Real-Time Tau Protein Detection by Sandwich-Based Piezoelectric Biosensing: Exploring Tubulin as a Mass Enhancer

Li, Dujuan; Scarano, Simona; Lisi, Samuele; Palladino, Pasquale; Minunni, Maria

doi:10.3390/s18040946

Cited by 19 publications

(11 citation statements)

References 30 publications

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“…(C) Schematic representation of the proposed paperclip conformation of soluble tau in which the N-terminus domain, C-terminus domain, and MTBR are in close approximation. Schematic illustrations based on the following references: (43)(44)(45)(46)(47).…”

Section: Pathological Tau Metabolism In Als-ftsdmentioning

confidence: 99%

Alterations in Tau Metabolism in ALS and ALS-FTSD

2020

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There is increasing acceptance that amyotrophic lateral sclerosis (ALS), classically considered a neurodegenerative disease affecting almost exclusively motor neurons, is syndromic with both clinical and biological heterogeneity. This is most evident in its association with a broad range of neuropsychological, behavioral, speech and language deficits [collectively termed ALS frontotemporal spectrum disorder (ALS-FTSD)]. Although the most consistent pathology of ALS and ALS-FTSD is a disturbance in TAR DNA binding protein 43 kDa (TDP-43) metabolism, alterations in microtubule-associated tau protein (tau) metabolism can also be observed in ALS-FTSD, most prominently as pathological phosphorylation at Thr175 (pThr175tau). pThr175 has been shown to promote exposure of the phosphatase activating domain (PAD) in the tau N-terminus with the consequent activation of GSK3β mediated phosphorylation at Thr231 (pThr231tau) leading to pathological oligomer formation. This pathological cascade of tau phosphorylation has been observed in chronic traumatic encephalopathy with ALS (CTE-ALS) and in both in vivo and in vitro experimental paradigms, suggesting that it is of critical relevance to the pathobiology of ALS-FTSD. It is also evident that the co-existence of alterations in the metabolism of TDP-43 and tau acts synergistically in a rodent model to exacerbate the pathology of either.

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Section: Pathological Tau Metabolism In Als-ftsdmentioning

confidence: 99%

Alterations in Tau Metabolism in ALS and ALS-FTSD

2020

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“…Microfluidic exosome capture and lysing techniques featured in Ko 2017 and Ramshani 2019 could be utilized for isolation of neural exosomes from blood and freeing of their neuro biomarker cargo. Furthermore, once freely soluble, these neuro biomarkers can be detected for their clinical relevance and AD or PD diagnosis in a similar fashion to the previously described methods [41][42][43]47,[49][50][51]. Any combination of these techniques can be applied to enhance microfluidic neurodegenerative exosome research and offer a substantial effort in furthering more facile, real time, early detection of neurodegenerative disorders.…”

Section: Opportunities To Develop Technologies For Profiling Of Exosomal Cargo Biomarkersmentioning

confidence: 99%

“…Interestingly, they utilized a different method of secondary recognition for tau-binding outside of the conventional antibody-antigen binding. Li investigated if tubulin could be used as an alternative secondary recognition element for tau protein biosensing [47]. It is well known that tau is a microtubule-associated protein and interacts with tubulin, specifically in microtubule polymerization and stabilization [48].…”

Section: Microfluidic Detection Of Alzheimer's Disease Biomarkers: Tau Protein and Amyloid-betamentioning

confidence: 99%

The Microfluidic Toolbox for Analyzing Exosome Biomarkers of Aging

et al. 2021

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As the fields of aging and neurological disease expand to liquid biopsies, there is a need to identify informative biomarkers for the diagnosis of neurodegeneration and other age-related disorders such as cancers. A means of high-throughput screening of biomolecules relevant to aging can facilitate this discovery in complex biofluids, such as blood. Exosomes, the smallest of extracellular vesicles, are found in many biofluids and, in recent years, have been found to be excellent candidates as liquid biopsy biomarkers due to their participation in intercellular communication and various pathologies such as cancer metastasis. Recently, exosomes have emerged as novel biomarkers for age-related diseases. Hence, the study of exosomes, their protein and genetic cargo can serve as early biomarkers for age-associated pathologies, especially neurodegenerative diseases. However, a disadvantage of exosome studies includes a lack in standardization of isolating, detecting, and profiling exosomes for downstream analysis. In this review, we will address current techniques for high-throughput isolation and detection of exosomes through various microfluidic and biosensing strategies and how they may be adapted for the detection of biomarkers of age-associated disorders.

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“…As the nano/microelectromechanical system (NEMS/MEMS) sensor market continues to grow, a nanotechnology-based nanoresonator is expected to have various applications in the future, centering on the high-sensitivity sensor market. It can be applied as a biochemical sensor that is targeted for detecting protein, (1) the density or viscosity of the surrounding liquid, or DNA. (2) The surrounding medium, DNA adsorption, and so forth cause the change in the damping parameter or mass in the equivalent mechanical lumped-parameter model.…”

Section: Introductionmentioning

confidence: 99%

Open-loop Spectrum Analyzer Integrated Circuit for Nanoresonator Sensing

Heo¹,

Han²,

Kim³

et al. 2020

Sensors and Materials

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A nanoresonator can be applied as a biochemical sensor based on the change in the mass of the nanoresonator, and the mass change can be interpreted in the frequency domain. In this paper, we present an open-loop spectrum analyzer integrated circuit (IC) for a nanoresonator. The circuit determines the frequency characteristics of a nanoresonator, such as quality factor (Q-factor) and resonant frequency, and detects minute resistance changes of the nanoresonator that result in changes in Q-factor or resonant frequency. The proposed nanoresonator driver circuit is implemented using an open-loop system, and to characterize the open-loop frequency response of the nanoresonator, the IC includes a voltage-controlled oscillator, a transimpedance amplifier, and a 16-bit delta-sigma analog-to-digital converter. To compensate for the parasitic components that cause the distortions of the phase and magnitude response, a shunt-capacitance cancelling amplifier is used to cancel the effect of the shunt-parasitic capacitance of the nanoresonator. The simulated target nanoresonator is modeled using the Butterworth-Van Dyke equivalent circuit model with a resonant frequency of 10 MHz. The proposed nanoresonator driver circuit is fabricated using a standard 0.18 μm complementary metal oxide semiconductor process with an active area of 2.346 mm 2. The simulated resistive sensitivity of the IC is 5.1 mV/kΩ.

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Real-Time Tau Protein Detection by Sandwich-Based Piezoelectric Biosensing: Exploring Tubulin as a Mass Enhancer

Cited by 19 publications

References 30 publications

Alterations in Tau Metabolism in ALS and ALS-FTSD

Alterations in Tau Metabolism in ALS and ALS-FTSD

The Microfluidic Toolbox for Analyzing Exosome Biomarkers of Aging

Open-loop Spectrum Analyzer Integrated Circuit for Nanoresonator Sensing

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