Multicolor-Assay-on-a-Chip Processed by Robotic Operation (MACpro) with Improved Diagnostic Accuracy for Field-Deployable Detection.

The ability to deploy decentralized laboratories with autonomous and reliable disease diagnosis holds the potential to deliver accessible healthcare services for public safety. While microfluidic technologies provide precise manipulation of small fluid volumes with improved assay performance, their limited automation and versatility confine them to laboratories. Herein, we report the utility of multicolor assay-on-a-chip processed by robotic operation (MACpro), to address this unmet need. The MACpro platform comprises a robot-microfluidic interface and an eye-in-hand module that provides flexible yet stable actions to execute tasks in a programmable manner, such as the precise manipulation of the microfluidic chip along with different paths. Notably, MACpro shows improved detection performance by integrating the microbead-based antibody immobilization with enhanced target recognition and multicolor sensing via Cu2+-catalyzed plasmonic etching of gold nanorods for rapid and sensitive analyte quantification. Using interferon-gamma as an example, we demonstrate that MACpro completes a sample-to-answer immunoassay within 30 min and achieves a 10-fold broader dynamic range and a 10-fold lower detection limit compared to standard enzyme-linked immunosorbent assays (0.66 vs 5.2 pg/mL). MACpro extends the applications beyond traditional laboratories and presents an automated solution to expand diagnostic capacity in diverse settings.

Plasmonic LAMP: Improving the Detection Specificity and Sensitivity for SARS-CoV-2 by Plasmonic Sensing of Isothermally Amplified Nucleic Acids.

The ability to detect pathogens specifically and sensitively is critical to combat infectious diseases outbreaks and pandemics. Colorimetric assays involving loop-mediated isothermal amplification (LAMP) provide simple readouts yet suffer from the intrinsic non-template amplification. Herein, a highly specific and sensitive assay relying on plasmonic sensing of LAMP amplicons via DNA hybridization, termed as plasmonic LAMP, is developed for the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) RNA detection. This work has two important advances. First, gold and silver (Au-Ag) alloy nanoshells are developed as plasmonic sensors that have 4-times stronger extinction in the visible wavelengths and give a 20-times lower detection limit for oligonucleotides over Au counterparts. Second, the integrated method allows cutting the complex LAMP amplicons into short repeats that are amendable for hybridization with oligonucleotide-functionalized Au-Ag nanoshells. In the SARS-CoV-2 RNA detection, plasmonic LAMP takes ≈75 min assay time, achieves a detection limit of 10 copies per reaction, and eliminates the contamination from non-template amplification. It also shows better detection specificity and sensitivity over commercially available LAMP kits due to the additional sequence identification. This work opens a new route for LAMP amplicon detection and provides a method for virus testing at its early representation.

Platinum-Decorated Gold Nanoparticles with Dual Functionalities for Ultrasensitive Colorimetric in Vitro Diagnostics.

Au nanoparticles (AuNPs) as signal reporters have been utilized in colorimetric in vitro diagnostics (IVDs) for decades. Nevertheless, it remains a grand challenge to substantially enhance the detection sensitivity of AuNP-based IVDs as confined by the inherent plasmonics of AuNPs. In this work, we circumvent this confinement by developing unique dual-functional AuNPs that were engineered by coating conventional AuNPs with ultrathin Pt skins of sub-10 atomic layers (i.e., Au@Pt NPs). The Au@Pt NPs retain the plasmonic activity of initial AuNPs while possessing ultrahigh catalytic activity enabled by Pt skins. Such dual functionalities, plasmonics and catalysis, offer two different detection alternatives: one produced just by the color from plasmonics (low-sensitivity mode) and the second more sensitive color catalyzed from chromogenic substrates (high-sensitivity mode), achieving an "on-demand" tuning of the detection performance. Using lateral flow assay as a model IVD platform and conventional AuNPs as a benchmark, we demonstrate that the Au@Pt NPs could enhance detection sensitivity by 2 orders of magnitude.

Facile Colorimetric Detection of Silver Ions with Picomolar Sensitivity.

Although various colorimetric methods have been actively developed for the detection of Ag+ ions because of their simplicity and reliability, the limits of detection of these methods are confined to the nanomolar (nM) level. Here, we demonstrate a novel strategy for colorimetric Ag+ detection with picomolar (pM) sensitivity. This strategy involves the use of poly(vinylpyrrolidone)- (PVP-) capped Pt nanocubes as artificial peroxidases that can effectively generate a colored signal by catalyzing the oxidation of peroxidase substrates. In the presence of Ag+ ions, the colored signal generated by these Pt cubes is greatly diminished because of the specific and efficient inhibition of Ag+ toward the peroxidase-like activity of the Pt cubes. This colorimetric method can achieve an ultralow detection limit of 80 pM and a wide dynamic range of 10-2-104 nM. To the best of our knowledge, the method presented in this work shows the highest sensitivity for Ag+ detection among all reported colorimetric methods. Moreover, this method also features simplicity and rapidness as it can be conducted at room temperature, in aqueous solution, and requires only ∼6 min.

Ru Nanoframes with an fcc Structure and Enhanced Catalytic Properties.

Noble-metal nanoframes are of great interest to many applications due to their unique open structures. Among various noble metals, Ru has never been made into nanoframes. In this study, we report for the first time an effective method based on seeded growth and chemical etching for the facile synthesis of Ru nanoframes with high purity. The essence of this approach is to induce the preferential growth of Ru on the corners and edges of Pd truncated octahedra as the seeds by kinetic control. The resultant Pd-Ru core-frame octahedra could be easily converted to Ru octahedral nanoframes of ∼2 nm in thickness by selectively removing the Pd cores through chemical etching. Most importantly, in this approach the face-centered cubic (fcc) crystal structure of Pd seeds was faithfully replicated by Ru that usually takes an hcp structure. The fcc Ru nanoframes showed higher catalytic activities toward the reduction of p-nitrophenol by NaBH4 and the dehydrogenation of ammonia borane compared with hcp Ru nanowires with roughly the same thickness.

Controllable Synthesis of Cadmium-Free Blue-Emitting Cu-Ga-Zn-S-Based Nanocrystals for Solution-Processed Quantum-Dot Light-Emitting Diodes.

The utility of semiconductor nanocrystals (NCs) in light-emitting diodes (LED) has shown great potential in the field of display, whereas the challenge remains in developing efficient and stable cadmium-free blue-emitting LED devices due to the poor photophysical properties of blue-emitting NCs. Herein, we develop a controllable synthesis of Cu-Ga-Zn-S (CGZS) semiconductor NCs that show blue light emission with a relative photoluminescence quantum yield exceeding 90%. Furthermore, we have successfully fabricated a solution-processed quantum-dot LED (QLED) using CGZS NCs, achieving a notable maximum external quantum efficiency (EQE) of 1.00% at a luminance of 100 cd/m2. Our work lays a foundational framework for advancing cadmium-free blue-emitting QLEDs and facilitates the development of quantum dot electroluminescent panchromatic displays.

Facile one-step synthesis and transformation of Cu(I)-doped zinc sulfide nanocrystals to Cu(1.94)S-ZnS heterostructured nanocrystals.

A facile one-pot heating process without any injection has been developed to synthesize different Cu-Zn-S-based nanocrystals. The composition of the products evolves from Cu(I)-doped ZnS (ZnS:Cu(I)) nanocrystals into heterostructured nanocrystals consisting of monoclinic Cu1.94S and wurtzite ZnS just by controlling the molar ratios of zinc acetylacetonate (Zn(acac)2) to copper acetylacetonate (Cu(acac)2) in the mixture of n-dodecanethiol (DDT) and 1-octadecene (ODE). Accompanying the composition transformation, the crystal phase of ZnS is changed from cubic zinc blende to hexagonal wurtzite. Depending on the synthetic parameters including the reaction time, temperature, and the feeding ratios of Zn/Cu precursors, the morphology of the as-obtained heterostructured nanocrystals can be controlled in the forms of taper-like, matchstick-like, tadpole-like, or rod-like. Interestingly, when the molar ratio of Cu(acac)2 to Zn(acac)2 is increased to 9:1, the crystal phase of the products is transformed from monoclinic Cu1.94S to the mixed phase composed of cubic Cu1.8S and tetragonal Cu1.81S as the reaction time is further prolonged. The crystal-phase transformation results in the morphological change from quasi-spherical to rice shape due to the incorporation of Zn ions into the Cu1.94S matrix. This method provides a simple but highly reproducible approach for synthesis of Cu(I)-doped nanocrystals and heterostructured nanocrystals, which are potentially useful in the fabrication of optoelectronic devices.

Controllable synthesis of silver and silver sulfide nanocrystals via selective cleavage of chemical bonds.

A one-step colloidal process has been adopted to prepare silver (Ag) and silver sulfide (Ag2S) nanocrystals, thus avoiding presynthesis of an organometallic precursor and the injection of a toxic phosphine agent. During the reaction, a layered intermediate compound is first formed, which then acts as a precursor, decomposing into the nanocrystals. The composition of the as-obtained products can be controlled by selective cleavage of S-C bonds or Ag-S bonds. Pure Ag2S nanocrystals can be obtained by directly heating silver acetate (Ag(OAc)) and n-dodecanethiol (DDT) at 200 ° C without any surfactant, and pure Ag nanocrystals can be synthesized successfully if the reaction temperature is reduced to 190 ° C and the amount of DDT is decreased to 1 ml in the presence of a non-coordinating organic solvent (1-octadecene, ODE). Otherwise, the mixture of Ag and Ag2S is obtained by directly heating Ag(OAc) in DDT by increasing the reaction temperature or in a mixture of DDT and ODE at 200 ° C. The formation mechanism has been discussed in detail in terms of selective S-C and Ag-S bond dissociation due to the nucleophilic attack of DDT and the lower bonding energy of Ag-S. Interestingly, some products can easily self-assemble into two- or three-dimensional (2D or 3D) highly ordered superlattice structures on a copper grid without any additional steps. The excess DDT plays a key role in the superlattice structure due to the bundling and interdigitation of the thiolate molecules adsorbed on the as-obtained nanocrystals.

Shape-controlled synthesis of PbS nanocrystals via a simple one-step process.

A one-step colloidal process was adopted to prepare face-centered-cubic PbS nanocrystals with different shapes such as octahedral, starlike, cubic, truncated octahedral, and truncated cubic. The features of this approach avoid the presynthesis of any organometallic precursor and the injection of a toxic phosphine agent. A layered intermediate compound (lead thiolate) forms in the initial stage of the reaction, which effectively acts as the precursor to decompose into the PbS nanocrystals. The size and shape of the PbS nanocrystals can be easily controlled by varying the reaction time, the reactant concentrations, the reaction temperatures, and the amount of surfactants. In particular, additional surfactants other than dodecanethiol, such as oleylamine, oleic acid, and octadecene, play an important role in the shape control of the products. The possible formation mechanism for the PbS nanocrystals with various shapes is presented on the basis of the different growth directions of the nanocrystals with the assistance of the different surfactants. This method provides a facile, low-cost, highly reproducible process for the synthesis of PbS nanocrystals that may have potential applications in the fabrication of photovoltaic devices and photodetectors.

Digital plasmonic nanobubble detection for rapid and ultrasensitive virus diagnostics.

Rapid and sensitive diagnostics of infectious diseases is an urgent and unmet need as evidenced by the COVID-19 pandemic. Here, we report a strategy, based on DIgitAl plasMONic nanobubble Detection (DIAMOND), to address this need. Plasmonic nanobubbles are transient vapor bubbles generated by laser heating of plasmonic nanoparticles (NPs) and allow single-NP detection. Using gold NPs as labels and an optofluidic setup, we demonstrate that DIAMOND achieves compartment-free digital counting and works on homogeneous immunoassays without separation and amplification steps. DIAMOND allows specific detection of respiratory syncytial virus spiked in nasal swab samples and achieves a detection limit of ~100 PFU/mL (equivalent to 1 RNA copy/µL), which is competitive with digital isothermal amplification for virus detection. Therefore, DIAMOND has the advantages including one-step and single-NP detection, direct sensing of intact viruses at room temperature, and no complex liquid handling, and is a platform technology for rapid and ultrasensitive diagnostics.

Gold Nanourchins Improve Virus Targeting and Plasmonic Coupling for Virus Diagnosis on a Smartphone Platform.

Point-of-care detection of pathogens is critical to monitor and combat viral infections. The plasmonic coupling assay (PCA) is a homogeneous assay and allows rapid, one-step, and colorimetric detection of intact viruses. However, PCA lacks sufficient sensitivity, necessitating further mechanistic studies to improve the detection performance of PCA. Here, we demonstrate that gold nanourchins (AuNUs) provide significantly improved colorimetric detection of viruses in PCA. Using respiratory syncytial virus (RSV) as a target, we demonstrate that the AuNU-based PCA achieves a detection limit of 1400 PFU/mL, or 17 genome equivalent copies/µL. Mechanistic studies suggest that the improved detection sensitivity arises from the higher virus-binding capability and stronger plasmonic coupling at long distances (∼10 nm) by AuNU probes. Furthermore, we demonstrate the virus detection with a portable smartphone-based spectrometer using RSV-spiked nasal swab clinical samples. Our study uncovers important mechanisms for the sensitive detection of intact viruses in PCA and provides a potential toolkit at the point of care.

Single-Molecule Detection of SARS-CoV-2 by Plasmonic Sensing of Isothermally Amplified Nucleic Acids.

Single-molecule detection of pathogens such as SARS-CoV-2 is key to combat infectious diseases outbreak and pandemic. Currently colorimetric sensing with loop-mediated isothermal amplification (LAMP) provides simple readouts but suffers from intrinsic non-template amplification. Herein, we report that plasmonic sensing of LAMP amplicons via DNA hybridization allows highly specific and single-molecule detection of SARS-CoV-2 RNA. Our work has two important advances. First, we develop gold and silver alloy (Au-Ag) nanoshells as plasmonic sensors that have 4-times stronger extinction in the visible wavelengths and give 20-times lower detection limit for oligonucleotides than Au nanoparticles. Second, we demonstrate that the diagnostic method allows cutting the complex LAMP amplicons into short repeats that are amendable for hybridization with oligonucleotide-functionalized nanoshells. This additional sequence identification eliminates the contamination from non-template amplification. The detection method is a simple and single-molecule diagnostic platform for virus testing at its early representation.

Single-Particle Counting Based on Digital Plasmonic Nanobubble Detection for Rapid and Ultrasensitive Diagnostics.

Rapid and sensitive diagnostics of infectious diseases is an urgent and unmet need as evidenced by the COVID-19 pandemic. Here we report a novel strategy, based on DIgitAl plasMONic nanobubble Detection (DIAMOND), to address these gaps. Plasmonic nanobubbles are transient vapor bubbles generated by laser heating of plasmonic nanoparticles and allow single-particle detection. Using gold nanoparticles labels and an optofluidic setup, we demonstrate that DIAMOND achieves a compartment-free digital counting and works on homogeneous assays without separation and amplification steps. When applied to the respiratory syncytial virus diagnostics, DIAMOND is 150 times more sensitive than commercial lateral flow assays and completes measurements within 2 minutes. Our method opens new possibilities to develop single-particle digital detection methods and facilitate rapid and ultrasensitive diagnostics. ONE SENTENCE SUMMARY: Single-particle digital plasmonic nanobubble detection allows rapid and ultrasensitive detection of viruses in a one-step homogeneous assay.

Signal amplification and quantification on lateral flow assays by laser excitation of plasmonic nanomaterials.

Lateral flow assay (LFA) has become one of the most widely used point-of-care diagnostic methods due to its simplicity and low cost. While easy to use, LFA suffers from its low sensitivity and poor quantification, which largely limits its applications for early disease diagnosis and requires further testing to eliminate false-negative results. Over the past decade, signal enhancement strategies that took advantage of the laser excitation of plasmonic nanomaterials have pushed down the detection limit and enabled quantification of analytes. Significantly, these methods amplify the signal based on the current LFA design without modification. This review highlights these strategies of signal enhancement for LFA including surface enhanced Raman scattering (SERS), photothermal and photoacoustic methods. Perspectives on the rational design of the reader systems are provided. Future translation of the research toward clinical applications is also discussed.

Self-healing supramolecular hydrogels through host-guest interaction between cyclodextrin and carborane.

New self-healing hydrogels based on the strong host-guest interaction of carborane (CB) and ß-cylcodextrin (CD) were constructed through CB-grafted dextran and ß-CD-grafted poly(acrylic acid). The storage modulus of the hydrogels could reach as high as 10 kPa, and the hydrogels exhibited an outstanding self-healing rate in minutes.

Seed-mediated growth of heterostructured Cu1.94S-MS (M = Zn, Cd, Mn) and alloyed CuNS2 (N = In, Ga) nanocrystals for use in structure- and composition-dependent photocatalytic hydrogen evolution.

Multinary copper-based chalcogenide nanocrystals (NCs) as light-driven photocatalysts have attracted extensive research interest due to their great potential for generating sustainable energy without causing environmental concerns. However, systematic studies on the growth mechanism and related photocatalytic activities involving different valent metal ions (either M2+ or N3+) as foreign cations and monoclinic Cu1.94S NCs as the 'parent lattice' have rarely been carried out. In this work, we report an effective seed-mediated method for the synthesis of heterostructured Cu1.94S-MS NCs (M = Zn, Cd and Mn) and alloyed CuNS2 NCs (N = In and Ga). A typical cation exchange process took place prior to the growth of heterostructured NCs, while further inter-cation diffusion occurred only for the alloyed NCs. When compared with Cu1.94S NCs, all the heterostructured Cu1.94S-MS NCs and CuGaS2 NCs showed enhanced photocatalytic activities toward hydrogen production by water splitting, owing to their tailored optical band gaps and energy level alignments. Although optically favored, CuInS2 ANCs were not comparable to others due to their low conduction band minimum for the reduction of H2O to H2.

Template Regeneration in Galvanic Replacement: A Route to Highly Diverse Hollow Nanostructures.

The ability to produce a diverse spectrum of hollow nanostructures is central to the advances in many current and emerging areas of technology. Herein, we report a general method to craft hollow nanostructures with highly tunable physical and chemical parameters. The key strategy is to regenerate the nanoscale sacrificial templates in a galvanic replacement reaction through site-selective overgrowth. As examples, we demonstrate the syntheses of nanocages and nanotubes made of silver, gold, palladium, and/or platinum with well-controlled wall thicknesses and elemental distributions. Using the nanocages of silver and gold as models, we demonstrate they possess intriguing plasmonic properties and offer superior performance in biosensing applications. This study provides a powerful platform to customize hollow nanostructures with desired properties and therefore is expected to enable a variety of fundamental studies and technologically important applications.

Enhancing the sensitivity of colorimetric lateral flow assay (CLFA) through signal amplification techniques.

Colorimetric lateral flow assay (CLFA) is one of a handful of diagnostic technologies that can be truly taken out of the laboratory for point-of-care testing without the need for any equipment and skilled personnel. Despite its simplicity and practicality, it remains a grand challenge to substantially enhance the detection sensitivity of CLFA without adding complexity. Such a limitation in sensitivity inhibits many critical applications such as early detection of significant cancers and severe infectious diseases. With the rapid development of materials science and nanotechnology, signal amplification techniques that hold great potential to break through the existing detection limit barrier of CLFA have been developed in recent years. This article specifically highlights these emerging techniques for CLFA development. The rationale behind and advantages and limitations of each technique are discussed. Perspectives on future research directions in this niche and important field are provided.

From one-dimensional to two-dimensional wurtzite CuGaS2 nanocrystals: non-injection synthesis and photocatalytic evolution.

Multinary copper-based chalcogenides exhibit significant performance in photocatalytic hydrogen evolution due to their suitable optical bandgap for visible light absorption and environmentally friendly character. Herein, high-quality wurtzite CuGaS2 (CGS) nanocrystals (NCs) were synthesized by using a one-step heating-up process without any injection, and the morphology could be tuned from one-dimensional (1D) to two-dimensional (2D) by precise choice of surface ligands and gallium precursors. The formation mechanism of CGS NCs was studied comprehensively by means of the temporal-evolution of the morphology, crystal structure and optical absorption results. The reaction started from djurleite Cu31S16 NCs, and then proceeded with the formation of Cu31S16-CGS heteronanostructures (HNS), and finally the transformation from HNS to monophasic CGS nanorods took place with prolonging of the synthesis time. The optical bandgap and the energy level of the different-dimensional CGS NCs exhibited a strong dependence on the morphology change, which correlated with the percentage of the exposed {001} and {100} facets. The theoretical calculation based on density functional theory (DFT) revealed that the (001) surface facilitated the charge transport rather than the (100) surface, which was consistent with the electrochemical impedance spectroscopy (EIS) results. As a result, the 2D CGS nanoplates with more exposed {001} facets exhibited an attractive photocatalytic hydrogen production activity under simulated solar illumination as compared to 1D and quasi-2D counterparts. This study demonstrates that control over the dimension of I-III-V group semiconductor NCs could lead to a significant improvement of the photocatalytic hydrogen evolution.

A non-enzyme cascade amplification strategy for colorimetric assay of disease biomarkers.

A non-enzyme cascade amplification strategy, based on the dissolution of Ag nanoparticles and a Pt nanocube-catalyzed reaction, for colorimetric assay of disease biomarkers was developed. This strategy overcomes the intrinsic limitations of enzymes involved in conventional enzymatic amplification techniques, thanks to the utilization of noble-metal nanostructures with superior properties.