Apparatus for measuring electrophoretic mobility
By combining a long coherence length laser and IQ demodulation technology, the accuracy and stability problems of electrophoretic mobility measurement in existing technologies have been solved, enabling efficient and accurate measurement of electrophoretic mobility and inference of particle size.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- WYATT TECHNOLOGY CORP
- Filing Date
- 2024-09-26
- Publication Date
- 2026-04-24
AI Technical Summary
Existing technologies struggle to efficiently and accurately measure electrophoretic mobility in solutions, particularly due to the difficulty in directly tracking the phase/frequency of optical frequencies and the phase instability caused by mechanical vibrations.
By employing a combination of a long coherence length laser, fiber optic splitter, polarization-preserving acousto-optic modulator, sample cell, polarization-preserving combiner, photodetector, RF source, and in-phase quadrature phase demodulator, the Doppler frequency shift is extracted through IQ demodulation technology, and electrophoretic mobility is directly measured, avoiding the dependence on analytical time-domain beat frequency signals and local oscillators.
It enables precise measurement of electrophoretic mobility, distinguishes different mobility within a single sample, infers particle size, and simultaneously measures electrophoretic light scattering and dynamic light scattering, thus improving the accuracy and stability of the measurement.
Smart Images
Figure CN121925559A_ABST
Abstract
Description
[0001] Related applications
[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 586,696, filed September 29, 2023, entitled “Apparatus to Measure Electrophoretic Mobility,” the entire contents of which are incorporated herein by reference. Background Technology
[0003] This disclosure relates to electrophoretic mobility, and more specifically to an apparatus for measuring electrophoretic mobility. Summary of the Invention
[0004] This disclosure describes an apparatus for measuring electrophoretic mobility. In one exemplary embodiment, the apparatus includes: (1) a long coherence length laser; (2) an optical fiber splitter optically coupled to the laser; (3) a polarization-preserving (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-preserving combiner 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 combiner; (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 the output of the RF source to output in-phase data I and quadrature phase data Q of the frequency offset to be analyzed, thereby measuring electrophoretic mobility in the sample.
[0005] In one exemplary embodiment, the device includes: (1) a long coherence length laser; (2) an optical fiber splitter optically coupled to the laser; (3) a polarization-preserving (PM) acousto-optic modulator (AOM) optically coupled to the output of a reference arm of the splitter; (4) a sample cell for containing a sample and optically coupled to the output of a sample arm of the splitter; (5) a polarization-preserving combiner 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 combiner; (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 the output of the RF source to output in-phase data I and quadrature phase data Q of the frequency offset to be analyzed, thereby measuring electrophoretic mobility in the sample. Attached Figure Description
[0006] Figure 1A A device according to an exemplary embodiment is described.
[0007] Figure 1B A device according to an exemplary embodiment is described.
[0008] Figure 1C A device according to an exemplary embodiment is described.
[0009] Figure 2A A device according to an exemplary embodiment is described.
[0010] Figure 2B A device according to an exemplary embodiment is described.
[0011] Figure 3 A graph depicting the curves according to one implementation scheme is shown.
[0012] Figure 4 A graph depicting the curves according to one implementation scheme is shown.
[0013] Figure 5 A graph depicting the curves according to one implementation scheme is shown.
[0014] Figure 6A A graph depicting the curves according to one implementation scheme is shown.
[0015] Figure 6B A graph depicting the curves according to one implementation scheme is shown.
[0016] Figure 7 A graph depicting the curves according to one implementation scheme is shown.
[0017] Figure 8A graph depicting the curves according to one implementation scheme is shown. Detailed Implementation
[0018] This disclosure describes an apparatus for measuring electrophoretic mobility. In one exemplary embodiment, the apparatus includes: (1) a long coherence length laser; (2) an optical 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 combiner 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 combiner; (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 the output of the RF source to output in-phase data I and quadrature phase data Q of the frequency offset to be analyzed, thereby measuring electrophoretic mobility in the sample. In one embodiment, the laser is a single-frequency and polarized laser. In one embodiment, the splitter provides efficient use of the laser by having an asymmetric splitting ratio. In one embodiment, the AOM receives the light and shifts the frequency f of the light while leaking out some light that retains its original frequency. In one embodiment, the photodetector is a silicon photodiode, an avalanche photodiode, or a photomultiplier tube.
[0019] In one exemplary embodiment, the device includes: (1) a long coherence length laser; (2) an optical fiber splitter optically coupled to the laser; (3) a polarization-preserving (PM) acousto-optic modulator (AOM) optically coupled to the output of a reference arm of the splitter; (4) a sample cell for containing a sample and optically coupled to the output of a sample arm of the splitter; (5) a polarization-preserving combiner 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 combiner; (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 the output of the RF source to output in-phase data I and quadrature phase data Q of the frequency offset to be analyzed, thereby measuring electrophoretic mobility in the sample.
[0020] In one embodiment, unlike piezoelectric-based electrophoretic mobility measurement instruments, this device eliminates the need for (a) resolving the time-domain beat frequency signal and (b) detecting or resolving the local oscillator. In one embodiment, the device improves the phase stability between the local oscillator and the beat frequency signal. In one embodiment, the device filters out (i) frequencies exceeding the measurement bandwidth and (ii) frequencies that do not have a defined phase relationship with the local oscillator. In one embodiment, the in-phase quadrature phase (IQ) demodulator uses RF demodulation techniques to extract the Doppler frequency shift, thereby allowing for very precise generation of the quadrature signals required in demodulation. In another embodiment, the device also includes a narrowband filter that suppresses most noise outside the measurement bandwidth (i.e., "phase-locked loop" technique).
[0021] In one embodiment, the device allows the detection of multiple mobility substances in a sample by examining the frequency domain representation of the demodulated signal output from an in-phase quadrature phase (IQ) demodulator, thereby allowing direct measurement of the Doppler frequency shift of particles in the sample. In one embodiment, the device allows the calculation of the electrophoretic mobility of particles in the sample by multiplying the Doppler frequency shift by the electric field strength and the scattering vector. Furthermore, in one embodiment, the device directly measures the full spectrum of the (Doppler) frequency shift of particles in the sample, thereby allowing the differentiation of different mobilities within a single sample. In one embodiment, the device directly measures the spectral width of the Doppler frequency shift, thereby allowing inference of the particle size in the sample, and also allowing simultaneous measurement of electrophoretic light scattering and dynamic light scattering.
[0022] definition
[0023] Particles
[0024] Particles can be components of liquid samples or aliquots. These particles can be molecules, nanoparticles, virus-like particles, liposomes, emulsions, bacteria, and colloids of various types and sizes. The size range of these particles can be on the order of nanometers to micrometers.
[0025] Analysis of macromolecules or particulate matter in solution
[0026] Analysis of macromolecules or particulate matter in solution can be achieved by preparing a sample in a suitable solvent and then aliquoting it into a separation system, such as a liquid chromatography (LC) column or field flow fractionation (FFF) channel, in which the different particulate substances contained in the sample are separated into their various components. Once separated, the sample can typically be analyzed based on size, mass, or column affinity, using light scattering, refractive index, ultraviolet absorption, electrophoretic mobility, and viscosity response.
[0027] Light scattering
[0028] Light scattering (LS) is a non-invasive technique for characterizing macromolecules and various particles in solution. Two common types of light scattering detection used to characterize macromolecules are static light scattering and dynamic light scattering.
[0029] Dynamic light scattering
[0030] Dynamic light scattering, also known as quasi-elastic light scattering (QELS) and photon correlation spectroscopy (PCS), involves measuring the time-varying fluctuations in the scattered light signal using a fast photodetector. DLS measurements determine the diffusion coefficient of molecules or particles, which can then be used to calculate their hydrodynamic radii.
[0031] Static light scattering
[0032] Static light scattering (SLS) encompasses various techniques such as single-angle light scattering (SALS), two-angle light scattering (DALS), low-angle light scattering (LALS), and multi-angle light scattering (MALS). SLS experiments typically involve measuring the absolute intensity of light scattered from a sample in solution, illuminated by a narrow beam of light. Such measurements are often used for appropriate classes of particles / molecules to determine the size and structure of sample molecules or particles, and, when combined with knowledge of sample concentration, to determine the weight-average molar mass. Furthermore, the nonlinearity of the scattered light intensity as a function of sample concentration can be used to measure interparticle interactions and correlations.
[0033] Multi-angle light scattering
[0034] Multi-angle light scattering (MALS) is a type of light scattering (SLS) technique used to measure light scattered from a sample at multiple angles. It is used to determine the absolute molar mass and average size of molecules in a solution by detecting how they scatter light. The most common source is collimated light from a laser source; in this case, the technique is called multi-angle laser scattering (MALLS). The term "multi-angle" refers to detecting scattered light at different discrete angles, such as through measurements using a single detector that moves over a range of selected angles or an array of detectors fixed at specific angular positions.
[0035] MALS measurements require a set of auxiliary components. The most important of these is a collimated or focused beam (typically from a laser source that produces a collimated beam of monochromatic light) illuminating the sample area. The beam is usually plane-polarized light perpendicular to the measurement plane, but other polarizations can also be used, especially when studying anisotropic particles. Another required component is an optical cell, which holds the sample to be measured. Alternatively, a cell incorporating a device that allows measurement of a flowing sample can be used. If measuring the scattering properties of a single particle, a method must be provided to introduce such particles one at a time through the beam at points approximately equidistant from surrounding detectors.
[0036] While most MALS-based measurements are performed in a plane containing a set of detectors, typically equidistant from the centrally located sample through which the illumination beam passes, three-dimensional versions have also been developed. In these versions, the detectors are positioned on the surface of a sphere, with the sample controlled to pass through its center, where it intersects the path of the incident beam traveling along the diameter of the sphere. MALS techniques typically collect multiplexed data sequentially from the outputs of a set of discrete detectors. MALS light scattering photometers typically have multiple detectors.
[0037] Because different detectors in 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 signals captured by the photodetectors of the MALS detector at each angle. Without normalizing these differences, the MALS detector results may be meaningless and will inappropriately weight the different detector angles.
[0038] Electrophoretic light scattering
[0039] 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 typically converted to a zeta potential to allow comparison of materials under different experimental conditions. The basic physical principle is 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) will migrate toward the electrode with the opposite charge at a rate known as mobility, which is related to their zeta potential.
[0040] When an electric field is applied to a sample, any charged object in the sample will be affected by that field. The extra movement exhibited by particles due to their experience of the electric field is called electrophoretic mobility. Its typical unit is μm·cm / V·s (micrometers per volt-second), as it is the velocity [μm / s] per field strength [V / cm]. Electrophoretic mobility is a direct measurement from which the zeta potential can be derived (using the Smoluchowski / Debye-Hückel approximation or the full Henry function F(κa) to obtain the zeta potential from the mobility).
[0041] Current technology
[0042] Current ELS (Electronic Light Spectroscopy) instruments rely on comparing light scattered from a particle with unscattered light. Light scattered from a moving particle will shift in frequency (Doppler) by an amount proportional to the particle velocity. Therefore, light that has not been scattered and thus has not experienced a Doppler shift will have a slightly different frequency. By making a proper comparison, the presence of the Doppler shift can be detected, and the particle velocity can be extracted.
[0043] Due to the extremely high optical frequency (350 THz), it is difficult to directly track the phase / frequency of light (i.e., direct frequency comparison is difficult). A technique is typically used to downconvert this phase / frequency information to a manageable frequency (kHz), involving overlapping the light with a third beam that itself is frequency-shifted by a few kHz. The scattered light is then combined with this "reference" light, resulting in amplitude modulation at the difference frequency between the two beams (the result of overlapping two beams with different frequencies is often referred to as a "beat frequency signal"). Similarly, the unscattered light itself is combined with the reference light and forms its own beat frequency signal, the amplitude of which oscillates at the difference frequency between the unscattered light and the reference light. Typically, a moving mirror is used to generate a frequency-shifted reference light, resulting in two distinct beat frequency signals (whose frequencies are easily detectable), one with a Doppler frequency shift and the other without. Comparison of these two distinct beat frequency signals then allows the detection of the Doppler frequency shift.
[0044] Therefore, current technology relies on the generation and detection of two distinct beat frequency signals, requiring highly stable equipment, as any mechanical vibration will cause an unexpected (uncorrected) frequency shift in one beat frequency signal relative to the other. Furthermore, the magnitude of this frequency shift is limited to a few kHz due to the use of a moving mirror to generate the frequency-shifted reference light. Additionally, the mirror's motion is non-linear (it decelerates when the mirror reverses direction), thus generating a time-varying reference frequency. Therefore, a device is needed for measuring electrophoretic mobility.
[0045] In one implementation scheme Figure 1A and Figure 1BThe device is described, comprising: (1) a long coherence length laser 110; (2) an optical fiber splitter 115 optically coupled to the laser 110; (3) a polarization-preserving acousto-optic modulator 120 optically coupled to the sample arm output of the splitter 115; (4) a sample cell 125 for containing a sample and optically coupled to the output of the acousto-optic modulator 120; and (5) a polarization-preserving combiner 130 optically coupled to the reference arm of the splitter 115. The device includes (6) a photodetector 135 for detecting light output from the combiner 130, (7) an RF source 140 electrically coupled to the input of the acousto-optic modulator 120, and (8) a quadrature phase demodulator 145 electrically coupled to both the output of the photodetector 135 and the output of the RF source 140, to output in-phase data I and quadrature phase data Q of the frequency offset to be analyzed, thereby measuring the electrophoretic mobility in the sample. In another embodiment, the device further includes at least one polarization-maintaining (PM) fiber that couples any one of the laser 110, the splitter 115, the acousto-optic modulator 120, the sample cell 125, and the combiner 130 together. For example, the PM fiber is a standard coupler (e.g., an FCP coupler). In one embodiment, any one of the splitter 115, the acousto-optic modulator 120, and the combiner 130 is fused together, wherein such fused components can improve the performance of the device.
[0046] In one embodiment, the splitter 115 has a splitting ratio in which a majority of the laser emitted by the laser is directed to the sample cell 125. For example, the splitting ratio may allow 50% to 99.1% of the laser to be directed to the sample cell 125 (e.g., a 96:4 splitting ratio, where 96% of the laser is directed to the sample cell 125 and 4% is directed to the reference arm output of the splitter 115). In one embodiment, the sample cell 125 includes a light shield located between the cell housing and the collimator. In one embodiment, the acousto-optic modulator 120 includes a polarizer.
[0047] In another implementation scheme, such as Figure 1C As depicted, the device also includes a polarization-preserving attenuator 150, which is 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 in-phase quadrature-phase (IQ) demodulator 145 includes low-pass filters for in-phase data I and quadrature-phase data Q.
[0048] In one implementation scheme Figure 2AThe device is described, comprising: (1) a long coherence length laser 210; (2) an optical fiber splitter 215 optically coupled to the laser 210; (3) a polarization-preserving acousto-optic modulator 220 optically coupled to the reference arm output of the splitter 215; (4) a sample cell 225 for containing a sample and optically coupled to the sample arm output of the splitter 215; and (5) a polarization-preserving combiner 230 optically coupled to the acousto-optic modulator 220. The device includes (6) a photodetector 235 that detects light output from the combiner 230, (7) an RF source 240 electrically coupled to the input of the acousto-optic modulator 220, and (8) an in-phase quadrature phase demodulator 245 electrically coupled to both the output of the photodetector 235 and the output of the RF source 240, to output in-phase data I and quadrature phase data Q of the frequency offset to be analyzed, thereby measuring the electrophoretic mobility in the sample. In another embodiment, the device further includes at least one polarization-maintaining (PM) fiber that couples any one of the laser 210, the splitter 215, the acousto-optic modulator 220, the sample cell 225, and the combiner 230 together. For example, the PM fiber is a standard coupler (e.g., an FCP coupler). In one embodiment, any one of the splitter 215, the acousto-optic modulator 220, and the combiner 230 is fused together, wherein such fused components can improve the performance of the device.
[0049] In one embodiment, the splitter 215 has a splitting ratio in which a majority of the laser emitted by the laser is directed to the sample cell 225. For example, the splitting ratio may allow 50% to 99.1% of the laser to be directed to the sample cell 225 (e.g., a 96:4 splitting ratio, where 96% of the laser is directed to the sample cell 225 and 4% is directed to the reference arm output of the splitter 215). In one embodiment, the sample cell 225 includes a light shield located between the cell housing and the collimator. In one embodiment, the acousto-optic modulator 220 includes a polarizer.
[0050] In another implementation scheme, such as Figure 2B As depicted, the device also includes a polarization-preserving attenuator 250, which is 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 in-phase quadrature-phase (IQ) demodulator 245 includes low-pass filters for in-phase data I and quadrature-phase data Q.
[0051] Example
[0052] For example, Figure 3 The image depicts the device shifting the spectrum of data 310 0.025 kHz to the left (as shown by trace 315) and 0.025 kHz to the right (as shown by trace 320), where data 310 corresponds to data collected by photodetector 135 from a 200 nm polystyrene microsphere sample. In another example, Figure 4 The radius data extracted from the data output by the in-phase quadrature phase demodulators 145 and 245 is depicted. Specifically, Figure 4 The Lorentz fit is shown, which fits the width of the data trace to the radius extraction.
[0053] In addition, for example, Figure 5 The device is depicted shifting the spectrum of data 510 to the left by 0.015 kHz (as shown in trace 515) and to the right by 0.015 kHz (as shown in trace 520), where data 510 corresponds to data collected by photodetector 235 from a 2.5 mg / mL bovine serum albumin (BSA) sample.
[0054] In another example, Figure 6A The spectrum of the data output by in-phase and quadrature-phase demodulators 145 and 245, obtained by applying a Fast Fourier Transform (FFT) to the data, is depicted. In another example, Figure 6B The diagram illustrates how the data output by the in-phase quadrature phase demodulators 145 and 245 allows the device to resolve minute frequency shifts 615 and 620 in the data by observing the FFT of the data.
[0055] For example, Figure 7 The diagram illustrates how the in-phase quadrature phase demodulators 145 and 245 can filter and shape the outputs of photodetectors 13 and 235, enabling the observation of a single peak 710 (e.g., at 10 kHz). Furthermore, Figure 8 The diagram illustrates how in-phase quadrature phase demodulators 145, 245 and attenuators 150, 250 can generate a large signal-to-noise ratio (SNR), in which a high-power reference light is transmitted to photodetectors 135, 235, such that the noise from the light source is much larger (at least 10 times larger) than the noise equivalent power (NEP) (noise from the detectors) of photodetectors 135, 235.
[0056] In one implementation, the device generates and detects only a single beat frequency signal, which consists of the overlap between the scattered light and the reference light. For example, an acousto-optic modulator (AOM) generates an 80 MHz frequency shift for a beam transmitted through the AOM, wherein an 80 MHz electrical signal is applied to a piezoelectric transducer inside the AOM, causing the incident light to diffract and acquire an optical frequency shift that is perfectly synchronized / in phase with the applied 80 MHz electrical signal. A continuous and constant frequency shift exists (without nonlinear fluctuations), thus eliminating the need for linearization, data stitching, and a single known frequency.
[0057] In another example, the beam, shifted by 80 MHz, is then delivered to the sample, and the scattered light (further frequency-shifted due to moving particles) is collected and combined with an unmodulated laser beam to form a beat frequency signal at 80 MHz plus any Doppler shift introduced into the scattered light by the sample. The device then compares the beat frequency signal, for example, to the original 80 MHz electrical signal used to drive the AOM, which has significantly better phase and frequency stability compared to the second optical beat frequency signal and is perfectly matched in phase and frequency to the detected optical beat frequency signal. Furthermore, for example, the RF drive signal to the AOM can be used directly for demodulation.
[0058] Furthermore, for example, the device generates a reference frequency of 80 MHz instead of a few kHz, thereby allowing the beat frequency signal to be measured and demodulated (i.e. compared with) the original 80 MHz electrical signal over more cycles (e.g., using millions of cycles for comparison), thus improving frequency accuracy.
[0059] The descriptions of various embodiments of this disclosure are for illustrative purposes only and are not intended to be exhaustive or limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to explain the principles of the embodiments, their practical application or improvement relative to commercially available technology, or to enable others skilled in the art to understand the embodiments disclosed herein.
Claims
1. An apparatus, the apparatus comprising: Long coherence length laser; An optical fiber splitter, wherein the optical fiber splitter is optically coupled to the laser; A polarization-maintaining acousto-optic modulator, wherein the polarization-maintaining acousto-optic modulator is optically coupled to the sample arm output of the splitter; A sample cell, which is used to contain a sample and is optically coupled to the output of the acousto-optic modulator; A polarization-preserving combiner, which is optically coupled to the reference arm output of the splitter and the output of the sample cell; A photodetector is used to detect light output from the combiner; A radio frequency (RF) source, which is electrically coupled to the input terminal of the acousto-optic modulator; and An in-phase or quadrature phase demodulator is electrically coupled to the output of the photodetector and to the output of the radio frequency source to output in-phase data and quadrature phase data of the frequency offset to be analyzed, thereby measuring the electrophoretic mobility in the sample.
2. The device according to claim 1, further comprising at least one polarization-maintaining fiber, the at least one polarization-maintaining fiber coupling together any one of the laser, the splitter, the acousto-optic modulator, the sample cell, and the combiner.
3. The device of claim 1, wherein any one of the splitter, the modulator, and the combiner is fused together.
4. The device of claim 1, wherein the splitter has a splitting ratio, wherein a majority of the laser emitted by the laser is directed to the sample cell.
5. The apparatus of claim 1, wherein the sample cell includes a light shield located between the cell housing and the collimator.
6. The device of claim 1, wherein the acousto-optic modulator includes a polarizer.
7. The device of claim 1, further comprising a polarization-preserving attenuator optically coupled to the output of the reference arm of the splitter.
8. The device of claim 1, wherein the demodulator includes a low-pass filter for the in-phase data and the quadrature-phase data.
9. An apparatus, the apparatus comprising: Long coherence length laser; An optical fiber splitter, wherein the optical fiber splitter is optically coupled to the laser; A polarization-maintaining acousto-optic modulator, wherein the polarization-maintaining acousto-optic modulator is optically coupled to the output of the reference arm of the splitter; A sample cell for containing a sample and optically coupled to the sample arm output of the splitter; A polarization-maintaining combiner, which is optically coupled to the output of the acousto-optic modulator and the output of the sample cell; A photodetector is used to detect light output from the combiner; A radio frequency (RF) source, which is electrically coupled to the input terminal of the acousto-optic modulator; and An in-phase or quadrature phase demodulator is electrically coupled to the output of the photodetector and to the output of the radio frequency source to output in-phase data and quadrature phase data of the frequency offset to be analyzed, thereby measuring the electrophoretic mobility in the sample.
10. The apparatus of claim 9, further comprising at least one polarization-maintaining fiber, the at least one polarization-maintaining fiber coupling together any one of the laser, the splitter, the acousto-optic modulator, the sample cell, and the combiner.
11. The device of claim 9, wherein any one of the splitter, the acousto-optic modulator, and the combiner is fused together.
12. The apparatus of claim 9, wherein the splitter has a splitting ratio, wherein a majority of the laser emitted by the laser is directed to the sample cell.
13. The apparatus of claim 9, wherein the sample cell includes a light shield located between the cell housing and the collimator.
14. The device of claim 9, wherein the acousto-optic modulator includes a polarizer.
15. The device of claim 9, further comprising a polarization-preserving attenuator optically coupled to the output of the reference arm of the splitter.
16. The device of claim 9, wherein the demodulator includes a low-pass filter for the in-phase data and the quadrature-phase data.