Dual-Mode Scanning Optical System for Capillary Electrophoresis

Abstract

A dual-mode capillary electrophoresis system is disclosed, comprising: a plurality of capillaries for receiving a plurality of samples; a UV radiation source for generating UV radiation along a first path; a laser light source for generating laser radiation along a second path; and a galvanometric mirror configured to receive radiation from the UV radiation source along the first path, receive light from the laser light source along the second path, and direct the received UV radiation and the laser light onto a common optical path, the galvanometric mirror configured to scan the UV radiation and the laser light sequentially across the plurality of capillaries. The system may further include a detector for detecting UV radiation and a detector for detecting fluorescent radiation emitted by the samples in response to laser excitation via an optical fiber.

Description

Technical Field

[0001] (Related U.S. Application) This application claims the benefit of priority from U.S. Provisional Application No. 62 / 935,609, filed on November 14, 2019, the entire content of which is incorporated herein by reference.

[0002] (Field) The present disclosure generally relates to dual-mode capillary electrophoresis systems, and more specifically to capillary electrophoresis systems that can operate readily in at least two detection modes, such as UV absorption mode and laser-induced fluorescence (LIF) mode.

Background Art

[0003] (Background) Capillary electrophoresis is often employed for the high-speed separation and analysis of charged species such as synthetic polynucleotides, DNA sequencing fragments, DNA restriction fragments, amino acids, optical isomers of dansyl amino acids, and the separation of proteins, viruses, and bacteria. Micellar electrokinetic chromatography, isoelectric focusing, and on-column derivatization can all be performed on a CE column.

[0004] Current instruments can typically analyze only one sample at a time, which limits the throughput of the instrument. Further, changing the detection mode of current instruments is difficult and typically requires hardware modification and re-verification of the instrument.

Summary of the Invention

Means for Solving the Problems

[0005] (Summary) On one side, a dual-mode capillary electrophoresis system is disclosed. The dual-mode capillary electrophoresis system includes a plurality of capillaries for receiving a plurality of samples, a UV radiation source for generating UV radiation along a first path, a laser light source for generating laser radiation along a second path, a galvanometric mirror configured to receive radiation from the UV radiation source along the first path, receive light from the laser light source along the second path, and direct the received UV radiation and the laser light onto a common optical path, and further configured to sequentially scan the UV radiation and the laser light across the plurality of capillaries. The system may further include a first detector positioned with respect to the capillaries such that each of the capillaries receives at least a portion of the UV radiation passing through each of the capillaries when each of the capillaries is irradiated with UV radiation. A bundle of at least one optical fiber is positioned with respect to the capillaries to receive at least a portion of the fluorescent radiation emitted by a sample disposed within each of the capillaries in response to excitation of the sample in the capillary by the laser light. A second detector is optically coupled to an optical fiber for receiving at least a portion of the fluorescent radiation emitted by the capillaries.

[0006] When the UV radiation and the laser light are scanned across the capillaries, a lens may be disposed between the galvanometric mirror and the plurality of capillaries to focus the UV radiation and the laser light onto the capillaries. In some such embodiments, the lens is configured to focus the UV radiation and the laser light substantially onto the center of each of the capillaries.

[0007] In some embodiments, the laser radiation can excite the fluorescent label(s) attached to the sample disposed within the capillary. In some embodiments, ultraviolet (UV) radiation can be employed to excite the intrinsic fluorescence of the biological sample. The optical fiber can collect the fluorescent radiation. In some embodiments, a bundle of two optical fibers is employed to collect the laser-induced fluorescence or UV-induced fluorescence radiation. In some such embodiments, one bundle of the optical fibers is positioned above the lens to receive at least a portion of the laser-induced or UV-induced fluorescence radiation, angled downwardly towards the plurality of capillaries, and another bundle of the optical fibers is positioned below the lens to receive at least a portion of the laser-induced or UV-induced fluorescence radiation, angled upwardly towards the plurality of capillaries.

[0008] In some embodiments, the proximal ends of the optical fibers can be coupled to a plate for fixing them to the capillary. In some such embodiments, the distal ends of the optical fibers can be coupled to a coupling element that can align their distal ends relative to a second detector such that the light exiting the optical fibers can be detected by the detector. In some embodiments, the detector can measure the light having a plurality of wavelengths in parallel or can be a detector that provides spectral separation for measuring the plurality of wavelengths separately.

[0009] In some embodiments, the system may further include a controller for controlling the galvanometric mirror. The controller may be implemented in hardware, software and / or firmware. By way of example, the controller may include a processor and one or more memory modules that communicate with the processor via at least one communication bus. In some embodiments, instructions for operating the galvanometric mirror may be stored in a permanent memory module and transferred by the processor to a random access memory module during runtime to be executed to operate the galvanometric mirror. By way of example, the controller may sequentially cause the galvanometric mirror to illuminate a plurality of capillaries. In some such embodiments, the controller may communicate with a UV radiation source and a laser light source to activate the UV radiation source and the laser light source at these time intervals to transmit UV radiation or laser light to the galvanometric mirror at different time intervals. At each time interval, the mirror may scan UV radiation or laser light across a plurality of capillaries sequentially.

[0010] In some embodiments, the plurality of capillaries are stored within a cartridge. A mount may be provided on which the cartridge can be mounted to place the capillaries in the path of UV radiation and laser light.

[0011] In some embodiments, the UV radiation source may include a UV lamp for generating UV radiation and a plurality of filters that can be selectively deployed to select different wavelengths of the UV radiation emitted by the UV lamp. In some such embodiments, the UV lamp may generate UV radiation at wavelengths in the range of about 185 nm to about 400 nm. Further, in some embodiments, one or more filters may be disposed in front of a detector configured to detect fluorescence radiation, for example, to block excitation light and thereby increase the signal / noise level. In some embodiments, the light source may generate light having wavelengths in the range of about 372 nm to about 980 nm.

[0012] Various detectors can be employed to detect UV radiation and laser-induced fluorescence radiation. Some examples of suitable detectors include, but are not limited to, photodiodes and photomultiplier tubes, photomultiplier tubes and photodiode array spectrometers.

[0013] In some embodiments, the plurality of capillaries are disposed within a removable cartridge that is slidably insertable into the system, and the plurality of capillaries are aligned to receive the UV radiation and / or the laser light from the galvanometric mirror when the removable cartridge is in the inserted state of the system.

[0014] In another aspect, a cartridge for use with a dual-mode capillary electrophoresis system is described, the cartridge comprising a plurality of capillaries adapted to receive a plurality of samples, the cartridge being adapted to be insertable into a dual-mode capillary electrophoresis system between an inserted state and a removed state. The dual-mode capillary electrophoresis system includes a UV radiation source for generating UV radiation along a first path, a laser light source for generating laser radiation along a second path, a galvanometric mirror configured to receive radiation from the UV radiation source along the first path and light from the laser light source along the second path and to direct the received UV radiation and the laser light onto a common optical path, the galvanometric mirror further configured to sequentially scan the UV radiation and the laser light across the plurality of capillaries when the cartridge is in the inserted state, a first detector positioned relative to the capillaries to receive at least a portion of the UV radiation passing through each of the capillaries when each of the capillaries is irradiated with the UV radiation when the cartridge is in the inserted state, at least one bundle of optical fibers positioned relative to the capillaries to receive at least a portion of the fluorescence radiation emitted by a sample disposed within each of the capillaries in response to excitation of the sample in the capillary by the laser light or the UV radiation when the cartridge is in the inserted state, and a second detector optically coupled to the optical fibers for receiving at least a portion of the fluorescence radiation captured by the capillaries when the cartridge is in the inserted state. This specification also provides, for example, the following. (Item 1) A dual-mode capillary electrophoresis system comprising: a plurality of capillaries for receiving a plurality of samples; a UV radiation source for generating UV radiation along a first path; a laser light source for generating laser radiation along a second path; a galvanometric mirror configured to receive radiation from the UV radiation source along the first path and light from the laser light source along the second path, and to direct the received UV radiation and the laser light onto a common optical path, the galvanometric mirror being further configured to sequentially scan the UV radiation and the laser light across the plurality of capillaries; a first detector positioned relative to the capillaries to receive at least a portion of the UV radiation passing through each of the capillaries when each of the capillaries is irradiated with the UV radiation; at least one bundle of optical fibers positioned relative to the capillaries to receive at least a portion of the fluorescence radiation emitted by a sample disposed within each of the capillaries in response to excitation of the sample within the capillaries by the laser light or the UV radiation; a second detector optically coupled to the optical fibers for receiving at least a portion of the fluorescence radiation captured by the capillaries. A system comprising. (Item 2) The system of item 1, further comprising a lens disposed between the galvanometric mirror and the plurality of capillaries for focusing the UV radiation and the laser light onto the capillaries when the UV radiation and the laser light are scanned across the capillaries. (Item 3) The system of item 2, wherein the lens is configured to focus the UV radiation and the laser light substantially onto the center of each of the capillaries. (Item 4) The system of item 1, wherein the at least one bundle of optical fibers comprises a first bundle of optical fibers positioned above the scanning lens to receive at least a portion of the fluorescence radiation and angled towards the plurality of capillaries. (Item 5) The system according to item 1, wherein the bundle of at least one optical fiber is positioned below the scanning lens so as to receive at least a part of the fluorescence radiation, and comprises a bundle of second optical fibers angled towards the plurality of capillaries. (Item 6) The system according to item 1, further comprising a controller for controlling the galvanometric mirror. (Item 7) The system according to item 6, wherein the controller is configured to control the galvanometric mirror to scan the UV radiation and the laser light across the capillary at different time intervals. (Item 8) The system according to item 1, further comprising a cartridge containing the plurality of capillaries. (Item 9) The system according to item 1, further comprising a mount on which the cartridge can be mounted. (Item 10) The system according to item 9, further comprising a bracket to which the proximal end of the bundle of at least one optical fiber is coupled. (Item 11) The system according to item 10, further comprising a coupling element for receiving the proximal end of the bundle of at least one optical fiber and aligning the distal end with the second detector for coupling light from the optical fiber to the detector. (Item 12) The system according to item 1, wherein the UV radiation source comprises a UV lamp. (Item 13) The system according to item 1, wherein the UV radiation source comprises a plurality of filters selectively deployable to select different wavelength bands of the UV light emitted by the UV lamp. (Item 14) The system according to item 12, wherein the UV lamp generates UV radiation at wavelengths in the range of about 185 nm to about 400 nm. (Item 15) The system according to item 1, further comprising at least one filter disposed in front of the second detector for filtering out the fluorescence excitation light generated by the laser or UV source. (Item 16) The system according to item 1, wherein the laser light source generates light having a wavelength in the range of about 372 nm to about 980 nm. (Item 17) The system according to item 1, wherein the first detector comprises a photodiode. (Item 18) The system according to item 1, wherein the second detector comprises either a photomultiplier tube or a diode array spectrometer. (Item 19) The plurality of capillaries are disposed within a removable cartridge that is slidably insertable into the system, and the plurality of capillaries are aligned to receive the UV radiation and the laser light from the galvanometric mirror when the removable cartridge is in the inserted state within the system, the system of claim 1. (Item 20) A cartridge for use with a dual-mode capillary electrophoresis system, the cartridge comprising a plurality of capillaries adapted to receive a plurality of samples, the cartridge being adapted to be insertable into the dual-mode capillary electrophoresis system between an inserted state and a removed state, the dual-mode capillary electrophoresis system comprising a UV radiation source for generating UV radiation along a first path, a laser light source for generating laser radiation along a second path, a galvanometric mirror configured to receive radiation from the UV radiation source along the first path and light from the laser light source along the second path and to direct the received UV radiation and the laser light onto a common optical path, the galvanometric mirror being configured to sequentially scan the UV radiation and the laser light across the plurality of capillaries when the cartridge is in the inserted state, a first detector positioned relative to each of the capillaries to receive at least a portion of the UV radiation passing through each of the capillaries when each of the capillaries is irradiated with the UV radiation when the cartridge is in the inserted state, at least one bundle of optical fibers positioned relative to each of the capillaries to receive at least a portion of the fluorescent radiation emitted by a sample disposed within each of the capillaries in response to excitation of the sample within the capillaries by the laser light or the UV radiation when the cartridge is in the inserted state, a second detector optically coupled to the optical fibers for receiving at least a portion of the fluorescent radiation captured by the capillaries when the cartridge is in the inserted state A cartridge comprising.

Brief Description of the Drawings

[0015] (Brief Description of the Drawings) [[Figure 1A]] FIG. 1A schematically depicts a dual-mode capillary electrophoresis system according to an embodiment.

[0016] [[Figure 1B]] FIG. 1B schematically depicts certain components of the system shown in FIG. 1A.

[0017] [[Figure 1C]] FIG. 1C schematically depicts certain components of the system shown in FIG. 1A.

[0018] [[Figure 1D]] FIG. 1D schematically depicts a cartridge according to an embodiment including a plurality of capillaries and a cradle for receiving the cartridge.

[0019] [[Figure 1E]] FIG. 1E schematically depicts a UV radiation source suitable for use in the practice of some embodiments of the present teachings.

[0020] [[Figure 1F]] Figure 1F schematically depicts a lens employed in the system shown in Figure 1A for focusing either UV radiation or laser light onto a plurality of sample-holding capillaries.

[0021] [[Figure 1G]] Figure 1G shows a plurality of optical fibers for directing laser-induced fluorescence radiation to a detector, a plate for supporting the proximal ends of the optical fibers, a mount for receiving a cartridge containing the capillaries, and a translation stage for moving the mount and the plate.

[0022] [[Figure 2]] Figure 2 schematically depicts an example implementation of a controller for operating a galvanometric mirror.

[0023]

Figure 3A

Figure 3B

[0024]

Figure 4

[0025]

Figure 5

[0026]

Figure 6

[0027]

Figure 7

DETAILED DESCRIPTION

[0028] (Detailed Description) The present teachings provide a dual-mode capillary electrophoresis system that facilitates the analysis of multiple samples. In some embodiments, the system employs a galvanometric scanning mirror that can direct radiation from a laser or UV source sequentially across an array of capillaries, for example, through a single lens. In some embodiments, the array of capillaries can be implemented within a silicon chip with a window at each capillary location where the capillary is joined to the chip. The windows are configured to control the passage of light through the capillaries and provide optimal performance of the system. In some such embodiments, a photodiode is positioned, for example, along the optical axis to collect at least a portion of the UV radiation passing through the capillary to perform absorbance measurements, as discussed in further detail below. The photodiode can also serve to initially align the beam position with the center of each capillary window by sweeping the UV radiation or laser light across the array of capillaries and recording the center position.

[0029] During data acquisition, the galvanometric scanning mirror can step-scan the UV radiation or laser light to each capillary and maintain the radiation on each capillary for a preselected dwell time for data collection. In some embodiments, laser light is employed to excite a fluorescent label attached to the sample under investigation, or UV radiation is employed to excite intrinsic fluorescence (e.g., the intrinsic fluorescence of a biological sample). In response to such excitation, the biological sample exhibiting the fluorescent label or intrinsic fluorescence can emit fluorescent radiation, which can be detected as discussed below. As an example, in some embodiments, for such laser-induced fluorescence detection, an array of optical fibers (e.g., 24 optical fibers) is installed at an angle of 45 degrees above and below the optical axis of the radiation (e.g., 12 above and 12 below), and the intersection of the estimated extension lines from the tips of the fibers to the capillary is located at the center of the capillary, and the radiation enters the capillary at the intersection. The fibers can block the excitation light from reaching the photomultiplier tube and collect the fluorescent radiation from the entire capillary array after passing through a laser light or UV blocking filter and a bandpass filter to select the desired radiation bandwidth for detection and direct the fluorescent radiation to the photomultiplier tube. Alternatively, the radiation can be separated onto an array of photodiodes through an optical grating by wavelength. One advantage of the system according to the present teachings is to eliminate the need for hardware replacement to switch from UV radiation to laser light to interrogate the sample under study. Rather, in the system according to the present teachings, switching from one detection mode to another only involves moving the galvanometric mirror from one radiation source to another. In some embodiments, the user can simply select the detection mode of interest, for example, via a graphical user interface.

[0030] Referring to FIGS. 1A, 1B, 1C, 1D, 1E, and 1G, a dual-mode capillary electrophoresis system 100 according to an embodiment includes an array 122 of capillaries, the array 122 of capillaries being arranged within a cartridge 195, each of them being configured to receive a sample under study. The multi-capillary array 122 includes a silicon chip with windows at each capillary position where the capillaries are joined. The cartridge is insertable (either slidably or otherwise) into the system as described herein and, when in the inserted state, is mounted on the system. When the cartridge is in the inserted state, the capillaries 122 contained within the cartridge 195 are aligned to receive UV light and / or laser light from a galvo scanner and are also aligned with optical fibers and / or photodiodes that are part of the detection system.

[0031] By way of example, FIGS. 3A and 3B schematically depict an array 122 of capillaries joined to a chip 122a and having windows 122b through which laser light and / or UV radiation can be received or emitted. The windows control the passage of radiation through the capillaries for optimal performance of the system. As discussed in more detail below, the capillaries are positioned within the path of radiation generated by multiple radiation sources.

[0032] In this embodiment, system 100 includes an ultraviolet (UV) radiation source 131 (see FIG. 1E), an associated UV filter 130, and a laser source 110. The UV radiation source can be, for example, a UV lamp that can generate UV radiation (e.g., radiation with wavelengths in the range of about 185 nm to about 400 nm) to perform absorbance measurements of samples disposed within capillary 122, and the laser source 110 can be any suitable laser, which generates laser radiation by inducing fluorescence radiation from one or more samples disposed within the capillary (e.g., exciting a fluorescent label attached to one or more samples disposed within capillary 122). By way of example, the laser source 110 can generate radiation at one or more wavelengths in the range of about 372 nm to about 980 nm to perform laser-induced fluorescence studies of those samples. By way of example, as described above, in some embodiments, the sample disposed within the capillary can be labeled with one or more fluorescent tags, which can be excited by the laser radiation and, in response to such excitation, emit fluorescence radiation. In some embodiments, UV radiation can be employed to excite the intrinsic fluorescence of biological samples.

[0033] In this embodiment, the UV radiation source 120 includes a broad-spectrum UV lamp 120a. The UV source uses a single optical fiber (see joint 202 in FIG. 1E) that extends to a fiber collimator (see fiber collimator 120b in FIG. 1). A plurality of switchable UV filters 130 are provided, which can be selected one at a time to filter the radiation generated by the UV radiation source 120. A stepper motor can be used to switch the UV filter disposed along the path of the radiation generated by the UV radiation source 120, and a knob 130a is used to remove the UV filter. Thus, the wavelength of interest can be selected from the wavelengths generated by the broad-spectrum UV lamp. In addition, the UV source is adjustable by use of a stepper motor to maximize the optical power depending on the selected wavelength and the filter(s) utilized.

[0034] As shown in FIG. 1E, the lens pair 200 can focus the UV radiation generated by the lamp toward the UV output joint 202. The shutter 203 can be enabled to prevent the UV radiation generated by the lamp from exiting the source. The X-Y translation device 204 can be moved via a stepper motor to enable adjustment of the position of the UV output joint relative to the lens pair 200.

[0035] The dual-mode capillary electrophoresis system 100 further includes a suitable optical system for directing the radiation emitted by the laser source 110 and the UV radiation source 120 onto the array of capillaries 122. Such optical elements can include, but are not limited to, one or more mirrors, lenses (e.g., focusing lenses), among others. In this embodiment, the galvanometric scanning mirrors 116 can receive the radiation emitted by the UV radiation source 120 and the laser 110 along different paths (PA) and (PB), respectively, and direct the UV radiation and the laser light onto a common optical path that is directed to the focusing or scanning lens 114. As shown in FIG. 1F, the focusing lens 114 can be held in a fixed position via its coupling to the holder 114a.

[0036] In this embodiment, the galvanometric mirrors 116 receive the UV radiation and the laser light directly from the UV and laser sources, respectively, although in other embodiments, one or more optical elements (e.g., lenses) can be positioned between either the UV radiation source or the laser source and the galvanometric mirrors.

[0037] The focusing or scanning lens 114 can, in turn, focus the UV radiation and the laser light onto one of the capillaries of the capillary array 122. For example, in some embodiments, the lens 114 is configured to focus the UV radiation and the laser light at the center of a selected capillary. The galvanometric mirror 116 can be scanned to sequentially illuminate the samples contained within the capillaries of the capillary array with the UV radiation and the laser light.

[0038] System 100 may further include a plurality of detectors for detecting at least a portion of the UV radiation transmitted through the capillary and the fluorescent radiation emitted by one or more fluorescent labels attached to the sample(s) disposed within the capillary in response to excitation by laser light or excitation of the intrinsic fluorescence of one or more biomolecules of the biological sample by UV radiation. The detector may generate a detection signal in response to the detection of the UV radiation and / or the fluorescent radiation, and the detection signal may be analyzed to obtain information regarding the sample disposed within the capillary.

[0039] More specifically, in this embodiment, the UV detector 190 (e.g., a photodiode detector) is positioned relative to the capillary to receive at least a portion of the UV radiation transmitted through the sample disposed within the capillary. In this embodiment, the photodiode detector 190 is positioned substantially along a common optical path, and the galvanometric mirror 116 directs the UV radiation and the laser light along the common optical path.

[0040] In some embodiments, the photodiode detector 190 also serves to initially align the beam position to the center of each window. For example, the UV radiation may be swept across the array of capillaries, and the center position of the capillary may be recorded. There is a window in front of each capillary. When light passes through the window associated with the capillary during the sweep of the UV radiation, a signal indicating eight peaks is detected. The midpoint between the start and end of each peak corresponds to the center of the capillary window and thus to the capillary.

[0041] In this embodiment, system 100 further includes a fluorescence detector 180 for detecting laser-induced or UV-induced fluorescence, which, in this implementation, is a photomultiplier tube (PMT) for detecting fluorescence radiation emitted by a sample (e.g., fluorescence radiation emitted by a fluorescent marker attached to the sample or intrinsic fluorescence radiation of a biological sample excited by UV radiation). As discussed in more detail below, in this embodiment, the fluorescence detector receives the emitted fluorescence radiation via a plurality of optical fibers 185.

[0042] More specifically, an array of optical fibers 185a is positioned above the plane of the optical axis of the radiation (i.e., the common optical path), and the fibers are angled downward at approximately 45 degrees to receive at least a portion of the fluorescence radiation emitted by the sample(s) disposed within the capillary. Another array of optical fibers 185b is positioned below the plane of the optical axis, and the fibers of that array are angled upward at approximately 45 degrees to receive at least a portion of the fluorescence radiation emitted by the sample(s) disposed within the capillary. Generally, the upper and lower optical fibers are angled such that their estimated extension lines intersect the core of the capillary through which the radiation passes.

[0043] In this embodiment, each of the upper and lower bundles of optical fibers includes 12 fibers (i.e., a total of 24 optical fibers are employed), although in other embodiments, other numbers of optical fibers may be employed. In this embodiment, the proximal ends of the optical fibers 185 are attached to a plate 191 that is attached to a mount 193 on which a cartridge 195 containing the capillary can be mounted. As shown in FIG. 1G, the mount 193 can be coupled to a translation stage 193a, which enables adjustment of the height of the mount to align the capillary with the radiation / light beam. A plurality of guide rods (400) can bring the collection fibers close to the capillary.

[0044] The distal end of the optical fiber 185 is coupled to a fiber optic coupling element 196 that aligns the distal end of the optical fiber with a fluorescence detector for efficiently coupling fluorescence radiation (e.g., laser-induced or UV-induced fluorescence radiation) into the fluorescence detector.

[0045] In use, the galvanometric scanning mirror 116 scans across the capillary 122 by sequentially stepping the UV and laser beams across the central location of the capillary 122. During data acquisition, the beam is centered on the capillary for a selected dwell time when data (e.g., UV absorption data and / or fluorescence data) is being collected. The dwell time can vary, for example, based on the number of capillaries and the type of analysis.

[0046] In some embodiments, a controller 300 can control the scanning of the galvanometric mirror 116 to direct the UV radiation or laser light beam at the capillary. The controller 300 can be implemented in hardware, firmware, and / or software. By way of example, as shown in FIG. 2, the controller 300 can include a processor 302, a random access memory RAM 304, a permanent memory ROM 306, and a communication bus 308 that enables the processor 302 to communicate with the other components of the controller 300. A set of instructions for controlling the galvanometric mirror 116 can be stored in the ROM 306 and transferred to the RAM 304 during runtime to control the scanning of the galvanometric mirror 116.

[0047] The fluorescence radiation emitted by the sample disposed within the capillary is collected by the fiber 185, which then transmits the collected fluorescence radiation to the fluorescence detector 180. In this embodiment, the cartridge 135 includes a filter 135a for blocking scattered laser or UV excitation light and a band-pass filter 135b for positioning in front of the fluorescence detector 180, preventing scattered laser or UV excitation light from reaching the detector and enabling the desired bandwidth of the fluorescence radiation to reach the detector, thereby improving the signal-to-noise ratio of the detected fluorescence radiation.

[0048] In some embodiments, the capillary is illuminated with UV radiation and laser light during different time intervals, but in some embodiments, the capillary can be illuminated sequentially with UV radiation and laser light. In some embodiments, at least a portion of the UV radiation can be absorbed by the illuminated sample, and a portion of the UV radiation can be transmitted through the sample. The UV radiation (or at least a portion thereof) transmitted through the sample can be detected by the photodiode detector 190. The photodiode detector can generate a detection signal that can be employed to determine the UV absorption of the illuminated sample.

[0049] As schematically shown in FIG. 2, the system 100 can further include an analysis module 1000, which communicates with the photodiode 190 and the photomultiplier tube 180, receives detection signals from these detectors, and operates on the signals to obtain information regarding the sample under inspection. The analysis module 1000 can be implemented in hardware, firmware, and / or software in the manner discussed above in connection with the controller 300, for example. In some embodiments, a diode array spectrometer detector can be employed.

[0050] The dual-mode capillary electrophoresis system 100 according to the present teachings can provide several advantages. For example, in such a system, switching the operating mode from the UV absorption mode to the laser-induced fluorescence (LIF) or native fluorescence (also referred to as fluorescence spectroscopy) mode can be easily achieved by adjusting a galvanometric scanning mirror to receive radiation from the source of interest. In other words, since the system employs common components for the two modes, there is no need to remove and replace various components and switch from one operating mode to another.

[0051] (Example) (Example 1) The UV absorption of samples of deionized (DI) water containing different concentrations of caffeine (i.e., 2 μM, 5 μM, 20 μM, 100 μM, 500 μM, 1 mM, 2 mM, and 3 mM) was measured at a wavelength of 220 nm by passing a plurality of capillaries containing the samples through UV radiation. The decrease in the transmitted UV power was converted to UV absorption.

[0052] Figure 4 2 demonstrates the linear dynamic range in the detection of caffeine concentrations from 2 μm to a maximum of 2 mM with a linear correlation of R

[0053] Figure 5 shows a CZE separation using a test MixB sample (Sciex) performed simultaneously through eight capillaries. The relative standard deviation of the migration time was less than 0.5% both between runs and between capillaries. The relative standard deviation of the peak area was less than 2% between runs and less than 5% between capillaries. The UV signal crosstalk from adjacent capillaries was less than 0.08%.

[0054] (Example 2) Laser-induced fluorescence (LIF) was measured by placing fluorescence through a fiber optic array cable onto a photomultiplier detector. The excitation wavelength was 488 nm for sodium fluorescein and the LIF test Mix sample. Figure 6 shows the fluorescence intensity (relative fluorescence units, RFU) using different concentrations of sodium fluorescein (i.e., 100 pM, 200 pM, 1 nM, 5 nM, 20 nM, 100 nM, 500 nM, and 1 μm) in a 50-μm core capillary array. The dynamic range is at least 10,000:1 with R 2 = 0.9998.

[0055] Figure 7 shows the results of CZE (capillary zone electrophoresis) separation using an LIF test Mix sample (Sciex) performed simultaneously through eight capillaries. The LIF signal crosstalk from adjacent capillaries is below 0.015%.

Claims

**Claim 1**: A capillary electrophoresis system comprising: A plurality of capillaries for receiving a plurality of samples; A UV radiation source for generating UV radiation; A laser light source for generating laser light; A galvanometric mirror configured to receive the UV radiation, receive the laser light, and direct the received UV radiation and the received laser light onto a common optical path along mutually different paths, and further configured to sequentially scan the UV radiation and the laser light across the plurality of capillaries; A first detector positioned relative to the capillaries to receive at least a portion of the UV radiation passing through each of the capillaries when each of the capillaries is irradiated with the UV radiation; At least one bundle of optical fibers positioned relative to the capillaries to receive at least a portion of the fluorescence radiation emitted by a sample disposed within each of the capillaries in response to excitation of the sample within the capillaries by the laser light or the UV radiation; A second detector optically coupled to the optical fibers for receiving at least a portion of the fluorescence radiation received by the at least one bundle of optical fibers. A system comprising the above components. **Claim 2**: The system according to claim 1, further comprising a lens disposed between the galvanometric mirror and the plurality of capillaries for focusing the UV radiation and the laser light onto the capillaries when the UV radiation and the laser light are scanned across the capillaries. **Claim 3**: The system according to claim 2, wherein the lens is configured to focus the UV radiation and the laser light onto the center of each of the capillaries. **Claim 4**: The system according to claim 2, wherein the at least one bundle of optical fibers comprises a first bundle of optical fibers positioned above the lens to receive at least a portion of the fluorescence radiation and angled towards the plurality of capillaries. **Claim 5**: The system according to claim 2, wherein the bundle of at least one optical fiber comprises a bundle of second optical fibers positioned below the lens to receive at least a portion of the fluorescent radiation and angled toward the plurality of capillaries.

6. The system according to claim 1, further comprising a controller for controlling the galvanometric mirror.

7. The system according to claim 6, wherein the controller is configured to control the galvanometric mirror to scan the UV radiation and the laser light across the capillaries at different time intervals.

8. The system according to claim 1, further comprising a cartridge including the plurality of capillaries.

9. The system according to claim 8, further comprising a mount on which the cartridge can be mounted.

10. The system according to claim 9, further comprising a bracket to which the proximal end of the bundle of at least one optical fiber is coupled.

11. The system according to claim 10, further comprising a coupling element for receiving the distal end of the bundle of at least one optical fiber and aligning the distal end with the second detector to couple light from the optical fiber to the detector.

12. The system according to claim 1, wherein the UV radiation source comprises a UV lamp.

13. The system according to claim 12, wherein the UV radiation source comprises a plurality of filters selectively deployable to select different wavelength bands of the UV radiation emitted by the UV lamp.

14. The system according to claim 12, wherein the UV lamp generates UV radiation at a wavelength within the range of 185 nm to 400 nm.

15. The system according to claim 1, further comprising at least one filter disposed in front of the second detector to filter out the fluorescence excitation light generated by the laser or UV source.

16. The system according to claim 1, wherein the laser light source generates light having a wavelength within the range of 372 nm to 980 nm.

17. The system according to claim 1, wherein the first detector comprises a photodiode.

18. The system according to claim 1, wherein the second detector comprises either a photomultiplier tube or a diode array spectrometer.

19. The plurality of capillaries are disposed within a removable cartridge that is slidably insertable into the system, and the plurality of capillaries are aligned to receive the UV radiation and the laser light from the galvanometric mirror when the removable cartridge is in the inserted state in the system. The system according to claim 1.

20. A cartridge for use with a capillary electrophoresis system, the cartridge comprising a plurality of capillaries adapted to receive a plurality of samples, the cartridge being adapted to be insertable into the capillary electrophoresis system between an inserted state and a removed state, the capillary electrophoresis system comprising a UV radiation source for generating UV radiation, a laser light source for generating laser light, a galvanometric mirror configured to receive the UV radiation, receive the laser light, and direct the received UV radiation and the received laser light onto a common optical path along mutually different paths, and further configured to scan the UV radiation and the laser light sequentially across the plurality of capillaries when the cartridge is in the inserted state, a first detector positioned relative to the capillaries to receive at least a portion of the UV radiation passing through each of the capillaries when each of the capillaries is irradiated with the UV radiation when the cartridge is in the inserted state, at least one bundle of optical fibers positioned relative to the capillaries to receive at least a portion of the fluorescence radiation emitted by a sample disposed within each of the capillaries in response to excitation of the sample within the capillaries by the laser light or the UV radiation when the cartridge is in the inserted state, and a second detector optically coupled to the optical fibers for receiving at least a portion of the fluorescence radiation received by the at least one bundle of optical fibers when the cartridge is in the inserted state A cartridge comprising.

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