Publications by authors named "Ponnusamy Nandhakumar"

Timely and precise monitoring of inflammatory biomarkers is essential for the effective management of sepsis and related acute conditions. Current monitoring strategies depend mostly on centralized, benchtop systems. Here, we present compact and bioelectronic sensor platforms capable of rapid and simultaneous detection of lactate and interleukin-6 (IL-6) in human serum and interstitial fluid.

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Accurate health analysis demands real-time tracking of multiple biomarkers and vital signs under dynamic physiological conditions. Current multimodal hybrid platforms provide biochemical and biophysical data but are limited by active sweat collection for biochemical sensing and bulky designs for biophysical sensing. Here a touch-enabled platform is presented that simultaneously monitors vitals and metabolic markers.

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The growing need for reliable and rapid insulin testing to enhance glycemic management has spurred intensive exploration of new insulin-binding bioreceptors and innovative biosensing platforms for detecting this hormone, along with glucagon, in biological samples. Here, by leveraging the native protein receptors on the HepG2 cell membrane, we construct a simple and chemical-free biomimetic molecular recognition layer for the detection of insulin and glucagon. Unlike traditional affinity sensors, which require lengthy surface modifications on the electrochemical transducers and use of two different capture antibodies to recognize each analyte, this new biomimetic sensing strategy employs a simple drop-casting of a natural cell membrane recognition layer onto the electrochemical transducer.

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Diabetes management demands precise monitoring of key biomarkers, particularly insulin (I) and glucose (G). Herein, we present a bioelectronic chip device that enables the simultaneous detection of I and G in biofluids within 2 min. This dual biosensor chip integrates aptamer-based insulin sensing with enzymatic glucose detection on a single platform, employing a four-electrode sensor chip.

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Gut microbiome targeting has emerged as a new generation of personalized medicine and a potential wellness and disease driver. Specifically, the gut redox balance plays a key role in shaping the gut microbiota and its link with the host, immune system, and disease evolution. In this sense, precise and personalized nutrition has proven synergy and capability to modulate the gut microbiome environment through the formulation of dietary interventions, such as vitamin support.

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Article Synopsis
  • - The study presents a new type of diagnostic test called electrochemical LFA (eLFA), which enhances the sensitivity of traditional lateral-flow immunoassays (LFA) for detecting insulin.
  • - This innovation uses nanocatalytic redox cycling with gold nanoparticles (AuNP) to amplify signals, achieving a limit of detection as low as 12 pM, which is better than existing colorimetric and enzymatic methods.
  • - The eLFA can detect insulin in various biological fluids like saliva and serum without needing complex preparation steps, making it suitable for decentralized diagnostic applications.
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Tremendous progress has been made towards achieving tight glycaemic control in individuals with diabetes mellitus through the use of frequent or continuous glucose measurements. However, in patients who require insulin, accurate dosing must consider multiple factors that affect insulin sensitivity and modulate insulin bolus needs. Accordingly, an urgent need exists for frequent and real-time insulin measurements to closely track the dynamic blood concentration of insulin during insulin therapy and guide optimal insulin dosing.

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Biomolecule-conjugated metal nanoparticles (NPs) have been primarily used as colorimetric labels in affinity-based bioassays for point-of-care testing. A facile electrochemical detection scheme using a rapid nanocatalytic reaction of a metal NP label is required to achieve more quantitative and sensitive point-of-care testing. Moreover, all the involved components should be stable in their dried form and solution.

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An electron mediator with rapid dissolvability and high solubility in aqueous electrolyte solutions is essential for point-of-care testing based on mediated electrochemical detection. However, most ferrocenyl (Fc) compounds have slow dissolvability and poor solubility owing to high hydrophobicity of the Fc backbone. Moreover, many Fc compounds have poor stability and nonoptimal formal potential ().

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Article Synopsis
  • Traditional sandwich immunosensors use antibody layers to detect target proteins, but their construction can be complicated and prone to interference from complex samples.
  • The new bioelectronic affinity sensors utilize natural cell membranes from human macrophages and red blood cells to simplify the process into a single step, enhancing protein detection while minimizing unwanted binding.
  • This innovative design effectively detected the cytokine TNF-α at a sensitivity of 150 pM, showcasing its potential for a wide range of biosensing applications.
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Direct electron transfer (DET) between a redox label and an electrode has been used for sensitive and selective sandwich-type detection without a wash step. However, applying DET is still highly challenging in protein detection, and a single redox label per probe is insufficient to obtain a high electrochemical signal. Here, we report a wash-free, sandwich-type detection of thrombin using DET and catalytic signal amplification of multiple redox labels.

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Article Synopsis
  • - The study presents a novel method for silver (Ag) deposition using a redox enzyme and a quinone substrate that eliminates the need for a washing step, which is usually necessary to avoid oxidation during electrochemical processes.
  • - It was discovered that the quinone substrate is initially reduced by the enzyme and can then be restored while facilitating the deposition of silver, without undergoing unwanted oxidation during subsequent electrochemical oxidation.
  • - This improved Ag deposition method enables the detection of thyroid-stimulating hormone (TSH) in very low concentrations (down to about 100 fg/mL) in artificial serum, showcasing its potential for sensitive clinical diagnostics.
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The commonly required properties of diffusive electron mediators for point-of-care testing are rapid dissolubility, high stability, and moderate formal potential in aqueous solutions. Inspired by nature, various quinone-containing electron mediators have been developed; however, satisfying all these requirements remains a challenge. Herein, a strategic design toward quinones incorporating sulfonated thioether and nitrogen-containing heteroarene moieties as solubilizing, stabilizing, and formal potential-modulating groups is reported.

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Recombinase polymerase amplification (RPA) is considered one of the best amplification methods for realizing a miniaturized diagnostic instrument; however, it is notably challenging to obtain low detection limits in solid-phase RPA. To overcome these difficulties, we combined solid-phase RPA with electrochemical detection and used a new concentration combination of three primers (surface-bound forward primer, solution reverse primer, and an extremely low concentration of solution forward primer). When solid-phase RPA was performed on an indium tin oxide (ITO) electrode modified with a surface-bound forward primer in a solution containing a biotin-terminated solution reverse primer, an extremely low concentration of a solution forward primer, and a template DNA or genomic DNA for a target gene of hepatitis B virus (HBV), amplification occurred mainly in solution until all the solution forward primers were consumed.

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Horseradish peroxidase (HRP)-based electrochemical immunoassays are considered promising techniques for point-of-care clinical diagnostics, but the necessary addition of unstable HO in the enzymatic system may hinder their practical application. Although glucose oxidase (GOx) has been widely explored for in situ generation of HO in HRP-based immunoassay, the GOx-catalyzed reduction of oxidized peroxidase substrate may limit the immunosensing performance. Here, we report a sensitive electrochemical immunosensor based on a choline oxidase (ChOx)-HRP cascade reaction.

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Article Synopsis
  • Metal nanoparticles have been explored for two types of enzyme-like activities (peroxidase and oxidase), but not for esterase-like activities due to challenges in rapid catalytic hydrolysis.
  • This study demonstrates that metal nanoparticle surfaces can effectively catalyze non-redox ester hydrolysis using an electron-rich Pt nanoparticle generated from ammonia borane, enhancing the reaction with nucleophiles.
  • The developed nanozyme system shows superior performance in electrochemical immunosensing for thyroid-stimulating hormone, achieving a remarkable detection limit of around 0.3 pg/mL, indicating high sensitivity compared to natural enzymes.
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In horseradish peroxidase (HRP)-based electrochemical immunosensing, an appropriate HRP substrate needs to be chosen to obtain a high electrochemical signal-to-background ratio. This is limited by the unwanted electrochemical reduction of HO, oxidation of the substrate, and the slow electrochemical reduction of the product. Herein, we report acetaminophen (AMP) as a new HRP substrate that allows for highly sensitive immunosensing.

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  • Catalytic precipitation and electrochemical methods are commonly used in biosensors, but they face challenges like low detection limits and nonspecific reactions.
  • This study introduces a new, ultrasensitive immunosensor that detects parathyroid hormone (PTH) by utilizing DT-diaphorase to rapidly precipitate a compound, leading to a strong electrochemical signal.
  • The immunosensor, made with a special electrode surface, can detect PTH at very low concentrations (around 1 pg/mL) and shows consistent results with established commercial methods when testing clinical serum samples.
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  • Carboxyl esterases are typically poor choices for bioassay catalysts due to slow reactions, but DT-diaphorase (DT-D) shows promising carboxyl esterase-like activity in the presence of NADH, making it a more effective option.
  • DT-D enables a novel electrochemical immunosensor that amplifies signals threefold through hydrolysis of esters and two types of redox cycling (EC and EN) involving different components, resulting in enhanced sensitivity.
  • The best substrate identified for DT-D is 4-aminonaphthalene-1-yl acetate, as it undergoes rapid hydrolysis with DT-D, and the immunosensor shows a
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Article Synopsis
  • Researchers developed a fast silver deposition method for electrochemical biosensors that utilizes three signal amplification processes: enzymatic amplification, chemical-chemical redox cycling, and chemical-enzymatic redox cycling.
  • The method employs DT-diaphorase to convert a nitroso compound into an amine compound that effectively reduces silver ions, aided by NADH as a reducing agent in the redox cycling processes.
  • When tested on an electrochemical immunosensor for parathyroid hormone detection, this approach achieved a remarkable sensitivity with a detection limit as low as ∼100 fg/mL, showing promising applications in ultrasensitive biosensing.
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DT-diaphorase (DT-D) is known to mainly catalyze the two-electron reduction of quinones and nitro(so) compounds. Detection of Gram-negative bacterial outer membrane vesicles (OMVs) that contain pyrogenic lipopolysaccharides (LPSs, also called endotoxins) is required for evaluating the toxic effects of analytical samples. Here, we report that DT-D has a high dephosphorylation activity: DT-D catalyzes reductive dephosphorylation of a phosphate-containing substrate in the presence of NADH.

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Rapid and sensitive mold detection is becoming increasingly important, especially in indoor environments. Common mold detection methods based on double-mediated electron transfer between an electrode and molds are not highly sensitive and reproducible, although they are rapid and simple. Here, we report a sensitive and reproducible detection method specific to Aspergillus niger ( A.

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Simple and sensitive competitive immunosensors for small molecules are difficult to obtain, especially in serum containing numerous interfering species (ISs) with different concentrations. Herein, we report a washing-free and sensitive (competitive) displacement immunosensor for cortisol in human serum, based on electron mediation of Os(bpy)Cl between an electrode and a redox label [oxygen-insensitive diaphorase (DI)] (i.e.

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Enzyme-like nanocatalytic reactions developed for high signal amplification in biosensors are of limited use because of their low reaction rates and/or unwanted side reactions in aqueous electrolyte solutions containing dissolved O. Herein, we report a nitrosoreductase-like catalytic reaction, employing 4-nitroso-1-naphthol, Pd nanoparticles, and HN-BH, which affords a high reaction rate and minimal side reactions, enabling its use in ultrasensitive electrochemical biosensors. 4-Nitroso-1-naphthol was chosen after five hydroxy-nitro(so)arene compounds were compared in terms of high signal and low background levels.

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