C.L. Wong

Real-time protein biosensor arrays based on surface plasmon resonance differential phase imaging

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 x 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 0.77 microg/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.

Surface Plasmon Resonance Biosensor Incorporated in a Michelson Interferometer With Enhanced Sensitivity

A novel double-pass phase-sensitive surface plasmon resonance (SPR) biosensor based on a Michelson interferometer with differential phase interrogation is presented. The new setup provides an intrinsic resolution enhancement of up to two times in terms of achievable detection sensitivity due to an amplification effect in the SPR phase change when we place the SPR sensor head in the signal arm of the interferometer so that the interrogating optical beam traverses the sensor surface twice. Experimental results obtained from saltwater mixtures and antibody-antigen binding reactions confirmed the expected sensitivity enhancement as compared to the conventional SPR biosensor based on a Mach-Zehnder interferometer

Sensitivity enhancement of phase-sensitive surface plasmon resonance biosensor using multi-pass interferometry

A novel design of multi-pass phase-sensitive surface plasmon resonance (SPR) biosensor is presented. The system is based on differential phase interrogation scheme incorporated to the Michelson or Fabry-Perot interferometer configuration. An intrinsic phase amplification effect is achieved by placing the SPR sensor head in the signal arm of the interferometer so that the interrogating optical beam traverses the sensor surface multiple times. Experimental results obtained from antibody-antigen and protein-DNA binding reaction using both the Michelson and Fabry-Perot interferometer configurations indeed demonstrate the expected phase amplifications factors of 2 and 2.26 respectively in comparison to that obtained by the conventional Mach-Zehnder interferometer configuration. This phase amplification effect leads to the sensitivity enhancement and corresponding resolution improvement by at least 2 times.

Chemical and biological detection using microfluidic platform and surface plasmon resonance imaging sensor

A microfluidic platform integrated with a high-sensitivity surface plasmon resonance (SPR) imaging sensor based on Mach-Zehnder interferometer design is presented. The disposable polydimethylsiloxane (PDMS)-based microfluidic platform consists of four independent flow chambers that can be detected four different concentrated solutions by SPR imaging biosensor simultaneously. The novel feature of the SPR imaging biosensor is the use of a Wollaston prism through which the phase quantities of the p and s polarizations are interrogated synchronously. Since SPR affects only the p polarization, the signal due to the s polarization can be used as the reference. Consequently, the differential phase between the two polarizations allows us to eliminate all common-path phase noise while keeping the phase change caused by the SPR effect. Two experiments were conducted: 1) detecting different concentrations of salt-water mixtures, and 2) monitoring the reaction between BSA-BSA antibody. This technique is shown here to have a sensitivity of 0.44mug/ml for salt-water mixture. Given that we have now demonstrated the possibility of SPR phase extraction from digitized images, direct application of this technique in two-dimensional (four independent flow chambers) sensor arrays with high measurement throughput is also suggested

Two-dimensional surface plasmon resonance biosensor array based on phase-sensitive measurement

We report a 2-dimensional surface plasmon resonance (SPR) imaging array sensor based on differential phase measurement between p- and s-polarization. This parallel detection provides the advantage of high-throughput sensing, which is essential in recent biosensing technology. In the differential measurement approach, the signal (p) and reference (s) beams go through exactly identical optical path. This greatly improves the phase detection stability. In the present setup we use a low-cost imaging device and a simple data analysis program to perform the required arrayed sensing operation. The system demonstrates a refractive index resolution of 1x10-4 RIU per degree phase change.

Application of surface plasmon resonance to measurement of hydrostatic pressure in tribological lubricant layers

A new method for studying elastohydrodynamic lubrication (EHL) dimple is demonstrated. This technique uses the spectral characteristics of surface plasmon resonance (SPR) to perform imaging of the dimple. Due to SPR absorption shift for different refractive index values, the refractive index variation across the dimple can be investigated by the color variation in the reflecting dimple image. Several dimples produced at different impact force levels have been studied in our experiments and the refractive index changes associated with such experimental conditions have been successfully identified by the spectral SPR imaging. The internal pressure distribution within the dimple is discussed.

Biosensor Arrays based on Surface Plasmon Resonance Phase Imaging

In this paper we present a biosensor design based on phase imaging of surface plasmon resonance (SPR). The system is adapted from our previously reported differential phase measurement scheme. We first conducted experiments on measuring the concentration of salt concentration in water in order to demonstrate the operation of this system. Biosensing experiments were performed to monitor the H3 influenza antigen-antibody binding interaction. In recent years, the needs for high-throughput biosensors in life sciences and biomedical areas have been increasing rapidly. Our phase-imaging SPR sensor is a non-labeling, real-time quantitative sensing approach compatible with the micro-array chip platform. It should therefore have a promising potential for various bio-related detection applications, such as clinical diagnostics.

Two dimensional phase sensitive surface plasmon resonance biosensor array using microfluidic flow circuit platform

The integration between 2D SPR differential phase imaging sensor and microfluidic flow circuit is presented. It provides the advantages of high throughput, high sensitivity and label free detection to meet the present needs in biomechnical market. The differential phase scheme between p- and s- polarization enable elimination of all common-path phase noise while keeping the phase change caused by SPR effect. System sensitivity of the detection sensitivity of our setup is 0.44μg /ml is obtained for salt / water mixture sensing. BSA antigen and antibody binding reaction detection is further demonstrated. The system shows the capability of simultaneous detection for both specific and non-specific binding reactions in a micro-chamber array.

Surface plasmon resonance phase sensor arrays on a microfluidic platform

We report the deveopiment of a sensor array based on imaging the phase associated with surface plasmons resonance (SPR). The system is also integrated with a simple micro-fluidic sample stage. Given that it has previously been shown that differential SPR phase detection is a potentially promising approach for achieving high performance sensors, the new system brings SPR devices further towards medical diagnostics market where fluorescence labeling has been the main technique for signal transduction.

Highly Sensitive Photonic Biosensors Based on Interferometric Detection of Surface Plasmon Waves

Summary form only given. We previously demonstrated an interferometric surface plasmon resonance (SPR) biosensor design based on measuring the differential phase between the s- and p-polarization. In this presentation, we report our recent results on the development of sensor arrays achieved by analyzing interferograms generated under SPR conditions. The measurement approach has the merits of performing highly paralleled two-dimensional detection at fixed angle of incidence. In addition, we also demonstrate further improvement of detection resolution (in the order of 10-8 RIU) by incorporating novel ideas in the design of the optical interferometer.