Yunlei Xianyu

Nanomaterials for Ultrasensitive Protein Detection

The advances of nanomaterials have provided exciting technologies and novel materials for protein detection, based on the unique properties associated with nanoscale phenomena such as plasmon resonance, catalysis and energy transfer. This article reviews a series of nanomaterials including nanoparticles, nanofibers, nanowires, and nanosheets, and evaluates their performances in the application for protein detection, focusing on approaches that realize ultrasensitive detection. Many of these nanomaterials were used to analyze clinically relevant protein biomarkers. Their detection in the picomolar, femtomolar or even zeptomolar regime has been realized, sometimes even with naked-eye readout. We summarize the detection methods and results according to materials and targets, review the current challenges, and discuss the solution in the context of technological integration such as combining nanomaterials with microfluidics, and classical analytical technologies.

Size-based hydrodynamic rare tumor cell separation in curved microfluidic channels

In this work, we propose a rapid and continuous rare tumor cell separation based on hydrodynamic effects in a label-free manner. The competition between the inertial lift force and Dean drag force inside a double spiral microchannel results in the size-based cell separation of large tumor cells and small blood cells. The mechanism of hydrodynamic separation in curved microchannel was investigated by a numerical model. Experiments with binary mixture of 5- and 15-μm-diameter polystyrene particles using the double spiral channel showed a separation purity of more than 95% at the flow rate above 30 ml/h. High throughput (2.5 × 10(8) cells/min) and efficient cell separation (more than 90%) of spiked HeLa cells and 20 × diluted blood cells was also achieved by the double spiral channel.

A Plasmonic Nanosensor for Immunoassay via Enzyme-Triggered Click Chemistry

Current techniques for plasmonic immunoassay often require the introduction and additional conjugation of enzyme, and thus cannot accommodate conventional immunoassay platforms. Herein, we develop a plasmonic nanosensor that well accommodates conventional immunoassays and dramatically improves their sensitivity and stability. This plasmonic nanosensor directly employs alkaline phosphatase-triggered click chemistry between azide/alkyne functionalized gold nanoparticles as the readout. This straightforward approach broadens the applicability of nanoparticle-based immunoassays and has great potential for applications in resource-constrained settings.

One-Step Detection of Pathogens and Viruses: Combining Magnetic Relaxation Switching and Magnetic Separation

We report a sensing methodology that combines magnetic separation (MS) and magnetic relaxation switching (MS-MRS) for one-step detection of bacteria and viruses with high sensitivity and reproducibility. We first employ a magnetic field of 0.01 T to separate the magnetic beads of large size (250 nm in diameter) from those of small size (30 nm in diameter) and use the transverse relaxation time (T2) of the water molecules around the 30 nm magnetic beads (MB30) as the signal readout of the immunoassay. An MS-MRS sensor integrates target enrichment, extraction, and detection into one step, and the entire immunoassay can be completed within 30 min. Compared with a traditional MRS sensor, an MS-MRS sensor shows enhanced sensitivity, better reproducibility, and convenient operation, thus providing a promising platform for point-of-care testing.

A Dispersion-Dominated Chromogenic Strategy for Colorimetric Sensing of Glutathione at the Nanomolar Level Using Gold Nanoparticles.

A dispersion-dominated chromogenic strategy for glutathione sensing is developed. Glutathione prevents the aggregation of arginine-modified gold nanoparticles via mercury-thiol interaction, which allows for glutathione sensing at the nanomolar level (10.9 × 10(-9) m) with facile operation and naked-eye readout.

Surface Modification of Gold Nanoparticles with Small Molecules for Biochemical Analysis

As one of the major tools for and by chemical science, biochemical analysis is becoming increasingly important in fields like clinical diagnosis, food safety, environmental monitoring, and the development of chemistry and biochemistry. The advancement of nanotechnology boosts the development of analytical chemistry, particularly the nanoparticle (NP)-based approaches for biochemical assays. Functional NPs can greatly improve the performance of biochemical analysis because they can accelerate signal transduction, enhance the signal intensity, and enable convenient signal readout due to their unique physical and chemical properties. Surface chemistry is a widely used tool to functionalize NPs, and the strategy for surface modification is of great significance to the application of NP-mediated biochemical assays. Surface chemistry not only affects the quality of NPs (stability, monodispersity, and biocompatibility) but also provides functional groups (-COO-, -NH3+, -CHO, and so on) or charges that can be exploited for bioconjugation or ligand exchange. Surface chemistry also dictates the sensitivity and specificity of the NP-mediated biochemical assays, since it is vital to the orientation, accessibility, and bioactivity of the functionalized ligands on the NPs. In this Account, we will focus on surface chemistry for functionalization of gold nanoparticles (AuNPs) with small organic molecules for biochemical analysis. Compared to other NPs, AuNPs have many merits including controllable synthesis, easy surface modification and high molar absorption coefficient, making them ideal probes for biochemical assays. Small-molecule functionalized AuNPs are widely employed to develop sensors for biochemical analysis, considering that small molecules, such as amino acids and sulfhydryl compounds, are more easily and controllably bioconjugated to the surface of AuNPs than biomacromolecules due to their less complex structure and steric hindrance. The orientation and accessibility of small molecules on AuNPs in most cases can be precisely controlled without compromising their bioactivity as well, thus ensuring the performance, such as the specificity and sensitivity, of AuNP-based biochemical assays. This Account reviews recent progress in the surface chemistry of functionalized AuNPs for biochemical assays. The surface chemistries mainly include click chemistry, ligand exchange reaction, and coordination-based recognition. These surface-modified AuNPs allow for assaying a range of important biochemical markers including metal ions, small biomolecules, enzymes, and antigens and antibodies. Applications of these systems range from environmental monitoring to medical diagnostics. This Account highlights the advantages and limitations (sensitivity, detection efficiency, and stability) that AuNP-mediated assays still have compared with conventional analytical methods. This Account also discusses the future research directions of surface-modified AuNP-mediated biochemical analysis. The main aim of this Account is to summarize the current surface modification strategies for AuNPs and further demonstrate how to make use of surface modification strategies to effectively improve the performance of AuNP-mediated analytical methods for a wide variety of applications relating to biochemical analysis.

Culturing primary human osteoblasts on electrospun poly(lactic-co-glycolic acid) and poly(lactic-co-glycolic acid)/nanohydroxyapatite scaffolds for bone tissue engineering.

In this work, we fabricated polymeric fibrous scaffolds for bone tissue engineering using primary human osteoblasts (HOB) as the model cell. By employing one simple approach, electrospinning, we produced poly(lactic-co-glycolic acid) (PLGA) scaffolds with different topographies including microspheres, beaded fibers, and uniform fibers, as well as the PLGA/nanohydroxyapatite (nano-HA) composite scaffold. The bone-bonding ability of electrospun scaffolds was investigated by using simulated body fluid (SBF) solution, and the nano-HA in PLGA/nano-HA composite scaffold can significantly enhance the formation of the bonelike apatites. Furthermore, we carried out in vitro experiments to test the performance of electrospun scaffolds by utilizing both mouse preosteoblast cell line (MC 3T3 E1) and HOB. Results including cell viability, alkaline phosphatase (ALP) activity, and osteocalcin concentration demonstrated that the PLGA/nano-HA fibers can promote the proliferation of HOB efficiently, indicating that it is a promising scaffold for human bone repair.

Enzymatic Assay for Cu(II) with Horseradish Peroxidase and Its Application in Colorimetric Logic Gate

We report an ultrasensitive and colorimetric assay for Cu(II) via enzymatic amplification strategy. The enzymatic activity of horseradish peroxidase (HRP) is strongly inhibited by Cu(I), which can be used indirectly to assay Cu(II). The limit of detection (LOD) is 0.37 nM, and the detection of 20 nM Cu(II) in solution can be achieved with naked eyes. This assay can be used to construct a colorimetric logic gate.

Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer

Pancreatic cancer is one of the deadliest human cancers, whose progression is highly dependent on the nervous microenvironment. The suppression of gene expression of nerve growth factor (NGF) may have great potential in pancreatic cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA of NGF (GNC–siRNA) allows efficient NGF gene silencing and pancreatic cancer treatment. The GNC–siRNA complex increases the stability of siRNA in serum, prolongs the circulation lifetime of siRNA in blood and enhances the cellular uptake and tumour accumulation of siRNA. The GNC–siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects. Our study constitutes a straightforward but effective approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising therapeutic direction for pancreatic cancer.

Horseradish Peroxidase-Mediated, Iodide-Catalyzed Cascade Reaction for Plasmonic Immunoassays

This report outlines an enzymatic cascade reaction for signal transduction and amplification for plasmonic immunoassays by using horseradish peroxidase (HRP)-mediated aggregation of gold nanoparticles (AuNPs). HRP-catalyzed oxidation of iodide and iodide-catalyzed oxidation of cysteine is employed to modulate the plasmonic signals of AuNPs. It agrees well with the current immunoassay platforms and allows naked-eye readout with enhanced sensitivity, which holds great promise for applications in resource-constrained settings.