with several brain-related functions such as allergic, inflammatory responses and neuromodulation etc. [2,3] Also, it is responsible for majority of health problems associated with seafood consumption occurring worldwide [[4], [5], [6]]. Consequently, various approaches have been developed for the credible and sensitive determination of histamine in vivo or in vitro. Classical analytical methods such as liquid chromatography, capillary electrophoresis, can provide the advantages of separation and enrichment. Nonetheless, they always suffer from a long operation time and the limited spatial resolution. The widely-adopted fluorescence-based optical methods are possible to overcome above mentions with fast response time and simple procedures, whereas photobleaching and photodegradation are the critical obstacles. Thus, many efforts should be devoted to develop facile, rapid, and sensitive analytical strategies for detection of histamine.

Surface-enhanced Raman Spectroscopy (SERS) has demonstrated multiple advantages for bioanalysis since the high sensitivity and fingerprint information. Particularly, SERS technique can provide a narrow bandwidth than that of fluorescence emission, in which it enables the convenient multiplex detection in serum or urine [7,8]. In comparison with label SERS strategy, the label-free SERS detection always can clearly reflect the molecular fingerprint information and obtain spectra components of conformation and orientation information [9,10]. However, the majority of biomolecules such as HA [11,12] has a small Raman cross section and low polarizability with weak SERS response, as a consequence, the SERS label is necessary to express Raman signals of above analytes with the advantages of capturing and analyzing targets [[13], [14], [15], [16]]. For example, the SERS nanoprobe of 4-mercaptophenol-functionalized gold flowers has been used for biosensing of ClO⁻ and GSH based on the redox reaction [17]. Another example was the endogenous H₂S in living cells has been monitored by 4-acetamidobenzenesulfonyl azide-functionalized gold nanoparticles nanoprobe through the transformation of azide groups to amino groups [18]. HA with three functional groups, amino group and imidazole nitrogen, are the potential ability for coordination of metal ions [19]. Base on the report of nuclear magnetic resonance (NMR), histamine has a strong affinity for Ni²⁺ to form a histamine-Ni²⁺ complex with the stability constants (log K_a) of 10⁶ M⁻¹ [20], which indicates the UV–vis adsorption at wavelength of 500–600 nm [21]. Therefore, the Ni⁻metal complex can be acted as the ideal SERS probe for capturing and detecting the HA.

It is well known that the Raman intensity of analytes placing in close proximity to hot spots of SERS substrate, can be dramatically amplified [22,23]. However, the random distribution of hot spots on SERS substrates, only part of the molecules can be really accounted for. Thus, to obtain highly sensitive and reliable SERS signals, there have been several attempts to assemble high-density hot spots SERS substrates using different techniques [24,25]. The process of formation of well-ordered two dimensional particle arrays through evaporation-driven is facile and convenient [26,27], which includes two stages: nucleus formation from the action of attractive capillary immersion forces and crystal growth through the convective particle flux [28]. Considering the simplicity and efficiency, the evaporation-driven self-assembly method has been adopted to achieve high-quality planar colloidal films, further providing credible and stable SERS measurements.

In this report, inspired by the histamine-Ni²⁺ complex, the metal complex-based SERS nanoprobe nitrilotriacetic acid-Ni²⁺ (NTA-Ni²⁺) combined with self-assemble Au NPs active substrates has been demonstrated to capture and enhance the Raman signal of HA. On one hand, the metal complex NTA-Ni²⁺ can be acted as probe to capture the HA close to hot spots for amplifying the Raman signals owing to the presence of –NH₂ group and the function of organic chelating agents. On the other hand, the self-assembled Au NPs substrates with uniform and high density-hot spot offers stable and credible SERS signals. As a consequence, the NTA-Ni²⁺ probe decorated Au NPs film as SERS nanoprobe is convenient and beneficial to enhance Raman signals of HA with high sensitivity and stability. Furthermore, the practical applications of nanoprobe is validated by the detection of HA in serum with the detection limits of 1.0 μM level. The developed SERS nanoprobe has the prospects for sensitive and qualitative identification of HA molecules involving in biological specimen.