Spatial- and Valence-Matched Neutralizing DNA Nanostructure Blocks Wild-Type SARS-CoV-2 and Omicron Variant Infection.

Natural ligand-receptor interactions that play pivotal roles in biological events are ideal models for design and assembly of artificial recognition molecules. Herein, aiming at the structural characteristics of the spike trimer and infection mechanism of SARS-CoV-2, we have designed a DNA framework-guided spatial-patterned neutralizing aptamer trimer for SARS-CoV-2 neutralization. The ∼5.

Multichannel Paper Chip-Based Gas Pressure Bioassay for Simultaneous Detection of Multiple MicroRNAs.

Simultaneous detection of multi-biomarkers not only enhances the accuracy of disease diagnosis but also improves detection efficiency and reduces cost. It is vital to achieve portable, simple, low-cost, and simultaneous detection of biomarkers for point-of-care (POC) diagnostics in a low-resource setting. Herein, a multichannel paper chip-based gas pressure bioassay was developed for the simultaneous detection of multiple biomarkers by combining multichannel paper chips with a portable gas pressure meter.

Microfluidic generation of cholesteric liquid crystal droplets with an integrative cavity for dual-gain and controllable lasing.

The integration of one more gain media in droplet microlasers with morphology-dependent modes, which can be employed in optofluidic systems as multi-wavelength lasing sources, is highly attractive and demands new cavity design and fabrication approaches. Here, cholesteric liquid crystal (CLC) droplets with an integrative triple-emulsion cavity are fabricated via glass-capillary-based microfluidic technologies and dual-gain lasing with variable modes, flexibly configured by the combination and incorporation of gain dyes and CLCs into both the core and shell. The distributed feedback (DFB) mode, formed by the feedback from the self-assembled helix periodic structure of CLCs, the whispering gallery (WG) mode, and the hybrid, is selectively excited by controlling the spatial coupling between the pump beam and the droplet with gain.

Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes.

Currently, there are more than 200 fecal microbiota transplantation (FMT) clinical trials worldwide. However, our knowledge of this microbial therapy is still limited. Here we develop a strategy using sequential tagging with D-amino acid-based metabolic probes (STAMP) for assessing the viabilities of transplanted microbiotas.

Control of capillary behavior through target-responsive hydrogel permeability alteration for sensitive visual quantitative detection.

DNA hydrogels have received considerable attention in analytical science, however, some limitations still exist in the applications of intelligent hydrogels. In this paper, we describe a way to prepare gel film in a capillary tube based on the thermal reversible principle of DNA hydrogel and the principle of capillary action. Because of the slight change in the internal structure of gel, its permeability can be increased by the addition of some specific targets.

An Allosteric-Probe for Detection of Alkaline Phosphatase Activity and Its Application in Immunoassay.

A fluorescence strategy for alkaline phosphatase (ALP) assay in complicated samples with high sensitivity and strong stability is developed based on an allosteric probe (AP). This probe consists of two DNA strands, a streptavidin (SA) aptamer labeled by fluorophore and its totally complementary DNA (cDNA) with a phosphate group on the 5' end. Upon ALP introduction, the phosphate group on the cDNA is hydrolyzed, leaving the unhydrolyzed cDNA sequence for lambda exonuclease (λ exo) digestion and releasing SA aptamer for binding to SA beads, which results in fluorescence enhancement of SA beads that can be detected by flow cytometry or microscopy.

Rapid, real-time chemiluminescent detection of DNA mutation based on digital microfluidics and pyrosequencing.

To explore genome mutation meaningfully, it is in urgent need to develop an automated and inexpensive platform for DNA mutation analysis. Digital microfluidics is a powerful platform for a broad range of applications due to the advantages of high automatization and low reagent consumption. Pyrosequencing enables DNA sequencing based on non-electrophoresis bioluminescence, which is suitable for rapid and sensitive analysis of short sequences.

A tridecaptin-based fluorescent probe for differential staining of Gram-negative bacteria.

The traditional Gram-staining method, which was invented more than a century ago for differentiating bacteria as Gram positive or Gram negative, is still widely practiced in microbiology. However, Gram staining suffers from several problems which can affect the accuracy of the diagnosis. Here, we report a new Gram-negative-specific fluorescent probe, which is based on a narrow-spectrum antibiotic, tridecaptin A1, and allows selective staining of Gram-negative bacteria in different fixed bacterial samples.

Ultrasensitive and portable assay of mercury (II) ions via gas pressure as readout.

It is of the significant importance to achieve facile and on-site detection of heavy metal ions due to the serious harm to environment and human health. Herein, a facile and portable strategy was developed for detection of Hg via portable pressure meter. Biotinylated DNA1 was conjugated on the surface of streptavidin-coated magnetic beads (MBs) to form MBs-DNA1 complex.

Portable detection of serum HER-2 in breast cancer by a pressure-based platform.

A high serum HER-2 extracellular domain (sHER-2 ECD) level has a reverse association with tumor behaviors. In this study, a portable platform for the disease biomarker sHER-2 ECD detection has been established using a pressure-based bioassay. The pressure bioassay consists of a monoclonal antibody immobilized on an eight-well strip, the analyte HER-2, and another monoclonal antibody labeled with the Pt nanoparticles (PtNPs), which have the catalytic ability to decompose HO into HO and O(g).

Frequency-enhanced transferrin receptor antibody-labelled microfluidic chip (FETAL-Chip) enables efficient enrichment of circulating nucleated red blood cells for non-invasive prenatal diagnosis.

Fetal aneuploidy and other chromosomal aberrations affect 9 in 1000 live births. Unlike the invasive diagnosis with high risk of miscarriage, non-invasive prenatal diagnosis (NIPD) sampling from maternal blood becomes a promising way for fetal genetic screening. However, fetal cell-based NIPD has a major challenge due to the small number of fetal cells present in maternal blood.

A Synthetic Light-Driven Substrate Channeling System for Precise Regulation of Enzyme Cascade Activity Based on DNA Origami.

Substrate channeling, in which a metabolic intermediate is directly passed from one enzyme to the next enzyme in an enzyme cascade, accelerates the processing of metabolites and improves substrate selectivity. Synthetic design and precise control of channeling outside the cellular environment are of significance in areas such as synthetic biology, synthetic chemistry, and biomedicine. In particular, the precise control of synthetic substrate channeling in response to light is highly important, but remains a major challenge.

Ultrasensitive and Facile Detection of MicroRNA via a Portable Pressure Meter.

The upregulation of microRNA (miRNA) is highly related with some kinds of tumor, such as breast, prostate, lung, and pancreatic cancers. Therefore, for an important tumor biomarker, the point-of-care testing (POCT) of miRNA is of significant importance and is in great demand for disease diagnosis and clinical prognoses. Herein, a POCT assay for miRNA detection was developed via a portable pressure meter.

Target-responsive DNA hydrogel for non-enzymatic and visual detection of glucose.

We have successfully developed a target-responsive aptamer cross-linked hydrogel for the visual detection of glucose, an important biomedical analyte. In this work, the glucose-responsive hydrogel was prepared using the target aptamer and its two short complementary DNA strands grafted onto a linear polyacrylamide chain as cross-linkers. Gold nanoparticles (AuNPs) modified with thiol-PEG were encapsulated in the gel and used as the output signal for visible detection.

Detection of T4 Polynucleotide Kinase via Allosteric Aptamer Probe Platform.

As a vital enzyme in DNA phosphorylation and restoration, T4 polynucleotide kinase (T4 PNK) has aroused great interest in recent years. Therefore, numerous strategies have been established for highly sensitive detection of T4 PNK based on diverse signal amplification techniques. However, they often need sophisticated design, a variety of auxiliary reagents and enzymes, or cumbersome manipulations.

Point-of-Care Assay of Telomerase Activity at Single-Cell Level via Gas Pressure Readout.

Detection of telomerase activity at the single-cell level is one of the central challenges in cancer diagnostics and therapy. Herein, we describe a facile and reliable point-of-care testing (POCT) strategy for detection of telomerase activity via a portable pressure meter. Telomerase primer (TS) was immobilized onto the surface of magnetic beads (MBs), and then was elongated to a long single-stranded DNA by telomerase.

Integrating Target-Responsive Hydrogel with Pressuremeter Readout Enables Simple, Sensitive, User-Friendly, Quantitative Point-of-Care Testing.

Point-of-care testing (POCT) with the advantages of speed, simplicity, and low cost, as well as no need for instrumentation, is critical for the measurement of analytes in a variety of environments lacking access to laboratory infrastructure. In the present study, a hydrogel pressure-based assay for quantitative POCT was developed by integrating a target-responsive hydrogel with pressuremeter readout. The target-responsive hydrogels were constructed with DNA grafted linear polyacrylamide and the cross-linking DNA for selective target recognition.

Hydrogel Droplet Microfluidics for High-Throughput Single Molecule/Cell Analysis.

Heterogeneity among individual molecules and cells has posed significant challenges to traditional bulk assays, due to the assumption of average behavior, which would lose important biological information in heterogeneity and result in a misleading interpretation. Single molecule/cell analysis has become an important and emerging field in biological and biomedical research for insights into heterogeneity between large populations at high resolution. Compared with the ensemble bulk method, single molecule/cell analysis explores the information on time trajectories, conformational states, and interactions of individual molecules/cells, all key factors in the study of chemical and biological reaction pathways.

Portable visual quantitative detection of aflatoxin B1 using a target-responsive hydrogel and a distance-readout microfluidic chip.

Aflatoxin B1 (AFB1), as the secondary metabolite of molds, is the most predominant and toxic mycotoxin that seriously threatens the health of humans and animals. In this work, an AFB1-responsive hydrogel was synthesized for highly sensitive and portable detection of AFB1. The AFB1-responsive hydrogel was prepared using an AFB1 aptamer and its two short complementary DNA strands as cross-linkers.

Inhibition of the superantigenic activities of Staphylococcal enterotoxin A by an aptamer antagonist.

Staphylococcal enterotoxin A (SEA) is an important component of Staphylococcus aureus pathogenesis. SEA induces T lymphocytes activation and proliferation, resulting in the release of a large number of inflammatory cytokines. Blocking the toxic cascade triggered by SEA may be an effective strategy for the treatment of SEA-induced diseases.

Directional Regulation of Enzyme Pathways through the Control of Substrate Channeling on a DNA Origami Scaffold.

Artificial multi-enzyme systems with precise and dynamic control over the enzyme pathway activity are of great significance in bionanotechnology and synthetic biology. Herein, we exploit a spatially addressable DNA nanoplatform for the directional regulation of two enzyme pathways (G6pDH-MDH and G6pDH-LDH) through the control of NAD(+) substrate channeling by specifically shifting NAD(+) between the two enzyme pairs. We believe that this concept will be useful for the design of regulatory biological circuits for synthetic biology and biomedicine.

Distance-based microfluidic quantitative detection methods for point-of-care testing.

Equipment-free devices with quantitative readout are of great significance to point-of-care testing (POCT), which provides real-time readout to users and is especially important in low-resource settings. Among various equipment-free approaches, distance-based visual quantitative detection methods rely on reading the visual signal length for corresponding target concentrations, thus eliminating the need for sophisticated instruments. The distance-based methods are low-cost, user-friendly and can be integrated into portable analytical devices.

Microfluidic fabrication of cholesteric liquid crystal core-shell structures toward magnetically transportable microlasers.

We report a magnetically transportable microlaser with cholesteric liquid crystal (CLC) core-shell structure, operating in band-edge mode. The dye doped CLC shells as a water-in-oil-in-water (W/O/W) double emulsion were fabricated by microfluidics. Water-dispersible Fe3O4 magnetic nanoparticles were incorporated in the inner aqueous phase by taking advantage of the immiscibility with the middle CLC oil phase.

Enzyme-Encapsulated Liposome-Linked Immunosorbent Assay Enabling Sensitive Personal Glucose Meter Readout for Portable Detection of Disease Biomarkers.

There is considerable demand for sensitive, selective, and portable detection of disease-associated proteins, particularly in clinical practice and diagnostic applications. Portable devices are highly desired for detection of disease biomarkers in daily life due to the advantages of being simple, rapid, user-friendly, and low-cost. Herein we report an enzyme-encapsulated liposome-linked immunosorbent assay for sensitive detection of proteins using personal glucose meters (PGM) for portable quantitative readout.

Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging.

Gliosarcoma, a variant of glioblastoma multiforme (GBM), is a highly invasive malignant tumor. Unfortunately, this disease still marked by poor prognosis regardless of modern treatments. It is of great significance to discover specific molecular probes targeting gliosarcoma for early cancer diagnosis and therapy.