Innovative Nanosensor for Disease Diagnosis

ConspectusAs a futuristic diagnosis platform, breath analysis is gaining much attention because it is a noninvasive, simple, and low cost diagnostic method. Very promising clinical applications have been demonstrated for diagnostic purposes by correlation analysis between exhaled breath components and specific diseases. In addition, diverse breath molecules, which serve as biomarkers for specific diseases, are precisely identified by statistical pattern recognition studies. To further improve the accuracy of breath analysis as a diagnostic tool, breath sampling, biomarker sensing, and data analysis should be optimized. In particular, development of high performance breath sensors, which can detect biomarkers at the ppb-level in exhaled breath, is one of the most critical challenges. Due to the presence of numerous interfering gas species in exhaled breath, selective detection of specific biomarkers is also important.This Account focuses on chemiresistive type breath sensors with exceptionally high sensitivity and selectivity that were developed by combining hollow protein templated nanocatalysts with electrospun metal oxide nanostructures. Nanostructures with high surface areas are advantageous in achieving high sensitivity because the sensing signal is dominated by the surface reaction between the sensing layers and the target biomarkers. Furthermore, macroscale pores between one-dimensional (1D) nanostructures can facilitate fast gas diffusion into the sensing layers. To further enhance the selectivity, catalytic functionalization of the 1D metal oxide nanostructure is essential. However, the majority of conventional techniques for catalytic functionalization have failed to achieve a high degree of dispersion of nanoscale catalysts due to aggregation on the surface of the metal oxide, which severely deteriorates the sensing properties by lowering catalytic activity. This issue has led to extensive studies on monolithically dispersed nanoscale particles on metal oxides to maximize the catalytic performances.As a pioneering technique, a bioinspired templating route using apoferritin, that is, a hollow protein cage, has been proposed to obtain nanoscale (∼2 nm) catalyst particles with high dispersity. Nanocatalysts encapsulated by a protein shell were first used in chemiresistive type breath sensors for catalyst functionalization on 1D metal oxide structures. We discuss the robustness and versatility of the apoferrtin templating route for creating highly dispersive catalytic NPs including single components (Au, Pt, Pd, Rh, Ag, Ru, Cu, and La) and bimetallic catalysts (PtY and PtCo), as well as the core–shell structure of Au–Pd (Au-core@Pd-shell). The use of these catalysts is essential to establish high performance sensors arrays for the pattern recognition of biomarkers. In addition, novel multicomponent catalysts provide unprecedented sensitivity and selectivity. With this in mind, we discuss diverse synthetic routes for nanocatalysts using apoferritin and the formation of various catalyst–1D metal oxide composite nanostructures. Furthermore, we discuss detection capability of a simulated biomarker gas using the breath sensor arrays and principal component analysis. Finally, future prospects with the portable breath analysis platform are presented by demonstrating the potential feasibility of real-time and on-site breath analysis using chemiresistive sensors

Heterogeneous Sensitization of Metal–Organic Framework Driven Metal@Metal Oxide Complex Catalysts on an Oxide Nanofiber Scaffold Toward Superior Gas Sensors

We report on the heterogeneous sensitization of metal–organic framework (MOF)-driven metal-embedded metal oxide (M@MO) complex catalysts onto semiconductor metal oxide (SMO) nanofibers (NFs) via electrospinning for markedly enhanced chemical gas sensing. ZIF-8-derived Pd-loaded ZnO nanocubes (Pd@ZnO) were sensitized on both the interior and the exterior of WO₃ NFs, resulting in the formation of multiheterojunction Pd–ZnO and ZnO–WO₃ interfaces. The Pd@ZnO loaded WO₃ NFs were found to exhibit unparalleled toluene sensitivity (<i>R</i>_air<i>/R</i>_gas = 4.37 to 100 ppb), fast gas response speed (∼20 s) and superior cross-selectivity against other interfering gases. These results demonstrate that MOF-derived M@MO complex catalysts can be functionalized within an electrospun nanofiber scaffold, thereby creating multiheterojunctions, essential for improving catalytic sensor sensitization

Elaborate Manipulation for Sub-10 nm Hollow Catalyst Sensitized Heterogeneous Oxide Nanofibers for Room Temperature Chemical Sensors

Room-temperature (RT) operation sensors are constantly in increasing demand because of their low power consumption, simple operation, and long lifetime. However, critical challenges such as low sensing performance, vulnerability under highly humid state, and poor recyclability hinder their commercialization. In this work, sub-10 nm hollow, bimetallic Pt–Ag nanoparticles (NPs) were successfully formed by galvanic replacement reaction in bioinspired hollow protein templates and sensitized on the multidimensional SnO₂–WO₃ heterojunction nanofibers (HNFs). Formation of hollow, bimetallic NPs resulted in the double-side catalytic effect, rendering both surface and inner side chemical reactions. Subsequently, SnO₂–WO₃ HNFs were synthesized by incorporating 2D WO₃ nanosheets (NSs) with 0D SnO₂ sphere by <i>c</i>-axis growth inhibition effect and fluid dynamics of liquid Sn during calcination. Hierarchically assembled HNFs effectively modulate surface depletion layer of 2D WO₃ NSs by electron transfers from WO₃ to SnO₂ stemming from creation of heterojunction. Careful combination of bimetallic catalyst NPs with HNFs provided an extreme recyclability under exhaled breath (95 RH%) with outstanding H₂S sensitivity. Such sensing platform clearly distinguished between the breath of healthy people and simulated halitosis patients

Bimodally Porous WO₃ Microbelts Functionalized with Pt Catalysts for Selective H₂S Sensors

Bimodally meso- (2–50 nm) and macroporous (>50 nm) WO₃ microbelts (MBs) functionalized with sub-3 nm Pt catalysts were fabricated via the electrospinning technique followed by subsequent calcination. Importantly, apoferritin (Apo), tea saponin and polystyrene colloid spheres (750 nm) dispersed in an electrospinning solution acted as forming agents for producing meso- and macropores on WO₃ MBs during calcination. Particularly, mesopores provide not only numerous reaction sites for effective chemical reactions, but also facilitate gas diffusion into the interior of the WO₃ MBs, dominated by Knudsen diffusion. The macropores further accelerate gas permeability in the interior and on the exterior of the WO₃ MBs. In addition, Pt nanoparticles with mean diameters of 2.27 nm were synthesized by using biological protein cages, such as Apo, to further enhance the gas sensing performance. Bimodally porous WO₃ MBs functionalized by Pt catalysts showed remarkably high hydrogen sulfide (H₂S) response (<i>R</i>_air/<i>R</i>_gas = 61 @ 1 ppm) and superior selectivity to H₂S against other interfering gases, such as acetone (CH₃COCH₃), ethanol (C₂H₅OH), ammonia (NH₃), and carbon monoxide (CO). These results demonstrate a high potential for the feasibility of catalyst-loaded meso- and macroporous WO₃ MBs as new sensing platforms for the possibility of real-time diagnosis of halitosis

Mesoporous WO₃ Nanofibers with Protein-Templated Nanoscale Catalysts for Detection of Trace Biomarkers in Exhaled Breath

Highly selective detection, rapid response (<20 s), and superior sensitivity (<i>R</i>_air/<i>R</i>_gas> 50) against specific target gases, particularly at the 1 ppm level, still remain considerable challenges in gas sensor applications. We propose a rational design and facile synthesis concept for achieving exceptionally sensitive and selective detection of trace target biomarkers in exhaled human breath using a protein nanocage templating route for sensitizing electrospun nanofibers (NFs). The mesoporous WO₃ NFs, functionalized with well-dispersed nanoscale Pt, Pd, and Rh catalytic nanoparticles (NPs), exhibit excellent sensing performance, even at parts per billion level concentrations of gases in a humid atmosphere. Functionalized WO₃ NFs with nanoscale catalysts are demonstrated to show great promise for the reliable diagnosis of diseases