Hierarchical Electrohydrodynamic Structures for Surface‐Enhanced Raman Scattering

Surface enhanced Raman scattering (SERS) is a well‐established spectroscopic technique that requires nanoscale metal structures to achieve high signal sensitivity. While most SERS substrates are manufactured by conventional lithographic methods, the development of a cost‐effective approach to create nanostructured surfaces is a much sought‐after goal in the SERS community. Here, a method is established to create controlled, self‐organized, hierarchical nanostructures using electrohydrodynamic (HEHD) instabilities. The created structures are readily fine‐tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements. HEHD pattern formation enables the fabrication of multiscale 3D structured arrays as SERS‐active platforms. Importantly, each of the HEHD‐patterned individual structural units yield a considerable SERS enhancement. This enables each single unit to function as an isolated sensor. Each of the formed structures can be effectively tuned and tailored to provide high SERS enhancement, while arising from different HEHD morphologies. The HEHD fabrication of sub‐micrometer architectures is straightforward and robust, providing an elegant route for high‐throughput biological and chemical sensing.     

Sensitive and Reproducible Immunoassay of Multiple Mycotoxins Using Surface‐Enhanced Raman Scattering Mapping on 3D Plasmonic Nanopillar Arrays

A surface‐enhanced Raman scattering‐based mapping technique is reported for the highly sensitive and reproducible analysis of multiple mycotoxins. Raman images of three mycotoxins, ochratoxin A (OTA), fumonisin B (FUMB), and aflatoxin B1 (AFB1) are obtained by rapidly scanning the surface‐enhanced Raman scattering (SERS) nanotags‐anchoring mycotoxins captured on a nanopillar plasmonic substrate. In this system, the decreased gap distance between nanopillars by their leaning effects as well as the multiple hot spots between SERS nanotags and nanopillars greatly enhances the coupling of local plasmonic fields. This strong enhancement effect makes it possible to perform a highly sensitive detection of multiple mycotoxins. In addition, the high uniformity of the densely packed nanopillar substrate minimizes the spot‐to‐spot fluctuations of the Raman peak intensity in the scanned area when Raman mapping is performed. Consequently, this makes it possible to gain a highly reproducible quantitative analysis of mycotoxins. The limit of detections (LODs) are determined to be 5.09, 5.11, and 6.07 pg mL^?1 for OTA, FUMB, and AFB1, and these values are approximately two orders of magnitude more sensitive than those determined by the enzyme‐linked immunosorbent assays. It is believed that this SERS‐based mapping technique provides a facile tool for the sensitive and reproducible quantification of various biotarget molecules.     

Ultrasensitive Surface‐Enhanced Raman Spectroscopy Detection Based on Amorphous Molybdenum Oxide Quantum Dots

Surface‐enhanced Raman spectroscopy (SERS) based on plasmonic semiconductive material has been proved to be an efficient tool to detect trace of substances, while the relatively weak plasmon resonance compared with noble metal materials restricts its practical application. Herein, for the first time a facile method to fabricate amorphous H_xMoO₃ quantum dots with tunable plasmon resonance is developed by a controlled oxidization route. The as‐prepared amorphous H_xMoO₃ quantum dots show tunable plasmon resonance in the region of visible and near‐infrared light. Moreover, the tunability induced by SC CO₂ is analyzed by a molecule kinetic theory combined with a molecular thermodynamic model. More importantly, the ultrahigh enhancement factor of amorphous H_xMoO₃ quantum dots detecting on methyl blue can be up to 9.5 × 10⁵ with expending the limit of detection to 10^?9 m . Such a remarkable porperty can also be found in this H_xMoO₃‐based sensor with Rh6G and RhB as probe molecules, suggesting that the amorphous H_xMoO₃ quantum dot is an efficient candidate for SERS on molecule detection in high precision.     

Volume‐Enhanced Raman Scattering Detection of Viruses

Virus detection and analysis are of critical importance in biological fields and medicine. Surface‐enhanced Raman scattering (SERS) has shown great promise in small molecule and even single molecule detection, and can provide fingerprint signals of molecules. Despite the powerful detection capabilities of SERS, the size discrepancy between the SERS “hot spots” (generally, <10 nm) and viruses (usually, sub‐100 nm) yields poor detection reliability of viruses. Inspired by the concept of molecular imprinting, a volume‐enhanced Raman scattering (VERS) substrate composed of hollow nanocones at the bottom of microbowls (HNCMB) is developed. The hollow nanocones of the resulting VERS substrates serve a twofold purpose: 1) extending the region of Raman signal enhancement from the nanocone surface (e.g., surface “hot spots”) to the hollow area within the cone (e.g., volume “hot spots”)—a novel method of Raman signal enhancement, and 2) directing analyte such as viruses of a wide range of sizes to those VERS “hot spots” while simultaneously increasing the surface area contributing to SERS. Using HNCMB VERS substrates, greatly improved Raman signals of single viruses are demonstrated, an achievement with important implications in disease diagnostics and monitoring, biomedical fields, as well as in clinical treatment.     

Tracking Drug‐Induced Epithelial–Mesenchymal Transition in Breast Cancer by a Microfluidic Surface‐Enhanced Raman Spectroscopy Immunoassay

Epithelial–mesenchymal transition (EMT) is a primary mechanism for cancer metastasis. Detecting the activation of EMT can potentially convey signs of metastasis to guide treatment management and improve patient survival. One of the classic signatures of EMT is characterized by dynamic changes in cellular expression levels of E‐cadherin and N‐cadherin, whose soluble active fragments have recently been reported to be biomarkers for cancer diagnosis and prognosis. Herein, a microfluidic immunoassay (termed “SERS immunoassay”) based on sensitive and simultaneous detection of soluble E‐cadherin (sE‐cadherin) and soluble N‐cadherin (sN‐cadherin) for EMT monitoring in patients' plasma is presented. The SERS immunoassay integrates in situ nanomixing and surface‐enhanced Raman scattering readout to enable accurate detection of sE‐cadherin and sN‐cadherin from as low as 10 cells mL^?1. This assay enables tracking of a concurrent decrease in sE‐cadherin and increase in sN‐cadherin in breast cancer cells undergoing drug‐induced mesenchymal transformation. The clinical potential of the SERS immunoassay is further demonstrated by successful detection of sE‐cadherin and sN‐cadherin in metastatic stage IV breast cancer patient plasma samples. The SERS immunoassay can potentially sense the activation of EMT to provide early indications of cancer invasions or metastasis.     

Aptatag‐Based Multiplexed Assay for Protein Detection by Surface‐Enhanced Raman Spectroscopy

Silver‐nanoparticle dimers held together by a Raman reporter, capped with DNA aptamers and stabilized by polyethylene glycol chains, can be used to develop a multiplexed heterogeneous bioassay for protein detection with high sensitivity and selectivity.     

Hybrid Structures for Surface‐Enhanced Raman Scattering: DNA Origami/Gold Nanoparticle Dimer/Graphene

A combination of three innovative materials within one hybrid structure to explore the synergistic interaction of their individual properties is presented. The unique electronic, mechanical, and thermal properties of graphene are combined with the plasmonic properties of gold nanoparticle (AuNP) dimers, which are assembled using DNA origami nanostructures. This novel hybrid structure is characterized by means of correlated atomic force microscopy and surface‐enhanced Raman scattering (SERS). It is demonstrated that strong interactions between graphene and AuNPs result in superior SERS performance of the hybrid structure compared to their individual components. This is particularly evident in efficient fluorescence quenching, reduced background, and a decrease of the photobleaching rate up to one order of magnitude. The versatility of DNA origami structures to serve as interface for complex and precise arrangements of nanoparticles and other functional entities provides the basis to further exploit the potential of the here presented DNA origami–AuNP dimer–graphene hybrid structures.