Chien Chou

Noninvasive glucose monitoring in vivo with an optical heterodyne polarimeter

An amplitude-sensitive optical heterodyne polarimeter was set up to monitor noninvasively the aqueous glucose concentration in a rabbits eye. A Zeeman laser in conjunction with a Glan-Thompson analyzer was used to generate an optical heterodyne signal. The amplitude of the heterodyne signal linearly related to the optical rotation angle of the aqueous glucose. The concentration of the aqueous glucose in a rabbits eyeball was measured in vivo. There was a 30-min time delay between observations of aqueous glucose and blood glucose. The detection capability and the reproducibility of the experiment are demonstrated and discussed.

Polarization-sensitive optical coherence tomography for imaging human atherosclerosis

Polarization-sensitive optical coherence tomography (PS-OCT) combines the advantages of OCT with image contrast enhancement, which is based on its ability to detect phase retardation and the fast-axis angle. Both PS-OCT images and histopathology have demonstrated similar features that allowed differentiation of atherosclerotic structures (i.e., plaques) from normal tissue. Moreover, the picrosirius polarization method was used to confirm PS-OCT assessment of collagen in the fibrous cap of atherosclerotic plaques, and high-frequency (40 MHz) ultrasound images were used to identify calcium in the vessel wall. Our preliminary ex vivo investigation of human aortic specimens indicated that PS-OCT might help to identify atherosclerotic lesions.

Optical heterodyne surface-plasmon resonance biosensor

A novel optical heterodyne surface-plasmon resonance (SPR) biosensor with a Zeeman laser is proposed. Two surface plasma waves are excited by two correlated p-polarized waves in a SPR device of the Kretschmann configuration. Two reflected p waves are optically heterodyned such that the magnitude of the heterodyned signal is proportional to the multiplication of two attenuated reflected p waves. Then the detection sensitivity and the dynamic range based on this amplitude-sensitive method are enhanced. In the experiment, the kinetics between mouse immunoglobulin G (IgG) and rabbit antimouse IgG is obtained from sensograms of various concentrations of antimouse IgG. A detection sensitivity of 0.2 nM was achieved. In addition, a concentration of 5 ng/ml of protein G interacting with mouse IgG was measured successfully.

Differential-phase surface plasmon resonance biosensor.

In this paper, a novel differential-phase-sensitive surface plasmon resonance biosensor (DP-SPRB) is proposed and developed, in which a two-frequency laser is integrated with a differential amplifier in order to analytically convert the phase modulation into amplitude modulation. With the use of the conventional envelope detection technique, the differential phase is precisely decoded in real time in terms of the demodulated amplitude. In order to verify high detection sensitivity of the DP-SPRB, a sucrose-water solution and glycerin-water solution at low concentrations were both tested, and the experimental results confirm that the detection sensitivity on wt % concentration of the sucrose solution is 0.00001%. Moreover, the real-time monitoring mouse IgG/antimouse IgG interaction shows the minimum concentration of mouse IgG to be at 10 fg/mL. To our knowledge, this is the highest sensitivity ever measured by a surface plasmon resonance biosensor. However, because of the limited dynamic range of DP-SPRB, it can only apply to biomolecule interactions at extremely low concentration.

High speed interferometric ellipsometer

A novel high speed interferometric ellipsometer (HSIE) is proposed and demonstrated. It is based on a novel differential-phase decoder which is able to convert the phase modulation into amplitude modulation in a polarized heterodyne interferometer. Not only high detection sensitivity but also fast response ability on ellipsometric parameters (EP) measurements based on amplitude-sensitive method is constructed whereas different amplitudes with respect to P and S polarized heterodyne signals in this phase to amplitude modulation conversion is discussed. The ability of HSIE was verified by testing a quarter wave plate while a real time differential-phase detection of a liquid crystal device versus applied voltage by using HSIE was demonstrated too. These results confirm that HSIE is able to characterize the optical property of specimen in terms of EP at high speed and high detection sensitivity experimentally.

Common-path optical heterodyne profilometer: a configuration

A novel configuration that combines a linearly polarized He-Ne laser and a birefringent lens to produce a common-path polarized optical heterodyne profilometer with respect to the heterodyned P and S waves has been set up. In this profilometer a linear polarized frequency-stabilized He-Ne laser was used with an acousto-optical modulator to replace the Zeeman laser as the light source that had two polarization eigenstates in different temporal frequencies. The proposed interferometer shows a more symmetric and ideal common-path structure than the conventional optical heterodyne profilometers with the Zeeman laser. The phase error aroused by the elliptical polarization and the nonorthogonality of the two eigenpolarization modes of the Zeeman laser can be reduced. The systems resolution in the vertical direction reaches 2 A, and in a 27-mum scanning range the repeatability of the surface profile measurements is shown to be 5 A.

Fiber optic biosensor for the detection of C-reactive protein and the study of protein binding kinetics

Application of a fiber optic biosensor (FOB) to the real-time investigation of the interaction kinetics between FITC-conjugated monoclonal sheep anti-human C-reactive protein (CRP) antibody and CRP isoforms on the surface of optical fiber is described. Recently, both the native pentameric CRP (pCRP), an acute phase protein belonging to pentraxin family, and an isoform of pCRP, modified CRP (mCRP), have been suggested to have proinflammation effects on vascular cells in acute myocardial infarction (AMI). In current studies, we generate mCRP from pCRP, and use several methods including fluorescence spectral properties, circular dichroism, analytical ultracentrifuge, and Western blotting to demonstrate their differences in physical and chemical properties as well as the purity of pCRP and mCRP. In addition, we design and implement an FOB to study the real-time qualitative and quantitative biomolecular recognition of CRP isoforms. Specifically, the association and dissociation rate constants of the reaction between FITC-conjugated monoclonal sheep anti-human CRP antibody and the pCRP and mCRP are determined. The feasibility of our current approach to measure the association and dissociation rate constants of the reaction between tested CRP isoforms was successfully demonstrated.

Characteristics of a paired surface plasma waves biosensor.

A novel paired surface plasma wave biosensor (PSPWB) is described and setup. By integrating the features of a common-path optical heterodyne interferometer and the amplitude-ratio detection mode, the PSPWB not only produces a high detection sensitivity but also provides a large dynamic measurement range for effective refractive index (Deltan(eff)) based on amplitude-sensitive detection method. Thus, the performance of PSPWB becomes equivalent to shot-noise limited of a conventional SPR biosensor. To our knowledge, this novel PSPWB shows the highest detection sensitivity on (Deltan(eff)) when compared with conventional SPR biosensors using either a non-interferometric or interferometric technique. The experimental results correctly verify the properties of a PSPWB that the detection sensitivity is an order of 10(-7) refractive index unit (RIU) when measuring a 0.001% sucrose-water solution. This result confirms the detection sensitivity up to 10(-9) RIU of the IgG/anti-IgG interaction in real time successfully. Furthermore, a dynamic range of 10(5) using PSPWB was also obtained.

Optical heterodyne surface plasmon resonance biosensor

A novel optical heterodyne surface plasmon resonance (SPR) biosensor using Zeeman laser is proposed. There are two surface plasma waves (SPWs) being excited by two correlated P polarized waves in an SPR device of Kretschmann configuration. The two reflected P waves are optically heterodyned so that the amplitude of the heterodyned signal is proportional to the multiplication of two attenuated reflected P waves. The detection sensitivity and the dynamical range based on this amplitude sensitive method are enhanced. In the experiment, the kinetics between mouse IgG and anti-mouse IgG is obtained according to the sensograms of different concentrations of anti-mouse IgG. The detection sensitivity corresponding to 0.2 nM is achieved. In addition, a concentration of 5 ng/ml of protein G interacting with mouse IgG is measured successfully.

Balanced detector interferometric ellipsometer.

A novel balanced detector interferometric ellipsometer (BDIE), composed of a polarized common-path optical heterodyne interferometer incorporating a novel balanced detector, provides an amplitude-sensitive method for measurement of the elliptical parameters of a thin film. The requirement for equal amplitude of the polarized heterodyne signals for balanced detection results in the simultaneous measurement of the elliptical parameters in terms of the azimuth angle of a half-wave plate and the output intensity from the differential amplifier, respectively. The common-path feature of BDIE shows a common phase noise rejection mode and this enhances the sensitivity of the phase measurement. At the same time, the balanced detector configuration of BDIE reduces excess noise of laser intensity fluctuation to give better sensitivity during measurement. The error of measurement of BDIE is derived and analyzed. Finally, the elliptical polarization effect of the laser beam is found to be independent of the measurement of the elliptical parameters.