Xinling Liu

Rapid identification of free thiols is essential in pharmaceutical quality control and food safety. Herein, we demonstrate the sensing concept of “two signals from one event” by exploiting the intrinsic dual functionality of selenium (Se) nanomaterials to construct a signal-on, dual-mode sensing platform for free thiols. The single event is thiol-triggered seeded growth: free thiols interact with L-cysteine-modified Se seeds, driving seed fusion and crystallization into chiral trigonal Se structures. This same event yields two readouts simultaneously: a colorimetric response arising from particle size enlargement (UV-Vis red-shift) and a turn-on circular dichroism (CD) signal from long-range chiral ordering. The method achieves a detection threshold of 10 μmol/L for various free thiols and can be completed within 60 min from seed preparation to signal readout without complex instrumentation. It serves as a general indicator of total free thiols rather than distinguishing individual thiol species. Above the threshold, concentration-dependent color deepening and spectral redshifts provide semi-quantitative estimation of the concentration range. Its practicality was validated by detecting D-penicillamine in commercial tablets. This strategy offers an approach for on-site free thiol screening and highlights the potential of chiral inorganic nanomaterials in multi-mode sensing via chiral transfer and amplification.

Pesticides are essential for maintaining the global crop productivity and food security. Improving their efficiency and minimizing their environmental impact require a detailed understanding of their uptake and translocation in plants. However, existing techniques for tracking pesticides in living plants are largely destructive, ex situ, and incapable of real-time monitoring, which limits progress toward sustainable agriculture. To address this gap, we developed noninvasive, ratiometric surface-enhanced Raman scattering (SERS) nanosensors that enable in situ, real-time mapping of pesticide dynamics in plants. The nanosensors feature gap-enhanced gold nanorods (AuNNRs) with 4-mercaptobenzonitrile (4-MBN) embedded in the nanogap as a stable internal standard for ratiometric SERS quantification. Once delivered into the leaf intercellular spaces, the nanosensors create functional “sensor-equipped” plants for real-time mapping of pesticide distribution. Using this platform, we compared pesticide translocation under different application methods. The results show that root-irrigated tricyclazole moves upward in a concentration- and time-dependent manner, whereas foliar-sprayed pesticides are poorly absorbed due to the barrier posed by the leaf cuticle. Furthermore, commercial tricyclazole formulations are taken up and transported more efficiently than pure reagent-grade compounds. This SERS-based sensing strategy offers a powerful tool for optimizing pesticide delivery and supports the development of precision agriculture practices that are aimed at sustainability.

Surface-enhanced Raman scattering (SERS) based on semiconductor substrates offers advantages of low cost and high stability over noble metals, but its practical application is hindered by intrinsically weak signal enhancement. Herein, we report a simple molecular engineering strategy to dramatically boost the SERS performance of TiO₂ microspheres through phytic acid (PA) modification. The PA molecules anchor onto TiO₂ surfaces via Ti-O-P bonds, forming PA/TiO₂ composites in a single-step postsynthesis process. The optimized PA/TiO₂ substrate achieves an enhancement factor (EF) of 1.2 × 10⁷─comparable to typical noble metal substrates─and enables detection of the probe molecule 4-mercaptobenzoic acid at concentrations as low as 1 × 10^-9 mol/L. Comprehensive mechanistic investigation reveals a synergistic effect: (i) PA-induced coffee-ring aggregation for analyte enrichment, (ii) Mie resonance from the TiO₂ microspheres (∼253 nm) for electromagnetic field enhancement, and (iii) charge transfer (CT) resonance at the PA/TiO₂ interface for additional chemical contribution, supported by density functional theory calculations and finite-difference time-domain simulations. Leveraging this high-performance platform, we construct an SERS sensor for the endocrine disruptor bisphenol A (BPA), a common contaminant in thermal paper products. The sensor exhibits excellent analytical performance: a limit of detection (LOD) of 4.7 × 10^-7 mol/L, a wide linear range from 5.0 × 10^-6 to 1.0 × 10^-3 mol/L (R² = 0.9971), and satisfactory spike-recovery results (97.8-103.0%) in real thermal paper samples. This work demonstrates that molecular-level surface engineering offers a scalable and cost-effective route to high-performance semiconductor SERS substrates for environmental monitoring applications.

The human stratum corneum (SC) serves as a key barrier against exogenous molecules and is a living, heterogeneous system whose composition and microstructure vary along its depth. Noninvasive in vivo monitoring of its spatiotemporal microstructural changes is thus crucial yet challenging in many areas, such as transdermal drug delivery and cosmetics. Herein, we directly employed confocal Raman microspectroscopy on forearm skin to characterize the SC and its dynamic response to glycerin. To overcome low spectral resolution from signal overlap, two-dimensional correlation spectroscopy (2DCOS), moving window 2DCOS (MW2D), and perturbation-correlated MW2D (PCMW2D) were used to monitor the (1) trends and (2) sequence of Raman signal variations with depth. These served as unique Raman indicators to describe the multiscale structural features of SC, determine its thickness, and clarify glycerin's effects on lipid, keratin, and water molecular structures within SC. Further, a three-layer stratification of SC was proposed, revealing its spatially differential swelling upon adding glycerin. These glycerin-induced changes, from molecular structure to microscale swelling, would enhance the penetration of retinyl palmitate. Finally, the recovery of SC over time was assessed by the depth-dependent variations in the molecular conformations of SC components and the SC thickness, uncovering an unexpected application of glycerin as a temporary and mild skin penetration enhancer (SPE). Consequently, two-dimensional correlation Raman spectroscopy is promising in characterizing the SC and exploring qualified SPEs.

Surface-enhanced Raman scattering (SERS), despite its high sensitivity in molecular fingerprint detection, typically lacks chiral specificity. Chiral metal nanoclusters (CMNCs) with sub-3 nm cores hold promise for chiral molecular sensing, yet their application in SERS-based chiral recognition remains largely unexplored. In this study, two-dimensional self-assembly of Au nanoparticles (NPs, 30 ∼ 50 nm) functionalized with D- or L-penicillamine (Pen) stabilized sub-3 nm Au nanoclusters (NCs) were constructed as SERS-active substrates. On these substrates, distinct SERS signals were observed for L- versus D-phenylalanine (Phe) enantiomers, with a signal intensity difference of approximately 5-fold at a low concentration of 10^-6 mol/L, suggesting a good enantiomeric discrimination effect and detection sensitivity. Similar chiral discrimination phenomena were also found by using propranolol enantiomers or chiral Cu NCs. These findings demonstrate the significant potential of the integration of CMNCs into plasmonic SERS substrates for developing sensitive chiral sensing strategies based on nonchiral vibrational Raman spectroscopy and advancing the fundamental studies of metal nanocluster-molecule chiral interactions.

Putrescine is of concern due to its toxicity and applications in monitoring food spoilage and water quality. However, it is difficult to realize highly selective and sensitive detection of putrescine with interferences from other biogenetic amines with similar molecular structures. In this work, Au nanobowls modified by Cu‐MOF (core‐shell Au bowl@Cu MOF) together with o‐phthalaldehyde (OPA) are embedded into sodium alginate hydrogel to construct a unique SERS substrate (OPA‐Au bowl@Cu MOF/hydrogel) for sensing of putrescine. In the confined space of porous hydrogel, the Schiff base reaction between OPA and putrescine resulted in the product of N, N‐dibenzylidene‐n‐butylenediamine (OPA‐Putrescine), which is easily captured by Cu‐MOF via copper‐nitrogen coordination and then detected thanks to the high SERS activity of Au nanobowls and the large Raman scattering cross‐section of OPA‐Putrescine. The above reaction contributed to a high selectivity to greatly suppress the interferences from many amino group‐containing molecules. The limit of detection (LOD) of gaseous and liquid putrescine is 1.2 × 10 ⁻⁹ and 6.3 × 10 ⁻¹⁰ mol L ⁻¹ , respectively. Further, the application potential of this SERS‐sensor in food and environmental fields are demonstrated by the successful detection of putrescine in salmon and seawater samples.

We report on a surface-enhanced Raman scattering (SERS) platform for the detection of five beta-blockers (β-blockers): atenolol, esmolol, labetalol, sotalol, and propranolol. Key to this platform was a two-dimensional substrate formed by self-assembling large Ag@SiO₂ nanoparticles (Ag@SiO₂ NPs) on a silicon wafer. The close arrangement of these large nanoparticles on the surface generated a strong and uniform electromagnetic field, which enhanced SERS signal intensity for the detection of small amounts of the target molecules. The intensities of characteristic peaks of the five β-blocker drugs increased linearly with the increase of their concentrations in the range of 10^-5 to 10^-8 mol/L. The detection limits were 10^-10 mol/L for propranolol, 10^-9 mol/L for atenolol, labetalol, and sotalol, and 10^-8 mol/L for esmolol. Determination of these five β-blocker drugs added to human urine samples, using a portable Raman spectroscopy instrument, showed quantitative recovery (93-101%). Principal component analysis (PCA) and hierarchical cluster analysis (HCA) of SERS spectral data improved the differentiation among these five β-blockers. This study highlights the potential of the developed SERS platform for rapid, on-site detection of illicit drugs and for antidoping screening.

We detect nitrite with pATP/Au/ITO chip via ratiometric SERS method. With the 1008 cm⁻¹ SERS peak from ring deformation as the internal standard (replacing the traditional 1080 cm⁻¹ C-S stretching peak), the detection sensitivity is 10-fold increase.

Salivary d-alanine (d-Ala) and d-proline (d-Pro) are of concern for their potential in the noninvasive diagnosis of gastric cancer (GC). Most reports have succeeded in determining the total concentration of d-Ala and d-Pro. However, for personalized diagnosis and better elucidation of the underlying specific correlation of d-Ala (or d-Pro) with GC, it is desirable to determine the specific concentration of d-Ala or d-Pro. Herein, we propose an enantiomer-specific tandem assay of d-Ala based on the colorimetric reaction between 2,4-dinitrophenylhydrazine and pyruvic acid generated from the deamination of d-Ala catalyzed by d-amino acid oxidase, which is easily distinguished from l-form amino acids, d-Pro, and many other species. A linear concentration range is established from 20 to 400 μmol/L with a limit of detection of 1.01 μmol/L. Real saliva sample tests reveal that the levels of d-Ala in GC cases are remarkably higher than those in healthy individuals, which offers a simple and low-cost strategy for GC diagnosis. Simultaneously, the total concentrations of d-Ala and d-Pro in saliva are determined. Hence, the concentration of d-Pro and the proportion of d-Ala could be calculated, which further provides more molecule- and individual-specific information. This research may offer a convenient method for noninvasive diagnosis of GC and pave a new route to explore the potentials of rare d-form amino acids in disease diagnosis and treatment.

The unusual d-amino acids (d-AAs), as the counter enantiomer of usual l-amino acids (l-AAs), have evoked increasing attention because of their potential relevance with diseases. Accordingly, it is essential to establish sensitive and selective detection methods for d-AAs without the interferences from l-AAs. The surface-enhanced Raman scattering (SERS) technique is efficacious for the detection of molecules but routinely ineffective in enantiomeric differentiation. d-Proline (d-Pro) and d-alanine (d-Ala) are regarded as biomarkers of gastric cancer. Herein, Raman-active boronate modified SERS chips are constructed to develop a d-amino acid oxidase (DAAO)-mediated cascade reaction-based SERS enantioselective assay for d-Pro and d-Ala. The principle is that DAAO selectively catalyzes the deamination of d-Pro and d-Ala, and the produced H₂O₂ oxidizes boronate to present a new SERS peak at 883 cm^-1 for quantitative analysis in a ratiometric way. A linear range from 20 to 400 μmol/L and a limit of detection down to 14.8 μmol/L are reached. In addition, interferences from l-AAs and many other possible species coexisting in biofluids with the detection of d-Pro and d-Ala are ignorable. Enzyme-mediated cascade reaction-based SERS chips are further utilized for saliva sample analysis, and the total levels of d-Pro and d-Ala in salivary samples from gastric cancer patients are much higher than those of healthy persons. This work provides a solution for SERS enantioselective analysis and noninvasive screening chiral biomolecules for disease diagnosis.