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Abstract: This paper reports the application of differential phase surface plasmon resonance (SPR) imaging in two-dimensional (2D) protein biosensor arrays. Our phase imaging approach offers a distinct advantage over the conventional angular SPR technique in terms of utilization efficiency of optical sensor elements in the imaging device. In the angular approach, each biosensor site in the biosensor array requires a linear array of optical detector elements to locate the SPR angular dip. The maximum biosensor density that a two-dimensional imaging device can offer is a one-dimensional SPR biosensor array. On the other hand, the phase-sensitive SPR approach captures data in the time domain instead of the spatial domain. It is possible that each pixel in the captured interferogram represents one sensor site, thus offering high-density two-dimensional biosensor arrays. In addition, our differential phase approach improves detection resolution through removing common-mode disturbances. Experimental results demonstrate a system resolution of 8.8×10−7 RIU (refractive index unit). Real-time monitoring of bovine serum albumin (BSA)/anti-BSA binding interactions at various concentration levels was achieved using a biosensor array. The detection limit was 0.77μg/ml. The reported two-dimensional SPR biosensor array offers a real-time and non-labeling detection tool for high-throughput protein array analysis. It may find promising applications in protein therapeutics, drug screening and clinical diagnostics. [Copyright &y& Elsevier]

Abstract: A surface plasmon enhanced ellipsometry (SPEE) biosensor scheme based on the use of a photoelastic modulator (PEM) is reported. We show that the polarization parameters of a laser beam, tan ψ, cos Δ and ellipse orientation angle ϕ, can be directly measured by detecting the modulation signals at the first and second harmonics of the modulated frequency under a certain birefringence geometry. This leads to accurate measurement of refractive index variations within the evanescent field region close to the gold sensor surface, thereby enabling biosensing applications. Our experimental results confirm that the new scheme offers a respectable detection limit of 6×10−7 refractive index unit (RIU) or 15ng/ml of biomolecule solute concentration without any compromise in dynamic range. In addition, PEM offers the possibility of single-beam phase-sensitive SPR detection that drastically reduces the complexity of the optical system, thus readily making it possible for SPR to be adopted in label-free micro-array biochips. [Copyright &y& Elsevier]

Abstract: A novel design of multi-pass surface plasmon resonance (SPR) biosensor with differential phase interrogation based on multi-pass interferometry is presented. This new configuration provides an intrinsic phase amplification effect of over twofold by placing the SPR sensor head in a signal arm of the interferometer so that the interrogating optical beam will traverse the sensor surface infinite number of times. Experimental interferometers based on the Michelson and Fabry–Perot configurations have been employed to experimentally verify this amplification effect when they were compared with Mach–Zehnder configuration, results obtained from salt–water mixtures, antibody–antigen, and protein–DNA binding reaction confirmed the expected phase measurement enhancement, thus leading to the possibility of direct detection of small sized bio-molecules using SPR. [Copyright &y& Elsevier]