Multiplexed femtomolar detection of Alzheimer's disease biomarkers in biofluids using a reduced graphene oxide field-effect transistor

Park, Dongsung; Kim, Jae Hyun; Kim, Hye Jin; Lee, Dongtak; Lee, David S.; Yoon, Dae Sung; Hwang, Kyo Seon

doi:10.1016/j.bios.2020.112505

Cited by 65 publications

(41 citation statements)

References 33 publications

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“…Reprinted with permission from ref. [67] various AD related biomolecules in secretions of salivary glands, the conclusiveness of the results is still limited due to the lack of proper and sufficient standardization [93]. Similarly, the nasal secretions and olfactory fluids might also be considered as the promising non-invasive biosamples for the early detection of AD biomarkers [94][95][96].…”

Section: Detection Of Ad Biomarkers In Biosamplesmentioning

confidence: 99%

Advances in the development paradigm of biosample‐based biosensors for early ultrasensitive detection of alzheimer’s disease

et al. 2021

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This review highlights current developments, challenges, and future directions for the use of invasive and noninvasive biosample-based small biosensors for early diagnosis of Alzheimer’s disease (AD) with biomarkers to incite a conceptual idea from a broad number of readers in this field. We provide the most promising concept about biosensors on the basis of detection scale (from femto to micro) using invasive and noninvasive biosamples such as cerebrospinal fluid (CSF), blood, urine, sweat, and tear. It also summarizes sensor types and detailed analyzing techniques for ultrasensitive detection of multiple target biomarkers (i.e., amyloid beta (Aβ) peptide, tau protein, Acetylcholine (Ach), microRNA137, etc.) of AD in terms of detection ranges and limit of detections (LODs). As the most significant disadvantage of CSF and blood-based detection of AD is associated with the invasiveness of sample collection which limits future strategy with home-based early screening of AD, we extensively reviewed the future trend of new noninvasive detection techniques (such as optical screening and bio-imaging process). To overcome the limitation of non-invasive biosamples with low concentrations of AD biomarkers, current efforts to enhance the sensitivity of biosensors and discover new types of biomarkers using non-invasive body fluids are presented. We also introduced future trends facing an infection point in early diagnosis of AD with simultaneous emergence of addressable innovative technologies.

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Section: Detection Of Ad Biomarkers In Biosamplesmentioning

confidence: 99%

Advances in the development paradigm of biosample‐based biosensors for early ultrasensitive detection of alzheimer’s disease

et al. 2021

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“…Sensing events and signal conversion normally occur at heterogeneous interfaces. ,, In the field of FETs, 2D materials restrain charge flow solely on the surface, which directly exposes it to the environment and is entirely located at the interfaces of signal acquisition and conversion, leading to rapid and sensitive response upon exposure to the outer stimuli. ,, In detail, the advantages of 2D FET sensors are attributed to at least three aspects: (i) The free dangling bonds enable 2D materials to construct functional heterostructures with ideal vdW interfaces readily. − It reduces the scattering center, which is key to maintain their attractive electronic properties (e.g., high carrier mobility) even after different device fabrication and modification processes . (ii) The atomic thickness ensures direct exposure of the channel to functional interfaces and/or external environments, leading to a rapid response to foreign stimuli with ultrahigh sensitivity. − (iii) The large surface-to-volume ratio provides abundant modification sites for anchoring specific receptors, which ensures the sensitivity and specificity upon specific perturbations. − This section clarifies the motivation of using 2D materials, the concepts, and the fundamentals of the 2D FET sensors.…”

Section: Fundamentals and Motivationmentioning

confidence: 99%

“…The positive controls are set to validate sensor function in the presence of targeted analytes. , They are extensively used in cytotoxicity tests that are essential for biomedical applications . In practice, most studies expose 2D FET sensors to samples with a known concentration, which is designed to investigate the calibration relation between sensing response and sample concentration. ,,, For instance, Park et al used GFETs to measure the concentration of t-Tau protein in both PBS buffer and human plasma. The calibration results with positive controls confirmed their potential in clinical applications.…”

Section: Prototypical Designmentioning

confidence: 99%

Two-Dimensional Field-Effect Transistor Sensors: The Road toward Commercialization

2022

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The evolutionary success in information technology has been sustained by the rapid growth of sensor technology. Recently, advances in sensor technology have promoted the ambitious requirement to build intelligent systems that can be controlled by external stimuli along with independent operation, adaptivity, and low energy expenditure. Among various sensing techniques, field-effect transistors (FETs) with channels made of two-dimensional (2D) materials attract increasing attention for advantages such as label-free detection, fast response, easy operation, and capability of integration. With atomic thickness, 2D materials restrict the carrier flow within the material surface and expose it directly to the external environment, leading to efficient signal acquisition and conversion. This review summarizes the latest advances of 2D-materials-based FET (2D FET) sensors in a comprehensive manner that contains the material, operating principles, fabrication technologies, proof-of-concept applications, and prototypes. First, a brief description of the background and fundamentals is provided. The subsequent contents summarize physical, chemical, and biological 2D FET sensors and their applications. Then, we highlight the challenges of their commercialization and discuss corresponding solution techniques. The following section presents a systematic survey of recent progress in developing commercial prototypes. Lastly, we summarize the long-standing efforts and prospective future development of 2D FET-based sensing systems toward commercialization.

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“…In recent years, a series of new technologies have sprung up for accurately testing biomarkers in AD. Assays for peripheral biomarkers are based on classic methods or new ultrasensitive technologies, including ELISA, single-molecule array (Simoa), immunoprecipitation/MS, liquid chromatography–MS, immunomagnetic reduction (IMR), multimer detection system, reduced graphene oxide field-effect transistor, and cryo-electron microscopy (cryo-EM) [ 26 , 60 , 130 – 137 ]. Each biomarker has a suitable assay method, and researchers have finished a set of studies comparing the different technologies [ 138 ].…”

Section: Developing Technologies For Biomarkers In Admentioning

confidence: 99%

Biofluid Biomarkers of Alzheimer’s Disease: Progress, Problems, and Perspectives

2022

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Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer’s disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an “X” to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.

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Multiplexed femtomolar detection of Alzheimer's disease biomarkers in biofluids using a reduced graphene oxide field-effect transistor

Cited by 65 publications

References 33 publications

Advances in the development paradigm of biosample‐based biosensors for early ultrasensitive detection of alzheimer’s disease

Advances in the development paradigm of biosample‐based biosensors for early ultrasensitive detection of alzheimer’s disease

Two-Dimensional Field-Effect Transistor Sensors: The Road toward Commercialization

Biofluid Biomarkers of Alzheimer’s Disease: Progress, Problems, and Perspectives

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