Peroxidase mimics of platinum-group metals for in vitro diagnostics: opportunities and challenges.

Platinum-group metal (PGM) nanostructures with peroxidase-like catalytic activities (i.e., peroxidase mimics) have been actively developed and applied to in vitro diagnostics in recent years. This article provides our viewpoints on this emerging field from the perspectives of materials science and solid-state chemistry angles. We start with an introduction to PGM peroxidase mimics, their catalytic efficiencies, and insights into catalysis from computational simulations. We then discuss chemical approaches to the synthesis of PGM peroxidase mimics with desired physicochemical parameters and catalytic properties. Then, we elaborate on general methods for functionalizing the surfaces of PGM mimics with bioreceptors. Thereafter, we highlight the applications of PGM mimics in in vitro diagnostics, emphasizing the interactions of PGM mimics with other components of a diagnostic system. We conclude this article with our opinions on the challenges and opportunities in this field.

On the role of wall thickness in determining the plasmonic properties of silver-gold nanocages.

This work examines the roles played by wall thickness in determining the plasmonic properties of gold-silver (Ag-Au) nanocages. Ag-Au cages with different wall thicknesses, but the same void or outer size, shape, and elemental composition, were designed as a model platform. The experimental findings were understood with theoretical calculations. This study not only investigates the effect of wall thickness but also provides an effective knob to tailor the plasmonic properties of hollow nanostructures.

Noble Metal Nanoparticles for Point-of-Care Testing: Recent Advancements and Social Impacts.

Point-of-care (POC) tests for the diagnosis of diseases are critical to the improvement of the standard of living, especially for resource-limited areas or countries. In recent years, nanobiosensors based on noble metal nanoparticles (NM NPs) have emerged as a class of effective and versatile POC testing technology. The unique features of NM NPs ensure great performance of associated POC nanobiosensors. In particular, NM NPs offer various signal transduction principles, such as plasmonics, catalysis, photothermal effect, and so on. Significantly, the detectable signal from NM NPs can be tuned and optimized by controlling the physicochemical parameters (e.g., size, shape, and elemental composition) of NPs. In this article, we introduce the inherent merits of NM NPs that make them attractive for POC testing, discuss recent advancement of NM NPs-based POC tests, highlight their social impacts, and provide perspectives on challenges and opportunities in the field. We hope the review and insights provided in this article can inspire new fundamental and applied research in this emerging field.

Catalytic Gold-Iridium Nanoparticles as Labels for Sensitive Colorimetric Lateral Flow Assay.

The colorimetric lateral flow assay (CLFA, also known as test strip) is a widely used point-of-care diagnostic technology. It has been a challenge to significantly improve the detection sensitivity of CLFA without involving additional equipment and/or compromising its simplicity. In this work, we break through the detection limit barrier of CLFA by developing a type of catalytic nanoparticles (NPs) used as labels. Specifically, the NPs were engineered by coating conventional gold NPs (AuNPs) with iridium (Ir) to form an Au-Ir core-shell structure. Such Au-Ir NPs possess ultrahigh peroxidase-like catalytic activities. A single Au-Ir NP can generate up to 107 colored molecules per second by catalyzing peroxidase substrates. The strong color signal from the catalysis ensures a high sensitivity of associated CLFA. The Au-Ir NP-based CLFA was successfully applied to the detection of two different cancer biomarkers that achieved limits of detection at the low picogram per milliliter level, hundreds of times lower than those of conventional AuNP-based CLFA.

Rapid testing for coronavirus disease 2019 (COVID-19).

Rapid testing, generally refers to the paper-based diagnostic platform known as "lateral flow assay" (LFA), has emerged as a critical asset to the containment of coronavirus disease 2019 (COVID-19) around the world. LFA technology stands out amongst peer platforms due to its cost-effective design, user-friendly interface, and low sample-to-readout times. This article aims to introduce its design, use, and practicality for the purpose of diagnosing SARS-CoV-2 infection. A connection is made from the normal COVID-19 immune response to the design and efficacy of rapid testing. Interference in test results is a challenge shared by most diagnostic platforms and can be rooted in various underlying issues. The current knowledge and situation about interference in rapid COVID-19 tests due to variant strains as well as vaccination are discussed. The cost and societal impact are reviewed as they play important roles in determining how to properly implement public testing practices. Perspectives on improving the performance, especially detection sensitivity, of LFA for COVID-19 are provided.

Morphology-Invariant Metallic Nanoparticles with Tunable Plasmonic Properties.

Current methods for tuning the plasmonic properties of metallic nanoparticles typically rely on alternating the morphology (i.e., size and/or shape) of nanoparticles. The variation of morphology of plasmonic nanoparticles oftentimes impairs their performance in certain applications. In this study, we report an effective approach based on the control of internal structure to engineer morphology-invariant nanoparticles with tunable plasmonic properties. Specifically, these nanoparticles were prepared through selective growth of Ag on the inner surfaces of preformed Ag-Au alloyed nanocages as the seeds to form Ag@(Ag-Au) shell@shell nanocages. Plasmonic properties of the Ag@(Ag-Au) nanocages can be conveniently and effectively tuned by varying the amount of Ag deposited on the inner surfaces, during which the overall morphology of the nanocages remains unchanged. To demonstrate the potential applications of the Ag@(Ag-Au) nanocages, they were applied to colorimetric sensing of human carcinoembryonic antigen (CEA) that achieved low detection limits. This work provides a meaningful concept to design and craft plasmonic nanoparticles.

Nickel-Platinum Nanoparticles as Peroxidase Mimics with a Record High Catalytic Efficiency.

While nanoscale mimics of peroxidase have been extensively developed over the past decade or so, their catalytic efficiency as a key parameter has not been substantially improved in recent years. Herein, we report a class of highly efficient peroxidase mimic-nickel-platinum nanoparticles (Ni-Pt NPs) that consist of nickel-rich cores and platinum-rich shells. The Ni-Pt NPs exhibit a record high catalytic efficiency with a catalytic constant (Kcat) as high as 4.5 × 107 s-1, which is ∼46- and 104-fold greater than the Kcat values of conventional Pt nanoparticles and natural peroxidases, respectively. Density functional theory calculations reveal that the unique surface structure of Ni-Pt NPs weakens the adsorption of key intermediates during catalysis, which boosts the catalytic efficiency. The Ni-Pt NPs were applied to an immunoassay of a carcinoembryonic antigen that achieved an ultralow detection limit of 1.1 pg/mL, hundreds of times lower than that of the conventional enzyme-based assay.

Nanocrystals of platinum-group metals as peroxidase mimics for in vitro diagnostics.

Peroxidase mimics of nanoscale materials as alternatives to natural peroxidases have found widespread uses in biomedicine. Among various types of peroxidase mimics, platinum-group metal (PGM) nanocrystals have drawn considerable attention in recent years due to their superior properties. Particularly, PGM nanocrystals display high catalytic efficiencies, allow for facile surface modifications, and possess excellent stabilities. This feature article summarizes our recent work on development of PGM nanocrystals as peroxidase mimics and exploration of their applications in in vitro diagnostics. We begin with a brief introduction to controlled synthesis of PGM nanocrystals in solution phase. We then elaborate on a variety of physicochemical parameters that can be carefully tuned to optimize the peroxidase-like properties of PGM nanocrystals. Then, we highlight the applications of PGM nanocrystals in different in vitro diagnostic platforms. We conclude this article with personal perspectives on future research directions in this emerging field, where challenges and opportunities are remarked.

Size Effect in Pd-Ir Core-Shell Nanoparticles as Nanozymes.

Comprehensive studies on the size effect in nanozyme (i. e., nanomaterials with enzyme-like activities)-based catalysis have rarely been reported. In this work, we systematically investigated the size effect in nanozymes by using Pd-Ir core-shell nanoparticles with peroxidase-like activities as a model system. Pd-Ir nanoparticles with four different sizes (3.3, 5.9, 9.8 and 13.0 nm), but identical shapes and surface structures, were designed and synthesized. We found that the catalytic activity for individual nanozymes increased with particle size. The area-specific catalytic activity was similar for nanoparticles of 3.3-9.8 nm, but decreased slightly when particle size reached 13.0 nm. By using an enzyme-linked immunosorbent assay (ELISA) as a model platform, the size effect of Pd-Ir nanoparticles in biosensing applications was investigated; smaller nanoparticles were found to offer lower detection limits. This work not only demonstrates the size effect, but also provides an effective strategy to enhance the performance of nanozymes in certain applications.

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.

Strain Effect in Palladium Nanostructures as Nanozymes.

While various effects of physicochemical parameters (e.g., size, facet, composition, and internal structure) on the catalytic efficiency of nanozymes (i.e., nanoscale enzyme mimics) have been studied, the strain effect has never been reported and understood before. Herein, we demonstrate the strain effect in nanozymes by using Pd octahedra and icosahedra with peroxidase-like activities as a model system. Strained Pd icosahedra were found to display 2-fold higher peroxidase-like catalytic efficiency than unstrained Pd octahedra. Theoretical analysis suggests that tensile strain is more beneficial to OH radical (a key intermediate for the catalysis) generation than compressive strain. Pd icosahedra are more active than Pd octahedra because icosahedra amplify the surface strain field. As a proof-of-concept demonstration, the strained Pd icosahedra were applied to an immunoassay of biomarkers, outperforming both unstrained Pd octahedra and natural peroxidases. The findings in this research may serve as a strong foundation to guide the design of high-performance nanozymes.

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.

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.

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.

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.

An Enzyme-Free Signal Amplification Technique for Ultrasensitive Colorimetric Assay of Disease Biomarkers.

Enzyme-based colorimetric assays have been widely used in research laboratories and clinical diagnosis for decades. Nevertheless, as constrained by the performance of enzymes, their detection sensitivity has not been substantially improved in recent years, which inhibits many critical applications such as early detection of cancers. In this work, we demonstrate an enzyme-free signal amplification technique, based on gold vesicles encapsulated with Pd-Ir nanoparticles as peroxidase mimics, for colorimetric assay of disease biomarkers with significantly enhanced sensitivity. This technique overcomes the intrinsic limitations of enzymes, thanks to the superior catalytic efficiency of peroxidase mimics and the efficient loading and release of these mimics. Using human prostate surface antigen as a model biomarker, we demonstrated that the enzyme-free assay could reach a limit of detection at the femtogram/mL level, which is over 103-fold lower than that of conventional enzyme-based assay when the same antibodies and similar procedure were used.

Seed-Mediated Growth of Colloidal Metal Nanocrystals.

Seed-mediated growth is a powerful and versatile approach for the synthesis of colloidal metal nanocrystals. The vast allure of this approach mainly stems from the staggering degree of control one can achieve over the size, shape, composition, and structure of nanocrystals. These parameters not only control the properties of nanocrystals but also determine their relevance to, and performance in, various applications. The ingenuity and artistry inherent to seed-mediated growth offer extensive promise, enhancing a number of existing applications and opening the door to new developments. This Review demonstrates how the diversity of metal nanocrystals can be expanded with endless opportunities by using seeds with well-defined and controllable internal structures in conjunction with a proper combination of capping agent and reduction kinetics. New capabilities and future directions are also highlighted.

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.

Pd-Ir Core-Shell Nanocubes: A Type of Highly Efficient and Versatile Peroxidase Mimic.

Peroxidase mimics with dimensions on the nanoscale have received great interest as emerging artificial enzymes for biomedicine and environmental protection. While a variety of peroxidase mimics have been actively developed recently, limited progress has been made toward improving their catalytic efficiency. In this study, we report a type of highly efficient peroxidase mimic that was engineered by depositing Ir atoms as ultrathin skins (a few atomic layers) on Pd nanocubes (i.e., Pd-Ir cubes). The Pd-Ir cubes exhibited significantly enhanced efficiency, with catalytic constants more than 20- and 400-fold higher than those of the initial Pd cubes and horseradish peroxidase (HRP), respectively. As a proof-of-concept demonstration, the Pd-Ir cubes were applied to the colorimetric enzyme-linked immunosorbent assay (ELISA) of human prostate surface antigen (PSA) with a detection limit of 0.67 pg/mL, which is ∼110-fold lower than that of the conventional HRP-based ELISA using the same set of antibodies and the same procedure.

Shape-Controlled Synthesis of Colloidal Metal Nanocrystals: Thermodynamic versus Kinetic Products.

This Perspective provides a contemporary understanding of the shape evolution of colloidal metal nanocrystals under thermodynamically and kinetically controlled conditions. It has been extremely challenging to investigate this subject in the setting of one-pot synthesis because both the type and number of seeds involved would be changed whenever the experimental conditions are altered, making it essentially impossible to draw conclusions when comparing the outcomes of two syntheses conducted under different conditions. Because of the uncertainty about seeds, most of the mechanistic insights reported in literature for one-pot syntheses of metal nanocrystals with different shapes are either incomplete or ambiguous, and some of them might be misleading or even wrong. Recently, with the use of well-defined seeds for such syntheses, it became possible to separate growth from nucleation and therefore investigate the explicit role(s) played by a specific thermodynamic or kinetic parameter in directing the evolution of colloidal metal nanocrystals into a specific shape. Starting from single-crystal seeds enclosed by a mix of {100}, {111}, and {110} facets, for example, one can obtain colloidal nanocrystals with diversified shapes by adjusting various thermodynamic or kinetic parameters. The mechanistic insights learnt from these studies can also be extended to account for the products of conventional one-pot syntheses that involve self-nucleation only. The knowledge can be further applied to many other types of seeds with twin defects or stacking faults, making it an exciting time to design and synthesize colloidal metal nanocrystals with the shapes sought for a variety of fundamental studies and technologically important applications.