Apparatus for measuring electrophoretic mobility

Abstract

This disclosure describes an apparatus for measuring electrophoretic mobility. In one embodiment, the apparatus includes a laser, a fiber splitter optically coupled to the laser, a polarization-maintaining acousto-optic modulator optically coupled to the sample arm output of the splitter, a sample cell for containing a sample and optically coupled to the output of the acousto-optic modulator, a polarization-maintaining coupler optically coupled to the reference arm output of the splitter and the output of the sample cell, a photodetector for detecting light output from the coupler, a radio frequency source electrically coupled to the input of the acousto-optic modulator, and a demodulator electrically coupled to the output of the photodetector and electrically coupled to the output of the radio frequency source for outputting in-phase and quadrature-phase data analyzed for frequency shifts in order to measure electrophoretic mobility in a sample.

Description

TECHNICAL FIELD

[0001] (Related Applications) This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 586,696, filed on September 29, 2023, entitled "Apparatus to Measure Electrophoretic Mobility", the entire contents of which are incorporated herein by reference.

[0002] (Field of the Invention) The present disclosure relates to electrophoretic mobility, and more specifically, to an apparatus for measuring electrophoretic mobility. SUMMARY OF THE INVENTION

[0003] The present disclosure describes an apparatus for measuring electrophoretic mobility. In one exemplary embodiment, the apparatus includes (1) a long coherence length laser, (2) a fiber splitter optically coupled to the laser, (3) a polarization maintaining (PM) acousto-optic modulator (AOM) optically coupled to the sample arm output of the splitter, (4) a sample cell for containing a sample and optically coupled to the output of the acousto-optic modulator, (5) a polarization maintaining coupler optically coupled to the reference arm output of the splitter and the output of the sample cell, (6) a photodetector for detecting light output from the coupler, (7) a radio frequency (RF) source electrically coupled to the input of the acousto-optic modulator, and (8) an in-phase quadrature phase (IQ) demodulator electrically coupled to the output of the photodetector and electrically coupled to the output of the radio frequency source, for outputting in-phase data I and quadrature phase data Q that are analyzed for frequency shift to measure the electrophoretic mobility in the sample.

[0004] In one exemplary embodiment, the apparatus includes (1) a long coherence length laser, (2) a fiber splitter optically coupled to the laser, (3) a polarization-maintaining (PM) acousto-optic modulator (AOM) optically coupled to the reference arm output of the splitter, (4) a sample cell for containing a sample and optically coupled to the sample arm output of the splitter, (5) a polarization-maintaining coupler optically coupled to the output of the acousto-optic modulator and the output of the sample cell, (6) a photodetector for detecting light output from the coupler, (7) a radio frequency (RF) source electrically coupled to the input of the acousto-optic modulator, and (8) an in-phase orthogonal-phase (IQ) demodulator electrically coupled to the output of the photodetector and electrically coupled to the output of the radio frequency source for outputting in-phase data I and orthogonal-phase data Q to be analyzed for frequency shifts in order to measure electrophoretic mobility in the sample. [Brief explanation of the drawing]

[0005] [Figure 1A] An exemplary embodiment of the apparatus is illustrated. [Figure 1B] An exemplary embodiment of the apparatus is illustrated. [Figure 1C] An exemplary embodiment of the apparatus is illustrated. [Figure 2A] An exemplary embodiment of the apparatus is illustrated. [Figure 2B] An exemplary embodiment of the apparatus is illustrated. [Figure 3] A graph illustrating one embodiment is shown. [Figure 4] A graph illustrating one embodiment is shown. [Figure 5] A graph illustrating one embodiment is shown. [Figure 6A] A graph illustrating one embodiment is shown. [Figure 6B] A graph illustrating one embodiment is shown. [Figure 7] A graph illustrating one embodiment is shown. [Figure 8] A graph illustrating one embodiment is shown. [Modes for carrying out the invention]

[0006] This disclosure describes an apparatus for measuring electrophoretic mobility. In one exemplary embodiment, the apparatus includes (1) a long coherence-length laser, (2) a fiber splitter optically coupled to the laser, (3) a polarization-maintaining (PM) acousto-optic modulator (AOM) optically coupled to the sample arm output of the splitter, (4) a sample cell for containing the sample and optically coupled to the output of the acousto-optic modulator, (5) a polarization-maintaining coupler optically coupled to the reference arm output of the splitter and the output of the sample cell, (6) a photodetector for detecting light output from the coupler, (7) a radio frequency (RF) source electrically coupled to the input of the acousto-optic modulator, and (8) an in-phase orthogonal-phase (IQ) demodulator electrically coupled to the output of the photodetector and electrically coupled to the output of the radio frequency source for outputting in-phase data I and orthogonal-phase data Q to be analyzed for frequency shifts in order to measure electrophoretic mobility in the sample. In one embodiment, the laser is a single-frequency polarized laser. In one embodiment, the splitter provides efficient use of laser light by having an asymmetric splitting ratio. In one embodiment, the AOM receives light and shifts the frequency f of the light, while leaking out some of the light while maintaining its original frequency. In one embodiment, the photodetector is a silicon photodiode, an avalanche photodiode, or a photomultiplier tube.

[0007] In one exemplary embodiment, the apparatus includes (1) a long coherence length laser, (2) a fiber splitter optically coupled to the laser, (3) a polarization-maintaining (PM) acousto-optic modulator (AOM) optically coupled to the reference arm output of the splitter, (4) a sample cell for containing a sample and optically coupled to the sample arm output of the splitter, (5) a polarization-maintaining coupler optically coupled to the output of the acousto-optic modulator and the output of the sample cell, (6) a photodetector for detecting light output from the coupler, (7) a radio frequency (RF) source electrically coupled to the input of the acousto-optic modulator, and (8) an in-phase orthogonal-phase (IQ) demodulator electrically coupled to the output of the photodetector and electrically coupled to the output of the radio frequency source for outputting in-phase data I and orthogonal-phase data Q to be analyzed for frequency shifts in order to measure electrophoretic mobility in the sample.

[0008] In one embodiment, the device eliminates the need to (a) resolve the time-domain beat signal and (b) detect or resolve the local oscillator, similar to electrophoretic mobility measuring instruments based on the piezoelectric effect. In one embodiment, the device provides improved phase stability between the local oscillator and the beat signal. In one embodiment, the device removes all frequencies that (i) are outside the measurement bandwidth and (ii) do not have a constant phase relationship with the local oscillator. In one embodiment, an in-phase quadrature (IQ) demodulator uses RF demodulation techniques to extract the Doppler frequency shift, enabling highly accurate generation of the quadrature signal required in demodulation. In further embodiments, the device further includes a narrowband filter (i.e., a "lock-in" technique) that can eliminate much of the noise outside the measurement bandwidth.

[0009] In one embodiment, the device enables the detection of multiple mobility species in a sample and the direct measurement of the Doppler frequency shift of particles in the sample by focusing on the frequency domain representation of the demodulated signal output by an in-phase orthogonal-phase (IQ) demodulator. In one embodiment, the device enables the calculation of the electrophoretic mobility of particles in the sample by dividing the Doppler frequency shift by the electric field strength and the scattering vector. In another embodiment, the device enables the direct measurement of the entire spectrum of the (Doppler) frequency shift of particles in a sample and the distinction of different mobilities within a single sample. In one embodiment, the device enables the direct measurement of the spectral width of the Doppler shift to estimate the size of particles in a sample, and also enables the simultaneous measurement of electrophoretic light scattering and dynamic light scattering.

[0010] definition particle Particles can be components of aliquots in liquid samples. Such particles can be molecules of various types and sizes, nanoparticles, virus-like particles, liposomes, emulsions, bacteria, and colloids. These particles can range in size from nanometers to microns.

[0011] Analysis of polymer or particle species in solution Analysis of polymer or particle species in solution can be achieved by preparing a sample in a suitable solvent and then injecting aliquots thereof into a separation system such as a liquid chromatography (LC) column or field flow fractionation (FFF) channel, which separates different types of particles contained in the sample into their various components. Generally, once separated based on size, mass, or column affinity, the sample can be subjected to analysis by light scattering, refractive index, ultraviolet absorption, electrophoretic mobility, and viscosity response.

[0012] light scattering Light scattering (LS) is a non-invasive technique for characterizing polymers and a wide range of particles in solution. Two types of light scattering detection frequently used for polymer characterization are static and dynamic light scattering.

[0013] Dynamic light scattering Dynamic light scattering is also known as quasi-elastic light scattering (QELS) and photon correlation spectroscopy (PCS). DLS experiments use fast photodetectors to measure the time-dependent variation of the scattered light signal. DLS measurements can determine the diffusion coefficient of molecules or particles, which can then be used to calculate their hydrodynamic radius.

[0014] static light scattering Static light scattering (SLS) encompasses various techniques, including single-angle light scattering (SALS), dual-angle light scattering (DALS), low-angle light scattering (LALS), and multi-angle light scattering (MALS). SLS experiments generally involve measuring the absolute intensity of light scattered from a sample in a solution irradiated by a narrow beam of light. Such measurements are often used to determine the size and structure of sample molecules or particles for a suitable class of particles / molecules, and, combined with knowledge of the sample concentration, to determine the weight-average molar mass. In addition, the nonlinearity of the scattered light intensity as a function of the sample concentration can be used to measure inter-particle interactions and associations.

[0015] Multi-angle light scattering Multi-angle light scattering (MALS) is an SLS technique for measuring light scattered by a sample at multiple angles. It is used to determine both the absolute molar mass and the average size of molecules in a solution by detecting how the molecules scatter light. Collimated light from a laser light source is most frequently used, in which case this technique can be referred to as multi-angle laser light scattering (MALLS). The term "multi-angle" refers to the detection of scattered light at different discrete angles, for example, measured by a single detector moved over a range that includes a particular selected angle, or by an array of detectors fixed at specific angular positions.

[0016] MALS measurements require a set of auxiliary elements. The most important of these is a collimated or focused light beam (usually from a laser light source that produces a collimated beam of monochromatic light) that illuminates the region of the sample. The beam is generally plane-polarized perpendicular to the measurement plane, although other polarizations may be used, especially when investigating anisotropic particles. Another required element is an optical cell for holding the sample being measured. Alternatively, a cell incorporating means to allow measurement of a flowing sample may be used. If it is desired to measure the scattering properties of single particles, means must be provided for introducing such particles one by one through the light beam at points approximately equidistant from the surrounding detectors.

[0017] Most MALS-based measurements are performed in a plane that includes a set of detectors typically arranged equidistant from the centrally located sample through which the illumination beam passes, although three-dimensional versions have also been developed, in which case the detectors lie on the surface of a sphere, the sample is controlled to pass through the center of the sphere, where the sample intersects the path of the incident light beam passing along the diameter of the sphere. MALS techniques generally collect multiplexed data sequentially from the outputs of a set of discrete detectors. MALS light scattering photometers generally have multiple detectors.

[0018] Because different detectors within a MALS detector may (i) have slightly different quantum efficiencies and different gains, and (ii) may view different geometric scattering volumes, it may be necessary to normalize the signal captured by the photodetector of the MALS detector at each angle. Without normalizing these differences, the results of the MALS detector may be meaningless and inappropriately weighted for different detector angles.

[0019] Electrophoretic Light Scattering Electrophoretic light scattering (ELS) is a technique used to measure the electrophoretic mobility of particles in a dispersion or molecules in a solution. This mobility is often converted to zeta potential to enable comparison of materials under different experimental conditions. The basic physical principle is the principle of electrophoresis. The dispersion is introduced into a cell containing two electrodes. An electric field is applied to the electrodes, and particles or molecules with a net charge, or more precisely a net zeta potential, move toward the oppositely charged electrode at a speed known as mobility related to their zeta potential.

[0020] When an electric field is applied to a sample, any charged object in the sample is affected by the electric field. The additional motion exhibited by a particle as a result of the particle being subjected to the electric field is referred to as electrophoretic mobility. Its common unit is velocity [μm / s] per electric field strength [V / cm], which is μm·cm / V·s (micrometer centimeter per volt second). Electrophoretic mobility is a direct measurement from which zeta potential can be derived (to obtain zeta potential from mobility, either the Smoluchowski / Debye-Hueckel approximation or the complete Henry function F(κa) is used).

[0021] Current Technology Current ELS (Earth-Liquid Saturation) measurement instruments rely on comparing light scattered from a particle with unscattered light. Light scattered from a moving particle undergoes a frequency (Doppler) shift by an amount proportional to the particle's velocity. Unscattered light, and therefore undoppler-shifted, thus has a slightly different frequency. Through a proper comparison, the presence of a Doppler shift can be detected, and the particle velocity can be extracted.

[0022] Because the optical frequency is extremely high (350 THz), directly tracking the phase / frequency of light is difficult (i.e., directly comparing frequencies is difficult). A technique is commonly used to reduce this phase / frequency information to a manageable frequency (kHz), which involves superimposing light with a third beam that itself has a frequency shift of several kHz. Scattered light is combined with this "reference" light, and the result is amplitude modulation at the difference frequency of the two optical beams (the result of superimposing two beams with distinct frequencies is generally called a "beat signal"). Similarly, non-scattered light is combined with the reference light to form its own beat signal, the amplitude of which oscillates at the difference frequency between the non-scattered light and the reference light. Typically, a moving mirror is used to generate a frequency-shifted reference light, resulting in two distinct beat signals (at easily detectable frequencies), one with a Doppler shift and the other without. A comparison of these two distinct beat signals then makes it possible to detect the Doppler shift.

[0023] Therefore, current technology relies on the generation and detection of two different beat signals, requiring a highly stable apparatus because any mechanical vibration causes an undesirable (unexplainable) frequency shift in one beat signal compared to the other. Furthermore, since a moving mirror is used to generate a frequency-shifted reference light, the size of this frequency shift is limited to a few kHz. Also, the movement of the mirror is nonlinear (it decelerates when the direction is reversed), thus generating a reference frequency that changes over time. Consequently, an apparatus is needed to measure electrophoretic mobility.

[0024] In one embodiment, Figures 1A and 1B show an apparatus comprising: (1) a long coherence laser 110; (2) a fiber splitter 115 optically coupled to the laser 110; (3) a polarization-maintaining acousto-optic modulator 120 optically coupled to the sample arm output of the splitter 115; (4) a sample cell 125 containing a sample and optically coupled to the output of the acousto-optic modulator 120; and (5) a polarization-maintaining acousto-optic modulator optically coupled to the reference arm output of the splitter 115 and the output of the sample cell 125. The present invention describes an apparatus comprising: (6) a coupler 130; (7) a photodetector 135 for detecting light output from the coupler 130; (8) a radio frequency source 140 electrically coupled to the input of an acousto-optic modulator 120; and (9) a common-phase orthogonal-phase demodulator 145 electrically coupled to the output of the photodetector 135 and electrically coupled to the output of the radio frequency source 140 for outputting common-phase data I and orthogonal-phase data Q to be analyzed for frequency shifts in order to measure electrophoretic mobility in a sample. In further embodiments, the apparatus further includes at least one polarization-maintaining (PM) fiber that couples together any of the laser 110, splitter 115, acousto-optic modulator 120, sample cell 125, and coupler 130. For example, the PM fiber is standard coupled (e.g., FCP coupled). In one embodiment, any of the splitter 115, acousto-optic modulator 120, and coupler 130 are fused together, and such fused components may result in better performance of the apparatus.

[0025] In one embodiment, the splitter 115 includes a splitting ratio such that the majority of the laser light emitted by the laser is directed to the sample cell 125. For example, the splitting ratio may be such that 50% to 99.1% of the laser light is directed to the sample cell 125 (for example, with a splitting ratio of 96:4, 96% of the laser light is directed to the sample cell 125 and 4% of the light is directed to the reference arm output of the splitter 115). In one embodiment, the sample cell 125 includes a shutter between the cell housing and the collimator. In one embodiment, the acousto-optic modulator 120 includes a polarizer.

[0026] In a further embodiment, as illustrated in Figure 1C, the apparatus further includes a polarization-maintaining attenuator 150 optically coupled to the reference arm output of the splitter 115. In one embodiment, the attenuator 150 controls the power level of the photodetector 135. In one embodiment, the common-mode orthogonal-phase (IQ) demodulator 145 includes a low-pass filter for common-mode data I and orthogonal-phase data Q.

[0027] In one embodiment, Figure 2A shows an apparatus comprising: (1) a long coherence laser 210; (2) a fiber splitter 215 optically coupled to the laser 210; (3) a polarization-maintaining acousto-optic modulator 220 optically coupled to the reference arm output of the splitter 215; (4) a sample cell 225 containing a sample and optically coupled to the sample arm output of the splitter 215; and (5) a polarization-maintaining coupler optically coupled to the output of the acousto-optic modulator 220 and the output of the sample cell 225. The apparatus is described, comprising (6) a photodetector 235 for detecting light output from the coupler 230, (7) a radio frequency source 240 electrically coupled to the input of the acousto-optic modulator 220, and (8) a common-phase orthogonal-phase demodulator 245 electrically coupled to the output of the photodetector 235 and electrically coupled to the output of the radio frequency source 240 for outputting common-phase data I and orthogonal-phase data Q to be analyzed for frequency shift in order to measure the electrophoretic mobility in the sample. In further embodiments, the apparatus further includes at least one polarization-maintaining (PM) fiber that couples together any of the laser 210, splitter 215, acousto-optic modulator 220, sample cell 225, and coupler 230. For example, the PM fiber is standard coupled (e.g., FCP coupled). In one embodiment, any of the splitter 215, acousto-optic modulator 220, and coupler 230 are fused together, and such fused components may result in better performance of the apparatus.

[0028] In one embodiment, the splitter 215 includes a splitting ratio such that the majority of the laser light emitted by the laser is directed to the sample cell 225. For example, the splitting ratio may be such that 50% to 99.1% of the laser light is directed to the sample cell 225 (for example, with a splitting ratio of 96:4, 96% of the laser light is directed to the sample cell 225 and 4% of the light is directed to the reference arm output of the splitter 215). In one embodiment, the sample cell 225 includes a shutter between the cell housing and the collimator. In one embodiment, the acousto-optic modulator 220 includes a polarizer.

[0029] In a further embodiment, as illustrated in Figure 2B, the apparatus further includes a polarization-maintaining attenuator 250 optically coupled to the reference arm output of the splitter 215. In one embodiment, the attenuator 250 controls the power level of the photodetector 235. In one embodiment, the common-mode orthogonal-phase (IQ) demodulator 245 includes a low-pass filter for common-mode data I and orthogonal-phase data Q. [Examples]

[0030] For example, Figure 3 illustrates an apparatus that shifts the spectrum of data 310 0.025 kHz to the left, as shown in trace 315, and 0.025 kHz to the right, as shown in trace 320, where data 310 corresponds to data collected by photodetector 135 from a sample of 200 nm polystyrene spheres. In another embodiment, Figure 4 illustrates radius data extracted from data output by in-phase orthogonal phase demodulators 145, 245. In particular, Figure 4 shows fitting the width of the data traces to a Lorentz fit for radius extraction.

[0031] Furthermore, for example, Figure 5 illustrates a device that shifts the spectrum of data 510 0.015 kHz to the left, as shown in trace 515, and shifts it 0.015 kHz to the right, as shown in trace 520, where data 510 corresponds to data collected by the photodetector 235 from a sample of 2.5 mg / mL bovine serum albumin (BSA).

[0032] In another embodiment, Figure 6A illustrates the spectrum of the data output by the in-phase orthogonal phase demodulators 145 and 245, obtained by applying a Fast Fourier Transform (FFT) to the data. In a further embodiment, Figure 6B illustrates how the data output by the in-phase orthogonal phase demodulators 145 and 245 can enable the instrument to resolve minute frequency shifts 615 and 620 in the data by observing the FFT of the data.

[0033] For example, Figure 7 illustrates how the common-mode quadrature phase demodulators 145, 245 can clean up the outputs of the photodetectors 13, 235 so that a single peak 710 (for example, at 10 kHz) can be observed. Also, Figure 8 illustrates how the common-mode quadrature phase demodulators 145, 245 and attenuators 150, 250 can result in a higher signal-to-noise ratio (SNR) when a higher-power reference light is transmitted to the photodetectors 135, 235, resulting in noise from the light source being much greater (at least 10 times greater) than the noise equivalent power (NEP) of the photodetectors 135, 235 (noise from the detectors).

[0034] In one embodiment, the device generates and detects only one beat signal, which consists of the overlap between scattered light and a reference light. For example, an acousto-optic modulator (AOM) generates an 80 MHz frequency shift in a light beam transmitted through the AOM, and an 80 MHz electrical signal is applied to a piezoelectric transducer inside the AOM, causing the incident light to diffract and obtaining an optical frequency shift that is perfectly synchronized / in phase with the applied 80 MHz electrical signal. There is a continuous and constant frequency shift (no nonlinear push and pull), and therefore no linearization, no data stitching, and only a single known frequency.

[0035] In a further example, an 80 MHz shifted optical beam is then transmitted into the sample, and the scattered light (further frequency-shifted due to moving particles) is collected. This is then combined with unmodulated laser light, which, in addition to the 80 MHz beat signal, forms an arbitrary Doppler shift introduced to the scattered light by the sample. For example, the instrument then compares the beat signal to the original 80 MHz electrical signal used to drive the AOM, and this electrical signal has far superior phase and frequency stability than the second optical beat signal and is very well phase and frequency matched with the detected optical beat signal. Alternatively, for example, the RF drive signal to the AOM can be used directly in demodulation.

[0036] Furthermore, for example, the device generates a reference frequency that is 80 MHz instead of several kHz, allowing beat signals of many more cycles to be measured and demodulated (i.e., compared to) the original 80 MHz electrical signal (e.g., using millions of cycles for comparison), thereby improving frequency accuracy.

[0037] The descriptions of the various embodiments of this disclosure have been presented for illustrative purposes only and are not intended to be exhaustive or limitful to the embodiments disclosed. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the embodiments described. The terms used herein have been selected to describe the principles of the embodiments, their practical applications to or improvements of technologies found in the market, or to enable those skilled in the art to understand the embodiments disclosed herein.

Claims

1. It is a device, Long coherence lasers, A fiber splitter optically coupled to the laser, A polarization-maintaining acousto-optic modulator is optically coupled to the sample arm output of the splitter, A sample cell for containing the sample and optically coupled to the output of the acousto-optic modulator, A polarization-maintaining coupler is optically coupled to the reference arm output of the splitter and the output of the sample cell, A photodetector for detecting the light output from the coupler, A radio frequency source electrically coupled to the input of the acousto-optic modulator, An apparatus comprising a common-mode orthogonal-phase demodulator, electrically coupled to the output of the photodetector and electrically coupled to the output of the radio frequency source, for measuring the electrophoretic mobility in the sample and outputting common-mode and orthogonal-phase data that are analyzed with respect to frequency shifts.

2. The apparatus according to claim 1, further comprising at least one polarization-maintaining fiber for coupling together any of the laser, the splitter, the acousto-optic modulator, the sample cell, and the coupler.

3. The apparatus according to claim 1, wherein any of the splitter, the modulator, and the coupler are fused together.

4. The apparatus according to claim 1, wherein the splitter includes a splitting ratio such that most of the laser light emitted by the laser is directed towards the sample cell.

5. The apparatus according to claim 1, wherein the sample cell is provided with a shutter between the cell housing and the collimator.

6. The apparatus according to claim 1, wherein the acousto-optic modulator comprises a polarizer.

7. The apparatus according to claim 1, further comprising a polarization-maintaining attenuator optically coupled to the reference arm output of the splitter.

8. The apparatus according to claim 1, wherein the demodulator includes a low-pass filter for the common-mode data and the quadrature-phase data.

9. It is a device, Long coherence lasers, A fiber splitter optically coupled to the laser, A polarization-maintaining acousto-optic modulator is optically coupled to the reference arm output of the splitter, A sample cell for containing the sample and optically coupled to the sample arm output of the splitter, A polarization-maintaining coupler is optically coupled to the output of the acousto-optic modulator and the output of the sample cell. A photodetector for detecting the light output from the coupler, A radio frequency source electrically coupled to the input of the acousto-optic modulator, An apparatus comprising a common-mode orthogonal-phase demodulator, electrically coupled to the output of the photodetector and electrically coupled to the output of the radio frequency source, for measuring the electrophoretic mobility in the sample and outputting common-mode and orthogonal-phase data that are analyzed with respect to frequency shifts.

10. The apparatus according to claim 9, further comprising at least one polarization-maintaining fiber for coupling together any of the laser, the splitter, the acousto-optic modulator, the sample cell, and the coupler.

11. The apparatus according to claim 9, wherein any of the splitter, the acousto-optic modulator, and the coupler are fused together.

12. The apparatus according to claim 9, wherein the splitter includes a splitting ratio such that the majority of the laser light emitted by the laser is directed towards the sample cell.

13. The apparatus according to claim 9, wherein the sample cell is provided with a shutter between the cell housing and the collimator.

14. The apparatus according to claim 9, wherein the acousto-optic modulator comprises a polarizer.

15. The apparatus according to claim 9, further comprising a polarization-maintaining attenuator optically coupled to the reference arm output of the splitter.

16. The apparatus according to claim 9, wherein the demodulator includes a low-pass filter for the common-mode data and the quadrature-phase data.

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