アルツハイマー病とパーキンソン病のバイオマーカーを検出するワイヤレス、ハンドヘルド、非侵襲性デバイス(This Wireless, Handheld, Non-invasive Device Detects Alzheimer’s and Parkinson’s Biomarkers)

2023-11-13 カリフォルニア大学サンディエゴ校(UCSD)

<関連情報>

• https://today.ucsd.edu/story/this-wireless-handheld-non-invasive-device-detects-alzheimers-and-parkinsons-biomarkers
• https://www.pnas.org/doi/10.1073/pnas.2311565120
• https://www.pnas.org/doi/10.1073/pnas.2206521119

脳の変性疾患診断のために: DNAアプタマーを装着した携帯型グラフェンバイオセンサーで認知症バイオマーカーを検出 In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor

Tyler Andrew Bodily, Anirudh Ramanathan, Shanhong Wei, Abhijith Karkisaval, Nemil Bhatt, Cynthia Jerez, Md Anzarul Haque, Armando Ramil, Prachi Heda, Yi Wang, Sanjeev Kumar, Mikayla Leite, Tie Li, Jianlong Zhao jlzhao, and Ratnesh Lal
Proceedings of the National Academy of Sciences  Published:November 13, 2023
DOI:https://doi.org/10.1073/pnas.2311565120

Significance

Our memories define us and connect us to others. Without them, we are lost. This is the driving force behind the global push to treat neurodegenerative diseases of the older population. How does one know they have a disease that has few outward symptoms until later stages? The current testing methods for diseases such as Alzheimer’s and Parkinson’s require a spinal tap and imaging tests such as MRI. This has made early detection of these diseases an incredible challenge. This work highlights a DNA aptamer-modified graphene field-effect transistor biosensor to detect unprocessed biomarker proteins in easily accessible biofluids derived from patients with Alzheimer’s disease, in pursuit of an affordable early-onset detection of neurodegenerative diseases.

Abstract

Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (Aβ), Tau (τ), and α-Synuclein (αS) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1–10 pM, 10–100 fM for Aβ, τ, and αS, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. The detection of each amyloid was specific to their aptamers; Aβ, τ, and αS peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.

携帯型無線グラフェンバイオセンサーで唾液中のSARS-CoV-2およびその亜種の未処理ウイルスを迅速に自己検査 Rapid self-test of unprocessed viruses of SARS-CoV-2 and its variants in saliva by portable wireless graphene biosensor

Deependra Kumar Ban, Tyler Bodily, Abhijith G. Karkisaval, Yongliang Dong, Shreyam Natani, Anirudh Ramanathan, Armando Ramil, Sunil Srivastava, Prab Bandaru, Gennadi Glinsky, and Ratnesh Lal
Proceedings of the National Academy of Sciences  Published:June 28, 2022
DOI:https://doi.org/10.1073/pnas.2206521119

Significance

“Am I positive or negative?” Everyone wants to know the answer with speed and accuracy. Rapid and accurate at-home testing is the best defense against the COVID-19 pandemic and ensuing endemics. Current rapid tests are often imprecise, test for denatured and processed viral components, and lack specificity for new variants. We developed a simple at-home test using saliva swabs that answers “positive or negative” in minutes and transmits results to stakeholders. The test uses a DNA aptamer-derivatized graphene field-effect transistor (GFET) to detect unprocessed intact SARS-CoV-2 and its variants at levels as low as 7 to 10 viruses. This method is tunable and adaptable for early-stage detection of emerging viral infections as well as many diseases with accessible biofluids.

Abstract

We have developed a DNA aptamer-conjugated graphene field-effect transistor (GFET) biosensor platform to detect receptor-binding domain (RBD), nucleocapsid (N), and spike (S) proteins, as well as viral particles of original Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus and its variants in saliva samples. The GFET biosensor is a label-free, rapid (≤20 min), ultrasensitive handheld wireless readout device. The limit of detection (LoD) and the limit of quantitation (LoQ) of the sensor are 1.28 and 3.89 plaque-forming units (PFU)/mL for S protein and 1.45 and 4.39 PFU/mL for N protein, respectively. Cognate spike proteins of major variants of concern (N501Y, D614G, Y453F, Omicron-B1.1.529) showed sensor response ≥40 mV from the control (aptamer alone) for fM to nM concentration range. The sensor response was significantly lower for viral particles and cognate proteins of Middle East Respiratory Syndrome (MERS) compared to SARS-CoV-2, indicating the specificity of the diagnostic platform for SARS-CoV-2 vs. MERS viral proteins. During the early phase of the pandemic, the GFET sensor response agreed with RT-PCR data for oral human samples, as determined by the negative percent agreement (NPA) and positive percent agreement (PPA). During the recent Delta/Omicron wave, the GFET sensor also reliably distinguished positive and negative clinical saliva samples. Although the sensitivity is lower during the later pandemic phase, the GFET-defined positivity rate is in statistically close alignment with the epidemiological population-scale data. Thus, the aptamer-based GFET biosensor has a high level of precision in clinically and epidemiologically significant SARS-CoV-2 variant detection. This universal pathogen-sensing platform is amenable for a broad range of public health applications and real-time environmental monitoring.