LSPR Chip for Parallel, Rapid, and Sensitive Detection of Cancer Markers in Serum

Abstract

Label-free biosensing based on metallic nanoparticles supporting localized surface plasmon resonances (LSPR) has recently received growing interest (Anker, J. N., et al. Nat. Mater. 2008, 7, 442−453). Besides its competitive sensitivity (Yonzon, C. R., et al. J. Am. Chem. Soc. 2004, 126, 12669−12676; Svendendahl, M., et al. Nano Lett. 2009, 9, 4428−4433) when compared to the surface plasmon resonance (SPR) approach based on extended metal films, LSPR biosensing features a high-end miniaturization potential and a significant reduction of the interrogation device bulkiness, positioning itself as a promising candidate for point-of-care diagnostic and field applications. Here, we present the first, paralleled LSPR lab-on-a-chip realization that goes well beyond the state-of-the-art, by uniting the latest advances in plasmonics, nanofabrication, microfluidics, and surface chemistry. Our system offers parallel, real-time inspection of 32 sensing sites distributed across 8 independent microfluidic channels with very high reproducibility/repeatability. This enables us to test various sensing strategies for the detection of biomolecules. In particular we demonstrate the fast detection of relevant cancer biomarkers (human alpha-feto-protein and prostate specific antigen) down to concentrations of 500 pg/mL in a complex matrix consisting of 50% human serum. KEYWORDS: Plasmonics, LSPR, parallel, biosensing, lab-on-a-chip, cancer T he biosensing community has long been striving for an idealistic device consisting of high sensitivity, specificity, selectivity, and parallel real-time detection, coupled with low production and operational costs. In addition this device should be both environmentally and user-friendly and be portable, robust, and resistant to a wide range of external conditions (temperature, electromagnetic (EM) radiation, humidity), among other things. On the road toward this biosensing "Holy Grail", contemporary technology has been able to deliver numerous classes of biosensors that are focused on a particular application or niche in the biosensing market; however, no such device currently exists that delivers all or most of these requirements. Among these, optical biosensors operating in a label-free format have positioned themselves as very promising candidates owing to the inherent properties of light. Speed, inertness to external interferences, and almost unlimited bandwidth for data transfer has made light a preferred choice of transduction. With the advent of nanotechnology, especially in the field of plasmonics, surface plasmon resonance (SPR) technology revolutionized the biosensing field in the last two decades. The gold standard status of SPR is owed largely to its highly sensitive transducing mechanism. Namely, surface propagating EM waves called surface plasmon polaritons (SPPs) exhibit extraordinary sensitivity to the refractive index interfacial changes at the boundary between metal and dielectric. However, the activation of this transducing mechanism requires rather complex supporti...

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