Avidity-Based Affinity Enhancement Using Nanoliposome-Amplified SPR Sensing Enables Low Picomolar Detection of Biologically Active Neuregulin 1
Journal article, 2019

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.

liposome

neuregulin

biosensing

receptor

surface plasmon resonance

avidity

biomarker

Author

Namik Akkilic

AstraZeneca AB

Mathias Liljeblad

AstraZeneca AB

Stefan Blaho

AstraZeneca AB

Mikko Hölttä

AstraZeneca AB

Fredrik Höök

Chalmers, Physics

S. Geschwindner

AstraZeneca AB

ACS Sensors

23793694 (eISSN)

Vol. 4 12 3166-3174

Subject Categories

Biochemistry and Molecular Biology

Analytical Chemistry

Medicinal Chemistry

DOI

10.1021/acssensors.9b01392

PubMed

31724395

More information

Latest update

1/24/2020