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KAIST Enables On-Site Disease Diagnosis in Just 3 Minutes... Nanozyme Reaction Selectivity Improved 38-Fold
<(From Left) Professor Jinwoo Lee, Ph.D candidate Seonhye Park and Ph.D candidate Daeeun Choi from Chemical & Biomolecular Engineering> To enable early diagnosis of acute illnesses and effective management of chronic conditions, point-of-care testing (POCT) technology—diagnostics conducted near the patient—is drawing global attention. The key to POCT lies in enzymes that recognize and react precisely with specific substances. However, traditional natural enzymes are expensive and unstable, and nanozymes (enzyme-mimicking catalysts) have suffered from low reaction selectivity. Now, a Korean research team has developed a high-sensitivity sensor platform that achieves 38 times higher selectivity than existing nanozymes and allows disease diagnostics visible to the naked eye within just 3 minutes. On the 28th, KAIST (President Kwang Hyung Lee) announced that Professor Jinwoo Lee’s research team from the Department of Chemical & Biomolecular Engineering, in collaboration with teams led by Professor Jeong Woo Han at Seoul National University and Professor Moon Il Kim at Gachon University, has developed a new single-atom catalyst that selectively performs only peroxidase-like reactions while maintaining high reaction efficiency. Using bodily fluids such as blood, urine, or saliva, this diagnostic platform enables test results to be read within minutes even outside hospital settings—greatly improving medical accessibility and ensuring timely treatment. The key lies in the visual detection of biomarkers (disease indicators) through color changes triggered by enzyme reactions. However, natural enzymes are expensive and easily degraded in diagnostic environments, limiting their storage and distribution. To address this, inorganic nanozyme materials have been developed as substitutes. Yet, they typically lack selectivity—when hydrogen peroxide is used as a substrate, the same catalyst triggers both peroxidase-like reactions (which cause color change) and catalase-like reactions (which remove the substrate), reducing diagnostic signal accuracy. To control catalyst selectivity at the atomic level, the researchers used an innovative structural design: attaching chlorine (Cl) ligands in a three-dimensional configuration to the central ruthenium (Ru) atom to fine-tune its chemical properties. This enabled them to isolate only the desired diagnostic signal. <Figure1. The catalyst in this study (ruthenium single-atom catalyst) exhibits peroxidase-like activity with selectivity akin to natural enzymes through three-dimensional directional ligand coordination. Due to the absence of competing catalase activity, selective peroxidase-like reactions proceed under biomimetic conditions. In contrast, conventional single-atom catalysts with active sites arranged on planar surfaces exhibit dual functionality depending on pH. Under neutral conditions, their catalase activity leads to hydrogen peroxide depletion, hindering accurate detection. The catalyst in this study eliminates such interference, enabling direct detection of biomarkers through coupled reactions with oxidases without the need for cumbersome steps like buffer replacement. The ability to simultaneously detect multiple target substances under biomimetic conditions demonstrates the practicality of ruthenium single-atom catalysts for on-site diagnostics> Experimental results showed that the new catalyst achieved over 38-fold improvement in selectivity compared to existing nanozymes, with significantly increased sensitivity and speed in detecting hydrogen peroxide. Even in near-physiological conditions (pH 6.0), the catalyst maintained its performance, proving its applicability in real-world diagnostics. By incorporating the catalyst and oxidase into a paper-based sensor, the team created a system that could simultaneously detect four key biomarkers related to health: glucose, lactate, cholesterol, and choline—all with a simple color change. This platform is broadly applicable across various disease diagnostics and can deliver results within 3 minutes without complex instruments or pH adjustments. The findings show that diagnostic performance can be dramatically improved without changing the platform itself, but rather by engineering the catalyst structure. <Figure 2.(a) Schematic diagram of the paper sensor (Zone 1: glucose oxidase immobilized; Zone 2: lactate oxidase immobilized; Zone 3: choline oxidase immobilized; Zone 4: cholesterol oxidase immobilized; Zone 5: no oxidase enzyme). (b) Single biomarker (single disease indicator) detection using the ruthenium single‑atom catalyst–based paper sensor.(c) Multiple biomarker (multiple disease indicator) detection using the ruthenium single‑atom catalyst–based paper sensor> Professor Jinwoo Lee of KAIST commented, “This study is significant in that it simultaneously achieves enzyme-level selectivity and reactivity by structurally designing single-atom catalysts.” He added that “the structure–function-based catalyst design strategy can be extended to the development of various metal-based catalysts and other reaction domains where selectivity is critical.” Seonhye Park and Daeeun Choi, both Ph.D. candidates at KAIST, are co-first authors. The research was published on July 6, 2025, in the prestigious journal Advanced Materials -Title: Breaking the Selectivity Barrier of Single-Atom Nanozymes Through Out-of-Plane Ligand Coordinatio - Authors: Seonhye Park (KAIST, co–first author), Daeeun Choi (KAIST, co–first author), Kyu In Shim (SNU, co–first author), Phuong Thy Nguyen (Gachon Univ., co–first author), Seongbeen Kim (KAIST), Seung Yeop Yi (KAIST), Moon Il Kim (Gachon Univ., corresponding author), Jeong Woo Han (SNU, corresponding author), Jinwoo Lee (KAIST, corresponding author -DOI: https://doi.org/10.1002/adma.202506480 This research was supported by the Ministry of Science and ICT and the National Research Foundation of Korea (NRF).
2025.07.29
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Innovative Nanosensor for Disease Diagnosis
(Figure 1. Sensing Device) (Figure 2. Protein templating route) Breath pattern recognition is a futuristic diagnostic platform. Simple characterizing target gas concentrations of human exhaled breath will lead to diagnose of the disease as well as physical condition. A research group under Prof. Il-Doo Kim in the Department of Materials Science has developed diagnostic sensors using protein-encapsulated nanocatalysts, which can diagnose certain diseases by analyzing human exhaled breath. This technology enables early monitoring of various diseases through pattern recognition of biomarker gases related to diseases in human exhalation. The protein-templated catalyst synthesis route is very simple and versatile for producing not only a single component of catalytic nanoparticles, but also diverse heterogeneous intermetallic catalysts with sizes less than 3 nm. The research team has developed ever more sensitive and selective chemiresistive sensors that can potentially diagnose specific diseases by analyzing exhaled breath gases. The results of this study, which were contributed by Dr. Sang-Joon Kim and Dr. Seon-Jin Choi as first authors were selected as the cover-featured article in the July issue of 'Accounts of Chemical Research,' an international journal of the American Chemical Society. In human breath, diverse components are found including water vapor, hydrogen, acetone, toluene, ammonia, hydrogen sulfide, and carbon monoxide, which are more excessively exhaled from patients. Some of these components are closely related to diseases such as asthma, lung cancer, type 1 diabetes mellitus, and halitosis. Breath analysis for disease diagnosis started from capturing exhaled breaths in a Tedlar bag and subsequently the captured breath gases were injected into a miniaturized sensor system, similar to an alcohol detector. It is possible to analyze exhaled breath very rapidly with a simple analyzing process. The breath analysis can detect trace changes in exhaled breath components, which contribute to early diagnosis of diseases. However, technological advances are needed to accurately analyze gases in the breath, which occur at very low levels, from 1 ppb to 1 ppm. In particular, it has been a critical challenge for chemiresistive type chemical sensors to selectively detect specific biomarkers in thousands of interfering gases including humid vapor. Conventionally, noble metallic catalysts such as platinum and palladium have been functionalized onto metal oxide sensing layers. However, the gas sensitivity was not enough to detect ppb-levels of biomarker species in exhaled breath. To overcome the current limitations, the research team utilized nanoscale protein (apoferritin) in animals as sacrificial templates. The protein templates possess hollow nanocages at the core site and various alloy catalytic nanoparticles can be encapsulated inside the protein nanocages. The protein nanocages are advantageous because a nearly unlimited number of material compositions in the periodic table can be assembled for the synthesis of heterogeneous catalytic nanoparticles. In addition, intermetallic nanocatalysts with a controlled atomic ratio of two different elements can be achieved using the protein nanocages, which is an innovative strategy for finding new types of catalysts. For example, highly efficient platinum-based catalysts can be synthesized, such as platinum-palladium (PtPd), platinum-nickel (PtNi), platinum-ruthenium (PtRu), and platinum-yttrium (PtY). The research team developed outstanding sensing layers consisting of metal oxide nanofibers functionalized by the heterogeneous catalysts with large and highly-porous surface areas, which are especially optimized for selective detection of specific biomarkers. The biomarker sensing performance was improved approximately 3~4-fold as compared to the conventional single component of platinum and palladium catalysts-loaded nanofiber sensors. In particular, 100-fold resistance transitions toward acetone (1 ppm) and hydrogen sulfide (1 ppm) were observed in exhaled breath sensors using the heterogeneous nanocatalysts, which is the best performance ever reported in literature. The research team developed a disease diagnosis platform that recognizes individual breathing patterns by using a multiple sensor array system with diverse sensing layers and heterogeneous catalysts, so that the people can easily identify health abnormalities. Using a 16-sensor array system, physical conditions can be continuously monitored by analyzing concentration changes of biomarkers in exhaled breath gases. Prof. Kim said, “New types of heterogeneous nanocatalysts were synthesized using protein templates with sizes around 2 nm and functionalized on various metal oxide nanofiber sensing layers. The established sensing libraries can detect biomarker species with high sensitivity and selectivity.” He added, “the new and innovative breath gas analysis platform will be very helpful for reducing medical expenditures and continuous monitoring of physical conditions” Patents related to this technology were licensed to two companies in March and June this year.
2017.07.19
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