Rich information format surface plasmon resonance biosensor based on array of diffraction gratings

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Abstract

We report a new optical biosensor platform for high throughput label-free monitoring of biomolecular interactions. This biosensor platform is based on spectroscopy of surface plasmons on an array of miniature diffraction gratings. Each miniature grating serves as an independent sensing element and allows the monitoring of refractive index changes induced by biomolecular interactions on the grating surface. The presented sensor concept shows potential for real-time observation of thousands of interactions on a single sensor chip. In this paper, we demonstrate a prototype device consisting of an SPR sensor chip with 216 sensing channels, a fluidic system for sample distribution on the sensor chip and an optical chip readout system.

Introduction

Over the last two decades an increasing attention has been devoted to label-free optical biosensors capable of direct real-time monitoring of biomolecular interactions [1]. In these biosensors, one of the interacting biomolecules is immobilized on the sensor surface and its interaction with its biospecific partner is measured through observation of changes in the surface optical density associated with binding. However, the existing devices suffer from a limited throughput, sensitivity and high cost. Therefore, in recent years, novel optical platforms for high throughput label-free biomolecular interaction analysis have been intensively pursued. Approaches allowing parallel monitoring of up to hundreds of biomolecular interactions on the sensor chip based on colorimetric resonant reflection [2] and SPR imaging [3], [4], [5] have been reported.

In principle, SPR biosensors are thin film refractometers, which measure refractive index changes induced by biomolecular interactions on a surface of a thin metal layer. Gold is used as an SPR-active metal most commonly as it is stable and numerous chemistries for attaching biomolecules on surfaces of gold layers are available [6]. Biomolecular interactions at the sensor surface alter the SPR on the surface and may be observed as changes in the intensity (SPR sensors with intensity modulation) or spectrum (SPR sensors based on surface plasmon spectroscopy) of light reflected from the SPR-active metal. Both these approaches were exploited for development of multichannel SPR sensors. The intensity modulation was employed in SPR imaging systems for parallel measurements in up to hundreds of sensing channels [3], [4], [5] with a typical accuracy in discrimination of SPR changes of 10−5 refractive index units (RIU). The SPR sensors based on surface plasmon spectroscopy were demonstrated to be capable of measurements of optical density changes as small as 3 × 10−7 RIU; however, they were rather limited in terms of number of sensing channels (<10) [7], [8]. In addition, most SPR biosensor systems use a glass sensor chips not compatible with low-cost mass fabrication. This drawback may be overcome by using sensor chips based on diffraction gratings [9], [10] which can be mass-produced from plastics by technologies such as injection molding [11].

In this paper, we introduce a novel SPR biosensor platform designed for applications where high throughput monitoring of biomolecular interactions is required. The presented approach is based on spectroscopy of surface plasmons on an array of miniature diffraction gratings and provides high accuracy in measuring SPR changes at the sensor surface as well as large number of sensing channels. A prototype sensor system with 216 channels is described and its performance evaluated.

Section snippets

Surface plasmon resonance on diffraction gratings

A surface plasma wave (SPW) propagating at planar metal–dielectric interface cannot be directly coupled with an optical wave in the dielectric as its propagation constant is lower than that of SPW [12]:kSP=2πλReεmnb2εm+nb2>2πλnbwhere kSP is the real part of the SPW propagation constant, λ the wavelength, ɛm the permittivity of the metal, and nb is the refractive index of the dielectric. There are two types of couplers which make it possible to enhance the optical wave propagation constant and

Fabrication of the SPR diffraction grating

A master grating with the sinusoidal modulation profile and parameters specified in the previous section was prepared by holographic method. A polished BK7 glass slide with a photoresist layer spin-coated on its top (SF1813, Shipley, USA) was exposed to an interference pattern of a coherent light (wavelength 442 nm from He–Cd laser) in an optical setup based on the Mach-Zehnder interferometer. After the exposition, the recorded relief grating was etched into the photoresist layer in the

Sensor characterization

Fig. 9a shows the sensor response of an individual grating, when liquids with different refractive indices were flowed across the sensor surface. These liquids were prepared from deionized water (refractive index 1.333) mixed with ethylene glycol (refractive index 1.426). The sensor sensitivity to bulk refractive index changes was measured to be about 160° RIU−1 and the angular distance was determined with the accuracy of 8 × 10−4° (standard deviation), therefore the minimum refractive index

Conclusions

In this paper, we report a new optical platform for high throughput SPR biosensing. This biosensor is based on a sensor chip with an array of diffraction gratings, each of which serving as an independent sensing channel. The SPR changes on each diffraction grating are measured by angle-modulated spectroscopy of surface plasmons. A laboratory prototype of the SPR biosensor supporting sensor chip with 216 sensing channels, fluidic system, and an optical system for readout of SPR changes on the

Acknowledgement

This work was supported by the Grant Agency of the Czech Republic under contracts 303/03/0249, 203/02/1326 and 102/03/0633 and by European Commission under contract QLK4-CT-2002-02323.

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