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- W2912936719 abstract "Accurate and rapid measurements of enzyme activity are critical to the development of therapeutics that target neurological disorders. An effective label-free measurement of enzyme activity can be achieved through the detection of small changes in the solution pH during enzyme-mediated phosphorylation of substrate proteins. Here, we report the measurements of solution pH by using ionic-liquid gated 2D field-effect transistors (FETs) with 200x higher sensitivity than previously reported. The FETs are fabricated with single-monolayer 2D transition metal dichalcogenide semiconducting films and are top-gated with an ionic-liquid. The high ionic-liquid polarizability allows strong coupling between the top gate (ionic liquid) and a back-gate dielectric (substrate oxide) which enables amplification of a voltage applied to the ionic-liquid gate. This amplification is limited by the intrinsic quantum capacitance of the single-monolayer MoS2 semiconducting channel; thus, the devices operate near their theoretical limits. We leveraged the high performance of the devices to enable pH measurements with sensitivities that greatly exceed the Nernst value of 59 mV/pH (at room temperature). The dramatically improved sensitivity allows the detection of pH changes as small as 80x10∧-6. The method allowed the rapid and quantitative estimation of the kinetics of enzymes that are implicated in Alzheimer's disease. We have demonstrated the ability of ionic-liquid-gated FETs to detect small changes in the solution pH during phosphorylation of the substrate protein, histone H1. We compared these FET measurements against enzyme activity measurements obtained from a radioactively labeled ATP assay (which involves handling radioactive materials and is slow to perform). The FET-based measurements are in excellent quantitative agreement with the ATP assay, while enabling results in minutes and can lead to rapid therapeutic screening." @default.
- W2912936719 created "2019-02-21" @default.
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- W2912936719 date "2019-02-01" @default.
- W2912936719 modified "2023-09-30" @default.
- W2912936719 title "Label-Free Enzyme Activity Measurements with Quantum-Limited Biosensors" @default.
- W2912936719 doi "https://doi.org/10.1016/j.bpj.2018.11.813" @default.
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