Wing Cheung Law

Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on the Mach–Zehnder configuration

A high-sensitivity surface plasmon resonance (SPR) biosensor based on the Mach-Zehnder interferometer design is presented. The novel feature of the new design is the use of a Wollaston prism through which the phase quantities of the p and s polarizations are interrogated simultaneously. 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. Experimental results obtained from glycerin-water mixtures indicate that the sensitivity limit of our scheme is 5.5 x 10(-8) refractive-index units per 0.01 degrees phase change. To our knowledge, this is a significant improvement over previously obtained results when gold was used as the sensor surface. Such an improvement in the sensitivity limit should allow SPR biosensors to become a possible replacement for conventional biosensing techniques based on fluorescence. Monitoring of the bovine serum albumin (BSA) binding reaction with BSA antibodies is also demonstrated.

Two-dimensional 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.

A vortex pump-based optically-transparent microfluidic platform for biotech and medical applications

Abstract This paper reports an automated polymer based microfluidic analysis system integrated with a surface plasmon resonance (SPR) biosensor that demonstrates the detection of specific binding of biomolecules and that qualitatively monitors cell adhesion on the sensor surface. Micropumps, microchannels, and an SPR biosensor were integrated into a single polymer (PMMA) based microfluidic system. The integrated system has been studied for its potential applications in bio-molecules detection and drugs discovery. Two experiments, (1) monitoring the reaction between the BSA-BSA antibody, and (2) monitoring the activities of living cells in the presence or absence of trypsin in a RPMI-1640 medium, were conducted to show the biomedical application capability. Because SPR based bio-detection requires optically transparent substrates, PMMA is a potential replacement for glass and silicon-glass in microfluidic systems, if bio-compatibility and low-cost are desired. Hence, our work has shown the feasibility of commercializing an SPR based bio-medical/chemical analysis system in the near future.

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.

Bio-molecular and cellular detection using SPR sensor and all-transparent microfluidic platform

This paper reports an automated polymer based microfluidic analysis system integrated with a surface plasm on resonance (SPR) biosensor for detecting the specific binding of biomolecules and qualitatively monitoring of cell adhesion on the sensor surface. Micropumps, microchannels, and a SPR biosensor were integrated into a single polymer (PMMA) based microfluidic system. Because SPR based bio-detection requires optically transparent substrates, PMMA is a potential replacement for glass and silicon-glass microfluidic systems, if bio-compatibility and low-cost are desired. The integrated system has been studied for its potential applications in bio-molecules detection and drug-discovery. Two experiments, 1) monitoring the reaction between BSA-BSA antibody, and 2) monitoring the activities of living cells in the presence or absence of trypsin in RPMI-1640 medium, were conducted to show its biomedical applications. The experimental setup and results of these tests are presented in this paper

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.

Automating micro cellular detection process using all-transparent microfluidic platform and surface plasmon resonance technique

This paper reports an automated polymer based microfluidic analysis system integrated with the surface plasmon resonance (SPR) biosensor for qualitatively monitoring of cell adhesion on the sensor surface. Micropumps, microchannels, and SPR biosensor were integrated into a single polymer (PMMA) based microfluidic system. The integrated system has been studied in its potential application in drugs discovery. An experiment, which is monitoring the activities of living cells in the presence or absence of trypsin in RPMI-1640 medium, was conducted to show the ability of its biomedical application. Because SPR based bio-detection requires optically transparent substrates, PMMA is a potential replacement for glass and silicon-glass in microfluidic systems, if biocompatibility and low-cost are desired. Hence, our work has shown the feasibility of commercializing SPR based biomedical/chemical analyses system in the near future. Furthermore, an advanced 2-dimensional multi-chamber microfluidic system with the SPR imaging detection system for detecting the specific binding of biomolecules was also conduced. It shows the possibility of the parallel detection process

Towards Automating Micro Cellular Detection Process Using Micro Vortex Pump Arrays

This paper reports a polymer based microfluidic analysis system integrated with a surface plasmon resonance (SPR) biosensor for detecting the specific binding of biomolecules and qualitatively monitoring of cell adhesion on the sensor surface. Micropumps, microchannels, and SPR biosensor were integrated into a single polymer (PMMA) based microfluidic system. The integrated system has been studied in its potential application in bio-molecules detection and drug discovery. Two experiments, 1) monitoring the reaction between BSA-BSA antibody, and 2) monitoring the activities of living cells in the presence or absence of trypsin in RPMI-1640 medium, were conducted to show the feasibility of real-time cellular and molecular detection. Based on these successful experimental results we have also developed a computer-controllable vortex micropump system that will eventually automate many bio-molecular detection and drug discovery processes.

Application of differential phase detection for sensitivity improvement in surface plasmon resonance sensors

Surface plasmon resonance (SPR) is an effective tool for quantitative detection of binding reaction between biomolecules. Currently SPR sensors are mainly based on measuring the angular shift associated with biomolecular adhesion. In fact it has been shown that the phase jump across the SPR dip is very steep, and consequently better sensitivity may be achieved by measuring the optical phase. In this presentation, we report interferometric techniques we have developed in our laboratory for achieving SPR phase detection. We also demonstrate that the incorporation of differential phase detection can further improve the performance of SPR biosensors. Currently the experimental sensitivity of our differential phase setup is 5.48/spl times/10/sup -8/ refractive index unit (RIU), which is three times better than that reported from conventional angular systems.