Surface-mediated fluorescent sensor array for identification of gut microbiota and monitoring of colorectal cancer.

The development of efficient, accurate, and high-throughput technology for gut microbiota sensing holds great promise in the maintenance of health and the treatment of diseases. Herein, we developed a rapid fluorescent sensor array based on surface-engineered silver nanoparticles (AgNPs) and vancomycin-modified gold nanoclusters (AuNCs@Van) for gut microbiota sensing. By controlling the surface of AgNPs, the recognition ability of the sensor can be effectively improved. The sensor array was used to successfully discriminate six gut-derived bacteria, including probiotics, neutral, and pathogenic bacteria and even their mixtures. Significantly, the sensing system has also been successfully applied to classify healthy individuals and colorectal cancer (CRC) patients rapidly and accurately within 30 min, demonstrating its clinically relevant specificity.

Fluorescent Probe for Investigating the Mitochondrial Viscosity and Hydrogen Peroxide Changes in Cerebral Ischemia/Reperfusion Injury.

Cerebral ischemia-reperfusion injury (CIRI), a cause of cerebral dysfunction during cerebral infarction treatment, is closely associated with mitochondrial viscosity and hydrogen peroxide (H2O2). However, the accurate measurement of mitochondrial viscosity and H2O2 levels in CIRI is challenging because of the lack of sufficient selectivity and blood-brain barrier (BBB) penetration of existing monitoring tools related to CIRI, hampering the exploration of the role of mitochondrial viscosity and H2O2 in CIRI. To address this issue, we designed an activatable fluorescent probe, mitochondria-targeting styryl-quinolin-ium (Mito-IQS), with excellent properties including high selectivity, mitochondrial targeting, and BBB penetration, for the visualization of mitochondrial viscosity and H2O2 in the brain. Based on the real-time monitoring capabilities of the probe, bursts of mitochondrial viscosity and H2O2 levels were visualized during CIRI. This probe can be used to monitor the therapeutic effects of butylphthalein treatment. More importantly, in vivo experiments further confirmed that CIRI was closely associated with the mitochondrial viscosity and H2O2 levels. This discovery provides new insights and tools for the study of CIRI and is expected to accelerate the process of CIRI diagnosis, treatment, and drug design.

Antimicrobial Agent Functional Gold Nanocluster-Mediated Multichannel Sensor Array for Bacteria Sensing.

Urinary tract infections (UTIs) have greatly affected human health in recent years. Accurate and rapid diagnosis of UTIs can enable a more effective treatment. Herein, we developed a multichannel sensor array for efficient identification of bacteria based on three antimicrobial agents (vancomycin, lysozyme, and bacitracin) functional gold nanoclusters (AuNCs). In this sensor, the fluorescence intensity of the three AuNCs was quenched to varying degrees by the bacterial species, providing a unique fingerprint for different bacteria. With this sensing platform, seven pathogenic bacteria, different concentrations of the same bacteria, and even bacterial mixtures were successfully differentiated. Furthermore, UTIs can be accurately identified with our sensors in ∼30 min with 100% classification accuracy. The proposed sensing systems offer a rapid, high-throughput, and reliable sensing platform for the diagnosis of UTIs.

Boronic Acid-Decorated Carbon Dot-Based Semiselective Multichannel Sensor Array for Cytokine Discrimination and Oral Cancer Diagnosis.

Cytokines are essential components of the immune system and are recognized as significant biomarkers. However, detection of a single cytokine is not precise and reliable enough to satisfy the requirements for diagnosis. Herein, we developed a pattern recognition-based method for the multiplexed sensing of cytokines, which involves three-color-emitting boronic acid-decorated carbon dots (BCDs) and arginine-modified titanium carbide (Ti3C2 MXenes) as the sensor array. Initially, the fluorescence signals of the three BCDs were quenched by Ti3C2 MXenes. In the presence of cytokines, the fluorescence intensity of the BCDs was restored or further quenched by different cytokines. The fluorescence response occurs in two steps: first, boronic acid interacts with cis-diol functional groups of cytokines, and second, arginine headgroup selectively interacts with glycans. By exploiting the different competing binding of the BCDs and the cytokines toward Ti3C2 MXenes, seven cytokines and their mixtures can be effectively discriminated at a concentration of 20 ng mL-1. Furthermore, our sensor array demonstrated an excellent performance in classifying human oral cancer saliva samples from healthy individuals with clinically relevant specificity. The noninvasive method offers a rapid approach to cytokine analysis, benefiting early and timely clinical diagnosis and treatment.

A sensitive electrochemical sensor for glutathione based on specific recognition induced collapse of silver-contained metal organic frameworks.

An electrochemical sensor capable of detecting glutathione (GSH) with high sensitivity and selectivity was developed based on the unique novel electroactive silver-based metal organic framework (Ag-MOF). The Ag-MOF obtained by silver nitrate and 1,3,5-benzoic acid (H3BTC) was thoroughly characterized and was modified onto the electrode via facile drop-casting method. The electrochemical response of GSH on the Ag-MOF modified electrode showed a significant reduction in the current signal because the Ag-GSH complex had stronger specific affinity than Ag-H3BTC and resulted in the collapse of the Ag-MOF. This sensor demonstrated an extensive linear dynamic range of 0.1 nM-1 µM, along with the low detection limit of 0.018 nM. Additionally, it exhibited good reproducibility, stability, and resistance to interfering compounds. The Ag-MOF modified electrode demonstrated superior performance attributed to its rapid electron transfer rate, outstanding electrochemical redox activity, and specific recognition/competitive reaction. These factors improved both sensitivity and selectivity. The high anti-interference ability allowed for the selective detection of GSH in intricate surroundings. In the real sample testing, the RSD was lower than 3.1% and the recovery was between 98.1 and 103%. This research highlights the potential of Ag-MOFs in developing electrochemical sensors and their promising applications in determining GSH for food screening and early disease diagnosis.

Consuming intracellular glucose and regulating the levels of O2/H2O2 via the closed cascade catalysis system of Cu-CeO2 nanozyme and glucose oxidase.

Imbalances in the intracellular environment caused by high levels of glucose, H2O2, and hypoxia can greatly impact cancer development and treatment. However, there is limited research on regulating the levels of these species simultaneously in tumor cells. Here, a pH-responsive nanozyme-enzyme hybrid system was developed to regulate intracellular glucose, H2O2 and O2. The system, named DMSN@Cu-CeO2@GOx, consists of Cu-CeO2 nanoparticles and glucose oxidase (GOx) immobilized in dendritic mesoporous silica (DMSN) spheres. GOx efficiently consumes glucose in tumor cells, causing a drop in pH and producing a significant amount of H2O2. Cu-CeO2 then catalyzes the conversion of H2O2 to O2 due to its high catalase-like (CAT) activity in weakly acidic conditions. The process was monitored by fluorescence probes, and the mechanism was investigated through fluorescence spectroscopy and confocal laser scanning microscopy. The cascade catalytic system with excellent biocompatibility continuously consumes glucose and elevates the level of O2 in cells. This hybrid nanomaterial offers a means to regulate the glucose/H2O2/O2 levels in cells and may provide insights into starvation therapy by modulating reactive species within cells.

Ag2S QDs integration with MnO2 nanosheets for the sensitive detection of Cr (VI) via the redox reaction induced photoelectrochemical variation.

The heavy metal Cr (VI) will remain, accumulate, and migrate after entering the environment or ecosystem, causing serious harm to the environment. Here, a photoelectrochemical sensor was developed for Cr (VI), utilizing the Ag2S quantum dots (QDs) and MnO2 nanosheets as photoactive components. By introducing Ag2S QDs with a narrow gap, a staggered energy level match is created which effectively prevents the carrier recombination in MnO2 nanosheets, resulting in an enhanced photocurrent response. In the presence of the electron donor, l-ascorbic acid (AA), the photocurrent of the Ag2S QDs and MnO2 nanosheets modified photoelectrode is further enhanced. As AA has the ability to convert Cr (VI) to Cr (Ⅲ), the photocurrent may decline due to the decrease in the electron donors when Cr (VI) is added. This phenomenon can be utilized for the sensitive detection of Cr (VI) over a wider linear range (100 pM-30 µM) with a lower detection limit of 6.46 pM (S/N = 3). This work using the strategy that the targets induced the variations of the electron donor shows the advantages of good sensitivity and nice selectivity. The sensor holds many advantages such as simple fabrication process, economical material expense, and consistent photocurrent signals. It also holds significant potential for environmental monitoring and serves as a practical photoelectric sensing approach for detecting Cr (VI).

General Strategy for Specific Fluorescence Imaging of Homocysteine in Living Cells and In Vivo.

The aberrantly changed level of homocysteine (Hcy) triggers a variety of pathological symptoms and subsequently Hcy-related diseases. Direct and selective visualization of Hcy in biological systems is pivotal to understanding the pathological functions of Hcy at the molecular level. Herein, a general strategy was developed for the specific fluorescence imaging of Hcy through the combination of dual-binding sites and the introduction of a nitro group at the 6-position of the 7-diethylaminocoumarin fluorophore. Also, a series of novel fluorescent probes were exploited for monitoring Hcy with excellent selectivity, high sensitivity, and far-red/near-infrared fluorescence emission. Furthermore, fluorescence imaging of endogenous Hcy dynamics in living cells and in vivo was achieved, providing direct and solid evidence for the increasement of endogenous Hcy in type 2 diabetes mellitus and Alzheimer's disease. This research will greatly advance the development and understanding of the molecular nexus between the Hcy metabolism cascade and the root causes of diseases related to Hcy.

Recognition Engineering-Mediated Multichannel Sensor Array for Gut Microbiota Sensing.

The composition and activity of the gut microbiota are crucial for health management and disease treatment. Herein, we develop a rapid and robust multichannel sensor array via a recognition engineering strategy using antimicrobial agent (vancomycin, bacitracin, and lysozyme) functional gold nanoclusters and gluconamide-modified Ti3C2 MXenes, which provide superior fingerprint patterns to distinguish gut-derived bacteria. The discrimination ability of the sensor array was highly improved via the synergistic recognition between the bacteria and the various antimicrobial agents. Five gut-derived bacteria, including probiotics, neutral, and pathogenic bacteria were clearly differentiated and discriminated from the bacteria mixtures. Furthermore, the sensing system was successfully applied for the accurate classification of human colorectal cancer samples from healthy individuals rapidly (30 min) with clinically relevant specificity. The rapidity, simplicity, and economic cost of this strategy offers a robust platform for gut microbiota analysis.

The target-induced redox and diazotized reaction for colorimetric ratio detection of nitrite using CoOOH nanosheets as mimetic oxidase.

Nitrite is a commonly used food additive and water contaminant that has received widespread attention due to its harmful effects on humans. Here, a colorimetric ratio sensing platform for the detection of nitrite in foods as well as aquatic systems was developed via the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by CoOOH nanosheets (CoOOH NSs). Interestingly, in the presence of nitrite, TMB complexes in acidic environments can be oxidized and diazotized to produce yellow oxidized TMB (oxTMB) and diazotized TMB, resulting in the nitrite concentration-dependent ratio variation for the absorbance peaks at 655 and 450 nm (A655/A450). The colorimetric ratio sensing offers higher sensitivity and better selectivity compared to conventional detection methods because of the specific target-induced reduction-oxidation and diazotized reaction, as well as the excellent mimetic oxidase activity of CoOOH NSs. Based on this strategy, a smartphone-assisted portable approach was designed for the in-situ/visual detection of nitrite, which has good application prospects.

A redox reaction-induced ratiometric fluorescence platform for the specific detection of ascorbic acid based on Ag2S quantum dots and multifunctional CoOOH nanoflakes.

In this work, a ratiometric fluorescent nanoplatform for the detection of ascorbic acid (AA) was constructed based on the Ag2S quantum dots (QDs) and multifunctional hydroxyl cobalt oxide nanoflakes (CoOOH NFs). Ag2S QDs can be assembled on the surface of CoOOH NFs by electrostatic adsorption, resulting in the quenching of the NIR fluorescence emission of Ag2S QDs at 680 nm effectively through the inner filter effect (IFE). o-Phenylenediamine (OPD), a common substrate of oxidase-like (OXD) mimic, is rapidly oxidized into the fluorescent product of 2,3-diaminophenazine (DAP) with the appearance of an emission peak at 575 nm under the catalysis of CoOOH NFs. After AA was added, the fluorescence emission of DAP declined because of the decline in the OXD-like activity of CoOOH NFs due to the transformation of Co2+. Simultaneously, Ag2S QDs were released, accompanied by the recovery of red fluorescence. These two fluorescent signals can be excited at the same excitation wavelength, simplifying the detection procedure. Using F575/F680 as the readout, the quantification of AA can be realized with the linear range and detection limit of 0.2 µM-20 mM and 0.014 µM, respectively. The ratiometric fluorescence sensor can be effectively used to determine the content of AA in real samples such as juice and serum. This work integrates the in-situ formation of the fluorescent species via the catalysis of the nanozyme and the redox reaction to destroy the CoOOH NFs nanozyme as well as the two dimensional nanoflake induced turn-off-on strategy for Ag2S QDs, which provides a specific strategy for the selective detection of AA and may offer a reliable approach for the construction of other biosensing platforms.

Self-Cascade Nanoenzyme of Cupric Oxide Nanoparticles (CuO NPs) Induced in Situ Catalysis Formation of Polyelectrolyte as Template for the Synthesis of Near-Infrared Fluorescent Silver Nanoclusters and the Application in Glutathione Detection and Bioimaging.

In this work, near-infrared fluorescent silver nanoclusters (Ag NCs) were prepared based on the in situ formed poly methacrylic acid (PMAA) as the template and stabilizer, which is synthesized by methacrylic acid (MAA) and hydroxyl radical (·OH) that is generated by the cascade nanoenzyme reaction of cupric oxide nanoparticles (CuO NPs). CuO NPs possess the intrinsic glutathione-like (GPx-like) and peroxidase-like (POD-like) activities, which can catalyze glutathione (GSH) and O2 to produce hydrogen peroxide (H2O2), and then transform into ·OH. The fluorescence intensity of Ag NCs decreases with the addition of GSH, because the -SH can easily anchor on the surface, resulting in the PMAA leaving the Ag NCs, and the coeffect of GSH and PMAA results in the aggregation to form larger Ag NPs. A good linear relationship between the fluorescence quenching rate and the GSH concentration was found in the range 0.01-40 µM with the detection limit 8.0 nM. The Ag NCs can be applied in the detection of GSH in the serum, as well as bioimaging of endogenous and exogenous GSH in cells with high sensitivity. Moreover, the normal and cancer cells can be distinguished through bioimaging because of the different GSH levels. The new method for the preparation of biocompatible nanoprobe based on the nanozyme tandem catalysis and the in situ formed template can avoid the direct usage of polymers or protein templates that hinder preparation and separation, providing a reliable approach for the synthesis, biosensing, and bioimaging of nanoclusters.

Novel ratiometric electrochemical sensing platform for uric acid based on electroactive cuprous oxide nanocubes combined with boron carbide.

Electrochemically active oxides play important roles in the fabrication of electrochemical sensing platforms, in which they can be utilized as electrochemical probes or catalysts in electrochemical reactions. Herein, a novel ratiometric electrochemical sensor for uric acid (UA) was developed based on the newly synthesized Cu2O nanocubes with good electrochemical activity combined with boron carbide (B4C) with excellent conductivity. The oxidation peak of Cu2O remained unchanged, which could be used as a reference, while the oxidation peak of UA catalyzed by the modified electrode increased with the concentration of UA. The two signals displayed a large peak-to-peak potential and thus a ratiometric electrochemical sensor for UA was established, which could further reduce the effects of unrelated factors, such as the environment influence. The sensor exhibited good linear ranges of 0.1-100 µM and 100-1000 µM, and showed good sensitivity, selectivity, repeatability, and stability. The sensor was successfully applied in the detection of UA in complex human serum and urine samples.

Picomolar glutathione detection based on the dual-signal self-calibration electrochemical sensor of ferrocene-functionalized copper metal-organic framework via solid-state electrochemistry of cuprous chloride.

Chemical biosensing techniques are essential for food analysis and disease diagnosis. Nanomaterials with redox activity show great potential in electrochemical analysis, acting as signal labels or signal amplification unit, which can reflect the targets concentration in foods and biological samples. Here, an ultra-sensitive dual-signal intrinsic self-calibration electrochemical platform for GSH was firstly fabricated based on the novel electroactive nanomaterial of ferrocene-functionalized copper metal-organic framework (Fc-Cu-MOF). Due to the solid-state electrochemical property of cuprous chloride (CuCl), a sharp characteristic peak with an increased signal appears with the coexistence of chloride ions in solution. The stronger specific affinity between Cu+ and GSH than that of Cu+ and Cl- triggers a "crowding effect" that causes the current signal of CuCl decrease greatly. Meanwhile, the peak current of ferrocene keeps unchanged as an internal reference. Based on the ratio of the peak current variation (ΔICu/ΔIFc) as the signal output, Fc-Cu-MOF modified electrode showed wider linear range in 0.1 nM -1 µM for GSH with the detection limit as low as 0.025 nM. And the sensor was successfully applied in the determination of GSH with excellent recoveries in various real samples such as food and serum samples, providing good prospect in application of bioanalysis and food screening.

Signal On-Off Electrochemical Sensor for Glutathione Based on a AuCu-Decorated Zr-Containing Metal-Organic Framework via Solid-State Electrochemistry of Cuprous Chloride.

A novel signal on-off glutathione (GSH) electrochemical sensor was developed based on a AuCu bimetal-decorated Zr-containing metal-organic framework (Zr-MOF), in which a signal amplification strategy promoted by solid-state electrochemistry of cuprous chloride (CuCl) was used. The Zr-MOF with a large surface area can be effectively used as the substrate for the in situ growth of AuCu bimetals to obtain the Zr-MOF@AuCu nanocomposite. The interaction between Cu in Zr-MOF@AuCu and Cl- in the solution accompanied with the formation of CuCl displays an enlarged stable oxidation current, which greatly declines with the addition of GSH owing to the specific Cu-GSH interaction. The conversion of CuCl into Cu-GSH triggered the "crowding-out effect" and resulted in a sharp drop in the peak current of CuCl, which can realize the ultrasensitive and selective detection of GSH. The detection mechanism was investigated, and the detection range was 10 pM-1 mM with the detection limit as low as 2.67 pM. The special response mechanism for the detection of GSH allows the highly selective detection of GSH in various real samples with reliable results, endowing the proposed electroanalysis sensor with broad application prospects in biological and food analysis.

Regulation of the Structure of Zirconium-Based Porphyrinic Metal-Organic Framework as Highly Electrochemiluminescence Sensing Platform for Thrombin.

An electrochemiluminescence (ECL) sensor provides a sensitive and convenient method for early diagnosis of diseases; however, it is still a challenge to develop simple and sensitive sensing platforms based on efficient ECL signals and luminophore groups. Porphyrin-based metal-organic frameworks (MOFs) show great potential in ECL sensing; however, the mechanism and structure-activity relationship, as well as application, are rarely reported. Herein, hydrothermal reactions obtained porphyrin Zr-MOFs (PCN-222) with different specific surface areas, pore sizes, structures, and surface charge states by tuning the reaction time were developed, which served both as the ECL luminophore, coreaction promoter for S2O82-, and a connection in the ECL immunoassay. By progressively controlling the condition of the hydrothermal reaction, PCN-222 with large surface area-abundant micropores can be obtained, which has good conductivity and positively charged surfaces, obtaining excellent ECL performance. The ECL performance and the enhancement mechanism were investigated in detail. Using PCN-222-6h with the best ECL intensity as the immobilization matrix for the aptamer, a highly sensitive and selective assay for thrombin was developed. The decrease of the ECL signal was logarithmically linear with the concentration of thrombin in the range from 50 fg mL-1 to 100 pg mL-1 with a low detection limit of 2.48 fg/mL. This proposed strategy provides a brand new approach for tuning of the structures of MOFs as effective ECL signal probes, thus providing wider possibilities for effective ECL immunoassays in the detection of other biomarkers in diagnosis of diseases.

A fluorescence nanoplatform for the determination of hydrogen peroxide and adenosine triphosphate via tuning of the peroxidase-like activity of CuO nanoparticle decorated UiO-66.

A novel nanocomposite of CuO nanoparticle-modified Zr-MOF (CuO/UiO-66) was synthesized and developed as a fluorescence nanoplatform for H2O2 and adenosine triphosphate (ATP) via the "turn-on-off" mode in the presence of terephthalic acid (TA). The structure of CuO/UiO-66 was thoroughly characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and other techniques. The CuO/UiO-66 with enhanced peroxidase-like (POD) activity obtained due to the Zr4+ in UiO-66 is beneficial to the aggregation of CuO NPs on its surface. As a result, the strengthened fluorescence at 425 nm with the excitation of 300 nm was found due to the highly fluorescent species of TAOH. This is produced by the oxidation of TA by ·OH that came from the catalysis of H2O2 via the peroxidase mimic of CuO/UiO-66. Hence the modification of CuO NPs on porous UiO-66 can provide a friendly and sensitive physiological condition for H2O2 detection. However, upon addition of ATP, the fluorescence intensity of TAOH at 425 nm effectively declined owing to the formation of complexation of Zr4+-ATP and the interaction of CuO to ATP which hampers the catalytic reaction of CuO/UiO-66 to H2O2. The specific interaction induced "inhibition of the peroxide-like activity" endows the sensitive and selective recognition of ATP. The detection limits were 16.87 ± 0.2 nM and 0.82 ± 0.1 nM, and linear analytical ranges were 0.02-100 µM and 0.002-30 µM for H2O2 and ATP, respectively. The novel strategy was successfully applied to H2O2 and ATP determination in serum samples with recoveries of 97.2-103.8% for H2O2 and 97.6-101.7% for ATP, enriching the avenue to design functional MOFs and providing new avenue of multicomponent bioanalysis.

Rapid semi-quantitative analysis of hemolytic triterpenoid saponins in Lonicerae Flos crude drugs and preparations by paper spray mass spectrometry.

Hemolytic triterpenoid saponins, as one of the index components of Lonicerae Flos (LF), are also the main components causing hemolytic risk of LF. In order to evaluate the quality and hemolytic risk of LF crude drugs and preparations, it was a key to establish a method for quantitative analysis of hemolytic triterpenoid saponins in LF. Here, a rapid method for quantitative determining hemolytic triterpenoid saponins had been developed via paper spray mass spectrometry (PS-MS), taking macranthoidin B (MaB), macranthoidin A (MaA) and dipsacoside B (DiB) as three target model compounds, and asperosaponin VI (ASA VI, a structural analogue) was used as internal standard. The sample solution was directly loaded and separated on chromatographic paper, sprayed and ionized by a high positive voltage, and ultimately analyzed by mass spectrometry. All analytes were detected with good linearity, precision, repeatability and accuracy. Compared with traditional high performance liquid chromatography with diode array detection (HPLC-DAD) method, PS-MS method had no significant difference in the semi-quantitative analysis of the actual samples, adding the advantages of shorter analysis time, lower reagent consumption and no-need chromatography separation process. This work provides a new strategy for fast determining hemolytic triterpenoid saponins in LF crude drugs and preparations.

Direct Quantification and Visualization of Homocysteine, Cysteine, and Glutathione in Alzheimer's and Parkinson's Disease Model Tissues.

Alzheimer's disease (AD) and Parkinson's disease (PD) are chronic neurodegenerative diseases with high morbidity and mortality. Homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) are closely related to AD and PD. However, the dynamics of Hcy, Cys, and GSH in the brain tissues and the potential pathogenesis between Cys/Hcy/GSH with AD and PD remain unclear. Herein, a novel fluorescent probe 1 with multiple binding sites was rationally designed and exploited for the direct quantification of serum total Hcy and Cys along with superior optical properties. Importantly, differentiation and simultaneity fluorescence imaging of Cys, Hcy, and GSH dynamics were achieved in living cells, tissues, and mouse models of AD and PD with this probe, providing direct evidences for the relationship between Hcy/Cys/GSH and AD/PD for the first time. In addition, pathogenesis studies demonstrated that elevated Hcy and Cys levels are closely related to imbalanced redox homeostasis, increased amyloid aggregates, and nerve cell cytotoxicity. These findings will greatly promote the understanding of the functions of Hcy/Cys/GSH in Alzheimer's and Parkinson's diseases, demonstrating clinical promise for the early diagnosis and prevention of AD and PD.

Universal Nanoplatform for Formaldehyde Detection Based on the Oxidase-Mimicking Activity of MnO2 Nanosheets and the In Situ Catalysis-Produced Fluorescence Species.

Formaldehyde (HCHO) pollution is a scientific problem of general concern and has aroused wide attention. In this work, a fluorometric method for sensitive detection of formaldehyde was developed based on the oxidase-mimicking activity of MnO2 nanosheets in the presence of o-phenylenediamine (OPD). The MnO2 nanosheets were prepared by the bottom-up approach using manganese salt as the precursor, followed by the exfoliation with bovine serum albumin. The as-prepared MnO2 nanosheets displayed excellent oxidase-mimicking activity, and can be used as the nanoplatform for sensing in fluorometric analysis. OPD was used as a typical substrate because MnO2 nanosheets can catalyze the oxidation of OPD to generate yellow 2,3-diaminophenazine (DAP), which can emit bright yellow fluorescence at the wavelength of 560 nm. While in the presence of formaldehyde, the fluorescence was greatly quenched because formaldehyde can react with OPD to form Schiff bases that decreased the oxidation reaction of OPD to DAP. The main mechanism and the selectivity of the platform were studied. As a result, formaldehyde can be sensitively detected in a wide linear range of 0.8-100 µM with the detection limit as low as 6.2 × 10-8 M. The platform can be used for the detection of formaldehyde in air, beer, and various food samples with good performance. This work not only expands the application of MnO2 nanosheets in fluorescence sensing, but also provides a sensitive and selective method for the detection of formaldehyde in various samples via a new mechanism.