Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample

Alessandro Surpi; Mauro Murgia; Sonia Lopez-Amoedo; Manuel Gonzalez Lopez; Yolanda Pineiro; Jose Rivas; Valeria Perugini; Matteo Santin; Tomas Sebrino; Pierpaolo Greco; Francisco Campos; Valentin Alek Dediu

doi:10.1186/s12951-023-02095-8

Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample

Alessandro Surpi, Mauro Murgia, Sonia Lopez-Amoedo, Manuel Gonzalez Lopez, Yolanda Pineiro, Jose Rivas, Valeria Perugini, Matteo Santin, Tomas Sebrino, Pierpaolo Greco, Francisco Campos, Valentin Alek Dediu

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. The progressive aging of the population is expected to exacerbate this problem in the next decades. Therefore, there is an urgent need to develop quantitative diagnostic methodologies to assess the onset the disease and its progression especially in the initial phases. Results: Here we describe a novel technology to extract one of the most important molecular biomarkers of AD (Aβ ₁₋₄₂) from a clinically-relevant volume − 100 µl – therein dispersed in a range of concentrations critical for AD early diagnosis. We demonstrate that it is possible to immunocapture Aβ ₁₋₄₂ on 20 nm wide magnetic nanoparticles functionalized with hyperbranced KVLFF aptamers. Then, it is possible to transport them through microfluidic environments to a detection system where virtually all (~ 90%) the Aβ ₁₋₄₂ molecules are concentrated in a dense plug of ca.50 nl. The technology is based on magnetic actuation by permanent magnets, specifically designed to generate high gradient magnetic fields. These fields, applied through submillimeter-wide channels, can concentrate, and confine magnetic nanoparticles (MNPs) into a droplet with an optimized shape that maximizes the probability of capturing highly diluted molecular biomarkers. These advancements are expected to provide efficient protocols for the concentration and manipulation of molecular biomarkers from clinical samples, enhancing the accuracy and the sensitivity of diagnostic technologies. Conclusions: This easy to automate technology allows an efficient separation of AD molecular biomarkers from volumes of biological solutions complying with the current clinical protocols and, ultimately, leads to accurate measurements of biomarkers. The technology paves a new way for a quantitative AD diagnosis at the earliest stage and it is also adaptable for the biomarker analysis of other pathologies. [Figure not available: see fulltext.]

Original language	English
Article number	329
Pages (from-to)	1-13
Number of pages	13
Journal	Journal of Nanobiotechnology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12951-023-02095-8
Publication status	Published - 15 Sept 2023

Bibliographical note

Funding Information:
This research has been funded from the European Union’s Horizon 2020 research and innovation programme under the projects MADIA - MAgnetic DIagnostic Assay for neurodegenerative disease – grant agreement n 732678, BOW - Biogenic Organotropic Wetsuits – grant agreement n 952183 and PANA - Promoting Active Agening: functional nanostructures for Alzheimer’s disease at ultra-early stages - grant agreement n 686009. And from the Italian National Recovery and Reliance Plan (NRRP), part of the European Union’s NextGenerationEU programme, under the project ECOSISTER - ECOSystem for sustainable transition of Emilia-Romagna - ECS 00000033. 0 0 0

Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.

Keywords

Alzheimer’s disease
in vitro diagnostics
Aβ1-42 amyloids
Aβ1-42 fibril inhibitors
optical waveguide lightmode spectroscopy
poly(epsilon-Lysine) dendrons
KLVFF

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Surpi_MagneticSeparationAbeta_JNanoBiotech2023Final published version, 2.39 MBLicence: CC BY

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Surpi, A., Murgia, M., Lopez-Amoedo, S., Gonzalez Lopez, M., Pineiro, Y., Rivas, J., Perugini, V., Santin, M., Sebrino, T., Greco, P., Campos, F., & Dediu, V. A. (2023). Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample. Journal of Nanobiotechnology, 21(1), 1-13. Article 329. https://doi.org/10.1186/s12951-023-02095-8

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title = "Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer{\textquoteright}s disease diagnosis in clinically-relevant volumes of sample",

abstract = "Background: Alzheimer{\textquoteright}s disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. The progressive aging of the population is expected to exacerbate this problem in the next decades. Therefore, there is an urgent need to develop quantitative diagnostic methodologies to assess the onset the disease and its progression especially in the initial phases. Results: Here we describe a novel technology to extract one of the most important molecular biomarkers of AD (Aβ 1−42) from a clinically-relevant volume − 100 µl – therein dispersed in a range of concentrations critical for AD early diagnosis. We demonstrate that it is possible to immunocapture Aβ 1−42 on 20 nm wide magnetic nanoparticles functionalized with hyperbranced KVLFF aptamers. Then, it is possible to transport them through microfluidic environments to a detection system where virtually all (~ 90%) the Aβ 1−42 molecules are concentrated in a dense plug of ca.50 nl. The technology is based on magnetic actuation by permanent magnets, specifically designed to generate high gradient magnetic fields. These fields, applied through submillimeter-wide channels, can concentrate, and confine magnetic nanoparticles (MNPs) into a droplet with an optimized shape that maximizes the probability of capturing highly diluted molecular biomarkers. These advancements are expected to provide efficient protocols for the concentration and manipulation of molecular biomarkers from clinical samples, enhancing the accuracy and the sensitivity of diagnostic technologies. Conclusions: This easy to automate technology allows an efficient separation of AD molecular biomarkers from volumes of biological solutions complying with the current clinical protocols and, ultimately, leads to accurate measurements of biomarkers. The technology paves a new way for a quantitative AD diagnosis at the earliest stage and it is also adaptable for the biomarker analysis of other pathologies. [Figure not available: see fulltext.]",

keywords = "Alzheimer{\textquoteright}s disease, in vitro diagnostics, Aβ1-42 amyloids, Aβ1-42 fibril inhibitors, optical waveguide lightmode spectroscopy, poly(epsilon-Lysine) dendrons, KLVFF",

author = "Alessandro Surpi and Mauro Murgia and Sonia Lopez-Amoedo and {Gonzalez Lopez}, Manuel and Yolanda Pineiro and Jose Rivas and Valeria Perugini and Matteo Santin and Tomas Sebrino and Pierpaolo Greco and Francisco Campos and Dediu, {Valentin Alek}",

note = "Funding Information: This research has been funded from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the projects MADIA - MAgnetic DIagnostic Assay for neurodegenerative disease – grant agreement n 732678, BOW - Biogenic Organotropic Wetsuits – grant agreement n 952183 and PANA - Promoting Active Agening: functional nanostructures for Alzheimer{\textquoteright}s disease at ultra-early stages - grant agreement n 686009. And from the Italian National Recovery and Reliance Plan (NRRP), part of the European Union{\textquoteright}s NextGenerationEU programme, under the project ECOSISTER - ECOSystem for sustainable transition of Emilia-Romagna - ECS 00000033. 0 0 0 Publisher Copyright: {\textcopyright} 2023, BioMed Central Ltd., part of Springer Nature.",

year = "2023",

month = sep,

day = "15",

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language = "English",

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Surpi, A, Murgia, M, Lopez-Amoedo, S, Gonzalez Lopez, M, Pineiro, Y, Rivas, J, Perugini, V, Santin, M, Sebrino, T, Greco, P, Campos, F & Dediu, VA 2023, 'Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample', Journal of Nanobiotechnology, vol. 21, no. 1, 329, pp. 1-13. https://doi.org/10.1186/s12951-023-02095-8

Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample. / Surpi, Alessandro; Murgia, Mauro; Lopez-Amoedo, Sonia et al.
In: Journal of Nanobiotechnology, Vol. 21, No. 1, 329, 15.09.2023, p. 1-13.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample

AU - Surpi, Alessandro

AU - Murgia, Mauro

AU - Lopez-Amoedo, Sonia

AU - Gonzalez Lopez, Manuel

AU - Pineiro, Yolanda

AU - Rivas, Jose

AU - Perugini, Valeria

AU - Santin, Matteo

AU - Sebrino, Tomas

AU - Greco, Pierpaolo

AU - Campos, Francisco

AU - Dediu, Valentin Alek

N1 - Funding Information: This research has been funded from the European Union’s Horizon 2020 research and innovation programme under the projects MADIA - MAgnetic DIagnostic Assay for neurodegenerative disease – grant agreement n 732678, BOW - Biogenic Organotropic Wetsuits – grant agreement n 952183 and PANA - Promoting Active Agening: functional nanostructures for Alzheimer’s disease at ultra-early stages - grant agreement n 686009. And from the Italian National Recovery and Reliance Plan (NRRP), part of the European Union’s NextGenerationEU programme, under the project ECOSISTER - ECOSystem for sustainable transition of Emilia-Romagna - ECS 00000033. 0 0 0 Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.

PY - 2023/9/15

Y1 - 2023/9/15

N2 - Background: Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. The progressive aging of the population is expected to exacerbate this problem in the next decades. Therefore, there is an urgent need to develop quantitative diagnostic methodologies to assess the onset the disease and its progression especially in the initial phases. Results: Here we describe a novel technology to extract one of the most important molecular biomarkers of AD (Aβ 1−42) from a clinically-relevant volume − 100 µl – therein dispersed in a range of concentrations critical for AD early diagnosis. We demonstrate that it is possible to immunocapture Aβ 1−42 on 20 nm wide magnetic nanoparticles functionalized with hyperbranced KVLFF aptamers. Then, it is possible to transport them through microfluidic environments to a detection system where virtually all (~ 90%) the Aβ 1−42 molecules are concentrated in a dense plug of ca.50 nl. The technology is based on magnetic actuation by permanent magnets, specifically designed to generate high gradient magnetic fields. These fields, applied through submillimeter-wide channels, can concentrate, and confine magnetic nanoparticles (MNPs) into a droplet with an optimized shape that maximizes the probability of capturing highly diluted molecular biomarkers. These advancements are expected to provide efficient protocols for the concentration and manipulation of molecular biomarkers from clinical samples, enhancing the accuracy and the sensitivity of diagnostic technologies. Conclusions: This easy to automate technology allows an efficient separation of AD molecular biomarkers from volumes of biological solutions complying with the current clinical protocols and, ultimately, leads to accurate measurements of biomarkers. The technology paves a new way for a quantitative AD diagnosis at the earliest stage and it is also adaptable for the biomarker analysis of other pathologies. [Figure not available: see fulltext.]

AB - Background: Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. The progressive aging of the population is expected to exacerbate this problem in the next decades. Therefore, there is an urgent need to develop quantitative diagnostic methodologies to assess the onset the disease and its progression especially in the initial phases. Results: Here we describe a novel technology to extract one of the most important molecular biomarkers of AD (Aβ 1−42) from a clinically-relevant volume − 100 µl – therein dispersed in a range of concentrations critical for AD early diagnosis. We demonstrate that it is possible to immunocapture Aβ 1−42 on 20 nm wide magnetic nanoparticles functionalized with hyperbranced KVLFF aptamers. Then, it is possible to transport them through microfluidic environments to a detection system where virtually all (~ 90%) the Aβ 1−42 molecules are concentrated in a dense plug of ca.50 nl. The technology is based on magnetic actuation by permanent magnets, specifically designed to generate high gradient magnetic fields. These fields, applied through submillimeter-wide channels, can concentrate, and confine magnetic nanoparticles (MNPs) into a droplet with an optimized shape that maximizes the probability of capturing highly diluted molecular biomarkers. These advancements are expected to provide efficient protocols for the concentration and manipulation of molecular biomarkers from clinical samples, enhancing the accuracy and the sensitivity of diagnostic technologies. Conclusions: This easy to automate technology allows an efficient separation of AD molecular biomarkers from volumes of biological solutions complying with the current clinical protocols and, ultimately, leads to accurate measurements of biomarkers. The technology paves a new way for a quantitative AD diagnosis at the earliest stage and it is also adaptable for the biomarker analysis of other pathologies. [Figure not available: see fulltext.]

KW - Alzheimer’s disease

KW - in vitro diagnostics

KW - Aβ1-42 amyloids

KW - Aβ1-42 fibril inhibitors

KW - optical waveguide lightmode spectroscopy

KW - poly(epsilon-Lysine) dendrons

KW - KLVFF

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U2 - 10.1186/s12951-023-02095-8

DO - 10.1186/s12951-023-02095-8

M3 - Article

VL - 21

SP - 1

EP - 13

JO - Journal of Nanobiotechnology

JF - Journal of Nanobiotechnology

IS - 1

M1 - 329

ER -

Magnetic separation and concentration of Aβ 1–42 molecules dispersed at the threshold concentration for Alzheimer’s disease diagnosis in clinically-relevant volumes of sample

Abstract

Bibliographical note

Keywords

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