arXiv subjects

Kuo Zhan

Publications and source records attributed to Kuo Zhan.

8 recordsLinked to original sources

arXiv2026

Physics-Aligned Deep Learning Enables SERS Resolving and Sequencing of Dynamic Single-Molecule DNA Oligomers in Plasmonic Nanocavity

Single-molecule surface-enhanced Raman spectroscopy (SM-SERS) captures dynamic molecular behavior with ultrahigh sensitivity, but its biopolymer analysis is hindered by strong spectral heterogeneity, transient hotspot sampling, and background interference. Here, we develop a physics-aligned deep learning framework integrating contrastive attention-based multiple-instance learning (CAMIL), a tri-channel multi-kernel CNN classifier, and trajectory-level transition-guided sequence reconstruction to decode single-molecule DNA oligomer dynamics in a plasmonic nanocavity. In this work, CAMIL mines informative spectra enriched with chain-embedded nucleotide and dinucleotide signatures from contrastive positive and negative DNA trajectory bags, generating a single-molecule DNA-segment spectral-states library. This library trains a 12-class CNN to assign query time-resolved DNA SM-SERS frames to high-confidence DNA-segment states, enabling trajectory-level analysis of state composition, dwell length, entropy, switching frequency, and transition matrix. The transition matrix is further converted into state-transition-edge evidence for candidate sequence scoring, enabling asymmetric DNA sequences inference from confined stochastic sampling dynamics. This framework transforms SM-SERS heterogeneity into quantitative analytical information, advancing dynamic single-molecule decoding.

physics.optics↗

arXiv2026

AI-Driven SERS for Non-invasive and Label-Free Extracellular Vesicle Detection Across Cellular Origins in Tears and Sweat

Wearable sensing technology capable of point-of-care, continuous and non-invasive analysis of exosomes in biofluid such as tears and sweat is an essential part for future personalized medicine. Major detection and identification methods of cell secreted Extracellular Vesicles (EVs) often require labeling and are time-consuming, resulting in low efficiency in EV mechanism research and disease diagnosis. While the label-free Surface-enhanced Raman spectroscopy (SERS) has been combined with deep learning model for EV identification in blood, their application to non-invasive detection of EVs in tears and sweat are missing. Here, we filled this gap by developing an artificial intelligence (AI)-assisted Surface-enhanced Raman spectroscopy (SERS) method based on salt-induced nanoparticle aggregation for fast EV identification in tears and sweat with high accuracy. Significantly, our label-free detection and AI differentiation of EVs from 6 cell lines (HepG2, Hela, 143B, LO-2, BMSC, H8) achieved the identification of EVs in tear fluids from 7 different disease sources with accuracies >92%. Our results showed that this platform can not only distinguish EVs from multiple cell sources but also generate highly reproducible and selective EV signals in tear fluids without a need for chemical labeling or separation steps. Molecular dynamics simulations revealed that silver atoms (Ag) form electrostatic interactions with oxygen atoms of multiple amino acid residues in proteins, suggesting a high affinity. This strategy realizes ultra-sensitive and anti-interference detection of EVs, providing a new idea for the rapid diagnosis of clinical diseases.

cond-mat.mes-hall↗

arXiv2026

Label-free SERS Discrimination of Native Proline Hydroxylation at Single-molecule peptide by Deep Learning-assisted plasmonic nanopore

Post-translational modifications (PTMs) play essential roles in regulating protein structure, function, and cellular signalling. However, peptide level discrimination of hydroxylation at the single-molecule level remains difficult. Here, we report a particle-in-pore single-molecule surface-enhanced Raman spectroscopy (SERS) platform combined with peak occurrence frequency (POF) analysis and a one-dimensional convolutional neural network (1D-CNN) for discriminating hydroxylated and non-hydroxylated HIF peptide fragments. Three peptide pairs containing the Pro-564 hydroxylation site, with lengths of 7, 9, and 15 amino acids (AAs), were investigated. POF analysis revealed reproducible hydroxylation-dependent spectral changes in the 7AA and 9AA peptide pairs, which were attributed to changes in adsorption conformation and surface interactions. CNN-based classification achieved post-evaluation accuracies of 72.98%, 78.55%, and 89.74% for the 7AA, 9AA, and 15AA peptide pairs, respectively, with AUC values above 0.80 for all the pairs, indicating a reliable discrimination. Gradient-weighted feature visualization further showed that CNN-sensitive regions overlapped with recurrent POF features, supporting the chemical relevance of the learned classification patterns. Notably, for the 15AA peptide pair, the enhanced citrate-associated band suggests that hydroxylation can substantially alter peptide-gold nanoparticle adsorption behaviour. This adsorption-mediated effect may amplify hydroxylation-induced spectral differences and contribute to the improved discrimination accuracy despite the increased structural complexity. These results demonstrate that the particle-in-pore sensor, assisted by deep learning, can capture hydroxylation-induced spectral and adsorption changes in peptide fragments, providing a promising strategy for ultrasensitive analysis of weak PTM signatures in peptides.

physics.bio-ph↗

arXiv2026

Resolving Single-Peptide Phosphorylation Dynamics in Plasmonic Nanopores using Physics-Informed Bi-Path Model

Protein phosphorylation provides a dynamic readout of cellular signaling yet remains difficult to detect at low abundance and stoichiometry. Single-molecule surface-enhanced Raman spectroscopy (SM-SERS) using particle-in-pore plasmonic nanopores offers label-free molecular detection with submolecular sensitivity. However, reliable identification of subtle post-translational modifications (PTMs) is hindered by the stochastic nature of SM-SERS signals, partial excitation of peptide residues within the plasmonic hotspot, and background interference. Here, we introduce a physics-informed deep learning framework to decode complex SM-SERS dynamics and identify single-peptide PTMs. The model integrates multiple-instance learning with a temporal encoder combining temporal convolutional networks and bidirectional gated recurrent units to capture both local spectral variability and long-range blinking dynamics. To address diffusion-driven spectral heterogeneity, long spectral trajectories are segmented using Pearson-correlation, enabling weakly supervised training under label ambiguity. This framework robustly distinguishes single peptide phosphorylation despite strong background interference and stochastic signal fluctuations. By coupling nanoplasmonic confinement with spatiotemporal deep learning, our approach enables high-fidelity detection of single-molecule phosphorylation events and advances ultrasensitive phosphoproteomic analysis.

cond-mat.mes-hall↗

arXiv2025

Bridging Optical Sensing and Wearable Health Monitoring: A Functionalized Plasmonic Nanopillar for Non-Invasive Sweat Glucose Detection

Continuous glucose monitoring (CGM) is vital for diabetes care, but current systems rely on invasive implants or electrochemical sensors that often cause discomfort and skin irritation. Non-invasive alternatives remain limited by low sensitivity and poor compatibility with complex sweat environments, highlighting the urgent need for a comfortable and reliable solution. Here, we report the development of a wearable optical sensor watch that integrates surface plasmon resonance (SPR) technology with a functionalized silver-coated silicon nanowire (Ag/SiNW) substrate for real-time, non-invasive glucose monitoring in sweat. The nanostructured sensor is functionalized with 4-mercaptophenylboronic acid (4-MPBA), enabling selective glucose capture and optical signal transduction through both Raman scattering and SPR shift. The dual-mode detection strategy was systematically optimized, and a miniaturized SPR system operating at 638 nm was successfully integrated into a wearable watch format with wireless data transmission to a mobile application. This wearable device demonstrated excellent sensitivity (LOD down to 0.12 mM) and high selectivity in detecting glucose within physiological sweat concentration ranges. Human subject trials confirmed its applicability in real-life scenarios. This study offers a promising non-invasive alternative to traditional CGM and highlights the potential of integrating nanophotonic sensors with wearable platforms for continuous health monitoring and personalized medicine.

physics.optics↗

arXiv2024

Label-free SERS Discrimination of Proline from Hydroxylated Proline at Single-molecule Level Assisted by a Deep Learning Model

Discriminating the low-abundance hydroxylated proline from hydroxylated proline is crucial for monitoring diseases and eval-uating therapeutic outcomes that require single-molecule sensors. While the plasmonic nanopore sensor can detect the hydrox-ylation with single-molecule sensitivity by surface enhanced Raman spectroscopy (SERS), it suffers from intrinsic fluctuations of single-molecule signals as well as strong interference from citrates. Here, we used the occurrence frequency histogram of the single-molecule SERS peaks to extract overall dataset spectral features, overcome the signal fluctuations and investigate the citrate-replaced plasmonic nanopore sensors for clean and distinguishable signals of proline and hydroxylated proline. By ligand exchange of the citrates by analyte molecules, the representative peaks of citrates decreased with incubation time, prov-ing occupation of the plasmonic hot spot by the analytes. As a result, the discrimination of the single-molecule SERS signals of proline and hydroxylated proline was possible with the convolutional neural network model with 96.6% accuracy.

physics.chem-ph↗

arXiv2024

Deep learning assisted SERS detection of prolines and hydroxylated prolines using nitrilotriacetic acid functionalized gold nanopillars

Proline (Pro) is one kind of proteinogenic amino acid and an important signaling molecule in the process of metabolism. Hydroxyproline (Hyp) is a product on Pro oxygen sensing post-translational modification (PTM), which is efficiently modulated tumor cells for angiogenesis. Distinguishing between Pro and Hyp is crucial for diagnosing connective tissue disorders, as elevated levels of Hyp can indicate abnormal collagen metabolism, often associated with diseases like osteogenesis imperfecta or fibrosis. However, there is a very small difference between molecular structures of Pro and Hyp, which is a big challenge for current detection technologies to distinguish them. For surface-enhanced Raman scattering (SERS) sensors, the similar molecule structure leads to similar Raman spectra that are difficult to distinguish. Furthermore, another problem is the weak affinity between amino acids sample and SERS-active substrates by physical adsorption. The selecting capturing of Pro and Hyp in the mixture of amino acids is not easy to achieve. In this work, we designed a new method for Pro and Hyp specifical detection and recognition by using gold nanopillars as the SERS substrate and combing nitrilotriacetic acid (NTA) with nickel (Ni) to form NTA-Ni structure as a specifical affinity agent. One side of NTA-Ni was attached to gold nanopillars through thiol binding. Another side captured the amino acids using reversible binding by receptor-ligand interaction between Ni and amino acids. Because of the different binding time with NTA-Ni and amino acids, the sensor can recognize Pro and Hyp from amino acids mixture. Then we used automatic peak assignment program for data analysis and machine learning model to distinguish between Pro and Hyp. The label-free SERS detection of amino acids PTM using gold nanopillars provides a potential method to further biomolecule detection and specifical capture.

q-bio.BM↗

arXiv2024

Label-free detection of exosomes from different cellular sources based on surface-enhanced Raman spectroscopy combined with machine learning models

Exosomes are significant facilitators of inter-cellular communication that can unveil cell-cell interactions, signaling pathways, regulatory mechanisms and disease diagnostics. Nonetheless, current analysis required large amount of data for exosome identification that it hampers efficient and timely mechanism study and diagnostics. Here, we used a machine-learning assisted Surface-enhanced Raman spectroscopy (SERS) method to detect exosomes derived from six distinct cell lines (HepG2, Hela, 143B, LO-2, BMSC, and H8) with small amount of data. By employing sodium borohydride-reduced silver nanoparticles and sodium borohydride solution as an aggregating agent, 100 SERS spectra of the each types of exosomes were collected and then subjected to multivariate and machine learning analysis. By integrating Principal Component Analysis with Support Vector Machine (PCA-SVM) models, our analysis achieved a high accuracy rate of 94.4% in predicting exosomes originating from various cellular sources. In comparison to other machine learning analysis, our method used small amount of SERS data to allow a simple and rapid exosome detection, which enables a timely subsequent study of cell-cell interactions, communication mechanisms, and disease mechanisms in life sciences.

q-bio.BM↗