Jwa-Min Nam

Nanogap-engineerable Raman-active nanodumbbells for single-molecule detection

Surface-enhanced Raman scattering (SERS)-based signal amplification and detection methods using plasmonic nanostructures have been widely investigated for imaging and sensing applications. However, SERS-based molecule detection strategies have not been practically useful because there is no straightforward method to synthesize and characterize highly sensitive SERS-active nanostructures with sufficiently high yield and efficiency, which results in an extremely low cross-section area in Raman sensing. Here, we report a high-yield synthetic method for SERS-active gold-silver core-shell nanodumbbells, where the gap between two nanoparticles and the Raman-dye position and environment can be engineered on the nanoscale. Atomic-force-microscope-correlated nano-Raman measurements of individual dumbbell structures demonstrate that Raman signals can be repeatedly detected from single-DNA-tethered nanodumbbells. These programmed nanostructure fabrication and single-DNA detection strategies open avenues for the high-yield synthesis of optically active smart nanoparticles and structurally reproducible nanostructure-based single-molecule detection and bioassays.

Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap

An ideal surface-enhanced Raman scattering (SERS) nanostructure for sensing and imaging applications should induce a high signal enhancement, generate a reproducible and uniform response, and should be easy to synthesize. Many SERS-active nanostructures have been investigated, but they suffer from poor reproducibility of the SERS-active sites, and the wide distribution of their enhancement factor values results in an unquantifiable SERS signal. Here, we show that DNA on gold nanoparticles facilitates the formation of well-defined gold nanobridged nanogap particles (Au-NNP) that generate a highly stable and reproducible SERS signal. The uniform and hollow gap (∼1 nm) between the gold core and gold shell can be precisely loaded with a quantifiable amount of Raman dyes. SERS signals generated by Au-NNPs showed a linear dependence on probe concentration (R(2) > 0.98) and were sensitive down to 10 fM concentrations. Single-particle nano-Raman mapping analysis revealed that >90% of Au-NNPs had enhancement factors greater than 1.0 × 10(8), which is sufficient for single-molecule detection, and the values were narrowly distributed between 1.0 × 10(8) and 5.0 × 10(9).

UV/Ozone-Oxidized Large-Scale Graphene Platform with Large Chemical Enhancement in Surface-Enhanced Raman Scattering

We fabricated a highly oxidized large-scale graphene platform using chemical vapor deposition (CVD) and UV/ozone-based oxidation methods. This platform offers a large-scale surface-enhanced Raman scattering (SERS) substrate with large chemical enhancement in SERS and reproducible SERS signals over a centimeter-scale graphene surface. After UV-induced ozone generation, ozone molecules were reacted with graphene to produce oxygen-containing groups on graphene and induced the p-type doping of the graphene. These modifications introduced the structural disorder and defects on the graphene surface and resulted in a large chemical mechanism-based signal enhancement from Raman dye molecules [rhodamine B (RhB), rhodamine 6G (R6G), and crystal violet (CV) in this case] on graphene. Importantly, the enhancement factors were increased from ∼10(3) before ozone treatment to ∼10(4), which is the largest chemical enhancement factor ever on graphene, after 5 min ozone treatment due to both high oxidation and p-doping effects on graphene surface. Over a centimeter-scale area of this UV/ozone-oxidized graphene substrate, strong SERS signals were repeatedly and reproducibly detected. In a UV/ozone-based micropattern, UV/ozone-treated areas were highly Raman-active while nontreated areas displayed very weak Raman signals.

Biomimetic nanopatterns as enabling tools for analysis and control of live cells.

It is becoming increasingly evident that cell biology research can be considerably advanced through the use of bioengineered tools enabled by nanoscale technologies. Recent advances in nanopatterning techniques pave the way for engineering biomaterial surfaces that control cellular interactions from the nano- to the microscale, allowing more precise quantitative experimentation capturing multi-scale aspects of complex tissue physiology in vitro. The spatially and temporally controlled display of extracellular signaling cues on nanopatterned surfaces (e. g., cues in the form of chemical ligands, controlled stiffness, texture, etc.) that can now be achieved on biologically relevant length scales is particularly attractive enabling experimental platform for investigating fundamental mechanisms of adhesion-mediated cell signaling. Here, we present an overview of bio-nanopatterning methods, with the particular focus on the recent advances on the use of nanofabrication techniques as enabling tools for studying the effects of cell adhesion and signaling on cell function. We also highlight the impact of nanoscale engineering in controlling cell-material interfaces, which can have profound implications for future development of tissue engineering and regenerative medicine.

Tumor Targeting and Imaging Using Cyclic RGD‐PEGylated Gold Nanoparticle Probes with Directly Conjugated Iodine‐125

Radioactive iodine-labeled, cyclic RGD-PEGylated gold nanoparticle (AuNP) probes are designed and synthesized for targeting cancer cells and imaging tumor sites. These iodine-125-labeled cRGD-PEG-AuNP probes are stable in various conditions including a range of pHs and high salt and temperature conditions. These probes can target selectively and be taken up by tumor cells via integrin αvβ3-receptor-mediated endocytosis with no cytotoxicity. The probes show a significant increase in the avidity of αvβ3 integrin compared to the corresponding free cRGD peptides. In-vivo SPECT/CT imaging results show that the iodine-125-labeled cRGD-PEG-AuNP probes can target the tumor site as soon as 10 min after injection, and also that cyclic RGD peptides are needed for efficient and long-term in-vivo monitoring. The results suggest that the probes circulate through the whole body, including renal filtration, and are excretable. These promising results show that radioactive-iodine-labeled gold nanoprobes have potential for highly specific and sensitive tumor imaging or for use as angiogenesis-targeted SPECT/CT imaging probes.

Tuning and Maximizing the Single-Molecule Surface-Enhanced Raman Scattering from DNA-Tethered Nanodumbbells

We extensively study the relationships between single-molecule surface-enhanced Raman scattering (SMSERS) intensity, enhancement factor (EF) distribution over many particles, interparticle distance, particle size/shape/composition and excitation laser wavelength using the single-particle AFM-correlated Raman measurement method and theoretical calculations. Two different single-DNA-tethered Au-Ag core-shell nanodumbbell (GSND) designs with an engineerable nanogap were used in this study: the GSND-I with various interparticle nanogaps from ∼4.8 nm to <1 nm or with no gap and the GSND-II with the fixed interparticle gap size and varying particle size from a 23-30 nm pair to a 50-60 nm pair. From the GSND-I, we learned that synthesizing a <1 nm gap is a key to obtain strong SMSERS signals with a narrow EF value distribution. Importantly, in the case of the GSND-I with <1 nm interparticle gap, an EF value of as high as 5.9 × 10(13) (average value = 1.8 × 10(13)) was obtained and the EF values of analyzed particles were narrowly distributed between 1.9 × 10(12) and 5.9 × 10(13). In the case of the GSND-II probes, a combination of >50 nm Au cores and 514.5 nm laser wavelength that matches well with Ag shell generated stronger SMSERS signals with a more narrow EF distribution than <50 nm Au cores with 514.5 nm laser or the GSND-II structures with 632.8 nm laser. Our results show the usefulness and flexibility of these GSND structures in studying and obtaining SMSERS structures with a narrow distribution of high EF values and that the GSNDs with < 1 nm are promising SERS probes with highly sensitive and quantitative detection capability when optimally designed.

DNA-embedded Au/Ag core–shell nanoparticles

Here, we synthesized highly stable DNA-embedded Au/Ag core-shell nanoparticles (NPs) by a straightforward silver-staining of DNA-modified Au nanoparticles (AuNPs); unlike conventional DNA-surface modified NPs that present particle stability issues, DNA-embedded core-shell NPs offer an extraordinary stability with nanoscale controllability of silver shell thickness; these DNA-embedded core-shell NPs show excellent biorecognition properties and Ag shell-thickness-based optical properties, distinctively different from those of a mixture of AuNPs and AgNPs or Ag/Au alloy nanoparticles.

Responsive nematic gels from the self-assembly of aqueous nanofibres

Aqueous nanofibres constructed by the self-assembly of small amphiphilic molecules can become entangled to form hydrogels that have a variety of applications including tissue engineering, and controlled drug delivery. The hydrogels are formed through the random physical cross-linkings of flexible nanofibres. Here we report that self-assembled nanofibres with a nematic substructure are aligned into a nematic liquid crystal and are spontaneously fixed in the aligned state to give rise to anisotropic gels. The liquid-crystal gels respond to temperature by transforming into a fluid solution upon cooling. Thus, the nanofibre solution can be mixed with cells at room temperature and then can be transformed into gels to encapsulate the cells in a three-dimensional environment upon being heated to physiological temperatures. We found that the cells grow within the three-dimensional networks without compromising the cell viability, and that subsequent cooling triggers the encapsulated cells to be released through a sol-gel transition.

Plasmonic nanosnowmen with a conductive junction as highly tunable nanoantenna structures and sensitive, quantitative and multiplexable surface-enhanced Raman scattering probes.

The precise design and synthesis of plasmonic nanostructures allow us to manipulate, enhance, and utilize the optical characteristics of metallic materials. Although many multimeric structures (e.g., dimers) with interparticle nanogap have been heavily studied, the plasmonic nanostructures with a conductive junction have not been well studied mostly because of the lack of the reliable synthetic methods that can reproducibly and precisely generate a large number of the plasmonic nanostructures with a controllable conductive nanojunction. Here, we formed various asymmetric Au-Ag head-body nanosnowman structures with a highly controllable conductive nanojunction and studied their plasmon modes that cover from visible to near-infrared range, electromagnetic field enhancement, and surface-enhanced Raman scattering (SERS) properties. It was shown that change in the plasmonic neck region between Au head and Ag body nanoparticles and symmetry breaking using different sizes and compositions within a structure can readily and controllably introduce various plasmon modes and change the electromagnetic field inside and around a nanosnowman structure. The charge-transfer and capacitive coupling plasmon modes at low frequencies are tunable in the snowman structure, and subtle change in the conductive junction area of the nanosnowman dramatically affects the resulting electromagnetic field and optical signal. The relationships between the electromagnetic field distribution and enhancement in the snowman structure, excitation laser wavelength, and Raman dye were also studied, and it was found that the strongest electromagnetic field was observed in the crevice area on the junction and synthesizing a thinner and sharper neck junction is critical to generate the stronger electromagnetic field in the crevice area and to obtain the charge-transfer mode-based near-infrared signal. We have further shown that highly reproducible SERS signals can be generated from these nanosnowman structures with a linear dependence on particle concentration (5 fM to 1 pM) and the SERS-enhancement factor values of >10(8) can be obtained with the aid of the resonance effect in SERS. Finally, a wide range of LSPR bands with high tunability along with high structural reproducibility and high synthetic yield make the nanosnowman structures as very good candidates for practically useful multiple-wavelength-compatible, quantitative and sensitive SERS probes, and highly tunable nanoantenna structures.

Directional synthesis and assembly of bimetallic nanosnowmen with DNA.

Synthesizing and assembling nanoscale building blocks to form anisotropic nanostructures with the desired composition and property are of paramount importance for the understanding and use of nanostructured materials. Here we report a salt-tuned synthetic strategy using DNA-modified Au nanoparticles (DNA-AuNPs) to form Au-Ag head-body nanosnowman structures in >95% yield. We propose a mechanism for the formation of asymmetric Au-Ag nanosnowmen from DNA-AuNPs, salts, and Ag-precursor-loaded polymers. Importantly, we show that oriented assemblies of various nanostructures are readily obtained using nanosnowmen with asymmetrically modified DNA as building blocks.