Avidity-Based Affinity Enhancement Using Nanoliposome-Amplified SPR Sensing Enables Low Picomolar Detection of Biologically Active Neuregulin 1

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Akkilic, NamikAstraZeneca AB (author)

Avidity-Based Affinity Enhancement Using Nanoliposome-Amplified SPR Sensing Enables Low Picomolar Detection of Biologically Active Neuregulin 1

Article/chapterEnglish2019

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2019-11-14
American Chemical Society (ACS),2019

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LIBRIS-ID:oai:research.chalmers.se:6ff6cf34-0b06-4749-af36-b370c32f1690
https://doi.org/10.1021/acssensors.9b01392DOI
https://research.chalmers.se/publication/515077URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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Biomarkers serve as indicators of disease progression or therapeutic response of an medical intervention, and means for enabling a reliable and sensitive biomarker detection are therefore vital in clinical settings. Most biosensor assays require high-affinity interactions in combination with an enzyme or fluorescent tag to enable detection and frequently employ extensive washing procedures prior to signal readout. Attempts to overcome this limitation by using natural biological partners tend to be demanding, because their very low affinity is frequently not compatible with the need of reaching low limits of detection (LODs), especially for circulating biomarkers that possess short half-lives. To address these challenges, we developed a label-free surface plasmon resonance (SPR) platform for the detection of neuregulin 1 (NRG1) using ErbB4-modified liposomes offering both signal amplification and affinity enhancement via functional multivalent interactions. Through the functional avidity interaction between NRG1 and ErbB4, an LOD of 3.5 picomolar was reached, which is about 60-fold higher than traditional SPR and miniaturized immunoassays. The biosensor displays also an 8-fold higher sensitivity when compared with a single-molecule immunoassay employing the natural binding partner rather than a high-affinity antibody as one of the interaction partners. In fact, the liposome-induced avidity between NRG1 and ErbB4 offered an LOD that was comparable to that obtained using a high-affinity antibody and enabled detection of NRG1 in plasma with a LOD of 36 pM. Employing the liposome-enhanced platform in conjunction with a low-affinity biomarker receptor thus enables the assessment of the functional state of the biomarker at competitive LODs and eliminates the need for high-affinity antibodies.

Subject headings and genre

NATURVETENSKAP Kemi Analytisk kemi hsv//swe
NATURAL SCIENCES Chemical Sciences Analytical Chemistry hsv//eng
NATURVETENSKAP Fysik Annan fysik hsv//swe
NATURAL SCIENCES Physical Sciences Other Physics Topics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Läkemedelskemi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medicinal Chemistry hsv//eng
neuregulin
biomarker
avidity
biosensing
liposome
receptor
surface plasmon resonance

Added entries (persons, corporate bodies, meetings, titles ...)

Liljeblad, MathiasAstraZeneca AB (author)
Blaho, StefanAstraZeneca AB (author)
Hölttä, MikkoAstraZeneca AB (author)
Höök, Fredrik,1966Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)fredrikh (author)
Geschwindner, S.AstraZeneca AB (author)
AstraZeneca ABChalmers tekniska högskola (creator_code:org_t)

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In:ACS Sensors: American Chemical Society (ACS)4:12, s. 3166-31742379-3694

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By the author/editor: Akkilic, Namik; Liljeblad, Mathi ...; Blaho, Stefan; Hölttä, Mikko; Höök, Fredrik, 1 ...; Geschwindner, S.

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NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Analytical Chemi ...

NATURAL SCIENCES: NATURAL SCIENCES; and Physical Science ...; and Other Physics To ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medicinal Chemis ...

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