Zhi-Chao Lei

Label-Free Surface-Enhanced Raman Spectroscopy Detection of DNA with Single-Base Sensitivity

Direct, label-free detection of unmodified DNA is a great challenge for DNA analyses. Surface-enhanced Raman spectroscopy (SERS) is a promising tool for DNA analyses by providing intrinsic chemical information with a high sensitivity. To address the irreproducibility in SERS analysis that hampers reliable DNA detection, we used iodide-modified Ag nanoparticles to obtain highly reproducible SERS signals of single- and double-strand DNA in aqueous solutions close to physiological conditions. The phosphate backbone signal was used as an internal standard to calibrate the absolute signal of each base for a more reliable determination of the DNA structure, which has not been achieved before. Clear identification of DNA with single-base sensitivity and the observation of a hybridization event have been demonstrated.

Au@Pt Nanoparticle Encapsulated Target‐Responsive Hydrogel with Volumetric Bar‐Chart Chip Readout for Quantitative Point‐of‐Care Testing

Point-of-care testing (POCT) with the advantages of speed, simplicity, portability, and low cost is critical for the measurement of analytes in a variety of environments where access to laboratory infrastructure is lacking. While qualitative POCTs are widely available, quantitative POCTs present significant challenges. Here we describe a novel method that integrates an Au core/Pt shell nanoparticle (Au@PtNP) encapsulated target-responsive hydrogel with a volumetric bar-chart chip (V-Chip) for quantitative POCT. Upon target introduction, the hydrogel immediately dissolves and releases Au@PtNPs, which can efficiently catalyze the decomposition of H2 O2 to generate a large volume of O2 to move of an ink bar in the V-Chip. The concentration of the target introduced can be visually quantified by reading the traveling distance of the ink bar. This method has the potential to be used for portable and quantitative detection of a wide range of targets without any external instrument.

Supersaturation-Dependent Surface Structure Evolution: From Ionic, Molecular to Metallic Micro/Nanocrystals

Deduced from thermodynamics and the Thomson-Gibbs equation that the surface energy of crystal face is in proportion to the supersaturation of crystal growth units during the crystal growth, we propose that the exposed crystal faces can be simply tuned by controlling the supersaturation, and higher supersaturation will result in the formation of crystallites with higher surface-energy faces. We have successfully applied it for the growth of ionic (NaCl), molecular (TBPe), and metallic (Au, Pd) micro/nanocrystals with high-surface-energy faces. The above proposed strategy can be rationally designed to synthesize micro/nanocrystals with specific crystal faces and functionality toward specific applications.

Translating Molecular Recognition into a Pressure Signal to enable Rapid, Sensitive, and Portable Biomedical Analysis

Herein, we demonstrate that a very familiar, yet underutilized, physical parameter—gas pressure—can serve as signal readout for highly sensitive bioanalysis. Integration of a catalyzed gas-generation reaction with a molecular recognition component leads to significant pressure changes, which can be measured with high sensitivity using a low-cost and portable pressure meter. This new signaling strategy opens up a new way for simple, portable, yet highly sensitive biomedical analysis in a variety of settings.

Plasmonic photoluminescence for recovering native chemical information from surface-enhanced Raman scattering

Surface-enhanced Raman scattering (SERS) spectroscopy has attracted tremendous interests as a highly sensitive label-free tool. The local field produced by the excitation of localized surface plasmon resonances (LSPRs) dominates the overall enhancement of SERS. Such an electromagnetic enhancement is unfortunately accompanied by a strong modification in the relative intensity of the original Raman spectra, which highly distorts spectral features providing chemical information. Here we propose a robust method to retrieve the fingerprint of intrinsic chemical information from the SERS spectra. The method is established based on the finding that the SERS background originates from the LSPR-modulated photoluminescence, which contains the local field information shared also by SERS. We validate this concept of retrieval of intrinsic fingerprint information in well controlled single metallic nanoantennas of varying aspect ratios. We further demonstrate its unambiguity and generality in more complicated systems of tip-enhanced Raman spectroscopy (TERS) and SERS of silver nanoaggregates.

Extraction of Absorption and Scattering Contribution of Metallic Nanoparticles Toward Rational Synthesis and Application

Noble metal nanoparticles have unique localized surface plasmon resonance (LSPR), leading to their strong absorption and scattering in the visible light range. Up to date, the common practice in the selection of nanoparticles for a specific application is still based on the measured extinction spectra. This practice may be erroneous, because the extinction spectra contain both absorption and scattering contribution that may play different roles in different applications. It would be highly desirable to develop an efficient way to obtain the absorption and scattering spectra simultaneously. Herein, we develop a method to use the experimentally measured extinction and scattering signals to extract the absorption and scattering spectra that is in excellent agreement with that simulated by discrete dipole approximation (DDA). The heating curve measurement on the three types of gold nanorods, with almost the same extinction spectra but different absorption and scattering contribution, convincingly reveals an excellent correlation between the heating effect and the absorption strength rather than the extinction strength. The result demonstrates the importance to obtain the scattering and absorption spectra to predict the potential application for different types of nanoparticles, which in turn will screen efficiently nanoparticles for a specific application.

Identifying mass transfer influences on Au nanoparticles growth process by centrifugation

A comparative study of gold nanoparticles (Au NPs) growth employing cetyltrimethylammonium bromide (CTAB) adsorbent was performed. Au nanooctahedrons transformed into slightly truncated nanocubes without centrifugation, whereas they transformed into nanocubes with centrifugation. Our results indicate that the mass transfer of Au monomers can influence the shape evolution of NPs.

Highly Sensitive and Automated Surface Enhanced Raman Scattering-based Immunoassay for H5N1 Detection with Digital Microfluidics

Digital microfluidics (DMF) is a powerful platform for a broad range of applications, especially immunoassays having multiple steps, due to the advantages of low reagent consumption and high automatization. Surface enhanced Raman scattering (SERS) has been proven as an attractive method for highly sensitive and multiplex detection, because of its remarkable signal amplification and excellent spatial resolution. Here we propose a SERS-based immunoassay with DMF for rapid, automated, and sensitive detection of disease biomarkers. SERS tags labeled with Raman reporter 4-mercaptobenzoic acid (4-MBA) were synthesized with a core@shell nanostructure and showed strong signals, good uniformity, and high stability. A sandwich immunoassay was designed, in which magnetic beads coated with antibodies were used as solid support to capture antigens from samples to form a beads-antibody-antigen immunocomplex. By labeling the immunocomplex with a detection antibody-functionalized SERS tag, antigen can be sensitively detected through the strong SERS signal. The automation capability of DMF can greatly simplify the assay procedure while reducing the risk of exposure to hazardous samples. Quantitative detection of avian influenza virus H5N1 in buffer and human serum was implemented to demonstrate the utility of the DMF-SERS method. The DMF-SERS method shows excellent sensitivity (LOD of 74 pg/mL) and selectivity for H5N1 detection with less assay time (<1 h) and lower reagent consumption (∼30 μL) compared to the standard ELISA method. Therefore, this DMF-SERS method holds great potentials for automated and sensitive detection of a variety of infectious diseases.