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. 2019 Jun 3;19(11):2533.
doi: 10.3390/s19112533.

Point-of-Care Surface Plasmon Resonance Biosensor for Stroke Biomarkers NT-proBNP and S100β Using a Functionalized Gold Chip with Specific Antibody

Dorin Harpaz  1   2   3 , Brescia Koh  4 , Robert S Marks  5   6   7 , Raymond C S Seet  8 , Ibrahim Abdulhalim  9   10   11 , Alfred I Y Tok  12   13
Affiliations

Point-of-Care Surface Plasmon Resonance Biosensor for Stroke Biomarkers NT-proBNP and S100β Using a Functionalized Gold Chip with Specific Antibody

Dorin Harpaz et al. Sensors (Basel). .

Abstract

Surface-plasmon-resonance (SPR) is a quantum-electromagnetic phenomenon arising from the interaction of light with free electrons at a metal-dielectric interface. At a specific angle/wavelength of light, the photon's energy is transferred to excite the oscillation of the free electrons on the surface. A change in the refractive-index (RI) may occur, which is influenced by the analyte concentration in the medium in close contact with the metal surface. SPR has been widely used for the detection of gaseous, liquid, or solid samples. In this study, a functionalized specific SPR chip was designed and used in a novel point-of-care SPR module (PhotonicSys SPR H5) for the detection of the stroke biomarkers NT-proBNP and S100β. These biomarkers have proven to be good for stroke diagnosis, with sensitivity and specificity of >85%. Specific detection was done by binding a biomolecular-recognizing antibody onto the Au SPR-chip. Detection was tested in water and plasma samples. NT-proBNP and S100β were detected in a range of concentrations for stroke, from 0.1 ng/mL to 10 ng/mL. The RI of the blank plasma samples was 1.362412, and the lowest concentration tested for both biomarkers showed a prominent shift in the RI signal (0.25 ng/mL NT-proBNP (1.364215) and S100β (1.364024)). The sensor demonstrated a clinically relevant limit-of-detection of less than ng/mL.

Keywords: Au SPR-chip; NT-proBNP; S100β; biomarkers; biosensor; diagnostics; point-of-care; refractive-index; stroke; surface-plasmon-resonance.

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Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
Stroke Triaging. After stroke occurrence, Time = Brain. Efficacy of care is correlated to a timely diagnosis and treatment. First, a CT/MRI scan is conducted to differentiate between an ischemic and hemorrhagic stroke. This is followed by stroke mechanisms (e.g., using the criteria of Trial of Org 10172 in Acute Stroke Treatment, TOAST classification) to identify a cardioembolic stroke. Patients with cardioembolic stroke harbor a higher risk of poorer stroke outcomes and timely treatment with acute reperfusion treatment is necessary (intravenous tissue plasminogen activator (IV-tPA)) within the time-limited window of 4.5 h. The ability to accurately measure stroke biomarkers (e.g., NT-proBNP and S100β) within 15 min is highly desirable, in order to shorten the classification time.
Figure 2
Figure 2
Point-of-care surface plasmon resonance biosensor. (A) The surface plasmon resonance biosensor is 5 cm tall and weighs 1 kg, the measurement is conducted with a connection to a pump. (B) A two-channel structure on top of the surface-plasmon-resonance (SPR) gold chip. (C) The SPR gold chip (25 mm × 15 mm × 1 mm).
Figure 3
Figure 3
Biosensor calibration of pixel to refractive index.
Figure 4
Figure 4
Gold chip for surface plasmon resonance biosensor. The gold chip was functionalized with a specific antibody based on MUA-EDC/NHS reaction (MUA: 11-Mercaptoundecanoic acid; EDC: N-(3-Di-methylaminopropyl)-N′-ethyl carbodiimide hydrochloride; NHS: N-Hydroxysuccinimide).
Figure 5
Figure 5
Surface plasmon resonance biosensor system setup. (1) PhotonicSys SPR H5; (2) peristaltic pump; (3) source solution; (4) drain solution; (5) detection software.
Figure 6
Figure 6
Gold SPR chip functionalization.
Figure 7
Figure 7
Stroke biomarkers measurement using bold SPR chip. (A) NT-proBNP; (B) S100β.
Figure 8
Figure 8
Validation in spiked plasma samples. (A) NT-proBNP; (B) S100β.
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