Design of plasmonic nanomaterials for diagnostic spectrometry

Abstract

Molecular diagnostics relies on the efficient extraction of biomarker information from the given bio-systems. Plasmonic nanomaterials with tailored structural parameters are promising for the development of biomarker assays due to enrichment effect and signal enhancement. Herein, we overview the recent progress on the development of plasmonic nanomaterials for diagnostic spectrometry, encompassing the interface, mechanism, and application of these materials. For interface, we summarized the types of plasmonic nanomaterials used as interfaces between different materials and light. For mechanism, we descirbe the key parameters (e.g., hot carriers and heat) that characterize the plasmonic effect of materials. For application, we highlighted recent advances in matrix assisted laser desorption/ionization mass spectrometry (MALDI MS) and surface enhanced Raman spectroscopy (SERS) toward precision in in vitro and in vivo diagnostics. We foresee the upcoming era of precision diagnostics by nano-assisted spectrometry methods in both academy and industry, which will require the interest and effort of scientists with diverse backgrounds.

Fig. 1. Schematics of the development of plasmonic nanomaterials for diagnostic spectrometry. We summarize the types of plasmonic nanomaterials, addressing the interface between different materials and light. The mechanism demonstrating key parameters such a generation of hot carriers, heat, surface plasmon polariton, and interband transitions to characterize the plasmonic effect of these materials. With regard to applications, we highlight the recent advances in MALDI MS and SERS for precision in vitro and in vivo diagnostics.

Fig. 2. Engineered plasmonic nanomaterials for diagnostic applications. (A) Schematic of Pep-1-induced formation of spherical coral-shaped gold nanoparticles and TEM images demonstrating the monodispersity of the nanoparticles. Reproduced with permission. Copyright 2018, Nature Publishing Group. (B) Schematic of polyethyleneimine (PEI)-mediated overgrowth of Cu nanopolyhedra by highly specific CuP growth on AuNPs on a glass slide along with structural validation using scanning electron microscopy (SEM). Reproduced with permission. Copyright 2017, Wiley-VCH. (C) Synthesis of eight varieties of size-tunable transition-metal-decorated aluminum nanocrystals. Adapted with permission. Copyright 2017, American Chemical Society. (D) Schematic illustration and material characterization of Janus hybrids for detection of small metabolites. Reproduced with permission. Copyright 2018, Royal Society of Chemistry.

Fig. 3. Mechanism of plasmonic nanomaterials. (A) Experimental model system demonstrating the electron transfer from plasmonically excited gold NPs. Adapted with permission. Copyright 2018, Macmillan Publishers Limited, Springer Nature. (B) Schematic illustration of a bimetallic core–shell nanoparticle for generation of hot electrons or hot holes with 100 different combinations. Reproduced with permission. Copyright 2018, Springer Nature. (C) Simplified hot-carrier model showing comparison of the injected hot-electron distributions in the semiconductor with a “box” distribution ranging from the Fermi level to the plasmon frequency. Reproduced with permission. Copyright 2018, American Chemical Society. (D) Gap-enhanced Raman tags (GERTs) for studying electron transport across plasmonic molecular nanogaps using the classical electromagnetic model (CEM) and quantum-corrected model (QCM). Adapted with permission. Copyright 2017, American Chemical Society.

Fig. 4. Application of plasmonic nanomaterials for LDI MS-based diagnostics. (A) MS detection of small molecules in serum and exosomes using plasmonic Au chips for diagnosis of early-stage lung cancer. Reproduced with permission. Copyright 2018, American Chemical Society. (B) LDI MS-based in vitro diagnostics of small metabolites using plasmonic silver nanoshells. Adapted with permission. Copyright 2017, Nature Publishing Group. (C) LDI MS of metabolites extracted from HepG2/C3A cells and mouse brain sections directly analyzed in positive ion mode using elevated bow tie nanostructures. Adapted with permission. Copyright 2018, Wiley-VCH. (D) Experimental workflow for data-dependent acquisition imaging and automatic structural identification of detected lipids using ALEX123 software. Adapted with permission. Copyright 2018, Springer Nature. (E) Optical images and mass spectrometric (MS) images of a mouse hippocampal tissue slice. Adapted with permission. Copyright 2017, Springer Nature.

Fig. 5. Application of plasmonic nanomaterials for SERS-based diagnostics. (A) Intraoperative Raman imaging of residual microtumors after surgical resection of primary tumors using gap-enhanced Raman tags (GERTs). Adapted with permission. Copyright 2018, American Chemical Society. (B) Ultraphotostable mesoporous silica-coated GERTs for high-speed bioimaging with a representative TEM image of GERTs, photostability measurement of time-resolved SERS spectra of solid MS GERTs on a silicon wafer during continuous irradiation for 30 min and imaging of orthotopic prostate tumors in mice in bright-field, and corresponding Raman images (2.21 × 10⁵ W cm⁻² power density). Reproduced with permission. Copyright 2017, American Chemical Society. (C) High-contrast intraoperative Raman imaging of sentinel lymph nodes (SLNs). Adapted with permission. Copyright 2018, Elsevier B. V. (D) In vivo intraoperative Raman-guided chemo-photothermal therapy of advanced ovarian cancers with disseminated microtumors represented by schematic diagrams, disseminated tumors (indicated by the gray circles), the corresponding detected Raman signals, representative histological analyses of the microtumors obtained from mice, and the representative TEM images showing the presence of GERTs within the tumor cell. Adapted with permission. Copyright 2018, Wiley-VCH.

Fig. 6. Application of plasmonic nanomaterials for other spectrometry-based diagnostics. (A) Colorimetric detection of acetylcholinesterase (AChE) activity with a schematic illustration of the sensing approach, UV-vis spectra of CTAB-AuNPs in the presence of various AChE concentrations, and the corresponding optical images of the mixtures. Adapted with permission. Copyright 2018, Wiley-VCH. (B) Schematic illustration of AgNPs-enhanced FRET imaging for protein-specific sialylation of the cell surface, with confocal images of protein-specific sialylation on the cell surface in the absence (A, C) and presence (B and D) of AgNPs, and quantitative analysis of the FRET signal intensity in the absence (a) and presence (b) of AgNPs. Adapted with permission. Copyright 2017, Royal Society of Chemistry. (C) Near-infrared fluorescence-enhanced biomarker detection using plasmonic gold chips probed by IRDye800, demonstrating the nanoscopic gold island morphology using SEM, and comparative fluorescence mapping results for different concentrations of analytes using the plasmonic gold chip (left), glass slide (middle), and gold slide (right) along with standard calibration curves. Adapted with permission. Copyright 2016, Wiley-VCH.

Deepanjali Dattatray Gurav

Yi (Alec) Jia

Jian Ye

Kun Qian