HK1163255B - Optical sensing devices and methods for detecting samples using the same - Google Patents

Description

Optical sensing device and method for detecting sample using the same

Technical Field

The present application relates to optical devices for chemical and biological detection and methods of detecting samples using the same.

Background

Surface Plasmon Resonance (SPR) technology has been widely used for chemical and biological sensing through several decades of research and development. This technique offers the possibility of replacing traditional fluorescence-based biosensing techniques. This is because SPR biosensors can provide label-free real-time quantitative analysis of biomolecular interactions by monitoring changes in the optical response of a functionalized sensing surface, typically changes in angular reflectivity, spectral characteristics or corresponding phase shifts.

According to the measurement scheme for light waves modulated by surface plasmons, the operation of most SPR biosensors is currently roughly divided into three categories: (1) angular reflectivity; (2) spectroscopy; and (3) phase-shift interferometry.

Devices such as Biacore TM's T100 or Texas instruments Spreeta are based on monitoring the location of the minimum of the angular reflectance curve when the SPR sensing surface is illuminated by a monochromatic light beam over a range of incident angles (Enzyme and microbiological Technology, 32, 3-13, 2003). Surface plasmon resonance refers to the effect that at a certain angle of incidence, the p-polarized component of incident light can couple with a Surface Plasmon Wave (SPW) along the interface between a nano-scale conductive layer on a glass prism and a sample medium. This photon-to-plasmon energy conversion appears as a sharp attenuation of the reflectivity, and the resonance angle depends on the refractive index of the sample medium. This means that real-time monitoring of the immobilization of biomolecules to the functionalized biosensor surface can be achieved by continuously monitoring the change of the resonance angle. However, the measurement accuracy (or limit of detection LOD) of such SPR biosensors is only about 10^-6To 10^-7This LOD scale also does not compare favorably with fluorescence-based techniques between RIUs, and for most biogenetic applications.

Another method for SPR bioassay is to use spectroscopic measurements. In this case, polychromatic light from a halogen lamp is collimated into a large diameter parallel beam directed to a prism coupler. Similar to the angular method, the p-polarized component of the incident light wave is transferred to the SPW, which appears as a sharp spectral attenuation dip in the reflection spectrum. For further sensitivity enhancement, detection accuracy can be improved with other possible techniques by incorporating long-range surface plasmon resonance (LRSPR) excitation in the biosensor thin film stack. When the sensor layer stack is designed such that the dielectric layer can be sandwiched between two metal layers with appropriate properties and couple the SPW propagation on both sides of the metal thin film (i.e., LRSPR). This is a special case of SPR, the Table thereofExhibits a very sharp resonance and thus provides detection accuracy with much improvement. Homola et al propose to achieve an improvement of accuracy to 10^-8The long range SPR sensor of RIU (Sensors and Actuators B, 123, 10-12, 2007), but its spectral measurement scheme remained unchanged.

On the other hand, Nelson et al first proposed a feasible system for measuring SPR phase in 1996 (Sensors and Actuators B, 35-36, 187-191, 1996). The benefit of measuring the phase is that the phase change has a steep slope when the system is subject to resonance. The rate of change is much higher than the rate of change caused by measuring the angular or spectral intensity associated with SPR. This means that phase measurement theoretically provides higher detection accuracy.

Ho et al, the Chinese university in hong Kong, proposed a very sensitive phase-sensitive SPR sensor based on a Mach-Zehnder interferometer and demonstrated its accuracy at 10^-8Of the order of magnitude (Optics Letter, 29, 2378-. In this design, a Wollaston prism is placed in the output arm of the interferometer for analyzing the phase changes of the p-and s-polarized components. Although only the phase change of p-polarization is associated with SPR, the phase change of s-polarization is used as a reference. The differential phase between the p-and s-polarized components should be free of any common mode noise, which may be many times larger than the phase signal itself. This also means that the theoretical accuracy limit provided by the phase sensitive approach can be practically realized. Recently, the research group also proposed that the system sensitivity obtained by using the Michelson interferometer can be twice that of a single-pass Mach Zehnder device (IEEE Sensors Journal, 7, 70-73, 2007)

Although phase sensitive SPR biosensors provide better detection accuracy due to the steep slope in resonance, their measurement range is narrow compared to angle or spectrum sensitive SPR biosensors. Therefore, achieving both wide dynamic range and high sensitivity on a single device remains a challenge for all phase detection SPR sensors.

Disclosure of Invention

According to one aspect of the present application, an optical sensing device is provided. The optical sensing device includes: a light source unit that generates a polychromatic light beam containing a p-polarized component and an s-polarized component; an interferometric unit that divides the light beam into a probe beam passing through the first path and a reference beam passing through the second path, and recombines the probe beam output from the first path and the reference beam output from the second path; a sensing unit disposed in the first path to introduce a first SPR effect associated with the target sample to the probe beam; and a detection unit detecting a characteristic of the target sample by obtaining an intensity spectrum of the recombined light beam.

In one embodiment, the apparatus may further comprise a reference cell disposed in the second path to introduce a second SPR effect associated with the reference sample to the reference beam. According to the present application, the reference cell for introducing the second SPR effect may provide optical path compensation for the spectral dispersion introduced by the sensing cell. The reference unit is used to eliminate common mode noise by direct subtraction between phase values obtained from the probe beam, thereby enhancing detection accuracy.

In one embodiment, the sensing unit and the reference unit are both long range SPR sensing units.

According to another aspect of the present application, a method for detecting a characteristic of a target sample is provided. The method comprises the following steps: generating a polychromatic light beam containing a p-polarized component and an s-polarized component from a light source unit; splitting the optical beam into a probe beam passing through the first path and a reference beam passing through the second path, and recombining the probe beam output from the first path and the reference beam output from the second path; introducing a first SPR effect associated with the target sample to the probe beam in the first pass; obtaining an intensity spectrum of the recombined beam; and detecting a characteristic of the target sample based on the obtained intensity spectrum.

In one embodiment, the method may further include introducing a second SPR effect associated with the reference sample to the reference beam in the second pass.

In one embodiment, the first SPR effect introduced is a first long-range SPR effect associated with the target sample and the second SPR effect introduced is a second long-range SPR effect associated with the reference sample.

Drawings

FIG. 1a is a block diagram of a wide dynamic range spectral phase sensitive LRSPR biosensor according to one embodiment of the present application.

FIG. 1b is a block diagram of a wide dynamic range spectral phase sensitive LRSPR biosensor according to another embodiment of the present application.

Fig. 2 is a schematic diagram of fig. 1 showing a polychromatic light source unit, a spatial filtering unit, a beam calibration unit and a broadband linear polarization unit.

FIG. 3 is a schematic diagram of a spectral interferometer according to the present application.

FIG. 4 is a schematic illustration of an LRSPR sensing surface configuration according to the present application.

FIG. 5a is a schematic diagram of an SPR sensor consistent with the present application.

FIG. 5b is an SPR sensor with temporal phase stepping according to the present application.

Fig. 6 is an original spectral oscillation signal obtained from the present application.

Figure 7a shows differential spectrum phase results of LRSPR sensing surface configurations obtained from experiments using sodium chloride solutions of different concentrations, where the weight ratio of sodium chloride in the solution is 0%, 2%, 4%, 6%, 8%, 10% and 12%.

FIG. 7b shows differential spectrum phase results for standard SPR sensing surface configurations obtained from experiments using sodium chloride solutions of varying concentrations, wherein the weight ratio of sodium chloride in the solution is 0%, 0.5%, 1%, 2%, 4%, 6%, 8%, 10% and 10.5%.

FIG. 8 shows simulation results of phase responses in SPR and LRSPR sensing surface configurations.

FIG. 9 shows simulation results of phase response in a spectral phase sensitive SPR sensor having a wide dynamic range of SPR sensing surface configurations.

FIG. 10 shows simulation results of phase response in a broad dynamic range spectral phase sensitive SPR sensor with LRSPR sensing surface configurations.

Detailed Description

The present application and various benefits thereof are described with reference to exemplary embodiments in conjunction with the following figures.

FIG. 1a shows one embodiment of a sensor according to the present application. In this embodiment, the sensor includes a light source unit 100, an interferometric measuring unit 200, a sensing unit 300, and a detection unit 500, wherein the light source unit 100 is configured to generate a polychromatic light beam containing p-polarized and s-polarized components, the interferometric measuring unit 200 is configured to split the light beam into a probe beam passing through a first channel and a reference beam passing through a second channel, and to recombine the probe beam output from the first channel and the reference beam output from the second channel, the sensing unit 300 is disposed in the first channel to introduce a first SPR effect associated with a target sample to the probe beam, and the detection unit 500 determines a target sample characteristic by detecting an intensity spectrum of the recombined light beam. The intensity spectrum includes a light intensity distribution within the wavelength range of the recombined light beam. In the present application, the use of a polychromatic light source may increase the range of incident wavelengths, thereby increasing the dynamic range of the phase-sensitive SPR biosensor.

Fig. 1b shows another embodiment of a sensor according to the present application. As shown in fig. 1b, the apparatus may further include a reference cell 400 located in the second channel to introduce a second SPR effect associated with the reference sample to the reference beam. The reference cell 400 for introducing the second SPR effect may provide optical path compensation for the spectral propagation introduced by the sensing cell. The reference unit may be used to cancel common mode noise by direct subtraction between phase values obtained from the reference beam, resulting in an improvement in detection accuracy.

As shown in fig. 2, the light source unit 100 may comprise a broadband polychromatic electromagnetic radiation source 101, a spatial filter 102, a collimator 103, and a broadband linear polarizer 104.

Polychromatic electromagnetic radiation source 101 may include a Quartz Tungsten Halogen (QTH) lamp, a solid-state White Light Emitting Diode (WLED), a broadband super-luminescent diode (SLD), a super-continuum laser source that generates a super-continuum by propagating ultra-short laser pulses in a microstructured fiber, or any other suitable polychromatic electromagnetic radiation source. The radiation source 101 emits a light beam comprising a randomly polarized component. For example, a QTH lamp with an electrical power of 250 watts may be used, the polarization of which is considered random.

The spatial filter 102 is used to select the wavelength of the light beam emitted from the light source. Optionally, the spatial filter 102 is a tunable filter for selecting wavelengths. In this way, the obtained intensity spectrum may comprise a light intensity distribution over the selected wavelength range. The collimator 103 converts the input beam into a parallel beam having a plane wavefront. By rotating the polarization angle of polarizer 104, polarizer 104 can be used to select the content ratio between the p-polarized and s-polarized components of the light source. The polarization angle of the polarizer 104 may be set to be offset by 45 degrees with respect to the p-polarization optical axis to obtain equal content of p-polarization component and s-polarization component. As shown in fig. 2, the polarization angle may also be adjusted to compensate for SPR spectral attenuation effects in the probe beam.

A spectral interferometry unit 200 is shown in fig. 3, which is capable of extracting SPR phase changes due to the presence of a target analyte or biomolecule type. As shown in fig. 3, the interferometric measuring unit 200 may be a typical Michelson interferometer, which includes a broadband non-polarizing splitter 201 and two reflecting units 202 and 203, e.g., two high-precision mirrors 202 and 203. The beam splitter 201 serves to split the light beam into a first portion in the first path and a second portion in the second path. The first path is for the probe beam and the second path is for the reference beam. Both beams comprise p-polarized and s-polarized components. The first mirror 202 is located at the end of the first path to reflect light so that the light beam in the first path can pass through the sensing unit twice. The light beam reflected by the mirror 202 in the first path and the light beam reflected by the mirror 203 in the second path are recombined at the wave splitter 201 of the interferometric measuring unit 200. Mirrors 202 and 203 are positioned to introduce sufficient OPD between the two paths so that sufficient spectral oscillation can be observed for signal analysis. In one embodiment, a linear micro-displacement stage may be provided, with one mirror placed thereon. The linear micro-displacement stage is adjustable to provide an optical path difference between the first path and the second path. In the current setup, a Michelson interferometer can be used to introduce self-interference between the probe beam and the reference beam. Since the polychromatic beam has a very short coherence length, the path difference between the two arms should be controlled to a very small extent. A linear displacement stage may be used to adjust the path difference to achieve the highest stripe contrast possible.

For sensing unit 300, a conventional SPR configuration may be used. Alternatively, an LRSPR configuration may be used.

In this embodiment, a prism coupling scheme using an LRSPR configuration (prism/metal layer/dielectric layer/metal layer/sample) is used, which is shown in fig. 4. In the LRSPR configuration, the prism coupling scheme includes a prism 301, a conversion layer of the sensing surface 302 made of a dielectric layer 306 sandwiched by two conductive materials 305 and 307 (e.g. gold or silver on the prism 301), and a sample flow chamber 304 associated with the prism 301 for directing the sample 303 to flow over the surface of the conductive material 307.

The prism 301 may be made of a transparent dielectric material, such as plastic or glass, to enhance the momentum of the light to match the momentum of the SPW. In this embodiment, a right-angled triangular prism made of BK7 glass is used. In this embodiment, the first layer of conductive material 305 forming the prism surface is gold with a thickness of 48 nm. The second layer of dielectric material 306 is silicon dioxide with a thickness of 453 nm. The third layer of conductive material 307 is gold with a thickness of 2 nm. The thickness of the layers is chosen depending on the application and the choice of material. The sample 303 is typically used in an aqueous form. In the experimental illustration, sodium chloride solutions were used in 1% increments from 0% to 8% by weight. The sample flow chamber 304 is designed to allow the sample 303 to flow into and out of the chamber 304 and into contact with the sensing surface. The introduction of the LRSPR effect into the SPR sensing surface can enable the resonance peak to be sharper, so that the detection accuracy of the phase-sensitive SPR biosensor can be further improved.

For reference cell 400, the rest is the same as sensing cell 300 except for the sample in the flow chamber, and is made of the same materials, structure and dimensions. The reference cell 500 may be used for two purposes: (1) compensating for excessive scattering introduced into the optical path of the detection interferometry path due to the arrangement of the prism; and (2) contact with the reference sample throughout the process and the refractive index remains constant so that unknown refractive index changes occurring in the probe path can be compared to a fixed reference. The reference sample may be a reference solution or a reference gas with a fixed refractive index, i.e. air at standard temperature, volume and pressure.

The detection unit 500 may comprise a light detection unit 510 and a processing unit 520, wherein the light detection unit 510 is configured to obtain an intensity spectrum of the recombined light beam, and the processing unit 520 is configured to determine the sample characteristic based on the intensity spectrum obtained by the light detection unit 510.

As shown in fig. 5a, the optical detection unit 510 may comprise a splitter 511 and a two-channel analyzer 512, wherein the splitter 511 is configured to separate a p-polarized component and an s-polarized component from the recombined beam, and the two-channel analyzer 512 is configured to capture respective spectral intensity oscillation signals of the p-polarized component and the s-polarized component.

The splitter 511 may be a broadband polarization splitter or a Wollaston prism that separates the p-polarized and s-polarized components from the recombined beam before it enters the differential spectrum analyzer unit 512 so that they can interfere between themselves. Each of the two channels of the spectrum analyzer 512 may include a dispersion grid for separating the beam into spatially dispersed wavelengths, and a detector array having a plurality of pixels, each for measuring an intensity oscillation signal of one of the spatially dispersed wavelengths. The detector array may be a linear Charge Coupled Device (CCD) detector array for capturing spectral intensity oscillations of the p-polarized component and the s-polarized component, respectively. The signal traces from the entire optical detector array contain all the information needed to calculate the spectral phase change and spectral intensity drop due to energy conversion associated with the SPR effect at all incident wavelengths at a fixed angle.

To illustrate the spectral oscillation obtained from the detection unit 510, fig. 6 shows a raw intensity spectrum signal to be processed by the unit 520. The intensity recorded by each pixel in the detector array is the trench intensity spectrum shown in fig. 6, which can be described by the following equation:

wherein, I₀(λ) is the reference spectrum, and V (λ) is the visibility of the spectral fringesΔ λ is the spectral phase information directly related to the SPR condition of the target sample. The phase term Δ λ can be extracted by appropriate signal processing methods to determine the change in refractive index by the change in SPR wavelength due to the change in refractive index and the introduction of a fixed time delay between the two optical paths.

As shown in fig. 5a, the processing unit 520 is connected to the optical detection unit 510. The processing unit 520 may include a personal microcomputer or any other processor. Which is used to calculate the phase of the reference channel and the detection channel to obtain the phase difference and thus the refractive index change associated with binding of the biomolecule to the sensor surface. In one embodiment, processing unit 520 may collect spectral intensity oscillation signals of the p-polarized component and the s-polarized component from detection unit 510 and then determine the target sample by calculating a differential phase between the p-polarized component and the s-polarized component to detect a refractive index change associated with the target sample.

As described above, the sensing unit 300 may be a conventional SPR sensing unit. To illustrate the wide dynamic range of the present application, experiments were conducted using dielectric/metal/dielectric SPR sensing results. A triangular prism made of BK7 glass was used. In a conventional SPR configuration, the conversion layer of the sensing surface is made of a conductive material such as gold. For example, a thin layer of gold, nominally 48nm thick, can be used, which has good chemical resistance. The target sample is a sodium chloride solution. Fig. 7a and 7b show the corresponding simulation results with LRSPR and the experimental results with standard SPR, respectively. The concentration of these solutions ranged from 0% to 12% (from curve 711 to curve 717 in fig. 7 a) and was increased by weight at 2%, with corresponding unit Refractive Indices (RIU) ranging from 1.3330 to 1.3541. The curves in fig. 7b (from curve 721 to curve 729) represent solutions with weight ratios of 0%, 0.5%, 1%, 2%, 4%, 6%, 8%, 10% and 10.5%, respectively. From these graphs, it can be seen that the system covers 2 × 10^-2The dynamic range of the RIU, and the spectral range covers 600nm to 800 nm.

Fig. 8 shows simulation results of the phase response of the SPR and LRSPR configurations. The sensor layer structure for SPR configuration is thicknessA thin layer of 48nm gold, the sensor structure layer for the LRSPR configuration is a gold/silica/gold multilayer stack with thicknesses of 48nm, 620nm and 2nm, respectively. The results show that for a spectral phase change of 1 deg., the corresponding refractive change for the SPR configuration is 8.53X 10^-7The corresponding refractive change for RIU, LRSPR configuration was 1.95X 10^-8RIU. This means that the detection accuracy of the LRSPR configuration is approximately 44 times higher than that of the SPR configuration. Fig. 9 and 10 show simulation results of spectral phase responses when SPR and LRSPR configurations, respectively, incorporate a wide dynamic range phase sensitive SPR sensor. The angle of incidence used in the simulation was fixed at approximately 65.5 ° and the resulting signal traces were detected by a 3648 cell spectrometer covering the range from 600nm to 800nm and spaced at approximately 0.05nm for both SPR and LRSPR configurations. The curve (from curve 901 to curve 910) represents the spectral phase response of the sensing layer at each wavelength interval, which is the phase signal detected at each spectral element within the spectrum analyzer. In particular, curves 901 through 910 represent the spectral phase response of the sensing layer at wavelengths of 655nm, 660nm, 665nm, 670nm, 674nm, 679nm, 684nm, 689nm, 694nm, and 699nm, respectively. FIG. 9 shows the resulting phase response curves for the SPR configuration, with a refractive index sensing range of 1.333RIU to 1.375RIU (i.e., a dynamic range of about 4X 10)^-2RIU)。

When the refractive index shifts away from the optimum, the accuracy is from 3.57 × 10^-6RIU/degree is gradually reduced to 8.41 multiplied by 10^-5RIU/degree. FIG. 10 shows simulation results of phase response in a wide dynamic range spectrum phase sensitive SPR sensor having an LRSPR sensing surface configuration. Curves 1001 to 1015 respectively represent the spectral phase response of the sensing layer at each wavelength, in particular at wavelengths 660nm, 665nm, 670nm, 674nm, 679nm, 684nm, 689nm, 694nm, 699nm, 704nm, 709nm, 714nm, 718nm, 723nm, 728nm and 733 nm. As shown in FIG. 10, the phase response of the LRSPR configuration is shown to be at 4 × 10^-2The precision is only from 3.36 multiplied by 10 in the dynamic range of the RIU^-8RIU/degree change to 7.73X 10^-8RIU/degree. Thus, the multi-wavelength spectrum phase interrogation system can be matched with standard SPRCompatible with the LRSPR configuration so that the measurable dynamic range can be greatly extended for both configurations.

In another embodiment, a phase stepping technique may be implemented in the present application. For example, a phase stepping unit 204 may be provided to introduce a common time delay for the p-polarized component between the first path and the second path and the s-polarized component between the first path and the second path. That is, the phase stepping unit may introduce a common time delay for the p-polarized and s-polarized components of the recombined beam at the exit of the spectral interferometer before they enter the respective channels, so that each pixel of the detector array of the analyzer unit 512 may detect its own temporal oscillation. As shown in fig. 5b, the phase stepping unit 204 may be a piezo driven mirror located in the mirror 203. Alternatively, the phase drive unit may be a piezo-driven mirror located in the mirror 202. Which is used to provide additional data points so that the spectral phase can be estimated with greater accuracy. The phase stepping technique can be understood as:

where τ is the time delay introduced by the piezoelectric driven mirror. Thus, each pixel on the spectral CCD array includes its own oscillation in the time domain. However, SPR phase information is preserved so that differential phase along the time dimension can be extracted. The greater the number of time periods, the better the accuracy of extracting the SPR phase. Fig. 5b shows a scheme of adding a piezo-controlled phase stepping mirror.

According to another aspect of the present application, a method for detecting a characteristic of a target sample is provided. The method comprises the following steps: generating a polychromatic light beam containing a p-polarized component and an s-polarized component from a light source unit; splitting the optical beam into a probe beam passing through the first path and a reference beam passing through the second path, and recombining the probe beam output from the first path and the reference beam output from the second path;

introducing a first SPR effect associated with the target sample to the probe beam in the first pass; obtaining an intensity spectrum of the recombined beam; and detecting a characteristic of the target sample based on the obtained intensity spectrum. The intensity spectrum includes an intensity distribution over the entire wavelength range of the recombined beam.

In one embodiment, the method further comprises introducing a second SPR effect associated with the reference sample to the reference beam in the second pass.

In one embodiment, the first SPR effect introduced is a first long-range SPR effect associated with the target sample and the second SPR effect introduced is a second long-range SPR effect associated with the reference sample.

In one embodiment, the step of generating a polychromatic light beam containing a p-polarized component and an s-polarized component from a light source unit comprises: emitting a polychromatic light beam comprising random polarizations; converting the beam into a parallel beam having a plane wavefront; and selecting a content ratio between the p-polarized component and the s-polarized component. Optionally, the step further comprises selecting a wavelength of the emitted light beam.

In one embodiment, the step of obtaining the intensity spectrum of the recombined light beam comprises: separating the p-polarized component and the s-polarized component from the recombined beam; and capturing the spectral intensity oscillation signals of the p-polarized component and the s-polarized component. Optionally, the step of capturing comprises separating the p-polarized component into spatially dispersed wavelengths and separating the s-polarized component into spatially dispersed wavelengths; and capturing the spectral intensity oscillation signal by measuring the intensity oscillation signal at each of the wavelengths of the spatial dispersion of the p-polarization component and the intensity oscillation signal at each of the wavelengths of the spatial dispersion of the s-polarization component.

In one embodiment, the step of detecting the target sample characteristic based on the obtained intensity spectrum comprises: collecting the spectral intensity oscillation signals of the p-polarized component and the s-polarized component; and detecting the target sample characteristic by calculating a differential phase between the p-polarized component and the s-polarized component to determine a change in refractive index associated with the target sample.

In one embodiment, the method further comprises introducing a common time delay to a p-polarized component between the first path and the second path and an s-polarized component between the first path and the second path.

The present application is based on the use of spectra to interrogate the wavelength-dependent phase of SPR systems by differential spectral interferometry. To achieve a wide dynamic range, a polychromatic light source can be calibrated and directed at a fixed angle to the SPR sensing surface and cover a large wavelength range. In fact, the emitted beam selectively modulated by the SPW contains SPR information accompanied by the spectral bandwidth of the polychromatic light source. By collecting the light energy of the entire reflection spectrum using a spectral detection unit, the signals from the individual detector elements are equivalent to performing SPR detection with a large number of monochromatic light sources. By performing spectral interferometry, the signal traces collected by the detection unit contain all the information needed to obtain spectral SPR reflectivity dip and simultaneously obtain the spectral SPR phase of the polychromatic spectrum.

The sensor according to the present application has advantages over conventional monochromatic laser based phase sensitive SPR schemes in terms of the operational dynamic range of refractive index measurements. The introduction of polychromatic light sources in spectral phase sensitive SPR sensor systems increases the detection dynamic range of the system. It also allows the introduction of an LRSPR sensor layer design which is known to provide high phase detection accuracy due to the narrow resonance peak, so that the limited operating range can be compensated for by the multi-wavelength method. The resulting system can therefore provide high measurement accuracy and a wide dynamic range, enabling the system to be used in a wide variety of biological detection applications.

While embodiments of the present application have been described above, it should be understood that the basic configuration may be altered to provide other embodiments that utilize the processes and components of the present application. It will therefore be appreciated that the scope of the present application is defined by the appended claims rather than by the specific embodiments provided herein by way of example.

Claims (19)

1. An optical sensing device comprising:

a light source unit that generates a polychromatic light beam containing a p-polarized component and an s-polarized component;

an interferometric unit that splits the optical beam into a probe beam that passes through a first path and a reference beam that passes through a second path, and recombines the probe beam output from the first path and the reference beam output from the second path, the probe beam and the reference beam each including a p-polarized component and an s-polarized component;

a sensing unit disposed in the first pathway to introduce a first SPR effect associated with a target sample to the probe beam;

a detection unit to detect a characteristic of the target sample by obtaining an intensity spectrum of the recombined light beam, wherein the detection unit includes a dual-channel analyzer, each channel of the dual-channel analyzer including:

a dispersion grid separating the light beam into spatially dispersed wavelengths; and

a detector array having a plurality of pixels, each pixel for measuring an intensity oscillation signal of one of the spatially dispersed wavelengths;

and

a reference cell disposed in the second path to introduce a second SPR effect associated with a reference sample to the reference beam to provide optical path compensation for spectral propagation introduced by the sensing cell.

2. The optical sensing device of claim 1, wherein the sensing unit and the reference unit each comprise:

a prism;

the conversion layer is covered on the surface of the prism and used as a sensing surface; and

a sample flow chamber associated with the prism and allowing the sample to flow across the sensing surface.

3. The optical sensing device of claim 1, wherein the sensing cell and the reference cell are both long range SPR sensing cells.

4. The optical sensing device of claim 3, wherein the long range SPR sensing unit comprises:

a prism;

a conversion layer covering the surface of the prism to serve as a sensing surface and made of a dielectric layer sandwiched between two conductive layers; and

a sample flow chamber associated with the prism and for directing sample flow over the sensing surface.

5. The optical sensing device of claim 1, wherein the light source unit comprises:

a light source emitting a polychromatic light beam comprising random polarizations;

a collimator that converts the light beam into a parallel light beam having a plane wavefront; and

a polarizer selecting a content ratio between the p-polarized component and the s-polarized component.

6. The optical sensing device of claim 5, wherein the light source unit further comprises:

a filter that selects wavelengths of the polychromatic light beam emitted from the light source.

7. The optical sensing device of claim 1, wherein the light source unit comprises a quartz tungsten halogen lamp, a solid state white light emitting diode, a broadband super-radiation emitting diode, or a super-continuum laser light source.

8. The optical sensing device of claim 1, wherein the interferometric measuring unit is a mach-zehnder interferometer and comprises:

a beam splitter that splits the optical beam into the probe beam and the reference beam;

a first reflection unit located in the first path, reflecting the probe beam to pass the probe beam through the sensing unit twice;

a second reflecting unit located in the second path, reflecting the reference beam to pass the reference beam through the reference unit twice,

wherein the beam splitter recombines the reflected probe beam and the reflected reference beam.

9. The optical sensing device of claim 1, wherein the detection unit comprises:

an optical detection unit that obtains an intensity spectrum of the recombined light beam; and

a processing unit to determine the sample characteristic based on the intensity spectrum.

10. The optical sensing device of claim 9, wherein the optical detection unit comprises:

a demultiplexer that separates the p-polarized component and the s-polarized component from the recombined light beam; and

the dual-channel analyzer captures spectrum intensity oscillation signals of the p-polarized component and the s-polarized component.

11. The optical sensing device of claim 9, wherein the processing unit collects spectral intensity oscillation signals of the p-polarized component and the s-polarized component and determines the target sample characteristic by calculating a differential phase between the p-polarized component and the s-polarized component to detect a change in refractive index associated with the target sample.

12. The optical sensing device of claim 1, further comprising:

a phase stepping unit, configured to introduce a common time delay to the p-polarization component and the s-polarization component between the first path and the second path.

13. The optical sensing device of claim 12 wherein the phase stepping unit is a piezo-driven mirror.

14. A method for detecting a characteristic of a target sample, comprising:

generating a polychromatic light beam containing a p-polarized component and an s-polarized component from a light source unit;

splitting the optical beam into a probe beam passing through a first path and a reference beam passing through a second path, and recombining the probe beam output from the first path and the reference beam output from the second path, the probe beam and the reference beam each including a p-polarized component and an s-polarized component;

introducing a first SPR effect associated with the target sample to the probe beam in the first path;

obtaining an intensity spectrum of the recombined beam of light, comprising:

separating the p-polarized component and the s-polarized component from the recombined beam;

separating the p-polarized component into spatially dispersed wavelengths and separating the s-polarized component into spatially dispersed wavelengths; and

capturing the spectral intensity oscillation signal by measuring an intensity oscillation signal of each of the wavelengths of the spatial dispersion of the p-polarization component and measuring an intensity oscillation signal of each of the wavelengths of the spatial dispersion of the s-polarization component;

detecting a characteristic of the target sample based on the obtained intensity spectrum; and

introducing a second SPR effect associated with a reference sample to the reference beam in the second path, thereby providing optical path compensation for spectral propagation introduced in the first path.

15. The method of claim 14, wherein the first SPR effect introduced is a first long-range SPR effect associated with the target sample and the second SPR effect introduced is a second long-range SPR effect associated with the reference sample.

16. The method of claim 14, wherein generating the polychromatic light beam comprises:

emitting a polychromatic light beam comprising random polarizations;

converting the light beam into a parallel light beam with a plane wave front; and

selecting a content ratio between the p-polarized component and the s-polarized component.

17. The method of claim 16, wherein the step of generating the polychromatic light beam further comprises:

the wavelength of the emitted light beam is selected.

18. The method of claim 17, wherein detecting the target sample characteristic based on the obtained intensity spectrum comprises:

collecting spectral intensity oscillation signals of the p-polarized component and the s-polarized component; and

detecting the target sample characteristic by determining a change in refractive index associated with the target sample by calculating a differential phase between the p-polarized component and the s-polarized component.

19. The method of claim 18, further comprising:

introducing a common time delay between the first path and the second path for the p-polarized component and the s-polarized component.