Wansun Kim

Facile Fabrication of a Silver Nanoparticle Immersed, Surface-Enhanced Raman Scattering Imposed Paper Platform through Successive Ionic Layer Absorption and Reaction for On-Site Bioassays

We introduce a novel, facile, rapid, low-cost, highly reproducible, and power-free synthesizable fabrication method of paper-based silver nanoparticle (AgNP) immersed surface-enhanced Raman scattering (SERS) platform, known as the successive ionic layer absorption and reaction (SILAR) method. The rough and porous properties of the paper led to direct synthesis of AgNPs on the surface as well as in the paper due to capillary effects, resulting in improved plasmon coupling with interparticles and interlayers. The proposed SERS platform showed an enhancement factor of 1.1 × 10(9), high reproducibility (relative standard deviation of 4.2%), and 10(-12) M rhodamine B highly sensitive detection limit by optimizing the SILAR conditions including the concentration of the reactive solution (20/20 mM/mM AgNO3/NaBH4) and the number of SILAR cycles (six). The applicability of the SERS platform was evaluated using two samples including human cervical fluid for clinical diagnosis of human papillomavirus (HPV) infection, associated with cervical cancer, and a malachite green (MG) solution for fungicide and parasiticide in aquaculture, associated with human carcinogenesis. The AgNP-immersed SERS-functionalized platform using the SILAR technique allowed for high chemical structure sensitivity without additional tagging or chemical modification, making it a good alternative for early clinical diagnosis of HPV infection and detection of MG-activated human carcinogenesis.

Instrument-Free Synthesizable Fabrication of Label-Free Optical Biosensing Paper Strips for the Early Detection of Infectious Keratoconjunctivitides

We introduce a surface-enhanced Raman scattering (SERS)-functionalized, gold nanoparticle (GNP)-deposited paper strip capable of label-free biofluid sensing for the early detection of infectious eye diseases. The GNP biosensing paper strip was fabricated by the direct synthesis and deposition of GNPs on wax-divided hydrophilic areas of a permeable porous substrate through a facile, power-free synthesizable, and highly reproducible successive ionic layer absorption and reaction (SILAR) technique. To maximize localized surface plasmon resonance-generated SERS activity, the concentration of the reactive solution and number of SILAR cycles were optimized by controlling the size and gap distance of GNPs and verified by computational modeling with geometrical hypotheses of Gaussian-estimated metallic nanoparticles. The responses of our SERS-functionalized GNP paper strip to Raman intensities exhibited an enhancement factor of 7.8 × 10(8), high reproducibility (relative standard deviation of 7.5%), and 1 pM 2-naphthalenethiol highly sensitive detection limit with a correlation coefficient of 0.99, achieved by optimized SILAR conditions including a 10/10 mM/mM HAuCl4/NaBH4 concentration and six SILAR cycles. The SERS-functionalized GNP paper is supported by a multivariate statistics-preprocessed machine learning-judged bioclassification system to provide excellent label-free chemical structure sensitivity for identifying infectious keratoconjunctivitis. The power-free synthesizable fabrication, label-free, rapid analysis, and high sensitivity feature of the SILAR-fabricated SERS-functionalized GNP biosensing paper strip makes it an excellent alternative in point-of-care applications for the early detection of various infectious diseases.

Controlling successive ionic layer absorption and reaction cycles to optimize silver nanoparticle-induced localized surface plasmon resonance effects on the paper strip

This study investigates why a silver nanoparticle (SNP)-induced surface-enhanced Raman scattering (SERS) paper chip fabricated at low successive ionic layer absorption and reaction (SILAR) cycles leads to a high SERS enhancement factor (7×108) with an inferior nanostructure and without generating a hot spot effect. The multi-layered structure of SNPs on cellulose fibers, verified by magnified scanning electron microscopy (SEM) and analyzed by a computational simulation method, was hypothesized as the reason. The pattern of simulated local electric field distribution with respect to the number of SILAR cycles showed good agreement with the experimental Raman intensity, regardless of the wavelength of the excitation laser sources. The simulated enhancement factor at the 785-nm excitation laser source (2.8×109) was 2.5 times greater than the experimental enhancement factor (1.1×109). A 532-nm excitation laser source exhibited the highest maximum local electric field intensity (1.9×1011), particularly at the interparticle gap called a hot spot. The short wavelength led to a strong electric field intensity caused by strong electromagnetic coupling arising from the SNP-induced local surface plasmon resonance (LSPR) effects through high excitation energy. These findings suggest that our paper-based SILAR-fabricated SNP-induced LSPR model is valid for understanding SNP-induced LSPR effects.

Highly Reproducible Au-Decorated ZnO Nanorod Array on a Graphite Sensor for Classification of Human Aqueous Humors

Gold-decorated, vertically grown ZnO nanorods (NRs) on a flexible graphite sheet (Au/ZnONRs/G) were developed for surface-enhanced Raman scattering (SERS)-based biosensing to identify trace amounts of human aqueous humors. This Au/ZnONRs/G SERS-functionalized sensor was fabricated via two steps: hydrothermal synthesis-induced growth of ZnO NRs on graphite sheets for nanostructure fabrication, followed by e-beam evaporator-induced gold metallization on ZnONRs/G for SERS functionalization. The thickness of the Au layer and the height of the ZnO NRs for enhancing SERS performance were adjusted to maximize Raman intensity, and the optimized Au/ZnONRs/G nanostructures were verified by the electric finite element computational models to maximize the electric fields. The proposed Au/ZnONRs/G SERS sensor showed an enhancement factor of 2.3 × 106 via rhodamine 6G Raman probe and excellent reproducibility (relative standard deviation of <10%) via Raman mapping of a SERS active area with a square of 100 × 100 μm2. To evaluate the actual bioapplicability of point-of-care-testing (POCT) analysis in clinics, SERS data acquisition was performed with an integration time of 1 s from a 1 μL analytic droplet of the sample. The performance of this Au/ZnONRs/G sensor was evaluated using human aqueous humors with cataract and two oxidative stress-induced eye diseases, age-related macular degeneration, and diabetic macular edema. These three eye diseases could be identified without any labeling or modification using the Au/ZnONRs/G SERS sensor and the computational algorithm incorporating a support vector machine and multivariate statistical prediction. Therefore, these findings indicate that our label-free, highly reproducible and flexible Au/ZnONRs/G SERS-functionalized sensor supported by a multivariate statistics-derived bioclassification method has great potential in POCT applications for identifying eye diseases.

Low-Cost Label-Free Biosensing Bimetallic Cellulose Strip with SILAR-Synthesized Silver Core–Gold Shell Nanoparticle Structures

We introduce a label-free biosensing cellulose strip sensor with surface-enhanced Raman spectroscopy (SERS)-encoded bimetallic core@shell nanoparticles. Bimetallic nanoparticles consisting of a synthesis of core Ag nanoparticles (AgNP) and a synthesis of shell gold nanoparticles (AuNPs) were fabricated on a cellulose substrate by two-stage successive ionic layer absorption and reaction (SILAR) techniques. The bimetallic nanoparticle-enhanced localized surface plasmon resonance (LSPR) effects were theoretically verified by computational calculations with finite element models of optimized bimetallic nanoparticles interacting with an incident laser source. Well-dispersed raspberry-like bimetallic nanoparticles with highly polycrystalline structure were confirmed through X-ray and electron analyses despite ionic reaction synthesis. The stability against silver oxidation and high sensitivity with superior SERS enhancement factor (EF) of the low-cost SERS-encoded cellulose strip, which achieved 3.98 × 108 SERS-EF, 6.1%-RSD reproducibility, and <10%-degraded sustainability, implicated the possibility of practical applications in high analytical screening methods, such as single-molecule detection. The remarkable sensitivity and selectivity of this bimetallic biosensing strip in determining aquatic toxicities for prohibited drugs, such as aniline, sodium azide, and malachite green, as well as monitoring the breast cancer progression for urine, confirmed its potential as a low-cost label-free point-of-care test chip for the early diagnosis of human diseases.

All-Carbon Electrode Consisting of Carbon Nanotubes on Graphite Foil for Flexible Electrochemical Applications

We demonstrate the fabrication of an all-carbon electrode by plasma-enhanced chemical vapor deposition for use in flexible electrochemical applications. The electrode is composed of vertically aligned carbon nanotubes that are grown directly on a flexible graphite foil. Being all-carbon, the simple fabrication process and the excellent electrochemical characteristics present an approach through which high-performance, highly-stable and cost-effective electrochemical applications can be achieved.

A label-free cellulose SERS biosensor chip with improvement of nanoparticle-enhanced LSPR effects for early diagnosis of subarachnoid hemorrhage-induced complications

It is very difficult to predict some complications after subarachnoid hemorrhage (SAH), despite rapid advances in medical science. Herein, we introduce a label-free cellulose surface-enhanced Raman spectroscopy (SERS) biosensor chip with pH-functionalized, gold nanoparticle (AuNP)-enhanced localized surface plasmon resonance (LSPR) effects for identification of SAH-induced cerebral vasospasm and hydrocephalus caused by cerebrospinal fluid (CSF). The SERS biosensor chip was implemented by the synthesis reaction of the AuNPs, which were charged positively through pH level adjustment, onto a negatively-charged cellulose substrate with ξ = -30.7 mV. The zeta potential, nanostructural properties, nanocrystallinity, and computational calculation-based electric field distributions of the cellulose-originated AuNPs were optimized to maximize LSPR phenomena and then characterized. Additionally, the performance of the SERS biosensor was compared under two representative excitation laser sources in the visible region (532 nm) and near-infrared region (785 nm). The Raman activities of our SERS biosensor chip were evaluated by trace small molecules (crystal violet, 2 µL), and the biosensor achieved an enhancement factor of 3.29 × 109 for the analytic concept with an excellent reproducibility of 8.5% relative standard deviation and a detection limit of 0.74 pM. Furthermore, the experimental results revealed that the five proposed SERS-based biomarkers could provide important information for identifying and predicting SAH-induced cerebral vasospasm and hydrocephalus complications (91.1% reliability and 19.3% reproducibility). Therefore, this facile and effective principle of our SERS biosensor chip may inspire the basis and strategies for the development of sensing platforms to predict critical complications in various neurosurgical diagnoses.

Label-free optical detection of age-related and diabetic oxidative damage in human aqueous humors.

In this study, we investigate the biochemical characteristics of oxidative stress in age‐related macular degeneration (AMD) and diabetic retinopathy (DR) by analyzing aqueous humors. Nondiabetic cataract aqueous humor was used as the control. The level of oxidative damage was evaluated based on changes in Raman spectral intensity. Seven prominent peaks were detected at 1002, 1043, 1062, 1352, 1419, 1454, and 1656 cm−1. We proposed four multimodal biomarkers to distinguish these peaks based on the ratios of Raman intensities in two wavelengths, including CHO (C–O stretching or C–O–H bending modes), AG (adenine and guanine), PRO‐AG (protein and AG), and PHEα (phenylalanine symmetric ring breath and amide I α‐helix) markers. The presence of oxidative damage was detected by CHO and AG markers associated with C–O stretching, C–O–H bending modes in carbohydrates (1043 cm−1), and the nucleic acids adenine and guanine (1352 cm−1), respectively. DR‐related oxidative damage was identified by PRO‐AG and PHEα markers associated with adenine, guanine, and protein components (1419 and 1454 cm−1) and amide I α‐helix protein structure (1656 cm−1), respectively. AMD‐related oxidative damage was identified by four biomarkers. Four multimodal biomarkers with simple linear threshold values achieved high sensitivity of 100% and high specificity of 100% for classifying oxidative stress‐induced AMD and DR diseases. Therefore, Raman‐based label‐free optical detection is effective for detecting the presence of age‐related or diabetic oxidative damage in aqueous humor.

Paper-Based Surface-Enhanced Raman Spectroscopy for Diagnosing Prenatal Diseases in Women

We report the development of a surface-enhanced Raman spectroscopy sensor chip by decorating gold nanoparticles (AuNPs) on ZnO nanorod (ZnO NR) arrays vertically grown on cellulose paper (C). We show that these chips can enhance the Raman signal by 1.25 × 107 with an excellent reproducibility of <6%. We show that we can measure trace amounts of human amniotic fluids of patients with subclinical intra-amniotic infection (IAI) and preterm delivery (PTD) using the chip in combination with a multivariate statistics-derived machine-learning-trained bioclassification method. We can detect the presence of prenatal diseases and identify the types of diseases from amniotic fluids with >92% clinical sensitivity and specificity. Our technology has the potential to be used for the early detection of prenatal diseases and can be adapted for point-of-care applications.