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A pump-free microfluidic device for fast magnetic labeling of ischemic stroke biomarkers

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Abstract

This research proposes a low-cost and simple operation microfluidic chip to enhance the magnetic labeling efficiency of two ischemic stroke biomarkers: cellular fibronectin (c-Fn) and matrix metallopeptidase 9 (MMP9). This fully portable and pump-free microfluidic chip is operated based on capillary attractions without any external power source and battery. It uses an integrated cellulose sponge to absorb the samples. At the same time, a magnetic field is aligned to hold the target labeled by the magnetic nanoparticles (MNPs) in the pre-concentrated chamber. By using this approach, the specific targets are labeled from the beginning of the sampling process without preliminary sample purification. The proposed study enhanced the labeling efficiency from 1 h to 15 min. The dynamic interactions occur in the serpentine channel, while the crescent formation of MNPs in the pre-concentrated chamber, acting as a magnetic filter, improves the biomarker-MNP interaction. The labeling optimization by the proposed device influences the dynamic range by optimizing the MNP ratio to fit the linear range across the clinical cutoff value. The limits of detection (LODs) of 2.8 ng/mL and 54.6 ng/mL of c-Fn measurement were achieved for undiluted and four times dilutions of MNP, respectively. While for MMP9, the LODs were 11.5 ng/mL for undiluted functionalized MNP and 132 ng/mL for four times dilutions of functionalized MNP. The results highlight the potential use of this device for clinical sample preparation and specific magnetic target labeling. When combined with a detection system, it could also be used as an integrated component of a point-of-care platform.

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Abbreviations

c-Fn:

Cellular fibronectin

MMP9:

Matrix metallopeptidase 9

MNP:

Magnetic nanoparticles

LOD:

Limit of detection

MR:

Magnetoresistive

rtPA:

Recombinant tissue plasminogen activator

PDMS:

Polydimethylsiloxane

PMMA:

Polymethyl methacrylate

CNC:

Computer numerical control

2D:

Two-dimensional

PVA:

Polyvinyl alcohol

PDMS-b-PEO:

Poly(Dimethylsiloxane-b-ethylene oxide) methyl terminated

SD:

Standard deviation

RT:

Room temperature

PPC:

Pores per centimeter

PB:

Phosphate buffer

PB-T:

Phosphate buffer with 0.05% Tween®20

BSA:

Bovine serum albumin

DI:

Deionized

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Funding

This work was supported by Fundação para a Ciência e a Tecnologia (FCT) through project FIM4Stroke (reference PTDC/MEC-URG/29561/2017).

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  1. INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga, s/n 4715-330, Braga, Portugal

    Briliant Adhi Prabowo, Elisabete Fernandes & Paulo Freitas

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Prabowo, B.A., Fernandes, E. & Freitas, P. A pump-free microfluidic device for fast magnetic labeling of ischemic stroke biomarkers. Anal Bioanal Chem 414, 2571–2583 (2022). https://doi.org/10.1007/s00216-022-03915-w

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